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N Simonsen

Publications and source records attributed to N Simonsen.

At least 19 recordsLinked to original sources

Dietary antioxidants, supplements, and risk of epithelial ovarian cancer.

Several studies of dietary and serum antioxidant micronutrients (vitamins A, C, and E and beta-carotene) suggest that higher levels may be protective for ovarian cancer. None of these has examined supplements. We used a food frequency questionnaire and additional questions on supplements to study 168 histologically confirmed epithelial ovarian cancer cases, 159 community controls, and 92 hospital-based controls. Antioxidant consumption from diet or supplements was calculated in milligrams or international units per day. In multivariate analyses using only community controls, the highest levels of intake of vitamins C and E from supplements were protective: odds ratio (OR) = 0.40 [95% confidence interval (CI) = 0.21-0.78] and OR = 0.33 (95% CI = 0.18-0.60), respectively. Consumption of antioxidants from diet was unrelated to risk. In analyses combining antioxidant intake from diet and supplements, vitamins C (> 363 mg/day) and E (> 75 mg/day) were associated with reduced risks: OR = 0.45 (95% CI = 0.22-0.91) and OR = 0.44 (95% CI = 0.21-0.94), respectively. Results were similar, with some attenuation toward the null, in analyses combining both control groups. The levels of vitamins C and E associated with the protective effect were well above the current US Recommended Dietary Allowances. These findings support the hypothesis that antioxidant vitamins C and E from supplements are related to a reduced risk of ovarian cancer.

Adult↗

Integrin activation by dithiothreitol or Mn2+ induces a ligand-occupied conformation and exposure of a novel NH2-terminal regulatory site on the beta1 integrin chain.

Integrins can be expressed in at least three functional states (i.e. latent, active, and ligand-occupied). However, the molecular bases for the transitions between these states are unknown. In the present study, changes in the accessibility of several beta1 epitopes (e.g. N29, B44, and B3B11) were used to probe activation-related conformational changes. Dithiothreitol or Mn2+ activation of integrin-mediated adhesion in the human B cell line, IM9, resulted in a marked increase in the exposure of the B44 epitope, while N29 expression levels were most sensitive to dithiothreitol treatment. These results contrasted with the epitope expression patterns of spontaneously adherent K562 cells, where N29 was almost fully accessible and B44 was low. Addition of a soluble ligand resulted in a marked increase in B44 levels, suggesting that this antibody detected a ligand-induced binding site. The N29 epitope was mapped to a cysteine-rich region near the NH2 terminus of the integrin chain, thus defining a novel regulatory site. These studies indicate that the activation of integrin function by different stimuli may involve related but nonidentical conformations. Both Mn2+ and dithiothreitol appear to induce localized conformational changes that mimic a ligand-occupied receptor. This differs from the "physiologically" activated integrins on K562 cells that display a marked increase in overall epitope accessibility without exposure of the ligand-induced binding site epitopes. The increased exposure of the N29 site on K562 cells may indicate a role for this region in the regulation of integrin function.

B-Lymphocytes↗

Adipose tissue omega-3 and omega-6 fatty acid content and breast cancer in the EURAMIC study. European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer.

The fatty acid content of adipose tissue in postmenopausal breast cancer cases and controls from five European countries in the European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Cancer (EURAMIC) breast cancer study (1991-1992) was used to explore the hypothesis that fatty acids of the omega-3 family inhibit breast cancer and that the degree of inhibition depends on background levels of omega-6 polyunsaturates. Considered in isolation, the level of omega-3 or omega-6 fat in adipose tissue displayed little consistent association with breast cancer across study centers. The ratio of long-chain omega-3 fatty acids to total omega-6 fat showed an inverse association with breast cancer in four of five centers. In Malaga, Spain, the odds ratio for the highest tertile relative to the lowest reached 0.32 (95% confidence interval 0.13-0.82). In this center, total omega-6 fatty acid was strongly associated with breast cancer. With all centers pooled, the odds ratio for long-chain omega-3 to total omega-6 reached 0.80 for the second tertile and 0.65 for the third tertile, a downward trend bordering on statistical significance (p for trend = 0.055). While not definitive, these results provide evidence for the hypothesis that the balance between omega-3 and omega-6 fat may play a role in breast cancer.

Adipose Tissue↗

Intake of fruits, vegetables, folic acid and related nutrients and risk of breast cancer in postmenopausal women.

