Search PubMed⌕ Search

Biomedical subjects

J Michaelis

Publications and source records attributed to J Michaelis.

At least 55 records · Page 3Linked to original sources
PubMed1998

Spatial clustering of childhood leukaemia: summary results from the EUROCLUS project.

The interpretation of reports of clusters of childhood leukaemia is difficult, first because little is known about the causes of the disease, and second because there is insufficient information on whether cases show a generalized tendency to cluster geographically. The EUROCLUS project is a European collaborative study whose primary objective is to determine whether the residence locations of cases at diagnosis show a general tendency towards spatial clustering. The second objective is to interpret any patterns observed and, in particular, to see if clustering can be explained in terms of either infectious agents or environmental hazards as aetiological agents. The spatial distribution of 13351 cases of childhood leukaemia diagnosed in 17 countries between 1980 and 1989 has been analysed using the Potthoff-Whittinghill method. The overall results show statistically significant evidence of clustering of total childhood leukaemia within small census areas (P=0.03) but the magnitude of the clustering is small (extra-Poisson component of variance (%) = 1.7 with 90% confidence interval 0.2-3.1). The clustering is most marked in areas that have intermediate population density (150-499 persons km[-2]). It cannot be attributed to any specific age group at diagnosis or cell type and involves spatial aggregation of cases of different ages and cell types. The results indicate that intense clusters are a rare phenomenon that merit careful investigation, although aetiological insights are more likely to come from investigation of large numbers of cases. We present a method for detecting clustering that is simple and readily available to cancer registries and similar groups.

Adolescent↗
PubMed1998

Recent epidemiological studies on ionizing radiation and childhood cancer in Germany.

PURPOSE: The results from recent epidemiological studies based on the German Childhood Cancer Registry are summarized. MATERIALS AND METHODS: An oecological study covers 16 years' incidence of childhood malignancies in areas surrounding nuclear facilities and in matched control regions. Two population-based case control studies explore potential risk factors of childhood leukaemia in the state of Lower Saxony (1988 93) and in all western states of Germany (1992-94). RESULTS: There was no increased incidence of childhood leukaemia and other malignancies in the vicinity of nuclear installations. X-ray examinations during pregnancy and in early childhood were not associated with an increased risk of childhood leukaemia. There were no data to support Gardner's hypothesis of an increased risk due to paternal pre-conception exposure to ionizing radiation. Following the Chernobyl accident, the reported incidence of neuroblastoma and infant leukaemia was increased. The increase cannot be explained by exposures due to the accident. CONCLUSIONS: Although the carcinogenic effect of ionizing radiation is well known, the recent population-based epidemiological studies show that under current conditions exposure to ionizing radiation in Germany does not constitute risks of childhood malignancies that are relevant to public health.

Case-Control Studies↗
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

Randomised, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the HANE study. HANE Trial Research Group.

OBJECTIVE: To compare the effectiveness and tolerability of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in patients with mild to moderate hypertension. DESIGN: Randomised multicentre trial over 48 weeks with double blind comparison of treatments. SETTING: 48 centres in four countries. PATIENTS: 868 patients with essential hypertension (diastolic blood pressure 95-120 mm Hg) INTERVENTIONS: Initial treatment (step 1) consisted of 12.5 mg hydrochlorothiazide (n = 215), 25 mg atenolol (n = 215), 10 mg nitrendipine (n = 218), or 5 mg enalapril (n = 220) once daily. If diastolic blood pressure was not reduced to < 90 mm Hg within four weeks, doses were increased to 25 mg, 50 mg, 20 mg, 10 mg, respectively, once daily (step 2) and after two more weeks to twice daily (step 3). The eight week titration phase was followed by an additional 40 weeks for patients who had reached the target diastolic pressure. MAIN OUTCOME MEASURES: Blood pressure by means of an automatic device with repeated measurements. RESULTS: After eight weeks the response rate for atenolol (63.7%) was significantly higher than for enalapril (50.0%), hydrochlorothiazide (44.7%), or nitrendipine (44.5%). After one year atenolol was still more effective (48.0%) than hydrochlorothiazide (35.4%) and nitrendipine (32.9%), but not significantly better than enalapril (42.7%). The treatment related dropout rate was higher (P < 0.001) in the nitrendipine group (n = 28). CONCLUSIONS: There is no evidence of superiority for antihypertensive effectiveness or tolerability of the "new" classes of antihypertensives (calcium channel blockers and angiotensin converting enzyme inhibitors). As these drugs are now widely used as treatment of first choice, our results further emphasise the need for studies confirming that they also reduce morbidity and mortality, as has been shown for diuretics and beta blockers.

