Biomedical subjects

A Andersen

Publications and source records attributed to A Andersen.

At least 73 records · Page 4Linked to original sources

PubMed1997

Birth defects among offspring of Norwegian farmers, 1967-1991.

We investigated birth defects (N = 4,565) reported to the Medical Birth Registry of Norway among 192,417 births between 1967 and 1991 to parents identified as farmers in five agricultural and horticultural censuses between 1969 and 1989. The prevalences at birth of all and specific birth defects deviated little from those among 61,351 births to non-farmers in agricultural municipalities. We classified exposure indicators on the basis of information provided at the agricultural censuses. The main hypotheses were that parental exposure to pesticides was associated with defects of the central nervous system, orofacial clefts, some male genital defects, and limb reduction defects. We found moderate increases in risk for spina bifida and hydrocephaly, the associations being strongest for exposure to pesticides in orchards or greenhouses [spina bifida: 5 exposed cases, odds ratio (OR) = 2.76, 95% confidence interval (CI) = 1.07-7.13; hydrocephaly: 5 exposed cases, OR = 3.49, 95% CI = 1.34-9.09]. Exposure to pesticides, in particular in grain farming, was also associated with limb reduction defects (OR = 2.50; 95% CI = 1.06-5.90). We also saw an association with pesticides for cryptorchism and hypospadias. We found less striking associations for other specific defects and pesticide indicators, animal farming, and fertilizer regimens.

Abnormalities, Drug-Induced↗

PubMed1997

Summary of avoidable cancers in the Nordic countries.

An overview is given of the most important known causes of cancer in the five Nordic countries and the resulting number of cancers that are potentially avoidable. The main causes include active and passive smoking, alcohol consumption, exposure to asbestos and other occupational carcinogens, solar and ionizing radiation, obesity, human papillomavirus infection in the female genital tract and infection with Helicobacter pylori. The organs most commonly affected are those of the respiratory system, the upper digestive tract and stomach, skin, the lower urinary tract and the uterine cervix. Annually, more than 18,000 cancers in men and 11,000 in women in the Nordic populations could be avoided by eliminating exposure to known carcinogens which is equivalent to 33% and 20% of all cancers arising in men and women, respectively, around the year 2000. Smoking habits account for a little more than half of these avoidable cases. Estimates of avoidable cancers are given for each Nordic country, separately.

Air Pollutants↗

PubMed1997

Effects of 3-deazaadenosine on apoptosis-related gene transcripts in HL-60 cells.

The effect of the transmethylation inhibitor 3-deazaadenosine on transcription levels of genes associated with apoptosis was investigated in HL-60 cells. After incubation of HL-60 cells with 100 microM 3-deazaadenosine for 45 min., a schedule known to perturb transmethylation metabolites and initiate apoptosis in these cells, a 50% decrease in c-myc and a 50% increase in bcl-2 RNA steady-state levels compared to control cells were observed. Transcription levels of c-myc continued to decrease after extended exposure to 3-deazaadenosine, while bcl-2 mRNA levels dropped to 25% and 30% below those in control cells after 1.5 hr and 3 hr, respectively. The expression levels of the bcl-2 related bax gene, showed a similar pattern as bcl-2; a 60% increase was initially measured, but after 1.5 and 3 hr, bax transcripts were 80% and 70% respectively, of those found in untreated cells. Another bcl-2 related gene, bcl-x, was previously reported to generate two transcripts in human cells. The long variant bcl-x1 acts as bcl-2, while the short form bcl-xs induces apoptosis. We were unable to detect bcl-xs transcripts in untreated and 3-deazaadenosine treated cells by the highly sensitive reverse transcriptase polymerase chain reaction method. This suggests that this gene product may not be involved in 3-deazaadenosine induced apoptosis in HL-60 cells. Bcl-x1 mRNA levels, however, slowly decreased with about 50% after 1.5 or 3 hr 3-deazaadenosine treatment. It is concluded that 3-deazaadenosine initiated apoptosis affects c-myc, bcl-2, bax and bcl-x1 mRNA levels.