OBJECTIVE: To determine the role of fruit and vegetable consumption and dietary intake of folic acid and related nutrients such as methionine, cysteine and alcohol in the aetiology of breast cancer. DESIGN: Population based case-control study. SETTING: Part of the European Community Multicentre Study on Antioxidants, Myocardial Infarction, and Cancer of the Breast (EURAMIC) in Berlin, Germany. SUBJECTS: As part of the EURAMIC study, dietary intake data were collected in 43 postmenopausal women diagnosed with breast cancer between 1991 and 1992 in Berlin, Germany, and compared to 106 population-based controls. RESULTS: Odds ratios (ORs) adjusted for major risk factors of breast cancer but not for total energy intake showed a non-significant inverse association between a high intake of vegetables (OR=0.76, 95% CI=0.48-1.20) and fruits (OR=0.74, 95% CI=0.48-1.15) and breast cancer. Once results were adjusted for total energy intake the associations became much weaker (vegetables: R=0.86, 95% CI=0.51-1.46; fruits: OR=0.82, 95% CI=0.51-1.32). For all nutrients, the effect of energy adjustment was more profound and the inverse associations disappeared when results were adjusted for energy intake (total folate-not energy adjusted: OR = 0.79, 95% CI=0.51-1.21; energy adjusted: OR=1.14, 95% CI=0.73-1.79; folate equivalents-not energy adjusted: OR=0.81, 95% CI=0.53-1.23; energy adjusted: OR=1.16, 95% CI=0.78-1.74; methionine-not energy adjusted: OR=0.60, 95% CI=0.35-1.03; energy adjusted: OR=1.29, 95% CI=0.76-2.19; cysteine-not energy adjusted: OR=0.52, 95% CI=0.29-0.94; energy adjusted: OR=1.22, 95% CI=0.75-1.97). Alcohol intake was inversely associated with breast cancer in a non-significant way, possibly due to the relatively low alcohol intake of the study population. CONCLUSIONS: The results of this study do not provide firm evidence that a high intake of fruits and vegetables, folic acid, methionine or cysteine reduces the risk of getting breast cancer.

Adult↗

Differences between plasma and adipose tissue biomarkers of carotenoids and tocopherols.

Biomarkers of dietary exposure or nutritional status are sought actively to overcome limitations of traditional dietary methodology. We compared plasma and adipose tissue biomarkers for carotenoids and tocopherols. The data consisted of samples from 91 men and 122 women, ages 45-70 years, from the control group of the European Community Multicentre Study on Antioxidants, Myocardial Infarction, and Cancer of the Breast (EURAMIC) Study. Pearson correlations between plasma and adipose tissue measurements for beta-carotene, lycopene, and alpha-tocopherol adjusted for smoking status displayed low, although significant, correlations of 0.39, 0.24, and 0.39, respectively. The correlation was further stratified by sex. After being corrected for measurement error using deattenuation factors obtained from a reproducibility study, the stratified correlation coefficients were as high as 0.80 for beta-carotene in men, 0.62 for lycopene in women, and 0.52 for alpha-tocopherol in women. In addition, plasma and adipose tissue measurements from the myocardial infarction (MI) subset of the EURAMIC study population were used to evaluate the odds of MI, adjusting for confounders. We found that the concentration of lycopene in plasma was not positively associated significantly with MI (odds ratio, 1.78; P = 0.26). Adipose tissue lycopene, in contrast to reports elsewhere on the total population, showed an inverse association with MI (odds ratio, 0.62; P = 0.15). These results suggest that plasma and adipose carotenoids represent different markers for nutritional status and cannot be used interchangeably in epidemiological and dietary validation studies.

Adipose Tissue↗

Adipose tissue trans fatty acids and breast cancer in the European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer.

To investigate the relationship between trans fatty acids and postmenopausal breast cancer in European populations differing greatly in their dietary fat intakes, a case control study using adipose tissue stores of trans fatty acids as a biomarker of exposure was conducted. Subjects included 698 postmenopausal incident cases of primary breast cancer and controls randomly drawn from local population and patient registries, ages 50-74 Concentrations of individual trans fatty acids in gluteal fat biopsies were measured in these women. The adipose concentration of trans fatty acids showed a positive association with breast cancer. The covariate-adjusted association with breast cancer. The covariate-adjusted OR was 1.40 (95% confidence interval: 1.02, 1.93) for the difference between the 75th and 25th percentiles of total adipose trans. The adjusted OR for trans in the lowest tertile of polyunsaturated fatty acid reached 3.6 (2.2, 6.1). These associations were not attributable to differences in age, body mass index, exogenous hormone use, or socioeconomic status. These findings suggest an association of adipose stores of trans fatty acids with postmenopausal breast cancer in European women. They require confirmation in other populations, with concomitant consideration of the potential roles of dietary saturated and monounsaturated fats.

Adipose Tissue↗

Review of occupational lung carcinogens.

