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Biomedical subjects

R Meinert

Publications and source records attributed to R Meinert.

At least 19 recordsLinked to original sources
PubMed2001

Risk factors for pediatric tumors of the central nervous system: results from a German population-based case-control study.

BACKGROUND: From 1993 to 1997 we conducted two population-based case-control studies on childhood cancer and a variety of potential risk factors in Germany. One case group involved children under the age of 15 years having a tumor of the central nervous system (CNS). PROCEDURE: For both studies, one conducted in the northwestern area of Germany, the other covering the whole of West Germany, incident cases were identified from the nationwide German Childhood Cancer Registry, and controls were randomly selected from complete population registration files. RESULTS: In total 466 pediatric CNS tumor cases and 2,458 controls were available for analyses. We observed only few positive associations, namely, between CNS tumors and low birth weight [<2,500 g; odds ratio (OR), 1.73; 95% confidence interval (CI), 1.06-2.84], between ependymoma and maternal smoking during pregnancy (>10 cigarettes per day: OR, 4.71; 95% CI, 1.69-13.1), and between astrocytoma and exposure to wood preservatives (OR, 1.91; 95% CI, 1.22-3.01). CNS tumors were not associated with high birth weight, duration of breast feeding, maternal age at time of delivery, duration of gestation, previous fetal losses, paternal smoking during pregnancy, maternal alcohol consumption, the child's exposure to pesticides, maternal diagnostic X-ray examinations during pregnancy, X-ray examinations of the child, or exposure to residential magnetic fields. CONCLUSIONS: Despite the large study population, we found only few factors that were associated with CNS tumors or one of the morphological subgroups. Therefore, our results suggest that aspects of the prenatal and neonatal period play only a minor role in the etiology of pediatric CNS tumors.

Adolescent↗
PubMed2001

High-birth weight and other risk factors for Wilms tumour: results of a population-based case-control study.

UNLABELLED: Wilms tumour, or nephroblastoma, is one of the childhood cancers included in two recent population-based case-control studies in West Germany. Altogether, 177 children under the age of 10 years with Wilms tumour diagnosed between 1988 and 1994 and 2006 control children sampled from population registration files participated. Information on potential risk factors was obtained from the parents using a questionnaire and by subsequent telephone interview. We found an association with a high birth weight >4000 g (odds ratio 1.58; 95% confidence interval 1.01-2.48), which was somewhat stronger for children aged 2 years or older. Findings for young maternal age at birth and certain parental occupationally related exposures were not reported by previous studies and thus may be chance findings. As opposed to previous studies, we failed to confirm associations with high parental age at birth, maternal coffee and tea consumption during pregnancy, and exposure to pesticides. CONCLUSION: Based on this large population-based case-control study, high birth weight may play a role in the aetiology of Wilms tumour, but many risk factors previously suggested are of less importance.

Alcohol Drinking↗
PubMed2001

Risk factors for neuroblastoma at different stages of disease. Results from a population-based case-control study in Germany.

Neuroblastoma is one of the childhood cancers included in two recent population-based case-control studies in West Germany. Altogether, 183 children under the age of 8 with neuroblastoma diagnosed in 1988-1994 and 1785 control children sampled from population registration files participated. Information on potential risk factors was obtained from the children's parents by a self-administered questionnaire and subsequent telephone interview. We observed positive associations with the use of oral contraceptives or other sex hormones during pregnancy (particularly with male offspring), a shorter gestational duration, lower birth weight, and maternal alcohol consumption during pregnancy. While the association with maternal use of oral contraceptives or sex hormones was strong for stages I/II (odds ratio 4.5, 95% confidence interval 1.2-16.5), the associations with shorter gestation duration (odds ratio 3.4, 95% confidence interval 1.7-6.7) as well as maternal alcohol consumption during pregnancy (>7 glasses/week odds ratio 5.2, 95% confidence interval 1.3-20.6) were observed only for the unfavourable advanced stages. It is notable that the associations in our study were either observed only for the advanced stages of disease or only for the less advanced stages, but not for both subgroups. This adds to evidence for the hypothesis that neuroblastoma consists of at least two distinct disease entities, which differ in clinical stage at the time of diagnosis.

Adult↗
PubMed2000

Leukemia and non-Hodgkin's lymphoma in childhood and exposure to pesticides: results of a register-based case-control study in Germany.

