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Biomedical subjects

L Kreienbrock

Publications and source records attributed to L Kreienbrock.

At least 19 recordsLinked to original sources

[Possibilities and limits of serological diagnosis in pig stocks in the case of Mycoplasma hyopneumoniae infection].

When conducting their investigations to diagnose infectious diseases in swine, practitioners are often forced to use reduced numbers of animals in their samples in order to minimize costs for farmers. A cross-sectional study was conducted approximating such field conditions to show the limits of interpretation with reduced sample sizes in case of Enzootic Pneumonia. Compared with other respiratory pathogens, Mycoplasma hyopneumoniae, the etiologic agent of Enzootic Pneumonia spreads very slowly, mainly when animals are in direct contact. Furthermore, the interpretation of serological results is difficult because several weeks must usually pass for serological reactions to become apparent. Serological testing is normally used to confirm a clinical diagnosis by detecting an increase in antibodies against the etiologic agent. Samples are collected at the beginning of disease and four to six weeks later. An increasing number of serological positive animals in a herd is usually interpreted as spread of infection. The ,,true" prevalence we observed in our investigation was used to make a statistical analysis describing the probability of detecting an increasing prevalence from 0.07 to 0.33 with a reduced sample size. We showed that the probability of detecting an increase of two seropositive animals was 44% if 5 samples per group were analysed. When only 3 samples were analysed per group, this probability decreases to 21%. Compromise must be found between epidemiological necessary and financially acceptable sample size; this could be a minimum of 10 samples per age group.

Animals↗

Population based study on the outcome of small for gestational age newborns.

OBJECTIVE: To explore whether and how population based data from a regional quality control programme can be used to investigate the hypothesis that small for gestational age (SGA) very low birthweight infants (VLBW, <1500 g) are at increased risk of death, severe intraventricular haemorrhage (IVH), and periventricular leucomalacia (PVL), but at decreased risk of respiratory distress syndrome (RDS). METHODS: Analyses of population based perinatal/neonatal data (1991-96) from a quality control programme in Lower Saxony, Germany. After assessment of data validity and representativeness, exclusion criteria were defined: birth weight >90th centile, severe malformations, siblings of multiple births, and gestational age (GA) <25 or >29 weeks. Outcomes of interest were death, severe IVH, PVL, and RDS. Multivariable analyses were performed by Cox proportional hazard and logistic regression models. RESULTS: Within the data validation procedure, an increase in proportions of both VLBW (from 0.95% in 1991 to 1.11% in 1996; +17%) and SGA (from 22.7% to 27.4%; +21%) infants became apparent (p<0.05). The study population consisted of 1623 infants (173 SGA). Mortality was 12.1% (n = 196), with an adjusted hazard ratio for SGA infants of 2.54, 95% confidence interval (CI) 1.70 to 3.79. Both groups were at similar risk of severe IVH (adjusted odds ratio 0.93, 95% CI 0.5 to 1.65) and PVL (1.54, 95% CI 0.78 to 2.87), but SGA infants had less RDS (0.57, 95% CI 0.35 to 0.93). Male sex, multiple birth, hypothermia (<35.5 degrees C), and sepsis were associated with IVH and RDS. Infants admitted to hospitals with <36 VLBW admissions/year had increased mortality (adjusted hazard ratio 1.56, 95% CI 1.12 to 2.18). CONCLUSIONS: SGA VLBW infants are at increased risk of death, but not of IVH and PVL, and at decreased risk of RDS. That mortality is higher in smaller hospitals needs further investigation.

Cerebral Hemorrhage↗

[Precision-controlled echocardiographic left ventricular function parameters by repeated measurement on three consecutive days in trained and untrained warmblood horses].

