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Biomedical subjects

M Blettner

Publications and source records attributed to M Blettner.

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

Serologic response to the E4, E6, and E7 proteins of human papillomavirus type 16 in pregnant women.

OBJECTIVE: In a seroepidemiologic study the effects of pregnancy and other factors on humoral response to human papillomavirus type 16 infection were examined. STUDY DESIGN: Multiple serum samples were taken at 3-month intervals for 15 months from 77 pregnant and 85 nonpregnant women. Serologic response to human papillomavirus type 16 proteins was analyzed with a peptide-based enzyme-linked immunosorbent assay. RESULTS: Seroreactivity was higher in nonpregnant women than in pregnant women, suggesting a reduced humoral immune response against human papillomavirus infections during pregnancy. Among the pregnant women a twofold to threefold decrease in mean reactivity in the E4 protein-based assay was detected between early gestation and delivery. The presence of human papillomavirus type 16 or 18 deoxyribonucleic acid was significantly associated with reactivity to the E6 protein (p = 0.0005) and the E4 protein (p = 0.06). Reactivity to the E4 protein also correlated with an abnormal Papanicolaou smear. CONCLUSIONS: The observation of changes in humoral response to genital human papillomavirus infections during pregnancy warrants further investigation with highly seroreactive assays.

Amino Acid Sequence↗
PubMed1998

The effect of oral contraceptive use on the prognosis of node positive breast cancer patients. German Breast Cancer Study Group.

The effect of oral contraceptive (OC) use as a risk factor for breast cancer was recently assessed in a large meta-analysis, but currently available data on the prognostic effect are still insufficient. We investigated the relationship between OC use and standard prognostic factors and the effect of OC use on recurrence-free survival (RFS) and overall survival (OS) in 422 premenopausal pT1a-3aN + M0 patients from two trials of the German Breast Cancer Study Group (GBSG). 137 patients (32.5%) were OC users. They were younger on average (mean age 41.5 years versus 45 years for non-OC users) and the percentage of patients with smaller tumours was higher in the group of OC users. Based on 163 events for RFS and 103 events for OS, no significant effect of OC use on RFS and OS could be demonstrated in univariate and multivariate analyses. In our study of node positive breast cancer cases, OC users were younger and had smaller tumours. This may be an effect of earlier detection of breast cancer, but OC users did not have a better prognosis, both before and after adjustment for tumour size and other prognostic factors.

Adult↗
PubMed1998

An international case-control study of adult glioma and meningioma: the role of head trauma.

BACKGROUND: Increased brain tumour risk after head trauma suggested by case reports and clinical series has been previously studied epidemiologically with mixed results. An international multicentre case-control study investigated the role of head trauma from injury or sports participation in adult brain tumour risk. METHODS: In all, 1178 glioma and 330 meningioma cases were individually or frequency matched to 2236 controls. Only exposures that occurred at least 5 years before diagnosis and head injuries that received medical attention were considered. RESULTS: Risk for ever having experienced a head injury was highest for male meningiomas (odds ratio [OR] = 1.5, 95% confidence interval [CI] : 0.9-2.6) but was lower for 'serious' injuries, i.e. those causing loss of consciousness, loss of memory or hospitalization (OR = 1.2, 95% CI: 0.6-2.3). Among male meningiomas, latency of 15 to 24 years significantly increased risk (OR = 5.4, 95% CI: 1.7-16.6), and risk was elevated among those who participated in sports most correlated with head injury (OR = 1.9, 95% CI: 0.7-5.3). Odds ratios were lower for male gliomas (OR = 1.2, 95% CI : 0.9-1.5 for any injury; OR = 1.1, 95% CI: 0.7-1.6 for serious injuries) and in females in general. CONCLUSIONS: Evidence for elevated brain tumour risk after head trauma was strongest for meningiomas in men. Findings related to sports should be interpreted cautiously due to cultural variability in our data and our lack of complete data on physical exercise in general which appeared to be protective.

Adult↗
PubMed1997

[Limitations of meta-analysis from published data in epidemiological research].

Metaanalyses of epidemiological studies have increased during the last years and are often used to evaluate the effect of risk factors which are inconsistent in different studies, mainly for small risk factors. Very often a metaanalysis is performed from published data. In this article we discuss this form of a metaanalysis and investigate whether the requirement to get reliable information is achievable with it. We mainly ask questions whether qualitative and quantitative dose-response analysis can be performed. We point out the differences between metaanalysis from experimental data and clinical randomized studies and epidemiological studies. We discuss different arguments that were given for performing metaanalysis in clinical trials and investigate whether they are also valid in observational studies. We mainly concentrate on the problem of estimating a single pooled risk estimate. Two examples from literature are used to show problems with metaanalysis from published data.