Previous studies have suggested an association between exposure to pesticides and different types of childhood cancer. This paper presents results from a population-based case-control interview study of parents of children less than 15 years of age, which was conducted in the states of West Germany from 1993 to 1997. Cases were 1,184 children with leukemia, 234 with non-Hodgkin's lymphoma, and 940 with a solid tumor; 2,588 controls were also included. Parental occupational exposures were found to be related to childhood cancer regardless of the time period of exposure and the type of cancer. This finding might partially be explained by different recall of past exposures by the parents of cases and controls. Residential use of insecticides was associated with childhood lymphoma: both extermination of insects by professional pest controllers (odds ratio (OR) = 2.6, 95% confidence interval (CI): 1.2, 5.7) and frequency of parental use of household insecticides (p for trend = 0.02) were significant risk factors for this diagnosis. The use of pesticides on farms was weakly related to childhood leukemia (OR = 1.5, 95% CI: 1.0, 2.2), while their use in gardens was not associated with childhood leukemia (OR = 1.0, 95% CI: 0.8, 1.2). The major strengths of this study were the population base and the large number of cases and controls included; a drawback was assessment of exposure on the basis of parental interviews. The data provide some evidence for an increased leukemia risk for children living on farms and for an association between use of household pesticides and risk of childhood leukemia or lymphoma.

Adolescent↗
PubMed2000

Risk of childhood leukemia and parental self-reported occupational exposure to chemicals, dusts, and fumes: results from pooled analyses of German population-based case-control studies.

A recent large-scale United States study reported an association between parental exposure to hydrocarbons at work and the risk of childhood leukemia. Parental occupational exposure to different chemicals and industrial dusts or fumes also was assessed in three German case-control studies that were conducted from 1992-1997. The design and methods of exposure assessment were similar for these studies; therefore, they were pooled for this analysis. In total, these three studies involved 1138 cases of acute lymphocytic leukemia (ALL) and 2962 controls. We found that maternal exposure to paints or lacquers during the preconception period (odds ratio, 1.6; 95% confidence interval, 1.1-2.4) and during the index pregnancy (odds ratio, 2.0; 95% confidence interval, 1.2-3.3) was related to an increased risk of childhood ALL. Whereas our findings for exposure to paints or lacquers confirmed observations from the United States study, we failed to confirm associations between risk of ALL and maternal exposure to solvents and parental exposure to plastic materials. Our studies provide some evidence that parental occupational exposure to certain substances may be associated with cancer risk in offspring; however, more specific studies are needed to identify such substances and the doses that may be hazardous.

Adolescent↗
PubMed1999

Activity of O(6)-methylguanine-DNA methyltransferase in relation to p53 status and therapeutic response in ovarian cancer.

The DNA-repair protein O(6)-methylguanine-DNA methyltransferase (alkyltransferase; MGMT) is a major determinant of resistance of cells to various alkylating cytostatic drugs. Its expression in tissues is highly variable, indicating complex regulatory mechanisms involved. Transfection-mediated expression of wild-type p53 has been shown to negatively regulate basal promoter activity of MGMT in vitro. To elucidate whether p53 is involved in regulation of MGMT in tumor tissue, we examined MGMT expression and the p53 status of 140 primary ovarian carcinomas and analyzed the data as to the correlation between MGMT and p53, as well as the survival response of the patients after chemotherapy. We show that MGMT expression is highly variable in ovarian carcinomas, ranging from zero level up to 2500 fmol/mg protein. MGMT activity was significantly lower in tumors with wild-type p53 (p53wt) than in tumors with mutant p53 (p53mt) (p = 0.045). As expected, the percentage of tumors with p53mt increased with increasing histologic grade of the tumors. Thus, p53mt was observed in 4, 45 and 64% of grades 1, 2 and 3 tumors, respectively (p = 0.001). Increase in p53mt was accompanied by an increase in MGMT activity, which was, on average, 460 +/- 66, 624 +/- 63 and 662 +/- 60 fmol/mg protein in grades 1, 2 and 3 tumors, respectively (p = 0.047). In addition, MGMT activity as well as p53mt were associated with the FIGO stage of the tumors. Mean MGMT activity was 472 +/- 48 fmol/mg for patients with FIGO stages I and II, as compared with 675 +/- 50 fmol/mg for patients with FIGO stages III and IV, (p = 0.0179). The percentage of p53mt was 27% and 54% in ovarian tumors with FIGO stages I/II and FIGO stages III/IV, respectively (p = 0.004). Thus, progression of ovarian tumors was clearly associated with increase of both MGMT activity and the percentage of p53mt. In tumors expressing low MGMT (<100 fmol/mg), p53mt was very rarely found. No significant association was observed between MGMT level in ovarian carcinomas and the survival of patients treated with cyclophosphamide and carboplatin. On the other hand, a clear correlation was found between histological type, grading, residual tumor mass and p53wt expression and duration of the patient's survival. The finding that p53wt expression was associated with low MGMT level in primary ovarian cancer supports the view that down-regulation of basal MGMT promoter activity by p53wt is also relevant in tumor cells in vivo. Int. J. Cancer (Pred. Oncol.) 84:388-395, 1999.

