Rolf Meinert

Efficacy of acupuncture for the prophylaxis of migraine: a multicentre randomised controlled clinical trial

BACKGROUND Our aim was to assess the efficacy of a part-standardised verum acupuncture procedure, in accordance with the rules of traditional Chinese medicine, compared with that of part-standardised sham acupuncture and standard migraine prophylaxis with beta blockers, calcium-channel blockers, or antiepileptic drugs in the reduction of migraine days 26 weeks after the start of treatment. METHODS This study was a prospective, randomised, multicentre, double-blind, parallel-group, controlled, clinical trial, undertaken between April 2002 and July 2005. Patients who had two to six migraine attacks per month were randomly assigned verum acupuncture (n=313), sham acupuncture (n=339), or standard therapy (n=308). Patients received ten sessions of acupuncture treatment in 6 weeks or continuous prophylaxis with drugs. Primary outcome was the difference in migraine days between 4 weeks before randomisation and weeks 23-26 after randomisation. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN52683557. FINDINGS Of 1295 patients screened, 960 were randomly assigned to a treatment group. Immediately after randomisation, 125 patients (106 from the standard group) withdrew their consent to study participation. 794 patients were analysed in the intention-to-treat popoulation and 443 in the per-protocol population. The primary outcome showed a mean reduction of 2 .3 days (95% CI 1.9-2.7) in the verum acupuncture group, 1.5 days (1.1-2.0) in the sham acupuncture group, and 2.1 days (1.5-2.7) in the standard therapy group. These differences were statistically significant compared with baseline (p<0.0001), but not across the treatment groups (p=0.09). The proportion of responders, defined as patients with a reduction of migraine days by at least 50%, 26 weeks after randomisation, was 47% in the verum group, 39% in the sham acupuncture group, and 40% in the standard group (p=0.133). INTERPRETATION Treatment outcomes for migraine do not differ between patients treated with sham acupuncture, verum acupuncture, or standard therapy.

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 childs 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.

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

The investigation of an association between increased exposure toresidential extremely-low frequency elec-tromagnetic fields (ELF-EMF) andchildhood leukemia was part of a population-based case-control study carriedout between 1992 and 1995 in the northwestern part of Germany. A total of 129children with leukemia and 328 controls participated in the EMF-study.Exposure assessment comprised measurements of the magnetic field over 24hours in the childs bedroom at the residence where the child had been livingfor the longest period before the date of diagnosis, and spot measurements atall residences where the child had been living for more than one year. Themedian of the 24h-measurement in the childs bedroom was regarded as the mostvalid exposure variable. For children exposed to more than 0.2 μT, anelevated but not significant odds ratio (OR) was observed (OR = 3.2, 95percent confidence interval = 0.7-14.9). These figures are based on only fourleukemia cases and three controls since only 1.5 percent of the studypopulation was classified as highly exposed. Exploratory analyses revealedORs that were not statistically significantly increased for othercharacteristics of the magnetic field at varying cut-points. The results arecomparable with those from other studies. Although not statisticallysignificant, they may indicate a positive association between EMF andchildhood leukemia.

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).

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.

Activity of O6-methylguanine-DNA methyltransferase in relation to p53 status and therapeutic response in ovarian cancer

The DNA‐repair protein O6‐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 patients 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.

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 childrens 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.

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 15km 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.

Quantitative assessment of aortic stenosis by three-dimensional echocardiography☆☆☆★

The purpose of this study was to assess the feasibility of three-dimensional echocardiography in aortic stenosis. Planimetric determination of valve area and dynamic volume-rendered display were performed. Three-dimensional echocardiography permits display of any desired plane of the cardiac structure. Thus in the case of aortic stenosis, the plane used for planimetric evaluation can be positioned exactly through the valve orifice. Dynamic volume-rendered display may provide a spatial demonstration of the stenotic valve. In 48 patients aortic valve area was measured by planimetry. The three-dimensional data set was acquired by a workstation in the course of a multiplane transesophageal examination. Results were compared with those obtained by multiplane transesophageal two-dimensional planimetric technique and invasive measurement. A dynamic three-dimensional reconstruction was displayed. Planimetric determination of valve area was possible in 42 (88%) of 48 cases. Statistical analysis of the data acquired showed a good agreement between three-dimensional echocardiography and transesophageal echocardiography (mean difference +0.018 cm2; SD = 0.086) and between three-dimensional echocardiography and the invasive technique (mean difference +0.012 cm2; SD = 0.12). Dynamic volume-rendered display was possible in 42 of 48 cases. Three-dimensional echocardiography permits accurate and reliable determination of aortic valve area. Preoperative spatial recognition of the stenotic valve is possible by dynamic volume-rendered display.

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 cases 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.