Apoptosis↗

PubMed1997

Avoidable cancers in the Nordic countries. Tobacco smoking.

Active smoking is causally associated with cancers of the lung, larynx, oral cavity, pharynx, oesophagus, pancreas, renal parenchyma, renal pelvis and urinary bladder, and passive smoking appears to be causally associated with cancer of the lung. Information on smoking habits for the years 1965, 1975 and 1985 shows that more men than women in the Nordic countries were current smokers. The rates of women were stable over time and those of men were decreasing, approaching those of women. Lung cancer, in particular, is strongly associated with active smoking: by increasing the number of cigarettes smoked per day (lifelong) to 5, 10, 20 and 40 or more, the risk increases by five-, eight-, 16- and 30-fold, respectively, over that of people who have never smoked. Thus, with approximately 35% current smokers and 25% former smokers among Nordic men in 1985 and approximately 30% current smokers and 15% former smokers among Nordic women in that year, by the year 2000 10,000 cases of lung cancer (6,500 in men and 3,500 in women) will be caused by active smoking; this is equivalent to 82% of all cases of lung cancer in these populations. Another 6,000 cancers of other types (4,000 in men and 2,000 in women) are caused annually by active smoking, yielding a total of 16,000 new cases each year around the turn of the century. This implies that 14% (19% in men and 9% in women) of all incident cancers in the Nordic countries around the year 2000 will be caused by active tobacco smoking. In comparison, passive smoking is a minor cause of lung cancer, responsible for approximately 0.6% of all new cases (approximately 70 cases annually) in this area around the turn of the century.

Female↗

PubMed1997

Avoidable cancers in the Nordic countries. Alcohol consumption.

Alcohol intake is causally associated with cancers of the larynx, oral cavity, pharynx, oesophagus and liver. In all five Nordic countries, alcohol consumption increased substantially between 1965 (6.5 litres per adult per year) and 1975 (10 litres), but remained at about 10 litres between 1975 and 1985. The daily consumption of men during the period was substantially higher than that of women, and that of both men and women was higher in Denmark than in the other Nordic countries. In about 2000, an annual total of almost 1,300 cancer cases (1,000 in men and 300 in women) would be avoided if alcohol drinking were eliminated. This corresponds to about 29% of all alcohol-related cancers, i.e. in the oesophagus (37%), oral cavity and pharynx (33%), larynx (29%) and liver (15%). About 2% of all cancers in men and 1% in women in the Nordic countries around the year 2000 will be caused by the drinking habits of the respective populations.

Alcohol Drinking↗

PubMed1997

Avoidable cancers in the Nordic countries. Occupation.

A number of chemicals encountered predominantly in occupational settings have been causally linked with cancer in humans; furthermore, several industrial processes and occupations have been associated convincingly with increased rates of cancer, although the specific carcinogens remain to be identified. The tissues affected are mainly the epithelial lining of the respiratory organs (nasal cavity, paranasal sinuses, larynx and lung), and urinary tract (renal parenchyma, renal pelvis and urinary bladder), the mesothelial linings, the bone marrow and the liver. During the period 1970-84, almost 4 million people (3.7 million men and 0.2 million women) in the Nordic countries were potentially exposed to above-average levels of one or more verified industrial carcinogens. It is expected that these exposures will result in a total of about 1,900 new cases of cancer every year in the Nordic countries around the year 2000, with 1,890 among men and fewer than 25 among women. The proportions that could be avoided if industrial carcinogens were eliminated would be 70% of mesotheliomas, 20% of cancers of the nasal cavity and sinuses, 12% of lung cancers, 5% of laryngeal cancers, 2% of urinary bladder cancers, 1% of the leukaemias, and 1% of renal cancers. Overall, it is estimated that verified industrial carcinogens will account for approximately 3% of all cancers in men and less than 0.1% of all cancers in women in the Nordic countries around the year 2000. No attempt was made to estimate the potential effects of suspected carcinogens in the workplace.

Air Pollutants, Occupational↗

PubMed1997

Avoidable cancers in the Nordic countries. External environment.