Disease-Free Survival↗
PubMed1999

Contribution of c-erbB-2 and topoisomerase IIalpha to chemoresistance in ovarian cancer.

Overexpression of the c-erbB-2 (HER-2/neu) oncogene, which encodes a transmembrane receptor tyrosine kinase, has been shown to be associated with poor prognosis in ovarian and breast cancer. Recent studies indicate that c-erbB-2 may also be involved in determining the chemosensitivity of human cancers. In the present study, we examined the role of c-erbB-2 for chemoresistance in ovarian cancer. Overexpression of c-erbB-2 mRNA in tumor tissue was associated with a shorter survival of patients with primary ovarian cancer (P = 0.0001; n = 77) and was an independent prognostic factor in the proportional-hazard model adjusted for International Federation of Gynecologists and Obstetricians stage, residual disease, chemotherapy, and age (P = 0.035). A significant association between expression of c-erbB-2 mRNA and survival was obtained for the subgroup of patients who received a standard chemotherapy with carboplatin or cisplatin and cyclophosphamide (P = 0.0003), whereas only a nonsignificant trend was observed for patients who did not receive a standard chemotherapy (P = 0.124). In addition, the application of a standard chemotherapy improved the survival of patients with relatively low c-erbB-2 expression (P = 0.013) but not of patients with overexpression of c-erbB-2 (P = 0.359). Expression of c-erbB-2 mRNA correlated with expression of topoisomerase IIalpha mRNA determined by a reverse semiquantitative PCR technique (P = 0.009), whereas expression of c-erbB-2 and topoisomerase IIbeta mRNA did not correlate (P = 0.221). To examine the hypothesis that coamplified and/or coregulated topoisomerase IIalpha contributes to the resistance of c-erbB-2-overexpressing carcinomas, we established a chemosensitivity assay using primary cells from an ovarian carcinoma that overexpressed both c-erbB-2 and topoisomerase IIalpha. The combination of carboplatin with nontoxic concentrations of the topoisomerase II inhibitors etoposide or novobiocin enhanced the toxicity of carboplatin. In contrast, the tyrosine kinase inhibitor emodin exhibited no chemosensitizing effect in cells of this individual carcinoma. In conclusion, overexpression of c-erbB-2 was associated with poor prognosis and poor response to chemotherapy. The data suggest that topoisomerase IIlalpha, which correlates with c-erbB-2 expression, contributes to the resistance of c-erbB-2-overexpressing carcinomas.

Antigens, Neoplasm↗
PubMed1999

Childhood cancer and residential radon exposure - results of a population-based case-control study in Lower Saxony (Germany).

