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J Michaelis

Publications and source records attributed to J Michaelis.

At least 37 records · Page 2Linked to original sources

A pooled analysis of magnetic fields and childhood leukaemia.

Previous studies have suggested an association between exposure to 50-60 Hz magnetic fields (EMF) and childhood leukaemia. We conducted a pooled analysis based on individual records from nine studies, including the most recent ones. Studies with 24/48-hour magnetic field measurements or calculated magnetic fields were included. We specified which data analyses we planned to do and how to do them before we commenced the work. The use of individual records allowed us to use the same exposure definitions, and the large numbers of subjects enabled more precise estimation of risks at high exposure levels. For the 3203 children with leukaemia and 10 338 control children with estimated residential magnetic field exposures levels < 0.4 microT, we observed risk estimates near the no effect level, while for the 44 children with leukaemia and 62 control children with estimated residential magnetic field exposures >/= 0.4 microT the estimated summary relative risk was 2.00 (1.27-3.13), P value = 0.002). Adjustment for potential confounding variables did not appreciably change the results. For North American subjects whose residences were in the highest wire code category, the estimated summary relative risk was 1.24 (0.82-1.87). Thus, we found no evidence in the combined data for the existence of the so-called wire-code paradox. In summary, the 99.2% of children residing in homes with exposure levels < 0.4 microT had estimates compatible with no increased risk, while the 0.8% of children with exposures >/= 0.4 microT had a relative risk estimate of approximately 2, which is unlikely to be due to random variability. The explanation for the elevated risk is unknown, but selection bias may have accounted for some of the increase.

Adolescent↗

[Epidemiology of childhood brain tumors].

The German Childhood Cancer Registry (GCCR) was established in 1980. From 1980 to 1997 4,447 CNS tumours in children below 15 years of age have been reported to the registry. From 1988 to 1997 the average annual incidence was 2.5/100,000 children. This corresponds to 19.2% of the registered diseases. Compared with incidence rates reported from other developed countries one can estimate that there is about 25% underreporting of CNS tumours in the GCCR. This is in contrast to the relatively complete ascertainment of other childhood malignancies (above 95%). Based on 3012 incident cases from 1988 to 1997 the Kaplan-Meier-estimate of 5-year-survival probability is 65% for all CNS tumours and 54% for PNETs and gliomas. An active long-term-follow-up shows that 30% of 142 children with secondary neoplasms following primary lymphoid leukaemias developed a CNS tumour. Following any primary childhood malignancies 45 CNS tumours were recorded, amongst these were one third leukaemias. The paper reports first results from a population based case control study which included 466 children with CNS tumours and 2,458 healthy controls. These indicate an increased risk for children with low birth weight and for children whose mothers smoked during pregnancy. Additional data can be found in the Internet (http:¿info.imsd.uni-mainz.de/K_Krebsregister).

Adolescent↗

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↗

[Pilot study on early diagnosis of renal cell carcinoma by sonography].

UNLABELLED: The goal of this study was to investigate the practicability and effectiveness of a systematic screening for renal cell carcinoma by ultrasound in the course of the established German Health Ministry screening programs. METHODS: In two centers (Mainz and Wuppertal) a screening program for renal cell carcinoma for all citizens (age > 40 years) was established. The screening was divided into two phases (time period 1 year): (1) All citizens over 40 years could attend voluntarily a cost-free ultrasound investigation. (2) A follow-up investigation for the entire screening population was provided. RESULTS: Ten thousand volunteers attended the screening program. Mean age was 60 years. Thirteen renal cell carcinomas were detected. The incidence of other findings was 15%; none of those required further treatment. CONCLUSION: Systematic screening for renal cell carcinoma by ultrasound is cost-effective and showed high acceptance and practicability in a German population. The rate of detection of renal cell carcinoma was higher than initially statistically calculated.

Aged↗

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↗

Spontaneous platelet aggregation as a predictive risk factor for vascular occlusions in healthy volunteers? Results of the HAPARG Study. Haemostatic parameters as risk factors in healthy volunteers.