Air pollutants arising from traffic clustering and industrial production include a number of chemical compounds that at high doses are carcinogenic in animal models and in some instances also in humans. Direct epidemiological evidence for a carcinogenic effect of air pollution in humans is, however, weak, and most of the available studies are limited by lack of adequate control of confounding factors and other methodological drawbacks. Limited evidence exists for a link between urban air pollution and lung cancer, with reported relative risks of 1.0-1.5. About one-third of the population of the Nordic countries, corresponding to 7.3 million people, lives in urban areas. If there is an excess risk associated with air pollution, the annual number of lung cancer cases around the year 2000 in the Nordic countries would range from 0 (no excess risk) to 1,800 (relative risk, 1.5). As the existence of a causal link between air pollution and cancer is not uncorroborated, measures for avoiding cancer from this source cannot be recommended.

Air Pollutants↗

PubMed1996

Exposure to styrene and mortality from nervous system diseases and mental disorders.

Chronic low-dose exposure to solvents has been associated in epidemiologic studies with chronic neurotoxicity, but the evidence is not consistent. Styrene causes acute disturbances in the central and peripheral nervous systems. To determine if exposure to styrene may contribute to chronic diseases of the central nervous system, the authors examined mortality from nervous system diseases, mental disorders, and suicide in relation to styrene exposure in an international historical cohort study. The cohort involved 35,443 workers employed during 1945-1991 in the reinforced plastics industry, where high exposures to styrene occur. Indicators of exposure were reconstructed through job histories and environmental and biologic monitoring data. Poisson regression was used for internal comparisons. Mortality from diseases of the central nervous system (27 deaths) increased with time since first exposure, duration of exposure, average level of exposure, and cumulative exposure to styrene. A quadratic model described best the dose-response shape for cumulative exposure and duration of exposure with the highest risks at around 300 ppm-years and 5 years, respectively, and a subsequent decrease in risk in the highest exposure categories. Mortality from epilepsy increased monotonically with all styrene exposure indicators, while associations for degenerative diseases of the central nervous system were generally weaker. Mortality from mental disorders and suicide decreased with increasing duration of exposure and cumulative exposure, while there was no trend with time since first exposure and average exposure to styrene. These findings suggest that, in addition to the known acute effects, exposure to styrene may contribute to chronic diseases of the central nervous system.

Cause of Death↗

PubMed1996

Selected novel flavones inhibit the DNA binding or the DNA religation step of eukaryotic topoisomerase I.

Topoisomerases are involved in many aspects of DNA metabolism such as replication and transcription reactions. Camptothecins, which stabilize the covalent intermediate of topoisomerase I and DNA are effective, though toxic, drugs for cancer therapy. In this study, a new class of topoisomerase I inhibitors was identified, and their mode of action was characterized using recombinant human topoisomerase I preparations and human HL-60 leukemic cells. Quercetin and the related natural flavones, acacetin, apigenin, kaempferol, and morin, inhibit topoisomerase I-catalyzed DNA religation. In contrast to camptothecin, these compounds do not act directly on the catalytic intermediate and also do not interfere with DNA cleavage. However, formation of a ternary complex with topoisomerase I and DNA during the cleavage reaction inhibits the following DNA religation step. 3,3',4',7-Tetrahydroxy-substituted flavones stabilize the covalent topoisomerase I-DNA intermediate most efficiently. Enhanced formation of covalent topoisomerase I-DNA complexes was also demonstrated in human HL-60 cells. In contrast, synthetic 3,5'-dibromo- 4'-hydroxy-3-methylflavones bind selectively to topoisomerase I in its non-DNA-bound form and block the following DNA binding step. As a consequence, these synthetic flavonoids are capable of counteracting topoisomerase I-directed effects of camptothecin. Inhibition of DNA binding is obtained by voluminous hydrophobic substituents in 6-position of the flavone structure. Our data show that selective inhibitors of both half-reactions of topoisomerase I can be derived from the flavone structure.

Base Sequence↗

PubMed1996

Cancer in offspring of parents engaged in agricultural activities in Norway: incidence and risk factors in the farm environment.