A population-based case-control study on risk factors for childhood malignancies was used to investigate a previously reported association between elevated indoor radon concentrations and childhood cancer, with special regard to leukaemia. The patients were all children suffering from leukaemia and common solid tumours (nephroblastoma, neuroblastoma, rhabdomyosarcoma, central nervous system (CNS) tumours) diagnosed between July 1988 and June 1993 in Lower Saxony (Germany) and aged less than 15 years. Two population-based control groups were matched by age and gender to the leukaemia patients. Long-term (1 year) radon measurements were performed in those homes where the children had been living for at least 1 year, with particular attention being paid to those rooms where they had stayed most of the time. Due to the sequential study design, radon measurements in these rooms could only be done for 36% (82 leukaemias, 82 solid tumours and 209 controls) of the 1038 families initially contacted. Overall mean indoor radon concentrations (27 Bq m(-3)) were low compared with the measured levels in other studies. Using a prespecified cutpoint of 70 Bq m(-3), no association with indoor radon concentrations was seen for the leukaemias (odds ratio (OR): 1.30; 95% confidence interval (95% CI): 0.32-5.33); however, the risk estimates were elevated for the solid tumours (OR: 2.61; 95% CI: 0.96-7.13), mainly based on 6 CNS tumours. We did not find any evidence for an association between indoor radon and childhood leukaemia, which is in line with a recently published American case-control study. There is little support for an association with CNS tumours in the literature.

Adolescent↗
PubMed1999

Association of childhood leukaemia with factors related to the immune system.

The childhood peak of common acute lymphoblastic leukaemia has been proposed as being a rare response to delayed exposure to a common infection. In this context, factors related to the child's immune system are of special interest. Information on such factors was obtained in a recent German case-control study comprising more than 1000 children with acute leukaemia. Neither being the first-born child, nor a short duration of breastfeeding, indicators of a deficit in viral contacts during infancy or the number of infectious diseases, were significant risk factors. We observed a strong association with fewer routine immunizations with a 3.2-fold increase for those children getting less than four immunizations, but this association could partly be explained by reporting bias. While tonsillectomy or appendectomy increased the risk of leukaemia in our studies, a protective effect of allergies could be seen. In summary, we found only weak support for the delayed exposure hypothesis. To some extent this may be due to the chosen surrogate markers which reflect, rather indirectly, immunological isolation in infancy and delayed exposure to common viruses. However, the significant findings for routine immunizations, tonsillectomy and allergies of the child or its parents merit further investigation.

Adolescent↗
PubMed1999

Association of childhood cancer with factors related to pregnancy and birth.

BACKGROUND: It has been hypothesized that risk factors of childhood cancers may already operate during the prenatal and neonatal period. Results of previous epidemiological studies have been inconsistent. METHODS: During 1992-1997 a large case-control study on childhood cancers and a variety of potential risk factors was conducted in Germany. Cases were ascertained by the German Childhood Cancer Registry. Each case was matched to a population-based control of the same age and gender, sampled from the district where the case lived at the date of diagnosis. For the analyses, 2358 cases and 2588 controls were available. RESULTS: Risk of childhood acute leukaemia increased with maternal age < or =20 years at time of delivery (odds ratio [OR] = 1.9, 95% CI: 1.1-3.2), lower (<2500 g: OR = 1.7, 95% CI: 1.1-2.8) and higher birthweight (>4000 g: OR = 1.4, 95% CI: 1.0-1.8, P < 0.05), and hormonal treatment because of infertility (OR = 1.6, 95% CI: 1.0-2.5, P < 0.05). No associations were seen for parental smoking habits, maternal alcohol consumption during pregnancy and fetal losses. Parity was associated only with subgroups of acute leukaemias. Regarding non-Hodgkin's lymphoma we observed an elevated OR for lower birthweight and heavy maternal smoking during pregnancy (>20 cigarettes/day) and a decreased OR for children with one or two siblings. Only a few significant findings were seen for the different groups of solid tumours. CONCLUSIONS: Overall, only weak associations were identified and the evaluated risk factors operating during the neonatal and prenatal period account at most for only a small proportion of childhood cancers.

Adolescent↗
PubMed1999

Associations between childhood cancer and ionizing radiation: results of a population-based case-control study in Germany.