Adult↗
PubMed1997

Influence of advanced glycation end-products and AGE-inhibitors on nucleation-dependent polymerization of beta-amyloid peptide.

Nucleation-dependent polymerization of beta-amyloid peptide, the major component of plaques in patients with Alzheimer's disease, is significantly accelerated by crosslinking through Advanced Glycation End-products (AGEs) in vitro. During the polymerization process, both nucleus formation and aggregate growth are accelerated by AGE-mediated crosslinking. Formation of the AGE-crosslinked amyloid peptide aggregates could be attenuated by the AGE-inhibitors Tenilsetam, aminoguanidine and carnosine. These experimental data, and clinical studies, reporting a marked improvement in cognition and memory in Alzheimer's disease patients after Tenilsetam treatment, suggest that AGEs might play an important role in the etiology or progression of the disease. Thus AGE-inhibitors may generally become a promising drug class for the treatment of Alzheimer's disease.

Alzheimer Disease↗
PubMed1997

Childhood leukemia and electromagnetic fields: results of a population-based case-control study in Germany.

The investigation of an association between increased exposure to residential extremely-low frequency electromagnetic fields (ELF-EMF) and childhood leukemia was part of a population-based case-control study carried out between 1992 and 1995 in the northwestern part of Germany. A total of 129 children with leukemia and 328 controls participated in the EMF-study. Exposure assessment comprised measurements of the magnetic field over 24 hours in the child's bedroom at the residence where the child had been living for the longest period before the date of diagnosis, and spot measurements at all residences where the child had been living for more than one year. The median of the 24h-measurement in the child's bedroom was regarded as the most valid exposure variable. For children exposed to more than 0.2 microT, an elevated but not significant odds ratio (OR) was observed (OR = 3.2, 95 percent confidence interval = 0.7-14.9). These figures are based on only four leukemia cases and three controls since only 1.5 percent of the study population was classified as highly exposed. Exploratory analyses revealed ORs that were not statistically significantly increased for other characteristics of the magnetic field at varying cut-points. The results are comparable with those from other studies. Although not statistically significant, they may indicate a positive association between EMF and childhood leukemia.

Adolescent↗
PubMed1996

Cancer consequences of the Chernobyl accident in Europe outside the former USSR: a review.

The accident which occurred during the night of April 25-26, 1986 in reactor 4 of the Chernobyl nuclear power plant in the Ukraine released considerable amounts of radioactive substances into the environment. Outside the former USSR, the highest levels of contamination were recorded in Bulgaria, Austria, Greece and Romania, followed by other countries of Central, Southeast and Northern Europe. Studies of the health consequences of the accident have been carried out in these countries, as well as in other countries in Europe. This report presents the results of a critical review of cancer studies of the exposed population in Europe, carried out on the occasion of the 10th anniversary of the Chernobyl accident. Overall, three is no evidence to date of a major public health impact of the Chernobyl accident in the field of cancer in countries of Europe outside the former USSR.

Adolescent↗
PubMed1996

Vitamin K and childhood cancer: a population based case-control study in Lower Saxony, Germany.