The HAPARG Study (haemostatic parameters as risk factors in healthy volunteers) was performed in a subset of volunteers taking part in the MARISK Study (Mainzer Risikoindikatoren Studie für die koronare Herzkrankheit) sponsored by the German Ministry of Research and started in 1984. A previous study (Yamanishi et al., Thromb Haemostas 1985;54:539-543) had shown that spontaneously enhanced platelet aggregation as measured with the PAT-III-test and higher fibrinogen concentrations are significant risk factors for new vascular occlusions in diabetic patients. It was the aim of the HAPARG Study to establish whether spontaneous platelet aggregation and other hemostatic variables are independent risk factors for vascular occlusions in healthy volunteers. Employees of a chemical/pharmaceutical company aged 40-65 years and personnel of the University of Mainz, aged 30-60 years were included in this prospective study. Besides anamnestic data such as on smoking, hypertension and diabetes, blood pressure, the ankle/arm Doppler-index and an ECG were recorded and serum cholesterol, HDL, LDL, triglycerides, uric acid and glucose were measured. Men (1884) and women (989) entered the study and were followed for 4-6 years. In the age group of 30-50 years, more women than men were included. During the observation period 53 vascular occlusions occurred (36 coronary and nine cerebral events and eight peripheral vascular occlusions). Only three of these endpoints occurred in women. Besides age (odds ratio = 1.7, P = 0.02) and gender as expected risk factors, the multivariate logistic stepwise regression analysis revealed smoking (odds ratio = 2.2, P = 0.008), lower HDL-levels (odds ratio = 2.2, P = 0.013), elevated diastolic blood pressure (odds ratio = 1.4. P = 0.004) followed by spontaneous platelet aggregation (odds ratio = 1.1, P = 0.037), and slightly elevated blood glucose (P = 0.0047) as significant risk factors for men. Higher fibrinogen levels missed significance in this analysis (P = 0.059). None of the other hemostatic parameters showed a significant correlation with the vascular events. To our knowledge, this has been the first prospective trial in a large population of healthy individuals in which a platelet function parameter has been studied together with other possible risk factors. Spontaneously enhanced platelet aggregation is probably an independent risk factor and, like elevated fibrinogen and other haemostatic variables, an indicator of an ongoing active atherosclerotic process.

Adult↗

Population density and childhood leukaemia: results of the EUROCLUS Study.

The EUROCLUS study assembled incidence data for 13,551 cases of childhood leukaemia (CL) diagnosed between 1980 and 1989 in 17 countries (or regions of countries). These were referenced by location at diagnosis to small census areas of which there were 25,723 in the study area. Population counts, surface area and, hence, population density were available for all these small areas. Previous analyses have shown limited extra-Poisson variation (EPV) of case counts within small areas; this is most pronounced in areas of intermediate population density (150-499 persons/km2). In this study, the data set was examined in more detail for evidence that variations in incidence and EPV of CL are associated with population density. Incidence showed a curvilinear association with population density and was highest in areas which were somewhat more densely populated (500-750 persons/km2), where the incidence rate ratio relative to areas having > or = 1000 persons/km2 was 1.16 (95% confidence interval 1.07-1.26) and the P value for quadratic trend across eight strata of population density was 0.02. Incidence in these areas is uniformly elevated and showed no evidence of heterogeneity (i.e. EPV). Statistically significant evidence of EPV was evident amongst some of the areas previously classified as intermediate density areas (specifically, those with a density of 250-499 persons/km2, P < 0.001 for CL). These results were interpreted in terms of the current aetiological hypotheses for CL which propose that exposure to localised epidemics of one or more common infectious agent may contribute to the development of leukaemia. They suggest that such epidemics arise regularly in moderately densely populated areas and also sporadically in areas which are somewhat less densely populated. Although other interpretations are possible, these results may assist in the identification of characteristics which infectious agents must possess if direct or indirect causes of CL.

Child↗

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↗

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↗

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↗

Pluripotent protective effects of carnosine, a naturally occurring dipeptide.

Carnosine is a naturally occurring dipeptide (beta-alanyl-L-histidine) found in brain, innervated tissues, and the lens at concentrations up to 20 mM in humans. In 1994 it was shown that carnosine could delay senescence of cultured human fibroblasts. Evidence will be presented to suggest that carnosine, in addition to antioxidant and oxygen free-radical scavenging activities, also reacts with deleterious aldehydes to protect susceptible macromolecules. Our studies show that, in vitro, carnosine inhibits nonenzymic glycosylation and cross-linking of proteins induced by reactive aldehydes (aldose and ketose sugars, certain triose glycolytic intermediates and malondialdehyde (MDA), a lipid peroxidation product). Additionally we show that carnosine inhibits formation of MDA-induced protein-associated advanced glycosylation end products (AGEs) and formation of DNA-protein cross-links induced by acetaldehyde and formaldehyde. At the cellular level 20 mM carnosine protected cultured human fibroblasts and lymphocytes, CHO cells, and cultured rat brain endothelial cells against the toxic effects of formaldehyde, acetaldehyde and MDA, and AGEs formed by a lysine/deoxyribose mixture. Interestingly, carnosine protected cultured rat brain endothelial cells against amyloid peptide toxicity. We propose that carnosine (which is remarkably nontoxic) or related structures should be explored for possible intervention in pathologies that involve deleterious aldehydes, for example, secondary diabetic complications, inflammatory phenomena, alcoholic liver disease, and possibly Alzheimer's disease.

