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R Frentzel-Beyme

Publications and source records attributed to R Frentzel-Beyme.

At least 19 recordsLinked to original sources
PubMed2004

Challenges to environmental toxicology and epidemiology: where do we stand and which way do we go?

Modern toxicology investigates a wide array of both old and new health hazards. Priority setting is needed to select agents for research from the plethora of exposure circumstances. The changing societies and a growing fraction of the aged have to be taken into consideration. A precise exposure assessment is of importance for risk estimation and regulation. Toxicology contributes to the exploration of pathomechanisms to specify the exposure metrics for risk estimation. Combined effects of co-existing agents are not yet sufficiently understood. Animal experiments allow a separate administration of agents which can not be disentangled by epidemiological means, but their value is limited for low exposure levels in many of today's settings. As an experimental science, toxicology has to keep pace with the rapidly growing knowledge about the language of the genome and the changing paradigms in cancer development. During the pioneer era of assembling a working draft of the human genome, toxicogenomics has been developed. Gene and pathway complexity have to be considered when investigating gene-environment interactions. For a best conduct of studies, modern toxicology needs a close liaison with many other disciplines like epidemiology and bioinformatics.

Animals↗
PubMed2003

Chromosome aberration analysis in peripheral lymphocytes of Gulf War and Balkans War veterans.

Chromosome aberrations and sister chromatid exchanges (SCEs) were determined in standard peripheral lymphocyte metaphase preparations of 13 British Gulf War veterans, two veterans of the recent war in the Balkans and one veteran of both wars. All 16 volunteers suspect exposures to depleted uranium (DU) while deployed at the two different theatres of war in 1990 and later on. The Bremen laboratory control served as a reference in this study. Compared with this control there was a statistically significant increase in the frequency of dicentric chromosomes (dic) and centric ring chromosomes (cR) in the veterans' group. indicating a previous exposure to ionising radiation. The statistically significant overdispersion of die and cR indicates non-uniform irradiation as would be expected after non-uniform exposure and/or exposure to radiation with a high linear energy transfer (LET). The frequency of SCEs was decreased when compared with the laboratory control.

Adult↗
PubMed2001

"Host factors"--evolution of concepts of individual sensitivity and susceptibility.

The detection of a rapidly increasing number of genetic polymorphisms in xenogen-metabolizing enzymes, of hereditary as well as acquired individual differences in DNA repair, and of the close associations between central nervous structures, the endocrine, and the immune system provides a challenge to develop an evidence-based, comprehensive model of susceptibility. Reviewing the evolution of respective approaches from 400 B.C. until today, this article proposes a conceptional framework that integrates the diverse, and sometimes puzzling contributions from all different fields of life science.

Biological Evolution↗
PubMed2001

The interaction between risk factors and self-regulation in the development of chronic diseases.

Most established risk factors for chronic disease incidence and mortality from cancer, such as cigarette smoke, alcohol drinking, occupational and environmental hazards and dietary factors, have been shown to vary in their importance in terms of relative risk. In studies which addressed the individual level of behaviour, but also coping and self-regulation, a strong modifying effect of long-lasting hopelessness and helplessness has been found to depend on personality. Autonomy and healthful self-regulation have been defined as the regulation of behaviour in those activities which are carried out in the physical and social environment and lead to stimulated feeling, pleasure, perception of inner and social security, and competence. Persons with such well-regulated behaviour are capable of coping with sources of listlessness, uncertainty and instability. Those individuals showing a well-regulated behaviour arrive at a psycho-neuro-physiological basis for better competence and defence against health hazards. The capability determined by the degree of self-regulation is measured with different instruments. The experience with a questionnaire for the assessment of self-regulation, its quantification and predictive value is presented here. The method of study is by prospective approach, which permits the demonstration of causal associations (promotion, co-causality) and facilitates the experimental approach through intervention. A causal association is likely if the effect of a modifier is not only found in a prospective (observational) follow-up but also if the (experimental) intervention shows an effect. The method of intervention by stimulation of self-regulation is the autonomy training developed by Grossarth-Maticek. Using several examples presenting the method, the modifying effect is shown by referring to four risk factors. If the risk factors are associated with an inhibited self-regulation, then the effect in terms of disease and pathological outcome is stronger. This was shown with the hazardous effects of smoking, alcohol drinking and dietary malnutrition as well as with automobile exhaust. It may be important, for example, whether a person feels self-determined when driving a car for hours but does not need to consume ethanol-containing drinks for feeling well. One's own capability to regulate well over time apparently modulates functions of the body and hence modifies the effects of physical factors. In epidemiological studies, which assess mostly only exogenous factors (so called established risk factors) this evidence has to be considered by including the pertinent data on the relevant questions in each field study.