OBJECTIVE: To confirm or refute a possible association of parenteral vitamin K prophylaxis and childhood cancer. DESIGN: Population based case-control study. Comparison of vitamin K exposure in children with leukaemia or other common tumours with two control groups. SETTING: State of Lower Saxony (north western part of Germany); case recruitment from the German childhood cancer registry. SUBJECTS: 272 children with leukaemia, nephroblastoma, neuroblastoma, rhabdomyosarcoma, and tumours of the central nervous system diagnosed between 1 July 1988 and 30 June 1993; children were aged between 30 days and 15 years at diagnosis. 334 population based controls without diagnoses of cancer matched to the leukaemia cases for age and sex. MAIN EXPOSURE MEASURES: Parenteral vitamin K prophylaxis (intramuscular and subcutaneous) versus oral and no vitamin K prophylaxis. RESULTS: An association between parenteral vitamin K exposure and childhood cancer (leukaemias and other tumours combined) could not be confirmed (odds ratio 1.04, 95% confidence interval 0.74 to 1.48). For leukaemias the observed odds ratio was only 0.98 (0.64 to 1.50) (comparison of leukaemia cases with local controls 1.24 (0.68 to 2.25); state controls 0.82 (0.50 to 1.36)). These odds ratios remained almost unchanged when several potential confounders were considered in the logistic regression model. CONCLUSIONS: This population based study adds substantial evidence that there is no association between parenteral vitamin K and childhood cancer.

Adolescent↗
PubMed1996

Sero-epidemiological analysis of the risk of virus infections for childhood leukaemia.

Virus infections have been thought to be involved in the development of childhood leukaemia. In order to address this issue we determined, in a case-control study, the prevalence of antibodies to viruses infecting blood or bone-marrow cells [Epstein-Barr virsus (EBV), human herpes virus type 6 (HHV-6), parvovirus B19] as well as to the human virus known for its tumour-suppressive properties, the adeno-associated virus type 2 (AAV-2), in the sera of 121 children with leukaemia in Germany, and in 197 control individuals, hospitalized for other reasons, and matched for age and gender to the cases. In addition, we developed a questionnaire to be answered by the children's parents, in order to gain information on previous infections of the children as well as to calculate for factors which may influence serological findings. Comparative determination of the prevalence of antibodies against AAV-2, B-19 or HHV-6 revealed no significant differences in cases and controls. However, antibodies to EBV were more frequently found in children with leukaemia younger than 6 years of age (age at the time of diagnosis of leukaemia) than in controls. Apparently, infection with AAV-2 has no protective effect in childhood leukaemia, in contrast to results observed for other malignancies. Similarly, and in accordance with results on leukaemia in adults, we found no indication of a protective effect of infection with the parvovirus B-19. The data suggest that EBV, which is known to be involved in various lymphomas, may play a role in the development of childhood leukaemia in young children.

Adolescent↗
PubMed1996

Meta-analyses of studies on the association between electromagnetic fields and childhood cancer.