In this study of cancer in offspring we demonstrate that factors linked to horticulture and use of pesticides are associated with cancer at an early age, whereas factors in animal husbandry, in particular poultry farming, are associated with cancers in later childhood and young adulthood. Incident cancer was investigated in offspring born in 1952-1991 to parents identified as farm holders in agricultural censuses in Norway in 1969-1989. In the follow-up of 323,292 offspring for 5.7 million person-years, 1,275 incident cancers were identified in the Cancer Registry for 1965-1991. The standardized incidence for all cancers was equal to the total rural population of Norway, but cohort subjects had an excess incidence of nervous-system tumours and testicular cancers in certain regions and strata of time that could imply that specific risk factors were of importance. Classification of exposure indicators was based on information given at the agricultural censuses. Risk factors were found for brain tumours, in particular non-astrocytic neuroepithelial tumours: for all ages, pig farming tripled the risk [rate ratio (RR), 3.11; 95% confidence interval (CI), 1.89-5.13]; indicators of pesticide use had an independent effect of the same magnitude in a dose-response fashion, strongest in children aged 0 to 14 years (RR, 3.37; 95% CI, 1.63-6.94). Horticulture and pesticide indicators were associated with all cancers at ages 0 to 4 years, Wilms' tumour, non-Hodgkin's lymphoma, eye cancer and neuroblastoma. Chicken farming was associated with some common cancers of adolescence, and was strongest for osteosarcoma and mixed cellular type of Hodgkin's disease. The main problem in this large cohort study is the crude exposure indicators available; the resulting misclassification is likely to bias any true association towards unity.

Acute Disease↗

PubMed1996

Truly late onset of eating disorders: a study of 11 cases averaging 60 years of age at presentation.

OBJECTIVE: To study late-onset cases of eating disorders in order to (1) document the occurrence of these cases as truly new onset, even if postmenopausal; (2) to alert clinicians to the category of late-onset eating disorders, especially clinical features and treatment response; (3) to challenge some prevailing assumptions of etiology. METHODS: Selection of cases of eating disorders with first onset after age 40 that met DSM-IV criteria, by review of eating disorders admissions to three university hospital programs. RESULTS: Eleven patients, approximately 1% of all cases of eating disorders, had first onset of an eating disorder after age 40 and as late as 77, with an average onset of 56 and clinical presentation at 60 years. They met DSM-IV criteria for all subtypes of eating disorders. In general, concurrent medical and comorbid psychiatric symptoms made recognition and treatment more complex. DISCUSSION: Truly late-onset cases do occur, challenging etiological theories requiring adolescent age of onset, premenopausal endocrine functioning, or adolescent psychodynamic conflicts. Late-occurring cases, after accurate diagnosis, require an appreciation of psychological themes pertinent to this age group, such as bereavement or unresolved body image issues. Age by itself is no barrier to onset of eating disorders, which may occur whenever self-starvation and/or binge-purge behaviors become entrenched as sustaining behaviors for amelioration of psychodynamic conflicts, mood disorders, or interpersonal distress.

Age of Onset↗

PubMed1996

Incidence of breast cancer in Norwegian female radio and telegraph operators.

Exposure to electromagnetic fields may cause breast cancer in women if it increases susceptibility to sex-hormone-related cancer by diminishing the pineal gland's production of melatonin. We have studied breast cancer incidence in female radio and telegraph operators with potential exposure to light at night, radio frequency (405 kHz-25 MHz), and, to some extent, extremely low frequency fields (50 Hz). We linked the Norwegian Telecom cohort of female radio and telegraph operators working at sea to the Cancer Registry of Norway to study incident cases of breast cancer. The cohort consisted of 2,619 women who were certified to work as radio and telegraph operators between 1920 and 1980. Cancer incidence was analyzed on the basis of the standardized incidence ratio (SIR), with the Norwegian female population as the comparison group. The incidence of all cancers was close to unity (SIR = 1.2). An excess risk was seen for breast cancer (SIR = 1.5). Analysis of a nested case-control study within the cohort showed an association between breast cancer in women aged 50+ years and shift work. In a model with adjustment for age, calendar year, and year of first birth, the rate ratio for breast cancer associated with being a radio and telegraph operator--in comparison with all Norwegian women born 1935 or later--analyzed with Poisson regression, was 1.5 after adjustment for fertility factors. These results support a possible association between work as a radio and telegraph operator and breast cancer. Future epidemiologic studies on breast cancer in women aged 50 and over, should address possible disturbances of chronobiological parameters by environmental factors.