Echocardiographic measurements have to be reliable and reproducible with only a low day to day variability for detecting pathological changes of left ventricular myocardial function in horses. The day dependent fluctuation margin represents an important indicator for the reproducibility of a method. To find out the day to day variability of echocardiographic parameter in healthy warmblood horses, in the present study repeated echocardiographic measurements at three consecutive days were carried out (at the same time and by the same examiner) at 11 untrained and 7 trained warmblood horses. The horses were examined from the right hemithorax, in five different B- and M-Mode views in the long and short heart axis. The echocardiographic measurements in the three-day examination interval showed with coefficient of variation between 3.4 and 25.8% a good reproducibility. In order to calculate the precision of echocardiographic parameters (reproducibility from day to day) statistical analysis was carried out by means of a linear model with random effects. Herefor the variation between repeated measurements over three days and within the horses (day to day intraindividual variation) as well as the variation between the horses (interindividual variation) were taken into account. In dependency of the echocardiographic parameters 46.2-95.7% (median 85.7%) of the variation is caused by the difference between the horses (intraclass correlation) and 4.3-53.8% (median 14.3%) of the variation is caused by the repeated measurements on different days. With a coefficient of variance from 6.6% and an intraclass correlation of 0.957 the left ventricular diastolic diameter at the level of the papillary muscles showed the lowest variation between repeated measurements on different days. The heart rate with a coefficient of variance of 10.3% and an intraclass correlation of 0.462 showed the highest variation with 53.8% between the repeated measurements on different days. The precision of single echocardiographic measurements is confirmed. All parameters were also tested for differences between trained and untrained horses. Significant differences (p<0.05) could be found in the left ventricular diameter at the level of the apex cordis and under the mitral valves as well as in the systolic left ventricular area.

Animals↗

Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies.

OBJECTIVE: To determine the risk of lung cancer associated with exposure at home to the radioactive disintegration products of naturally occurring radon gas. DESIGN: Collaborative analysis of individual data from 13 case-control studies of residential radon and lung cancer. SETTING: Nine European countries. SUBJECTS: 7148 cases of lung cancer and 14,208 controls. MAIN OUTCOME MEASURES: Relative risks of lung cancer and radon gas concentrations in homes inhabited during the previous 5-34 years measured in becquerels (radon disintegrations per second) per cubic metre (Bq/m3) of household air. RESULTS: The mean measured radon concentration in homes of people in the control group was 97 Bq/m3, with 11% measuring > 200 and 4% measuring > 400 Bq/m3. For cases of lung cancer the mean concentration was 104 Bq/m3. The risk of lung cancer increased by 8.4% (95% confidence interval 3.0% to 15.8%) per 100 Bq/m3 increase in measured radon (P = 0.0007). This corresponds to an increase of 16% (5% to 31%) per 100 Bq/m3 increase in usual radon--that is, after correction for the dilution caused by random uncertainties in measuring radon concentrations. The dose-response relation seemed to be linear with no threshold and remained significant (P = 0.04) in analyses limited to individuals from homes with measured radon < 200 Bq/m3. The proportionate excess risk did not differ significantly with study, age, sex, or smoking. In the absence of other causes of death, the absolute risks of lung cancer by age 75 years at usual radon concentrations of 0, 100, and 400 Bq/m3 would be about 0.4%, 0.5%, and 0.7%, respectively, for lifelong non-smokers, and about 25 times greater (10%, 12%, and 16%) for cigarette smokers. CONCLUSIONS: Collectively, though not separately, these studies show appreciable hazards from residential radon, particularly for smokers and recent ex-smokers, and indicate that it is responsible for about 2% of all deaths from cancer in Europe.

Air Pollutants, Radioactive↗

Outbreak of Salmonella Goldcoast infections linked to consumption of fermented sausage, Germany 2001.

Salmonella Goldcoast (SGC), an uncommon serotype in Germany, was identified in 25 isolates between 1 April and 7 May 2001. To determine the cause of the outbreak, we conducted a matched case-control study including 24 cases and 51 controls. In a multivariable regression model, only consumption of a raw fermented sausage manufactured by a local company remained significant (adjusted odds ratio 20.0, 95 % confidence interval 2.7-302.5). SGC isolated from case-patients shared an indistinguishable pulsed-field gel electrophoresis pattern. A part of the produced raw fermented sausage was sold after only 4 days of fermentation. Samples from the premises and products of the company were negative for SGC. However, short-time raw fermented sausage is more likely to contain pathogens. Irradiation of raw ingredients is not accepted by German consumers, thus strict adherence to good manufacturing practices, the use of HACCP programmes as well as on-farm programmes remain crucial to reduce Salmonella.