During the last 15 years several studies have investigated a possible relationship between exposure to electromagnetic fields (EMF) and childhood cancer. There is considerable variation between these studies with respect to methods of exposure assessment and reported results. Methods of exposure assessment range from simple visual criteria to costly and time consuming measurements or estimations of electric flux density. Additional individual refinements further hinder the comparability of results. We carried out several meta-analyses of data published so far taking into account the heterogeneity between studies as far as possible. Our particular interest was to investigate a potential dose-response-like relationship by comparing analyses for different cut-off points of exposure. Our meta-analyses suggest a marginal association between all cancer diagnoses combined and EMF exposure assessed by the two-level wire code (odds ratio, OR = 1.37, 95% confidence interval, CI: 0.94-2.00). Based on this criterion a significant effect was found for bases of leukemia (OR = 1.66, CI: 1.11-2.49) but not for central nervous system (CNS) tumors (OR = 1.5, CI: 0.69-3.26) or lymphomas (OR = 1.32, CI: 0.52-3.37). A significant increase in overall cancer risk with increasing stages of the four-level wire code (P = 0.003) could not be confirmed when data of the initial study performed by Wertheimer and Leeper were excluded (P = 0.17). When the exposure criterion was based on distance to the transmission line, estimated ORs for all cancers combined and for leukemias increased with distances decreasing from 100 to 25 m. Those analyses incorporating data on measured or calculated EMFs demonstrated also an increase of overall cancer risk with higher cut-off points. However, regarding individual diagnoses, this finding was reflected only in the group of brain tumors. One possible explanation for the high degree of heterogeneity between studies--especially with respect to methods of exposure assessment and choice of the respective cutpoint relevant for an increase in cancer risk--could be that published cut-off points were not always chosen in advance, but were selected because in exploratory analyses the most striking results were obtained with these specific cut-off values. Should this speculation be true at least partially, any meta-analysis will yield a false-positive finding. Further results of comparable studies with strictly a priori planned analyses are necessary to properly investigate a possible link between EMF and childhood cancer.

Child↗
PubMed1996

Childhood leukaemia and exposure to pesticides: results of a case-control study in northern Germany.

The association between childhood leukaemia and exposure to pesticides was examined in a population-based case-control study conducted in Lower Saxony, Northern Germany. Between July 1988 and June 1992, 219 newly diagnosed cases were identified, of whom 173 participated in the study. Two sex- and age-matched control groups were recruited: local controls from the same communities as the newly diagnosed cases of leukaemia and state controls from other randomly selected communities in Lower Saxony. An additional study group consisted of 175 cases of solid tumours. When the leukaemia cases were compared with the local controls, positive associations with parental occupational exposure, particularly agriculture-related exposure, were observed, which were statistically non-significant. A significant association was found for pesticide use in gardens (odds ratio = 2.52, 95% confidence interval: 1.0-6.1). No positive associations were seen when the leukaemia cases were compared to the state controls, but this finding could be explained by a higher proportion of state controls living in rural areas. In communities with a significantly elevated standardised incidence ratio of childhood leukaemia over the last decade (1984-1993), the prevalence of pesticide use in the garden was 21%, compared with the 10% in other communities. None of the examined risk factors were more common among cases of solid tumours. Our findings add some evidence to the hypothesis that pesticides are a risk factor for childhood leukaemia, and there are good reasons to consider abundant pesticide use in rural areas as a possible cause for clustering of childhood leukaemia.

Adolescent↗
PubMed1996

Childhood leukaemia in Europe after Chernobyl: 5 year follow-up.

The European Childhood Leukaemia - Lymphoma Incidence Study (ECLIS) is designed to address concerns about a possible increase in the risk of cancer in Europe following the nuclear accident in Chernobyle in 1986. This paper reports results of surveillance of childhood leukaemia in cancer registry populations from 1980 up to the end of 1991. There was a slight increase in the incidence of childhood leukaemia in Europe during this period, but the overall geographical pattern of change bears no relation to estimated exposure to radiation resulting from the accident. We conclude that at this stage of follow-up any changes in incidence consequent upon the Chernobyl accident remain undetectable against the usual background rates. Our results are consistent with current estimates of the leukaemogenic risk of radiation exposure, which, outside the immediate vicinity of the accident, was small.

Child↗
PubMed1996

Weekly high-dose leucovorin versus low-dose leucovorin combined with fluorouracil in advanced colorectal cancer: results of a randomized multicenter trial. Study Group for Palliative Treatment of Metastatic Colorectal Cancer Study Protocol 1.