Bias↗
PubMed1997

Familial aggregation of oesophageal cancer in a high incidence area in China.

BACKGROUND: The high incidence of oesophageal cancer in northern China is attributed predominantly to environmental factors. The role of genetic factors has not been extensively studied. METHODS: Our aim was to study familial aggregation of oesophageal cancer in pedigrees from a defined population base in a high incidence area in China and to quantify the risk associated with different first degree relatives using different analytical approaches. Detailed data on family members of three successive generations and the occurrence of oesophageal and other cancers in family members were collected from a population-based series of 244 oesophageal cancer cases which occurred between 1987 and mid-1992 in Huixian County, Henan. RESULTS: Compared to expected rates, the standardized mortality ratio (SMR) of oesophageal cancer among first degree relatives of oesophageal cancer patients was 2.4 (2.2 in male and 2.7 in female relatives). The corresponding SMR for first and second degree relatives were 1.6 and 2.2. The null hypothesis of 'no familial aggregation' was rejected using Tarone's one-sided score test for binomial distributions indicating some evidence for clustering within families. To account for variance due to between-pairs correlation and family and/or individual specific variables, we fitted a series of regression models using a Generalized Estimation Equations (GEE) approach. The pairwise odds ratios were 2.3 for parent-parent, 1.9 for sib-parent and 1.1 for sib-sib, adjusted for sex, age and sex of index case. DISCUSSION: The existence of familial aggregation of oesophageal cancer in the study population was confirmed using different analyses and a two- to threefold increased risk was found for first degree relatives. The clear association of disease between parent and sib provides some indication of a genetic component. The pairwise association between parents but not between sibs suggests that environmental factors have a stronger action after childhood.

Aged↗
PubMed1997

Controlling for continuous confounders in epidemiologic research.

Multiple regression models are commonly used to control for confounding in epidemiologic research. Parametric regression models, such as multiple logistic regression, are powerful tools to control for multiple covariates provided that the covariate-risk associations are correctly specified. Residual confounding may result, however, from inappropriate specification of the confounder-risk association. In this paper, we illustrate the order of magnitude of residual confounding that may occur with traditional approaches to control for continuous confounders in multiple logistic regression, such as inclusion of a single linear term or categorization of the confounder, under a variety of assumptions on the confounder-risk association. We show that inclusion of the confounder as a single linear term often provides satisfactory control for confounding even in situations in which the model assumptions are clearly violated. In contrast, categorization of the confounder may often lead to serious residual confounding if the number of categories is small. Alternative strategies to control for confounding, such as polynomial regression or linear spline regression, are a useful supplement to the more traditional approaches.

Bias↗
PubMed1996

Tel Aviv-Heidelberg three-generation offspring study: genetic determinants of plasma fibrinogen level.

Elevated plasma fibrinogen concentrations (fibrinogen) are an important independent risk factor of atherosclerotic disease. Using the kinetic method, we measured fibrinogen in 808 individuals, of which 757 were members of 204 pedigrees. Correlation analysis and two-way analysis of variance (ANOVA) showed a significant association of fibrinogen with age, body mass index (BMI), sex, smoking habits, sport activity, and other lifestyle factors. However, multivariate regression analysis of fibrinogen established an independent significant contribution of only the first three factors. Fibrinogen levels adjusted respectively were subjected to complex segregation analysis. Our aim was to identify the contribution of major gene effects and residual (within the genotype) family correlations on fibrinogen variation. Results of this study suggest codominant alleles at a major locus accounting for 39% of variation. There was also evidence of a significant residual parent/offspring correlation.

Age Factors↗
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

Longitudinal study of the effects of pregnancy and other factors on detection of HPV.

OBJECTIVE: An epidemiologic study of 108 pregnant and 192 non-pregnant women was carried out to determine the effects of pregnancy and other factors on the detection of HPV infection, since both or larger numbers of pregnancies and HPV infection are known to be risk factors for cervical cancer. PATIENTS AND METHODS: Study participants were followed up at 3-months intervals for a period of 15 months (1-6 months after delivery). At each visit, two cervical specimens were taken, one for routine cytology and a second for HPV DNA hybridization using Virapap/Viratype, and a 5-ml blood sample was taken and a self-administered questionnaire was completed. RESULTS: In cervical specimens of the initial examination, HPV DNA was detected among 5.0% of pregnant and 5.2% of nonpregnant women, whereas HPV 16/18 was found in 80% of the HPV-positive specimens. Using multiple cervical specimens taken over time, 13.9% of the pregnant and 15.1% of the nonpregnant women tested positive for HPV DNA at least once. Adjusted for study group, age, and the number of available cervical specimens, ever detection of HPV infection (any type) was associated with more sexual partners and larger numbers of cigarettes smoked daily. An autoregressive generalized linear model was used to analyze the time-dependent multiple observations per study subject. Adjusting for age and trimester of pregnancy, the determinants of detecting high-risk HPV types (16/18 and 31/33/35) in the cervical specimen were an abnormal Pap smear, a positive HPV result in a preceding specimen, more than six sexual partners in the lifetime, and currently smoking more than 20 cigarettes per day with odds ratios of 10.9, 5.6, 3.2, and 2.7, respectively. CONCLUSION: Our data provide no evidence for a higher detection rate of HPV during pregnancy.