Adult↗

Two dimensions of measurement error: classical and Berkson error in residential radon exposure assessment.

Measurement error in exposure assessment is unavoidable. Statistical methods to correct for such errors rely upon a valid error model, particularly regarding the classification of classical and Berkson error, the structure and the size of the error. We provide a detailed list of sources of error in residential radon exposure assessment, stressing the importance of (a) the differentiation between classical and Berkson error and (b) the clear definitions of predictors and operationally defined predictors using the example of two German case-control studies on lung cancer and residential radon exposure. We give intuitive measures of error size and present evidence on both the error size and the multiplicative structure of the error from three data sets with repeated measurements of radon concentration. We conclude that modern exposure assessment should not only aim to be as accurate and precise as possible, but should also provide a model of the remaining measurement errors with clear differentiation of classical and Berkson components.

Bias↗

[Considerations concerning diagnostic certainties and cut-off values for a bulk milk ELISA for Mycobacterium avium ssp. paratuberculosis].

Serological tests for the examination of individual samples from single animals are evaluated based on their ability to detect true positives above a defined threshold value. If results are obtained not from an individual but from a bulk sample this concept usually is adopted such that the threshold is set to allow the detection of a single positive sample within the pool. In conjunction with the development of a diagnostic paratuberculosis ELISA for the examination of bulk milk samples it is discussed which interpolations of this concept are justified when defining the true status of a herd based on the test parameters and the seroprevalence within the herd. Here, bulk milk from up to 50 animals each and the corresponding individual samples of 4241 dairy cows from 28 herds in the state of Brandenburg are investigated, and results are subjected to different evaluation approaches. Based on epidemiological considerations and test parameters a "critical prevalence" is defined which then serves as basis for the deduction of a cut-off value to be used for bulk milk samples. Finally, the practical relevance of this approach is demonstrated by suggesting an initial scheme for paratuberculosis classification of dairy herds with respect to possible control measures.

Animals↗

On the potential of measurement error to induce differential bias on odds ratio estimates: an example from radon epidemiology.

It is well established that odds ratios estimated by logistic regression are subject to bias if exposure is measured with error. The dependence of this bias on exposure parameter values, particularly for multiplicative measurement error, and its implications in epidemiology are not, however, as fully acknowledged. We have been motivated by a German West case-control study on lung cancer and residential radon, where restriction to a subgroup exhibiting larger mean and variance of exposure than the entire group has shown higher odds ratio estimates as compared to the full analysis. By means of correction formulae and simulations, we show that bias from additive classical type error depends on the exposure variance, not on the exposure mean, and that bias from multiplicative classical type error depends on the geometric standard deviation (in other words on the coefficient of variation of exposure), but not on the geometric mean of exposure. Bias from additive or multiplicative Berkson type error is independent of exposure distribution parameters. This indicates that there is a potential of differential bias between groups where these parameters vary. Such groups are commonly compared in epidemiology: for example when the results of subgroup analyses are contrasted or meta-analyses are performed. For the German West radon study, we show that the difference of measurement error bias between the subgroup and the entire group exhibits the same direction but not the same dimension as the observed results. Regarding meta-analysis of five European radon studies, we find that a study such as this German study will necessarily result in smaller odds ratio estimates than other studies due to the smaller exposure variance and coefficient of variation of exposure. Therefore, disregard of measurement error can not only lead to biased estimates, but also to inconsistent results and wrongly concluded effect differences between groups.

Air Pollutants, Radioactive↗

Quantification of thrombopoietic activity in bone marrow aspirates of dogs.

The aims of the study were to investigate possible influences of different numbers of counted fields on slides, and different slides on the counting of platelet precursors, and to establish guidelines for bone marrow examination in dogs. The study was based on bone marrow slides of 131 healthy dogs. The slides were prepared by a squash technique. On each slide the number of thrombopoietic cells at different levels of maturation were counted in all fragment-containing fields. The results of a variance component model revealed no influence of different slides, in contrast to a high variance related to different fields. Between 20 and 25 low power fields (100x magnification) had to be examined to achieve an imprecision of 20%. An imprecision of 10% required the counting of 100 fields. The lowest thrombopoietic activity was seen in the bone marrow of dogs aged one to six years. The total number of platelet percursors per field was significantly higher in adult female (10.4 +/- 2.67) than in male dogs (7.84 +/- 2.04, P = 0.0008) as was the number of megakaryocytes. We recommend assessment of thrombopoiesis on the basis of 20-25 fragment-containing low power fields and that age- and sex-related differences should be considered.