Lung cancer is the most common malignancy in the United States and is ranked second only to bladder cancer in the proportion of cases thought to be due to occupational exposures. We review the epidemiology of occupational lung cancer, focusing on agents identified as pulmonary carcinogens by the International Agency for Research on Cancer. We derive estimates of overall relative risks from the major studies of these lung carcinogens, and we also provide estimates of the number of exposed workers. Using our data as well as estimates from other authors, we estimate that approximately 9,000-10,000 men and 900-1,900 women develop lung cancer annually in the United States due to past exposure to occupational carcinogens. More than half of these lung cancers are due to asbestos. This estimate is likely conservative, in that we have restricted our analysis to confirmed lung carcinogens and have ignored occupations with documented excess risk but for which the specific agents are unknown. Also, our estimate of the proportion of workers exposed in the past is probably too low. Our estimate should be viewed only as broad approximation. Nevertheless, it is in line with other estimates by authors using different methods. The current number of cases estimated to be due to occupational exposure reflects past high exposures and is likely to drop in the future, unless other occupational lung carcinogens are confirmed or new carcinogens are introduced into the workplace.

Acrylonitrile↗

Dietary modifiers of carcinogenesis.

Dietary components express a wide range of activities that can affect carcinogenesis. Naturally occurring substances in foods have been shown in laboratory experiments to serve as dietary antimutagens, either as bioantimutagens or as desmutagens. Dietary desmutagens may function as chemical inactivaters, enzymatic inducers, scavengers, or antioxidants. Dietary components may also act later in the carcinogenic process as tumor growth suppressors. Examples of dietary factors acting in each of these stages of carcinogenesis are presented, and potential anticarcinogens such as the carotenoids, tocopherols, phenolic compounds, glucosinolates, metal-binding proteins, phytoestrogens, and conjugated linoleic acid are discussed. Individual foods typically contain multiple potential anticarcinogens. Many of these substances can influence carcinogenesis through more than one mechanism. Some substances exhibit both anticarcinogenic and carcinogenic activity in vitro, depending on conditions. Epidemiologic research indicates that high fruit and vegetable consumption is associated with lower cancer risk. Little research has focused on the effects of single substances or single foods in man. Realization of the potential of foodborne substances to reduce the human burden of cancer will only be achieved with better measurement of dietary exposures and funding of multidisciplinary research in this area commensurate with its importance.

Animals↗

Nosocomial outbreak of Pseudomonas aeruginosa folliculitis associated with a physiotherapy pool.

Outbreaks of community-acquired Pseudomonas aeruginosa folliculitis have recently been described in association with health spa whirlpools. In February 1984 we detected an outbreak of Pseudomonas folliculitis among hospital staff and patients using a swimming pool in a newly constructed physiotherapy unit. A rash developed in 5 (45%) of the 11 physiotherapists who had used the pool, as compared with 0 of the 17 who had not (p less than 0 005). Pseudomonas folliculitis also developed in 6 (21%) of 29 outpatients and 4 (33%) of 12 inpatients who had used the facility; Pseudomonas infection of a surgical wound also developed in 1 of the 4 inpatients. The epidemic curve was consistent with a continuing common-source outbreak. P. aeruginosa, serotype O:10, was isolated from three physiotherapists, the patient with an infected surgical wound and the pool. A case-control study of pool users did not identify risk factors for infection, although the physiotherapists had spent longer in the pool than had the patients. After hyperchlorination and structural repairs to the pool, no further cases were identified among pool users. This outbreak is the first reported nosocomial outbreak of Pseudomonas folliculitis. Further investigation is needed to determine the risk of serious Pseudomonas infections in hospitalized patients using physiotherapy pools.

Adult↗

Genetics and linkage relationships of the C3 polymorphism: discovery of C3-Se linkage and assignment of LES-C3-DM-Se-PEPD-Lu synteny to chromosome 19.

The C3 complement system was examined in our Danish material of normal families, which had earlier been examined for 59 marker systems, and in a myotonic dystrophy family material. A total of 8 alleles were recognized, with allele frequencies as follows: C3*S = 0.7902, C3*F = 0.2018, C3*S rare (3 lumped together) = 0.0036, C3*F rare (2 lumped together) = 0.0024; a silent allele was recognized in three families and its frequency estimated to C3*QO = 0.002. The distribution of unrelated individuals did not deviate significantly from the Hardy-Weinberg expectation, it was not significantly different between the sexes, and for none of the mating types was there any significant deviation from the expected ratios of children. As to linkage relationships of C3 with marker systems and with myotonic dystrophy, there was evidence (most of it first presented at the 6th International Congress of Human Genetics, Jerusalem 1981) for synteny with ABH secretion (Se): C3-Se (males) z = 4.35, theta = 0.12 and with Lewis secretion (LES): C3-LES (males z = 3.63, theta = 0.04). There were indicative or suggestive lod scores for Se-PEPD (males & females z = 2.41, theta = 0.00), C3-Lu (z = 1.88, theta = 0.15), C3-DM (z = 1.69, theta = 0.06) and PEPD-C3 (male z = 0.95, theta = 0.17). The most likely sequence of these 6 systems would appear to be LES-C3-DM-(Se-PEPD)-Lu and the synteny would reside on chromosome 19.