Adult↗

PubMed1996

Smoking habits and risk of cancers other than lung cancer: 28 years' follow-up of 26,000 Norwegian men and women.

The impact of tobacco smoking on lung cancer risk has been investigated thoroughly since the 1950s, but other types of cancer also have been associated with smoking. In the present study, the aim was to explore the variation in risk connected with cigarette, cigar, and pipe smoking of suspected smoking-associated cancers other than lung cancer. Data were obtained from a survey of a random sample of the Norwegian population. A self-administered mailed questionnaire, which included questions about smoking habits, was completed by 26,000 men and women in 1965 (response rate: 76 percent). The cohort was followed from 1966 through 1993, including registration of all incident cancer cases. A dose-response relationship of cigarette smoking to the risk of urinary bladder cancer and cancers of the upper digestive and respiratory tract was observed. For the latter forms of cancer, a dose-response relationship of pipe smoking also was observed. In cancer of the pancreas, a stronger association between cigarette smoking and cancer risk was observed when the analysis was confined to histologically confirmed cases only. Current cigarette smokers at baseline had a significantly higher risk of cervical cancer than those who never smoked cigarettes. In cancers of the stomach, colon, rectum, breast, corpus uteri, ovary, and prostate, and in leukemia, no association between smoking and cancer risk was observed.

Adult↗

PubMed1996

The impact of smoking habits on lung cancer risk: 28 years' observation of 26,000 Norwegian men and women.

While factory-made cigarettes dominate the market in most countries, the use of handrolled cigarettes accounts for a substantial proportion of the tobacco consumption in Norway. In the present study, we examined the impact of tobacco smoking on lung cancer in general, and the effect of handrolled cigarettes in particular. The data used was from a self-administered mailed questionnaire which included questions about smoking habits and which was completed by about 26,000 men and women in 1964-65. During the follow-up from 1966 to 1993, 333 lung cancers in men and 102 in women were registered. The analysis was performed by use of the Cox proportional hazards regression models. A clear dose-response relationship was found both for cigarette smoking, and for pipe smoking (in men). The dose-response relationship of cigarette smoking was seen in all the three histologic groups considered-squamous cell carcinoma, adenocarcinoma, and small cell carcinoma. The highest relative risks were noted in squamous cell and small cell carcinoma. A higher risk of lung cancer was found for cigarette-smoking women who started cigarette smoking before the age of 30 compared with similar groups of men. In a combined analysis of men and women, an elevated relative risk of 1.9 (95 percent confidence interval = 1.2-3.3) was found for those smoking only handrolled cigarettes compared with those smoking factory-made filter cigarettes only.

Adenocarcinoma↗

PubMed1996

Determination of extracellular methotrexate tissue levels by microdialysis in a rat model.

We used a microdialysis technique to determine tissue methotrexate (MTX) levels during steady state in a rodent model. Two different approaches were employed to measure the actual extracellular MTX concentrations in muscle, liver, and kidney tissues of anesthetized Wistar rats. With the reduced-perfusion-rate technique, the flow in the microdialysis perfusate was gradually decreased toward zero to permit calculation of zero-flow intercepts. Using the net change technique, microdialysis probes were perfused with different MTX concentrations to allow an assessment of equilibrium drug levels. For these two methods to be used, drug concentrations in the matrix to be analyzed must remain unchanged during the experimental procedure. In the animal model, steady state was attained after 1.5 h and maintained throughout the rest of the experiments by the administration of MTX as continuous infusions through a venous catheter. In vitro and in vivo, both the reduced-perfusion-rate and net change techniques gave reproducible data that permitted the estimation of extracellular drug concentrations in the dialyzed tissue compartments.The data suggest that the level of unbound MTX in the circulation is fairly similar to the extracellular concentrations in the muscle and liver. In the kidney, MTX levels were measured to be 3-8 times higher than those of unbound, circulating MTX, and a considerable discrepancy between the two methods used for estimations was apparent. These results demonstrate that both the net change and reduced-flow microdialysis techniques can produce reproducible and precise data. The results may constitute a basis for determining recoveries and, thus, true extracellular drug levels during in vivo microdialysis of MTX. This may be of importance in delineation of the relationship between tissue MTX levels and outcome in a variety of normally inaccessible compartments during cancer pharmacotherapy.