In order to investigate the associations between sources of exposure to ionizing radiation and childhood cancer in Germany, a matched case-control study including children under the age of 15 years was conducted. Cases were identified from the German Childhood Cancer Registry; controls came from population registration offices. Exposure was assessed via questionnaires and parental interviews. The study comprises 1184 leukemia cases, 234 non-Hodgkin's lymphomas, 940 solid tumors, and 2588 controls. Preconception parental occupational exposures were positively but not statistically significantly related to all of the cancer types in the study. Maternal occupational exposure during pregnancy was a risk factor for childhood lymphomas [odds ratio (OR) = 3.87, 95% confidence interval (CI): 1.54-9.75] but not for leukemia or solid tumors. ORs for parental occupational exposures were noticeably more pronounced in leukemia cases who were diagnosed in their first 18 months of life. A preconception paternal occupation in the nuclear industry under dosimetric surveillance yielded an OR of 1.80 (95% CI: 0.71-4.58). However, radiation doses of these fathers were often unknown or below the level of detection, and no dose exceeded 30 mSv. Prenatal X-ray examinations of the father (but not of the mother) were significantly related to childhood leukemia (OR = 1.33; 95% CI: 1.10-1.61). No effects were observed for postnatal X-ray examinations of the child. The results suggest that, in Germany at present, exposures to ionizing radiation do not play a noticeable role in the development of childhood cancers. The major strengths of the study are its size and the population basis. The validity of the data from parental questionnaires and the possibility of residual confounding by socioeconomic factors are potential drawbacks.

Adolescent↗
PubMed1998

An extended study on childhood malignancies in the vicinity of German nuclear power plants.

OBJECTIVES: The study was performed to validate exploratory results obtained in a former study on the incidence rates of childhood malignancies in the vicinity of German nuclear power plants and to evaluate the confirmatory results of this previous study. METHODS: Incidence rates near German nuclear installations were compared to rates in control regions based on the German Childhood Cancer Registry. RESULTS: No exploratory result could be reproduced. This is also true for children with acute leukemia younger than 5 years who were living within a 5 km radius of an installation: an observed relative risk (RR) of 1.39 was not significantly increased (95 percent confidence interval CI: 0.69-2.57). Former confirmatory results could be confirmed again. A pooled analysis of both studies based on 2390 cases resulted in RR of 0.99 for all malignancies (CI: 0.91-1.07) and of 1.00 for acute leukemias (CI: 0.87-1.16) (children younger than 15 years of age living within a 15 km radius). CONCLUSIONS: Results did not show significantly increased incidence rates for any subgroup with previously significant exploratory results. Therefore, it appears to be most likely that the previous results were just due to chance. Evaluating the previously confirmatory results with the combined data from the two study periods reassures that incidence rates are not increased in children younger than 15 years who are living within a 15 km radius, either for all malignancies or for acute leukemias. We conclude that at present, in Germany no further investigations of this kind are necessary.

Adolescent↗
PubMed1998

C-myc mRNA expression in epithelial ovarian carcinomas in relation to estrogen receptor status, metastatic spread, survival time, FIGO stage, and histologic grade and type.

Recently, it has been suggested that c-myc expression might correlate with estrogen receptor (ER) status and metastatic spread in ovarian cancer. In this study, expression of c-myc mRNA in 90 epithelial ovarian carcinomas was determined using the S1 nuclease protection assay. Expression of c-myc mRNA was detectable in 27 of 90 tumors. There was no significant association between c-myc mRNA expression and metastatic spread, survival time, FIGO stage, or histologic grade and type. C-myc mRNA was expressed in 45% of ER-positive tumors but only 24% of ER-negative tumors (p = 0.094; Fisher's exact test). Similarly, 44% of progesterone receptor (PR)-positive and 23% of PR-negative tumors expressed c-myc mRNA (p = 0.098). However, the association between c-myc mRNA expression and ER and PR status was not statistically significant. The ratio of mean expression of c-myc mRNA in patients with FIGO stages III/IV compared with patients with FIGO stages I/II was 2.1:1, an insignificant difference (p = 0.57, Wilcoxon rank sum test). In conclusion, c-myc was not significantly associated with the clinical parameters investigated in this study.

Carcinoma↗
PubMed1998

Cotinine excretion as a predictor of peak flow variability.

Environmental tobacco smoke (ETS) is suspected to be an important risk factor for bronchial hyperresponsiveness. In order to test the effect of ETS, we measured expiratory flow rates and urine cotinine excretion (UCE) within a narrow time window in two consecutive years. Maternal smoking habits and medical history were ascertained by standardized questionnaires. The percentage ratio of the amplitude over the mean (AVAM) of the diurnal peak flow rates of children (complete values from at least five consecutive days) was calculated as an indicator of bronchial responsiveness. The association of UCE and log10AVAM was analyzed by multiple linear regression. Complete data were available for a sample of 417 children. The median of UCE in children of parents who smoked (3.2 ng/mg and 2.9 ng/mg creatinine, Surveys 1 and 2, respectively) was higher than the median in children of nonsmoking parents (0 ng/mg in both surveys). With increasing UCE the log10AVAM rose in the first and second surveys, as well as in the longitudinal analysis (p = 0.003). This association, however, showed up only in boys (p = 0.0001) and not in girls (p = 0.31). Our data suggest that there is a need both for further analysis of the gender difference and for more support of strategies against passive smoking as far as children are concerned, since airway hyperresponsiveness is a risk factor for chronic airway impairment.