ABO Blood-Group System↗

Prognostic value of in vitro measurements of platelet aggregability and fibrinolytic activity in patients with reversible cerebral ischemic attacks.

Platelet aggregability and fibrinolytic activity were studied repeatedly in 83 patients with reversible cerebral ischemic attacks over a median follow-up period of 26 months. Platelet hyperaggregability, defined as in vitro secondary aggregation obtained by adenosine diphosphate concentration less than or equal to 1 mumol/l, was demonstrated in 36.1% or the patients examined 5-8 days after the attack, but only in 6% of age- and sex-matched blood donors (p less than 0.001). Fibrinolytic activity was reduced in 57.8% of the patients, as compared with 20.5% of the controls. At the time of follow-up only 8% of the survivors showed platelet hyperaggregability, whereas the fibrinolytic activity was still reduced in 44.4%. Over the observation period 21.7% of the patients had a stroke or died. No significant correlation was found between abnormalities of platelet aggregability or of fibrinolytic activity, when observed 5-8 days after the ischemic episode, and the subsequent risk of stroke or death. It is concluded that in patients with recent cerebral ischemic attacks the demonstration of platelet hyperaggregability or reduced fibrinolytic activity appears to be without prognostic significance.

Adult↗

Long-term prognosis after transient ischemic attacks.

A retrospective follow-up study of 243 patients with transient ischemic attacks (TIA) is reported. The long-term mortality of the patients was higher than that of the corresponding general population. It is demonstrated that the excess mortality over the whole period of observation, irrespective of the age and sex of the patients, can be characterized by a single figure expressing the slope of the curve obtained by semilogarithmic plotting of the ratios of observed to expected survival against time. The use of this numerical expression--in the present series -0.04--will thus facilitate comparisons of the survival of TIA patients drawn from different populations. Unfavourable prognostic factors were: carotid TIA, associated extracerebral disease, and a history of hypertension. Fatal strokes, being four times as frequent as expected according to published incidence figures, accounted for 20% of the deaths, heart disease 38%. Stroke deaths tended to occur earlier than cardiac deaths. The results support the concept that most TIAs, like strokes, are incidents in the progressive course of a generalized vascular disease. The finding of a constant excess mortality over the years following a TIA makes it difficult to recommend a discontinuation of prophylactic therapy at any particular time.

Age Factors↗

A comparative controlled study between carbamazepine and diphenylhydantoin in psychomotor epilepsy.

A double-blind study of the antiepileptic effect and side effects of carbamazepine (CARB) and diphenylhydantoin (DPH) was undertaken in 38 patients with psychomotor epilepsy and without grand mal epilepsy except for a single previous seizure. The patients were treated with CARB and DPH only, each in periods of 16 weeks and with a crossover of 4 weeks. The initial dosage of 6 mg/kg DPH or 15 mg/kg CARB was corrected according to the serum values aiming at therapeutic intervals of 8-16 mg/1 DPH and 6-10 mg/1 CARB. The trial had to be discontinued in 12 patients. The effect of the two drugs in preventing psychomotor seizures was the same. Some patients, however, had considerably fewer seizures while on CARB; others had fewer seizures on DPH. It seems advisable, therefore, to try both drugs separately before proceeding to combined medication. During CARB treatment the selected therapeutic interval was more easily reached and maintained than during DPH. During the latter treatment, one-third of the monthly serum value determinations were below the level in spite of dosage corrections. Side effects were equally mild and occurred as often during DPH as during CARB treatment.

Adolescent↗

A multidimensional study of personality traits ad modum Sjöbring.

Three groups of epileptic out-patients (juvenile myoclonic epilepsy, psychomotor epilepsy, and cryptogenic grand mal) were studied. The groups were matched as closely as possible with each other with regard to sex, age, and treatment. Out-patients suffering from Menière's disease served as a control group; these patients were treated with placebo and matched with the epilepsy groups with regard to sex, duration of disease and social level. The Marke-Nyman inventory was used as a quantitative assessment of personality traits. This inventory is an operative definition of Sjöbring's neurophysiological model of personality, including the three dimensions: validity, stability and solidity. Our results showed that epileptic patients irrespective of the type of seizures were substable. Low validity was found in patients with juvenile myoclonic epilepsy and in patients with psychomotor epilepsy with temporal EEG focus. In those latter epilepsy groups a tendency to subsolidity was also observed. In Sjöbring's frame of reference these substable patients of low validity have a psychological vulnerability since they are unable to overcome the small concrete adversities of life. They adhere to problems, and being unable to solve them they tend to react in a mood of discontent or of maladjustment. In the usual psychiatric frame of reference substable patients of low validity are classified as psychoastenic patients with emotional instability.

Adolescent↗