Animals↗

PubMed1996

Reversibility of brain tissue loss in anorexia nervosa assessed with a computerized Talairach 3-D proportional grid.

We describe the results of our follow-up magnetic resonance imaging (MRI) study of underweight patients with anorexia nervosa, using rigorous methodology to control for head position across time. All subjects first underwent an initial scan and rescan to verify that our computerized three-dimensional co-planar grid method for volume measurement was reliable and accurate, regardless of head positioning. After a period of several months, subjects had a follow-up scan to assess for changes that may have occurred following significant weight gain. Ventricular and total brain volume measurements from the initial scans were compared with the scans from an age- and sex-matched normal control group to determine whether we could replicate previous findings of ventricular enlargement compared with controls and whether brain volume is reduced compared with controls. Anorexic subjects had significantly larger ventricles when compared with normal controls but did not differ significantly in total brain volume. Using a repeated measures analysis of variance, a priori contrasts compared the initial/rescan pair volumes with each other and the initial/rescan pair volumes with the follow-up volume. These analyses showed that ventricular and total brain volumes derived from the initial/rescan pair were nearly identical, but that at follow-up ventricular volume decreased significantly and total brain volume increased significantly after weight gain.

Adolescent↗

PubMed1996

Internal fixation of femoral shaft fractures in children and adolescents: a ten- to twenty-one-year follow-up of 52 fractures.

In a long-term follow-up (mean 16 years) of 52 femoral shaft fractures treated by internal fixation in 50 children and adolescents, we noted a mean overgrowth of 1 mm after plating and a mean undergrowth or relative shortening of 2 and 9 mm after nailing with broad (IMN) and slender (flexible rods: IMR) intramedullary nails, respectively. The mean overgrowth was 8 mm in children, but adolescents had a mean undergrowth of 5 mm (p < 0.01). Excessive overgrowth tended to occur less frequently after intramedullary nailing than after plating (p = 0.1). Undergrowth tended to occur with increasing frequency with increasing age and attained troublesome levels in three patients with severe trauma. Three cases of moderate valgus deformity of the hip and one case of late arthrosis of the hip occurred after intramedullary nailing with IMN introduced through the greater trochanter. We conclude that this method should not be used in patients with open physes.

Adolescent↗

PubMed1996

Sustained-release Madopar HBS compared with standard Madopar in the long-term treatment of de novo parkinsonian patients.

In this Danish-Norwegian randomized double-blind parallel-group multicentre study, we compared the therapeutic response of slow-release Madopar HBS to standard Madopar in 134 de novo patients with idiopathic Parkinson's disease during a 5-year period. The drugs were dosed according to the individual need of the patients. The Webster, NUDS, UPDRS and Hoehn & Yahr scales were used for evaluation of symptoms. Addition of a morning dose of standard Madopar 62.5 mg was allowed after 6 months. Bromocriptine could be administered but not Selegiline. Sixty-five patients got Madopar HBS and 69 standard Madopar. Surprisingly, no differences were found as to the mean daily levodopa dose, the mean number of daily doses or the use of the doses of bromocriptine. Unexpectedly, we found a trend towards a more frequent use of a morning dose of standard Madopar in the group treated with the standard formulation. No differences were observed in the occurrence of motor fluctuations or dyskinesia, the incidence of which was relatively low. Sustained-release Madopar (HBS) thus proved to be as effective as standard Madopar in the long-term treatment of de novo parkinsonian patients, but the drug showed no advantage in postponing or reducing the long-term levodopa treatment problems.

Aged↗