Differences in allergy trends between East and West Germany and possible explanations.

BACKGROUND: At the time of the German reunification in 1990, manifestations of most allergic diseases were less prevalent in East than in West Germany. It was hypothesized that these East-West differences would diminish with lifestyle and pollution changes in East Germany. OBJECTIVE: To investigate whether changes in the prevalence of asthma, hayfever, eczema or allergic sensitization in East Germany approached the levels seen in West Germany and to identify possible lifestyle or environmental factors that may influence this. METHODS: Between 1991 and 2000, 6-year-old children from four areas in East Germany participated in an annual survey. Every 3rd year, a parallel survey was performed in four areas of West Germany. In total, 31 903 children were included. Parents completed a questionnaire regarding lifestyle factors and diagnoses and symptoms of asthma, hayfever and eczema. In sub-areas, eczema was clinically assessed by a dermatologist. Specific IgE sensitization was determined for 6121 children. Logistic regression was used to analyse differences in time trends and the influence of lifestyle and pollution changes. RESULTS: Lifestyle and pollution changed significantly differently between East and West Germany. The trends in hayfever and in strong (specific IgE >3.5) sensitization against pollen, and particularly birch pollen, were steeper in East than in West Germany. The trend towards marked pollen sensitization was four times stronger (95% confidence interval 1.2-13.9) in East than in West Germany. Increasing numbers of only children, less single-room heating with fossil fuels and increasing importance of traffic-related pollution in East Germany partly explained these differences in time trends. CONCLUSIONS: Hayfever and sensitization against pollen were the most sensitive allergic manifestations to changes experienced specifically in East Germany. Influences of lifestyle (single-room heating, living as a single child) were important in explaining different trend developments.

Allergic sensitization and disease in mother-child pairs from Germany: role of early childhood environment.

BACKGROUND: Early childhood influences are important for the development of the allergic phenotype. In East Germany, tremendous lifestyle changes took place after 1990 and it can be hypothesized that the allergic phenotypes in mothers and their children are less similar than in West Germany. This was investigated in our study done in mothers and their 6-year-old children from East and West Germany in the year 2000. METHODS: 1,393 mother-child pairs participated. A subgroup of 774 pairs gave blood for the determination of specific IgE. Regional differences in mother-child correlations and in prevalence of mother-child combinations with respect to allergic sensitization and disease were examined by logistic regression analysis. RESULTS: The adjusted association in positive allergic sensitization between mothers and their children was not significant in East Germany (OR 1.23, 95% CI: 0.68-2.24) but highly significant in West Germany (OR 2.89, 95% CI: 1.73-4.80). The probability for the combination of 'negative' mother and 'positive' child was significantly higher in East than in West Germany. CONCLUSIONS: Mother-child transmission of atopy predisposition can even be cancelled by environmental changes.

Circadian and pulsatile thyrotropin secretion in euthyroid man under the influence of thyroid hormone and glucocorticoid administration.

The inhibitory action of thyroid hormones (TH) and glucocorticoids on circadian and pulsatile TSH secretion was investigated in groups of five normal men by sampling blood every 10 min for 24 h (start, 1750 h). Serum TSH was measured by a sensitive immunoradiometric assay. Continuous infusion of 50 micrograms T3 or 250 micrograms T4 for 8 h (1900-0300 h) significantly suppressed serum TSH levels (T3, P less than 0.025; T4, P less than 0.05; by paired t test). Administration of 3 g sodium ipodate 7 h before TH infusion did not alter the TSH response to T3, but T4-dependent suppression was abolished. Pulsatile TSH secretion [basally, 5.8 +/- 1.3 (+/- SD) pulses/24 h, as analyzed by the PULSAR program; 6.8 +/- 1.9 by the Cluster program] was not significantly altered by any of the experimental conditions. The additional finding of blunting of the TSH response to TRH after TH alone or ipodate and T3 suggests a predominantly pituitary feedback action of TH exerted via conversion of T4 to T3. In contrast, bolus injections of 4 mg dexamethasone (dex) at 1900 and 2200 h abolished TSH pulses for at least 6 h (PULSAR, 6.6 +/- 1.6 pulses/24 h basally vs. 3.6 +/- 3.0 under dex; Cluster, 7.0 +/- 2.7 pulses/24 h basally vs. 1.6 +/- 1.6 under dex). Dex administration also resulted in a prompt, sustained, and significant suppression of basal TSH (P less than 0.0005). Together with a normal serum TSH response to TRH (in separate experiments 1, 9, and 19 h after dex administration), these data suggest that glucocorticoid feedback occurs at a suprapituitary level.

Physiological regulation of circadian and pulsatile thyrotropin secretion in normal man and woman.