Amyloid beta-Peptides↗

Neuroblastoma in Europe: differences in the pattern of disease in the UK. SENSE. Study group for the Evaluation of Neuroblastoma Screening in Europe.

BACKGROUND: Neuroblastoma is a major contributor to childhood cancer mortality, but its prognosis varies with age and stage of disease, and some tumours regress spontaneously. Urinary screening programmes or clinical examination may detect the disease before symptoms appear, but the benefit of early diagnosis is uncertain. We examined the incidence, pattern, and presentation of neuroblastoma in four European countries. METHOD: Population-based incidence rates were derived for France, Austria, Germany, and the UK. Age, sex, and stage distribution were analysed by Mantel-Haenszel techniques and Poisson regression. The proportion of incidental diagnoses (cases without symptoms found at routine health checks or during investigation of other disorders) and mortality rates were also compared. FINDINGS: Between 1987 and 1991, 1672 cases of neuroblastoma were diagnosed in children under 15 years old (France, 624; Austria, 69; Germany, 493; UK, 486). Age-standardised annual incidence was significantly lower in the UK (10.1/million) than in France (12.5) and Germany (11.4). In the UK a deficit of low-stage disease in infants was accompanied by an excess of stage IV in older children. The UK had significantly fewer incidental diagnoses (8%) than Austria (27%) and Germany (34%). UK mortality rates were significantly higher than German or French rates. INTERPRETATION: In the UK, neuroblastoma diagnosis is delayed, possibly because of a less rigorous system of health checks for children. Although some overdiagnosis occurs in mainland Europe, our data suggest that in the UK some low-stage cases, undetected in infancy, may later present as advanced disease. This finding has implications for screening programmes and organisation of routine surveillance of infant health in the UK.

Adolescent↗

Trends in infant leukaemia in West Germany in relation to in utero exposure due to Chernobyl accident.

A temporary increase in the incidence of infant leukaemia in Greece was reported by Petridou et al., which was attributed to in utero exposure to ionising radiation resulting from the Chernobyl accident. We performed a similar analysis based on the data of the German Childhood Cancer Registry in order to check whether the observation could be confirmed by means of independent data. Applying the same definitions as Petridou et al., we also observed an increased incidence of infant leukaemia in a cohort of children born after the Chernobyl accident. More detailed analyses, regarding areas with different contamination levels and dose rate gradients over time after the accident, showed, however, no clear trend with regard to exposure. It would therefore appear less likely that the observed effect was caused by exposure to ionising radiation due to the Chernobyl accident.

Child, Preschool↗

Multiple primary neoplasms in childhood: data from the German Children's Cancer Registry.

The German Children's Cancer Registry (GCCR) has documented all malignancies during the first 15 years of life in Germany since 1980. In a series of 20,388 cancer cases to the end of 1995, 127 children with multiple primary neoplasms up to the age of 15 years were identified. The children were monitored for 82,591 person-years with a mean observation time of 4.1 years. Relative and cumulative risk for the occurrence of second malignant neoplasms were estimated only for the first 15 years of life, as follow-up data beyond childhood are incomplete and valid data on the incidence of cancer in adolescents and adults are not available in Germany. The overall standardised incidence ratio for a second malignancy was 12.5 (95% CI: 10.4-14.9) which implies an absolute excess risk of 141.5 per 10(5). The estimated cumulative risk within 10 years after the first malignancy was 1.9% (95% CI: 1.5-2.3). It is expected that the risk will alter with prolongation of follow-up beyond childhood.

Adolescent↗

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↗

Spatial temporal patterns in childhood leukaemia: further evidence for an infectious origin. EUROCLUS project.

The EUROCLUS project included information on residence at diagnosis for 13351 cases of childhood leukaemia diagnosed in the period 1980-89 in defined geographical regions in 17 countries. A formal algorithm permits identification of small census areas as containing case excesses. The present analysis examines spatial-temporal patterns of the cases (n = 970) within these clustered areas. The objectives were, first, to compare these results with those from an analysis conducted for UK data for the period 1966-83, and, second, to extend them to consider infant leukaemias. A modification of the Knox test investigates, within the small areas, temporal overlap between cases in a subgroup of interest at a putative critical time and all other cases at any time between birth and diagnosis. Critical times were specified in advance as follows: for cases of acute lymphoblastic leukaemia aged 2-4 years, the 18-month period preceding diagnosis; for cases of total leukaemia aged 5-14 years, 1 year before to 1 year after birth; and for infant cases (diagnosed < 1 year), 1 year before to 6 months after birth. Each of the analyses found evidence of excess space-time overlap compared with that expected; these were 10% (P = 0.005), 15% (P= 0.0002) and 26% (P= 0.03) respectively. The results are interpreted in terms of an infectious origin of childhood leukaemia.

Adolescent↗