Adult↗
PubMed1996

Analysis of familial aggregation of atopic eczema and other atopic diseases by ODDS RATIO regression models.

In order to determine the relative importance of genetics and the environment on the occurrence of atopic diseases, we investigated the familial aggregation of atopic eczema, allergic rhinitis, and allergic asthma in the relatives of 426 patients with atopic eczema and 628 subjects with no history of eczema (5,136 family members in total). Analyses were performed by regression models for odds ratios (OR) allowing us to estimate OR for the familial aggregation and simultaneously to adjust for other covariates. Three models were analyzed assuming that the OR i) is the same among any two members of a family, ii) depends on different familial constellations, i.e., whether the pairs are siblings, parents, or parent/sibling pairs, and iii) is not the same between the father and the children and between the mother and the children. The OR of familial aggregation for atopic eczema was 2.16 (95% confidence interval (95%-CI) 1.58-2.96) if no distinction was made between the degree of relationship. Further analyses within the members of the family showed a high OR among siblings (OR = 3.86; 95%-CI 2.10-7.09), while the OR between parents and siblings was only 1.90 (95%-CI 1.31-2.97). Only for atopic eczema was the familial aggregation between fathers and siblings (ms: OR = 2.66; fs: OR = 1.29). This can be explained by stronger maternal heritability, shared physical environment of mother and child, or environmental events that affect the fetus in utero. Since for all atopic diseases a stronger correlation was found between siblings than between siblings and parents, our study indicates that environmental factors, especially during childhood, seem to explain the recently observed increased frequencies of atopic diseases.

Adult↗
PubMed1996

Effects of disease-dependent changes of exposure in cross-sectional studies.

The possibility of disease-related changes in exposure is a major limitation of many epidemiologic studies. This limitation particularly applies to cross-sectional studies, in which exposure and presence of disease are measured at the same point of time. In some cross-sectional studies, attempts are made to collect information not only on current exposure, but also on exposure at some period in the past. Various methods have been proposed to assess the relation of past and current exposure with disease in such situations. Systematic methodologic work is lacking, however, on the performance of these methods in the presence of disease-related changes of exposure. In this paper, we provide a model to assess the effects of such changes, and we illustrate the effects with a variety of numerical examples. We show that all of the proposed methods can yield seriously biased measures of current exposure effects in the presence of disease-related changes in exposure, and we illustrate the direction and order of magnitude of the biases. Our results imply that there is usually no alternative to longitudinal approaches to measure exposure in relation to disease onset if disease-related changes of exposure are of concern.

Bias↗
PubMed1995

Tel Aviv-Heidelberg three-generation offspring study: genetic determinants of apolipoprotein A1 and apolipoprotein B.

The contribution of major gene and multifactorial effects on variation of plasma apolipoproteins A1 and B has been tested in a large sample of population-based Israeli pedigrees. Our most parsimonious and best fitting model for both apolipoproteins is consistent with Mendelian transmissibility, with significant contribution of major genes (with 2 alleles recessive and dominant within each locus) and polygenes, but neglects effects of common sib environment as well as related intergeneration differences in polygenic effects. Total genetic effects explain 71 and 58% of phenotypic variance of APO-A1 and APO-B levels. The major genes account for about 44 and 32% of the variance in APO-A1 and APO-B, respectively, and the frequency of the recessive alleles determining the high level of apolipoproteins under the study in the Israeli population is in the vicinity of 40% at each locus.

Apolipoprotein A-I↗
PubMed1995

Logistic regression with incompletely observed categorical covariates--investigating the sensitivity against violation of the missing at random assumption.

Missing values in the covariates are a widespread complication in the statistical inference of regression models. The maximum likelihood principle requires specification of the distribution of the covariates, at least in part. For categorical covariates, log-linear models can be used. Additionally, the missing at random assumption is necessary, which excludes a dependence of the occurrence of missing values on the unobserved covariate values. This assumption is often highly questionable. We present a framework to specify alternative missing value mechanisms such that maximum likelihood estimation of the regression parameters under a specified alternative is possible. This allows investigation of the sensitivity of a single estimate against violations of the missing at random assumption. The possible results of a sensitivity analysis are illustrated by artificial examples. The practical application is demonstrated by the analysis of two case-control studies.

ABO Blood-Group System↗