Aging↗

[Animal-derived feedstuffs as possible vectors for bovine encephalopathy (BSE) in Germany. Part 2: Assessment of vector risk for compounded feed].

Specific conditions and practices of cattle feeding in Germany have to be taken into account for assessing the risk of feed born transmission of bovine spongiform encephalopathy, especially regarding the situation before the year 2000 when specific directives were introduced for feed production. The present retrospective epidemiological study includes data on feed production and the estimated amount of animal derived feedstuffs for the production of compounded feed for cattle. Risk assessment was performed based on the 'reproduction rate' (R0), that is defined as the estimated number of infections resulting from the processing of brain and spinal cord of BSE affected cattle that is recycled to bovines via feed. Under the conditions as given in Germany until the year 2000 the reproduction rate of BSE via the inclusion of animal derived feedstuffs in compounded feed production for cattle was estimated to be 1.1. Thus, it can be expected that BSE could be reproduced in the system, but with comparatively low efficiency. The expected incidence of BSE should be considerably lower compared to the situation during the 90th in the UK, due to the markedly lower recycling rate of animal protein in cattle feeding. Animal fat could have been a significant factor for BSE transmission due to contamination by proteinaceous brain and spinal cord material during the production process. The relative significance of fat containing feedstuffs for BSE transmission could have been higher in Germany compared to the situation in the UK where meat and bone meal was produced under different conditions and frequently used in higher proportions as an ingredient for compounded feed for ruminants.

Animal Feed↗

[Statistical principles of "good clinical practice" in veterinary medicine--a position paper for planning, implementation and evaluation of empirical studies].

The complexity of the design, conduct, analysis and evaluation of empirical studies necessitates a high degree of interdisciplinary collaboration in all areas of research. In order to make sure that no essential harmonisation is missed among the plenitude of processes, it has become common to provide direction on the essential operating procedures in so called "Good ... Practice" guidelines in recent years. In pharmaceutical research on human medicinal products guidelines on Good Clinical Practice have been an integral part of research and development in industry, academia, and the regulatory authorities for a long time. On the other hand, in the development and registration of pharmaceuticals for veterinary use such procedures are not yet established to this extent in Germany. Notwithstanding there being a lot of regulations on specialised subjects. This paper tries to summarise the current state of the discussion and to give an overview on the important points in the design, conduct, analysis and reporting of veterinary clinical studies mainly from an biometrical point of view.

Animals↗

Lung cancer in lifetime nonsmoking men - results of a case-control study in Germany.

Epidemiological studies of lung cancer among nonsmoking men are few. This case-control study was conducted among lifetime nonsmoking men between 1990 and 1996 in Germany to examine lung cancer risk in relation to occupation, environmental tobacco smoke, residential radon, family history of cancer and previous lung disease. A total of 58 male cases with confirmed primary lung cancer and 803 male population controls who had never smoked more than 400 cigarettes in their lifetime were personally interviewed by a standardized questionnaire. In addition, 1-year radon measurements in the living and bedroom of the subjects' last dwelling were carried out. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Having ever worked in a job with known lung carcinogens was associated with a two-fold significantly increased lung cancer risk (OR = 2.2; CI = 1.0-5.0), adjusted for age and region. The linear trend test for lung-cancer risk associated with radon exposure was close to statistical significance, demonstrating an excess relative risk for an increase in exposure of 100 Bq m(-3)of 0.43 (P = 0.052). Nonsignificantly elevated effects of exposure to environmental tobacco smoke in public transportation and in social settings were observed. No associations with a family history of cancer or previous lung diseases were found. Our results indicate that occupational carcinogens and indoor radon may play a role in some lung cancers in nonsmoking men.

Adenocarcinoma↗

Case-control study on lung cancer and residential radon in western Germany.