Alcohol Drinking↗
PubMed2001

An application of the challenge assay in boat builders exposed to low levels of styrene--a feasibility study of a possible biomarker for acquired susceptibility.

Sensitivity to carcinogens and susceptibility for malignant diseases may be related to genetic predisposition, e.g. polymorphisms in toxicant-metabolizing enzymes or DNA repair deficiencies. The latter may also be acquired by exposure to substances that interfere with DNA repair processes. Application of the challenge assay to an exposed population may allow scientists to study the interference of DNA repair as an acquired susceptibility phenomenon. The assay was therefore used in a feasibility study to evaluate its application. A group of 14 workers exposed to low levels of styrene (mean < 100 mg/m3 styrene in air; 35 micrograms/l styrene in blood) and a reference of seven controls were investigated for structural chromosomal aberrations using FISH. The rate of exchange-type aberrations per 100 metaphases was 0.14 (95% CI, 0.05-0.31) in controls and 0.22 (95% CI, 0.13-0.36) in exposed workers. The difference is not statistically significant. Interaction with DNA repair was measured in the 14 workers and 2 historical controls using the challenge assay. Exchange-type aberrations per 100 metaphases after X-ray challenge of 1.66 Gy were 13.26 (10.53-16.50) and 16.19 (15.00-17.40) for the controls and exposed, respectively. The difference is statistically significant (p < 0.038). Among the exposed group, the challenge response was also significantly correlated with the cumulative lifetime exposure to styrene (R2 = 0.3996; p < 0.015) but not with the current exposure as measured in blood (R2 = 0.0226; p = 0.700). The challenge responses in the short-term and long-term exposed subgroups were 15.55 (14.23-16.96) and 17.90 (15.64-20.39), respectively, based on sample sizes of 5 and 9, respectively. The difference was not significant. Hence, data from our study are consistent with the hypothesis that long-term exposure to styrene can interfere with DNA repair activities. The lack of statistically significant differences in some of the data may be due to the small sample size and a possible confounding by age in our investigation. Additional data from our ongoing study should clarify this uncertainty.

Adult↗
PubMed1999

The chromosome-based challenge assay using fluorescence in situ hybridization: a possible test for increased cancer susceptibility.

UNLABELLED: The challenge assay is a cytogenetic approach to measure the repair competence of cells. For in vitro studies, human lymphocytes are exposed to different substances and are irradiated simultaneously. To investigate subjects exposed occupationally or environmentally, untreated blood samples are directly irradiated without any further treatment. Certain substances like heavy metals reveal carcinogenic potential without well defined mechanism of action. While they are not mutagenic they may have an effect on DNA repair capacity. The challenge assay was successfully applied in vitro experiments with cadmium to detect an interaction of this heavy metal with the repair of X-ray-induced chromosome breaks. CdCl(2) alone had no effect on the formation of chromosome aberrations (CA), not even in the cytotoxic concentration (50 microM). However, cadmium showed an effect on the number of chromosomal rearrangements (CR) after X-ray challenge. For 0.5 microM CdCl(2), CA frequencies were significantly elevated compared to the rates for X-rays alone. For the two higher concentrations the rates showed a slight additional increase. Hence, the challenge assay appears suitable to test for chromosomal sensitivity induced by toxicants. Subsequently, a study of styrene exposed workers was initiated to address the question whether styrene exposure has an influence on the DNA repair. In addition, we investigated whether a polymorphism of genes coding for phase II detoxifying enzymes glutathione-S-transferases GSTM1 and GSTT1 had an influence on chromosomal sensitivity. First and preliminary data are presented. While there is a correlation of the rate of CR with cumulative lifetime exposure of styrene, the most recent styrene exposure had no effect. 'At risk' genotypes with higher incidence of CA could not be identified at this stage of the ongoing study. CONCLUSION: the challenge assay is able to detect enhanced susceptibility for CR caused by genetic predisposition for DNA repair deficiency. Our data indicate that environmental or occupational exposure to certain substances can interfere with DNA repair processes. As the process of induction of CR is associated with carcinogenesis, the challenge assay may provide a valuable biomarker for cancer epidemiology studies.