PURPOSE: To determine the most effective dose of leucovorin (folinic acid [FA]) within a weekly bolus fluorouracil (FU) schedule, we conducted a randomized multicenter trial to compare therapeutic effects and toxicity of high-dose FA versus low-dose FA combined with FU at equal doses in both treatment groups. PATIENTS AND METHODS: Patients with measurable inoperable or metastatic colorectal cancer were randomized to receive weekly FU 500 mg/m2 by intravenous (IV) bolus combined with high-dose FA 500 mg/m2 (group A) or low-dose FA 20 mg/m2 (group B) by 2-hour infusion. RESULTS: Of 291 assessable patients (group A, n = 148; group B, n = 143), we observed, in group A, complete response (CR)/partial response (PR) in 32 (21.6%), no change (NC) in 64 (43.2%), and progressive disease (PD) in 52 (35.1%); and in group B, CR/PR in 25 (17.5%), NC in 63 (44.1%), and PD in 55 (38.5%). The median response duration was 24.8 weeks in group A and 23.1 weeks in group B. Median progression-free intervals were 29.3 weeks (group A) and 30 weeks (group B). The median survival time was 55.1 weeks in group A and 54.1 weeks in group B. Overall toxicity was moderate. Mild nausea and vomiting, and stomatitis were common side effects in both groups. The incidence of World Health Organization (WHO) grade III/IV diarrhea was significantly higher in group A (40 v 23 patients). Severe side effects were observed only in a minority of patients in both arms. WHO grade IV diarrhea was observed in seven patients: four in group A and three in group B. The rate of toxicity-related adjustments of dose and schedule was comparable in both groups. CONCLUSION: High-dose FA/FU is not superior to low-dose FA/FU within a weekly treatment schedule. Response rates and survival were comparable in both treatment arms. Treatment-related toxicity was higher in group A (high-dose FA). Therefore, low-dose FA combined with weekly FU may be considered the preferred treatment for metastatic colorectal cancer.

Adult↗
PubMed1996

Pseudonyms for cancer registries.

In order to conform to the rigid German legislation on data privacy and security we developed a new concept of data flow and data storage for population-based cancer registries. A special trusted office generates a pseudonym for each case by a cryptographic procedure. This office also handles the notification of cases and communicates with the reporting physicians. It passes pseudonymous records to the registration office for permanent storage. The registration office links the records according to the pseudonyms. Starting from a requirements analysis we show how to construct the pseudonyms; we then show that they meet the requirements. We discuss how the pseudonyms have to be protected by cryptographic and organizational means. A pilot study showed that the proposed procedure gives acceptable synonym and homonym error rates. The methods described are not restricted to cancer registration and may serve as a model for comparable applications in medical informatics.

Anonyms and Pseudonyms↗
PubMed1995

Non-enzymatic glycosylation of the dipeptide L-carnosine, a potential anti-protein-cross-linking agent.

The dipeptide carnosine (beta-alanyl-L-histidine) was readily glycosylated non-enzymatically upon incubation with the sugars glucose, galactose, deoxyribose and the triose dihydroxyacetone. Carnosine inhibited glycation of actyl-Lys-His-amide by dihydroxyacetone and it protected alpha-crystallin, superoxide dismutase and catalise against glycation and cross-linking mediated by ribose, deoxyribose, dihydroxyacetone, dihydroxyacetone phosphate and fructose. Unlike certain glycated amino acids, glycated carnosine was non-mutagenic. The potential biological and therapeutic significance of these observations are discussed.

Alanine↗
PubMed1995

Applicability of the Poisson distribution to model the data of the German Children's Cancer Registry.

Since 1980 the German Children's Cancer Registry has documented all childhood malignancies in the Federal Republic of Germany. Various statistical procedures have been proposed to identify municipalities or other geographic units with increased numbers of malignancies. Usually the Poisson distribution, which requires the malignancies to be distributed homogeneously and uncorrelated, is applied. Other discrete statistical distributions (so-called cluster distributions) like the generalized or compound Poisson distributions are applicable more generally. In this paper we present a first explorative approach to the question of whether it is necessary to use one of these cluster distributions to model the data of the German Children's Cancer Registry. In conclusion, we find no indication that the Poisson approach is insufficient.

Child↗