In a 1990-1996 case-control study in western Germany, the authors investigated lung cancer risk due to exposure to residential radon. Confirmed lung cancer cases from hospitals and a random sample of community controls were interviewed by trained interviewers regarding different risk factors. For 1 year, alpha track detectors were placed in dwellings to measure radon gas concentrations. The evaluation included 1,449 cases and 2,297 controls recruited from the entire study area and a subsample of 365 cases and 595 controls from radon-prone areas of the basic study region. Rate ratios were estimated by using conditional logistic regression adjusted for smoking and for asbestos exposure. In the entire study area, no rate ratios different from 1.0 were found; in the radon-prone areas, the adjusted rate ratios for exposure in the present dwelling were 1.59 (95% confidence interval (CI): 1.08, 2.27), 1.93 (95% CI: 1.19, 3.13), and 1.93 (95% CI: 0.99, 3.77) for 50-80, 80-140, and >140 Bq/m3, respectively, compared with 0-50 Bq/m3. The excess rate ratio for an increase of 100 Bq/m3 was 0.13 (-0.12 to 0.46). An analysis based on cumulative exposure produced similar results. The results provide additional evidence that residential radon is a risk factor for lung cancer, although a risk was detected in radon-prone areas only, not in the entire study area.

Adenocarcinoma↗

[Eradication of paratuberculosis in dairy herds: determination of the initial herd prevalence and modelling of prevalence development].

A prerequisite for the success of any eradication programme is the accurate determination of the initial herd prevalence as well as a herd-specific prediction of prevalence development. This prerequisite is not currently given for the eradication of paratuberculosis in infected herds. In the work presented a method to predict the initial paratuberculosis prevalence in infected herds is presented; it is based on the formation of two groups (ELISA-positive and negative) and the determination of generally applicable factors (positive predictive value [ppvn] of the ELISA and sensitivity of fecal culture in the ELISA-negative group [senF]). The ppvn of the ELISA was determined to be 0.6 based on the cultural examination of the ileocaecal lymph node of 64 ELISA-positive animals; the value for senF was set to be 0.64 based on the cultural examination of feces and ileocaecal lymph nodes of 40 ELISA-negative animals. To calculate the initial herd prevalence the number of animals in each of the groups was multiplied with the ppvn of the ELISA or with the reciprocal value of senF (1.5). The values were added and divided by the size of the herd. The practicability of this model was examined on nine herds with a total of 708 animals. The development of herd prevalence was modelled based on the examination scheme given in the paratuberculosis control programme of the "Niedersächsische Tierseuchenkasse" (local board for infectious disease control in food animals in the state of Lower Saxony, Germany). For the calculation a yearly turnover-rate of 33% with restocking from within the herd and a possibility of paratuberculosis diagnosis only in animals two years and older were assumed. The development of herd prevalence is exemplarily presented for four herds with different initial prevalences.

Animals↗

[Modelling of prevalence development in a paratuberculosis control program in a dairy herd].

A modelling approach to calculate the success of a paratuberculosis control programme in dairy herds is presented. The essential parameters of the model are the prevalence at the beginning of the programme, diagnostic sensitivity and specificity of the tests used, discipline in culling test-positive animals, turnover in the herd, percentage of replacement with own stock and paratuberculosis prevalence in animals bought into the herd from outside, and a general hygiene-based factor. Diagnostic measures and time schedule used in the modelling approach are given by the paratuberculosis-control-programme of the local board for infectious disease control in food animals in the state of Lower Saxony. It was found by the model-calculations that in case of a high initial prevalence the anticipated six-year duration of the control programme is justified in order to ensure a lasting improvement of herd health. If hygienic measures are strictly obeyed and all test positive animals are culled a clear reduction on paratuberculosis prevalence can be achieved within the first year. According to the model in the second and third year the prevalence will increase again despite ongoing diagnostic measures in order to decrease again continuously with the beginning of the fourth year. Given an initial prevalence of 10%, 20% or 30% the prevalence after six years is calculated to be at 3%, 5% or 8% when all measures are followed as given in the control programme. The presented programme seems to be appropriate to predict prevalence development in paratuberculosis infected dairy herds if the herds are managed according to the guidelines of the "Tierseuchenkasse Niedersachsen", the local board for infectious disease control in food animals in the state of Lower Saxony, Germany. It becomes apparent that within six years a high decrease of the prevalence in the herds, but not a complete eradication of disease can be achieved by consistently complying with the rules given in these guidelines.