Cadmium↗
PubMed1999

Mortality in vegetarians and nonvegetarians: detailed findings from a collaborative analysis of 5 prospective studies.

We combined data from 5 prospective studies to compare the death rates from common diseases of vegetarians with those of nonvegetarians with similar lifestyles. A summary of these results was reported previously; we report here more details of the findings. Data for 76172 men and women were available. Vegetarians were those who did not eat any meat or fish (n = 27808). Death rate ratios at ages 16-89 y were calculated by Poisson regression and all results were adjusted for age, sex, and smoking status. A random-effects model was used to calculate pooled estimates of effect for all studies combined. There were 8330 deaths after a mean of 10.6 y of follow-up. Mortality from ischemic heart disease was 24% lower in vegetarians than in nonvegetarians (death rate ratio: 0.76; 95% CI: 0.62, 0.94; P<0.01). The lower mortality from ischemic heart disease among vegetarians was greater at younger ages and was restricted to those who had followed their current diet for >5 y. Further categorization of diets showed that, in comparison with regular meat eaters, mortality from ischemic heart disease was 20% lower in occasional meat eaters, 34% lower in people who ate fish but not meat, 34% lower in lactoovovegetarians, and 26% lower in vegans. There were no significant differences between vegetarians and nonvegetarians in mortality from cerebrovascular disease, stomach cancer, colorectal cancer, lung cancer, breast cancer, prostate cancer, or all other causes combined.

Adolescent↗
PubMed1998

Lung cancer mortality among European rock/slag wool workers: exposure-response analysis.

OBJECTIVES: The purpose was to analyze the relationship between semi-quantitative indices of exposure to manmade vitreous fibers and lung cancer mortality among European rock/slag wool (RSW) workers. METHODS: The study population comprised 9,603 male workers employed in RSW production in seven factories in Denmark, Norway, Sweden, and Germany, followed up for mortality as of 1990-91. Estimates of past exposure to respirable fibers were used to calculate cumulative exposure with a 15-year lag and maximum annual exposure based on employment history up to 1977. Rate ratios were estimated via multivariate Poisson regression, adjusting for country, age, calendar year, time since first employment, and employment status. RESULTS: A total of 159 lung cancer deaths were included in the analysis of which 97 among workers with more than one year of employment. We found nonstatistically significant trends in lung cancer risk according to cumulative exposure. Relative risks (RR) in the four quartiles were 1.0 (reference), 1.3 (95 percent confidence interval [CI] = 0.8-2.4), 1.2 (CI = 0.7-2.1), and 1.5 (CI = 0.7-3.0, P test for trend = 0.4). When workers with less than one year of employment were excluded, there was no increased risk; the RRs in the four quartiles were 1.0, 0.9 (CI = 0.4-2.0), 0.8 (CI = 0.3-1.9), and 1.0 (CI = 0.4-2.7). No trend was present according to maximum annual exposure. The results were not consistent among countries. CONCLUSIONS: We found a positive association between exposure to respirable fibers and lung cancer mortality. However, the lack of statistical significance, the dependence of the results on inclusion of short-term workers, the lack of consistency among countries, and the possible correlation between exposure to respirable fibers and to other agents reduce the weight of such evidence.

Adult↗
PubMed1998

Mortality in vegetarians and non-vegetarians: a collaborative analysis of 8300 deaths among 76,000 men and women in five prospective studies.