Asthma↗
PubMed1998

Combined risk estimates for two German population-based case-control studies on residential magnetic fields and childhood acute leukemia.

From 1992 to 1996, we obtained electromagnetic field measurements in two population-based case-control studies on childhood leukemia in the northwestern part of Germany and in Berlin. Exposure assessment comprised residential 24-hour measurements and short-term measurements. We obtained 24-hour measurements for a total of 176 cases and 414 controls. We compared subjects exposed to median 24-hour measurements of 0.2 microT or more with those exposed to lower amounts. Multivariate regression analysis revealed an odds ratio of 2.3 (95% confidence interval = 0.8-6.7).

Acute Disease↗
PubMed1997

mdm 2 mRNA expression is associated with survival in ovarian cancer.

Expression of mdm-2 mRNA was measured in 90 ovarian-cancer tissue specimens using the S1 nuclease assay, to investigate a possible association between MDM2 expression and prognosis. mdm-2 mRNA expression was an independent prognostic factor for patients with primary ovarian cancer, FIGO (International Federation of Gynecology and Obstetrics) stages III and IV (n = 57), who all received chemotherapy with carboplatin or cisplatin and cyclophosphamide. Median survival time for patients (FIGO stages III and IV) with no detectable expression of mdm-2 mRNA (n = 14) was 171 days, as compared with 839 days for patients (n = 43) with detectable mdm-2 mRNA (p = 0.0194; log-rank test). However, no association between mdm-2 mRNA expression and survival was observed for patients with FIGO stages I and II who did not receive chemotherapy. mdm-2 expression was not associated with FIGO stage, residual disease, histologic grade and type. Our results suggest that mdm-2, which is known to disrupt p53 function, sensitizes ovarian-cancer cells to cisplatin/cyclophosphamide, possibly by inhibition of p53-mediated G1 cell-cycle arrest and p53-stimulated nucleotide-excision repair.

Confidence Intervals↗
PubMed1997

The internal dose of passive smoking at home depends on the size of the dwelling.

As part of a longitudinal study two urine samples (survey 1 in 1991 and survey 2 in 1992) were collected from 602 elementary school children to investigate the relationship between urinary cotinine excretion (UCE) and the daily consumption of cigarettes at home (exposure). Size of the dwelling, educational level, and maternal smoking were taken into consideration as additional predictors. The history regarding parental smoking habits and confounding variables was ascertained by standardized questionnaires completed by the parents. Cotinine was measured using gas chromatography selected ion monitoring. UCE was expressed as cotinine/creatinine (ng/mg). In children with detectable UCE in survey 1 (35%) and in survey 2 (44%) the excretion ranged between 1.5 and 24.7 ng/mg (5-95%) and between 1.2 and 25.2 ng/mg, respectively. UCE measurements in both surveys were highly correlated (r = 0.65, P = 0.0001), and 59.6% of the UCE in survey 2 can be explained in linear regression by the UCE in survey 1. Using multiple linear regression, the categorized number of cigarettes reported to be consumed at home (20 cigarettes and more: 1991, P = 0.0001; 1992, P = 0.0003) and low educational level of the parents (P = 0.011 in 1991, P = 0.04 in 1992) were positively associated with UCE, whereas the size of the dwelling turned out to be negatively associated with UCE (P = 0.12 in 1991, P = 0.001 in 1992). In small dwellings (< or = 80 m2) the effect of exposure on UCE was much more pronounced. In conclusion, a single UCE measurement provides information which is widely stable within a yearly interval and is related to passive smoke history as well as to socio-economic status and the size of the dwelling. The latter variable should be considered as an effect modifier of exposure on internal dose and should be taken into account in future studies on passive smoke exposure.

Analysis of Variance↗