Animals↗

The use of sliding time windows for the exploratory analysis of temporal effects of smoking histories on lung cancer risk.

To examine the time-dependent effects of exposure histories on disease we use sliding time windows as an exploratory alternative to the analysis of variables like time since last exposure and duration of exposure. The method fits a series of risk models which contain total cumulative exposure and an additional covariate for exposures received during fixed time intervals. Characteristics of the fitted models provide insight into the influence of exposure increments at different times on disease risk. A simulation study is performed to check the validity of the approach. We apply the method to data from a recent German case-control study on smoking and lung cancer risk with about 4300 lung cancer cases and a similiar number of controls. The sliding time window approach indicates that the amount of cigarettes smoked from two to 11 years before disease incidence is most predicitive of lung cancer incidence. Among different smoking profiles that result in the same lifelong cumulative number of cigarettes smoked, those with a concentration of smoked cigarettes within 20 years before interview bear substantially larger risk than others.

Aged↗

Occupational lung cancer risk for men in Germany: results from a pooled case-control study.

Occupational exposures such as crystalline silica, diesel engine exhaust, polycyclic aromatic hydrocarbons, and man-made mineral fibers are strongly suspected to increase lung cancer risk. Two case-control studies in Germany conducted between 1988 and 1996 were pooled for a joint analysis. A total of 3,498 male cases and 3,541 male population controls, frequency matched for age and region, were included in the study. The lifelong history of all jobs and industries was coded and occupational exposures were evaluated by expert rating. Odds ratios, crude and adjusted for smoking and asbestos exposure, were calculated by conditional logistic regression. Job-related evaluation showed a statistically significant increased odds ratio adjusted for smoking among farmers; forestry workers, fishermen, and livestock workers; miners and quarrymen; chemical processors; cabinet makers and related wood workers; metal producers and processors; bricklayers and carpenters; road construction workers, pipelayers and well diggers; plasterers, insulators, and upholsterers; painters and lacquerers; stationary engine and heavy equipment operators; transport workers and freight handlers; and service workers. With regard to specific occupational exposures, elevated odds ratios (OR) (95% confidence intervals (CI)) for lung cancer risk adjusted for smoking and asbestos exposure were observed for man-made mineral fibers (OR = 1.48, 95% CI 1.17, 1.88); crystalline silica (OR = 1.41, 95% CI 1.22, 1.62); diesel engine exhaust (OR = 1.43, 95% CI 1.23, 1.67); and polycyclic aromatic hydrocarbons (OR = 1.53, 95% CI 1.14, 2.04). The risk of asbestos exposure, adjusted for smoking was also increased (OR = 1.41, 95% CI 1.24, 1.60).

Case-Control Studies↗

Environmental tobacco smoke and lung cancer: a case-control study in Germany.

To assess the association between exposure to environmental tobacco smoke (ETS) and lung cancer, the authors personally interviewed 292 lifelong nonsmoking lung cancer cases (recruited from 15 hospitals in the study area) and 1,338 nonsmoking controls (randomly selected by population registries) between 1990 and 1996 in Germany. Subjects were asked by a standardized questionnaire about exposure to ETS in childhood, by spouse, at work, and in transportation and social settings. Several indicators of these different sources of exposure were investigated, using not or low exposed subjects as the reference category. The most informative quantification index was weighted duration of exposure (hours x level of smokiness). No effect of ETS exposure during childhood and no clear effect of spousal ETS were observed. However, for the highest category of exposure, clear effects of ETS at the workplace (odds ratio (OR) = 1.93; 95% confidence interval (CI): 1.04, 3.58), in vehicles (OR = 2.64; 95% CI: 1.30, 5.36), and from all sources combined (OR = 1.39; 95% CI: 0.96, 2.01) were found. Adjustment for occupational carcinogens, radon, and diet did not appreciably change the results. These findings suggest that exposures to high levels of ETS at the workplace and in other public indoor settings appear to be important risk factors for lung cancer risk in nonsmokers.

Aged↗