OBJECTIVE: To compare the mortality rates of vegetarians and non-vegetarians. DESIGN: Collaborative analysis using original data from five prospective studies. Death rate ratios for vegetarians compared to non-vegetarians were calculated for ischaemic heart disease, cerebrovascular disease, cancers of the stomach, large bowel, lung, breast and prostate, and for all causes of death. All results were adjusted for age, sex and smoking. A random effects model was used to calculate pooled estimates of effect for all studies combined. SETTING: USA, UK and Germany. SUBJECTS: 76,172 men and women aged 16-89 years at recruitment. Vegetarians were those who did not eat any meat or fish (n = 27,808). Non-vegetarians were from a similar background to the vegetarians within each study. RESULTS: After a mean of 10.6 years of follow-up there were 8330 deaths before the age of 90 years, including 2264 deaths from ischaemic heart disease. In comparison with non-vegetarians, vegetarians had a 24% reduction in mortality from ischaemic heart disease (death rate ratio 0.76, 95% CI 0.62-0.94). The reduction in mortality among vegetarians varied significantly with age at death: rate ratios for vegetarians compared to non-vegetarians were 0.55 (95% CI 0.35-0.85), 0.69 (95% CI 0.53-0.90) and 0.92 (95% CI 0.73-1.16) for deaths from ischaemic heart disease at ages <65, 65-79 and 80-89 years, respectively. When the non-vegetarians were divided into regular meat eaters (who ate meat at least once a week) and semi-vegetarians (who ate fish only or ate meat less than once a week), the ischaemic heart disease death rate ratios compared to regular meat eaters were 0.78 (95% CI 0.68-0.89) in semi-vegetarians and 0.66 (95% CI 0.53-0.83) in vegetarians (test for trend P< 0.001). There were no significant differences between vegetarians and non-vegetarians in mortality from the other causes of death examined. CONCLUSION: Vegetarians have a lower risk of dying from ischaemic heart disease than non-vegetarians.

Adolescent↗
PubMed1998

Mortality of short-term workers in two international cohorts.

The purpose of this study was to compare the pattern of mortality of blue-collar workers employed less and more than 1 year in the man-made vitreous fiber (MMVF) and the reinforced plastic industries, the latter group being exposed to styrene. We conducted an analysis among 21,784 workers with less than 1 year of employment (short-term workers) and 19,117 workers with 1 or more years of employment (long-term workers) employed in eight European countries. We conducted analyses based on external as well as internal comparisons. In both cohorts, the standardized mortality ratio for all causes among short-term workers was approximately 40% higher, compared with that for longer-term workers. In internal comparisons, the difference was reduced to 9% in the MMVF cohort and 11% in the styrene cohort. Workers with less than 1 month of employment displayed an increased mortality in both cohorts and in most countries. The increased mortality among short-term workers was not concentrated shortly after they quit employment. In both cohorts, short-term workers had a higher mortality from external causes, while little difference was seen in mortality from ischemic heart disease and malignant neoplasms. Although extra-occupational factors may contribute to increase the mortality of short-term workers and, in particular, of those employed for less than 1 month, the difference observed in analyses adjusted for characteristics of employment suggested a relatively small difference in mortality from most causes.

Adult↗
PubMed1997

Comparison of information on occupation and lifestyle habits obtained from European man-made vitreous fibre production workers and their relatives.

BACKGROUND: Studies of the aetiology of fatal diseases often rely on data obtained from relatives, which can cause loss of precision and introduce bias. We assessed the quality of such information on demographics, occupation, smoking and alcohol habits. METHODS: We compared contemporary interviews, based on a structured questionnaire, with male workers from the man-made vitreous fibre production industry in four European countries and their relatives. The participation rate was 63% (74 pairs of workers and relatives). RESULTS: Only minor differences in the ability to answer the questions appeared among workers and relatives, except for specific occupational questions. There was moderate to excellent agreement for demographics, residential and work history (kappa or intraclass correlation range: 0.44-0.98). For smoking habits, beer and wine consumption the agreement was good to excellent (range: 0.59-0.99). In particular, number of different residential areas, jobs, industries, and duration of wine drinking were significantly underreported by the relatives. No general determinant for reduced agreement appeared. CONCLUSIONS: In general, the quality of information obtained from relatives appeared good. However, information on specific occupational exposures may be improved by supplementing the information from relatives with details obtained from colleagues, occupational hygiene experts or occupation-exposure matrices.

Adolescent↗
PubMed1997

Cancer mortality among man-made vitreous fiber production workers.

We have updated the follow-up of cancer mortality for a cohort study of man-made vitreous fiber production workers from Denmark, Finland, Norway, Sweden, United Kingdom, Germany, and Italy, from 1982 to 1990. In the mortality analysis, 22,002 production workers contributed 489,551 person-years, during which there were 4,521 deaths. Workers with less than 1 year of employment had an increased mortality [standardized mortality ratio (SMR) = 1.45; 95% confidence interval (CI) = 1.37-1.53]. Workers with 1 year or more of employment, contributing 65% of person-years, had an SMR of 1.05 (95% CI = 1.02-1.09). The SMR for lung cancer was 1.34 (95% CI = 1.08-1.63, 97 deaths) among rock/slag wool workers and 1.27 (95% CI = 1.07-1.50, 140 deaths) among glass wool workers. In the latter group, no increase was present when local mortality rates were used. Among rock/slag wool workers, the risk of lung cancer increased with time-since-first-employment and duration of employment. The trend in lung cancer mortality according to technologic phase at first employment was less marked than in the previous follow-up. We obtained similar results from a Poisson regression analysis limited to rock/slag wool workers. Five deaths from pleural mesothelioma were reported, which may not represent an excess. There was no apparent excess for other categories of neoplasm. Tobacco smoking and other factors linked to social class, as well as exposures in other industries, appear unlikely to explain the whole increase in lung cancer mortality among rock/slag wool workers. Limited data on other agents do not indicate an important role of asbestos, slag, or bitumen. These results are not sufficient to conclude that the increased lung cancer risk is the result of exposure to rock/slag wool; however, insofar as respirable fibers were an important component of the ambient pollution of the working environment, they may have contributed to the increased risk.

Aged↗
PubMed1994

Vegetarian diets and colon cancer: the German experience.

The study assessed mortality and morbidity risks as related to nutritional status of moderate and strict vegetarians in Germany. The total cohort of 1904 self-identified persons was followed up for 11 y. Compared with national mortality rates for Federal Republic of Germany, the observed deaths for all causes were below expectation by a factor of 0.44 for men and 0.53 for women. The mortality for colon cancer was reduced [standardized mortality ration (SMR 44.1 for men and 77.9 for women]. No deaths were observed from rectal cancer. A vegetarian lifestyle of long duration (> or = 20 y) was associated with decreased overall and cancer mortality. Other determinants of decreased cause-specific mortality were physical activity, body weight, and strictness of adherence to the life-style. The relationship between a vegetarian and fiber-rich diet and a decreased risk for colon cancer has been reported in many studies. In this study, the influence of other factors such as health-conscious behavior and a healthy lifestyle seem to indicate partly stronger effects than nutrition itself. This may explain the generally better health of moderate vegetarians.

Cardiovascular Diseases↗
PubMed1994

John R. Goldsmith on the usefulness of epidemiological data to identify links between point sources of radiation and disease.

Sometimes the demonstration of a plausible risk is met with inappropriate attempts to explain it away rather than to protect the health of the public. This may have occurred in the case of leukemia in the vicinity of nuclear installations. In 1989, John Goldsmith prepared a document on this topic for the World Health Organization that persuasively argued for the association to be examined vigorously and to be taken seriously as a potential health risk. However, other commentators on the problem have seemed intent on raising unsubstantial methodological objections and insisting on standards of evidence inappropriate to the justification of action intended to protect the health of the public. Recommendations for resolving this specific issue are made, but the overriding concern is that the level of proof required to justify action for health protection should be less than that required to constitute causation as a scientific principle.

Air Pollution, Radioactive↗
PubMed1993

Neuropsychological effects of chronic exposure to environmental dioxins and furans.

The environmental contamination by dioxins and furans (PCDD/PCDF) of a local area in southwest Germany due to pyrolytic processes led to a survey of health consequences in the exposed population. 2,3,7,8-TCDD (8000 ng/kg TE (ppt)) was found in the soil and up to 585000 ng/kg TE in attic dust in private homes. In a randomized study group of definitively exposed persons, a neuropsychological test battery was applied and its value as a diagnostic tool investigated. A total group of 19 persons participated in a standard neuropsychological examination including common procedures to evaluate mnestic and attentional performance and psychomotor speed (e.g., WAIS, WMS-R, TMT, and symptom and mood checklists). The range of PCDD/PCDF between 16 and 80 (mean 31) ppt did not vary substantially from blood fat values in a national sample. Results of neuropsychological testing showed only slight deviations from the expected range. Nevertheless, in a high-level exposure group, a reduction of verbal conceptualization, mnestic organization of verbal and visual stimuli, and psychomotor slowing was found. Among other correlations visual exploration speed (TMT) was most directly related to TE. Affective symptoms (such as irritability and emotional instability) were also related to exposure. Results indicate that standard neuropsychological testing can be recommended for the routine evaluation of chronic dioxin exposure.

Adolescent↗