The circadian and pulsatile TSH secretion profiles were investigated in 5 females at the time of menstruation and 21 healthy males by sampling blood every 10 min for 24 h. Computer-assisted analysis, i.e. the Cluster and Desade programs, revealed means of 9.9 +/- 1.7 (Cluster) and 11.4 +/- 3.9 (Desade) pulses/24 h. More than 50% of the TSH pulses were detected between 2000-0400 h. Male and female subjects showed no significant difference in the basal mean and pulsatile secretion of TSH or in the TSH response to TRH (200 micrograms). Repetition of the TSH secretion analysis in 4 healthy subjects after 1, 2, and 6 months (2 subjects) revealed a significantly better cross-correlation within than between individuals (P less than 0.0001). We modulate the circadian TSH secretion pattern by acute sleep withdrawal or prolonged sleep after a night of sleep withdrawal in six healthy male volunteers. Sleep withdrawal augmented the nightly TSH secretion (mean serum TSH, 2.1 +/- 1.3 mU/L; mean TSH in sleep, 1.3 +/- 0.5 mU/L; P less than 0.05), whereas sleep after sleep withdrawal almost completely suppressed the circadian variation (mean TSH, 1.1 +/- 0.7 mU/L; P less than 0.01). This modulation is due to a significant decrease in pulse amplitude, but not to an alteration in the frequency or temporal distribution of TSH pulses.

Physiological regulation of thyrotropin.

The pattern of TSH secretion in man in pulsatile in addition to the well known circadian variation. The mechanism triggering TSH pulses remains unclear to date. Infusions of somatostatin or dopamine rapidly lowering basal TSH levels without suppressing the pulsatile pattern suggest that an episodic disinhibition exerted by a physiological inhibitor is not a likely cause. On the same basis, thyroid hormones do not appear to be candidates, since they similarly inhibit basal TSH levels after a time lag of several hours but again do not suppress pulsatile release of the hormone. In contrast, bolus injections of dexamethasone completely abolish pulsatile release of TSH for several hours despite a normal sensitivity of the pituitary to exogenous TRH, suggesting a hypothalamic action of the drug. The hypothesis that pulsatile TSH release might be governed by a pulsatile mode of a hypothalamic stimulator is supported by the observation that an infusion of nifedipine, a calcium channel blocker, which in vitro selectively inhibits the TRH effect on TSH but not prolactin secretion, exerts a comparable effect when it is infused in vivo.

Occupational risk factors for renal cell carcinoma: agent-specific results from a case-control study in Germany. MURC Study Group. Multicenter urothelial and renal cancer study.

BACKGROUND: This case-control study was conducted to estimate the renal cell cancer (RCC) risk for exposure to occupation-related agents, besides other suspected risk factors. METHODS: In a population-based multicentre study, 935 incident RCC cases and 4298 controls matched for region, sex, and age were interviewed between 1991 and 1995 for their occupational history and lifestyle habits. Agent-specific exposure was expert-rated with two job-exposure matrices and a job task-exposure matrix. Conditional logistic regression was used to calculate smoking adjusted odds ratios (OR). RESULTS: Very long exposures in the chemical, rubber, and printing industries were associated with risk for RCC. Males considered as 'substantially exposed to organic solvents' showed a significant excess risk (OR = 1.6, 95% CI : 1.1-2.3). In females substantial exposure to solvents was also a significant risk factor (OR = 2.1, 95% CI : 1.0-4.4). Excess risks were shown for high exposure to cadmium (OR = 1.4, 95% CI : 1.1-1.8, in men, OR = 2.5, 95% CI : 1.2-5.3 in women), for substantial exposure to lead (OR = 1.5, 95% CI : 1.0-2.3, in men, OR = 2.6, 95% CI : 1.2-5.5, in women) and to solder fumes (OR = 1.5, 95% CI : 1.0-2.4, in men). In females, an excess risk for the task 'soldering, welding, milling' was found (OR = 3.0, 95% CI : 1.1-7.8). Exposure to paints, mineral oils, cutting fluids, benzene, polycyclic aromatic hydrocarbons, and asbestos showed an association with RCC development. CONCLUSIONS: Our results indicate that substantial exposure to metals and solvents may be nephrocarcinogenic. There is evidence for a gender-specific susceptibility of the kidneys.

Occupational risk factors for urothelial carcinoma: agent-specific results from a case-control study in Germany. MURC Study Group. Multicenter Urothelial and Renal Cancer.

BACKGROUND: This multicentre population-based case-control study was conducted to estimate the urothelial cancer risk for occupational exposure to aromatic amines, polycyclic aromatic hydrocarbons (PAH), and chlorinated hydrocarbons besides other suspected risk factors. METHODS: In a population-based multicentre study, 1035 incident urothelial cancer cases and 4298 controls matched for region, sex, and age were interviewed between 1991 and 1995 for their occupational history and lifestyle habits. Exposure to the agents under study was self-assessed as well as expert-rated with two job-exposure matrices and a job task-exposure matrix. Conditional logistic regression was used to calculate smoking adjusted odds ratios (OR) and to control for study centre and age. RESULTS: Urothelial cancer risk following exposure to aromatic amines was only slightly elevated. Among males, substantial exposures to PAH as well as to chlorinated solvents and their corresponding occupational settings were associated with significantly elevated risks after adjustment for smoking (PAH exposure, assessed with a job-exposure matrix: OR = 1.6, 95% CI: 1.1-2.3, exposure to chlorinated solvents, assessed with a job task-exposure matrix: OR = 1.8, 95% CI: 1.2-2.6). Metal degreasing showed an elevated urothelial cancer risk among males (OR = 2.3, 95% CI: 1.4-3.8). In females also, exposure to chlorinated solvents indicated a urothelial cancer risk. Because of small numbers the risk evaluation for females should be treated with caution. CONCLUSIONS: Occupational exposure to aromatic amines could not be shown to be as strong a risk factor for urothelial carcinomas as in the past. A possible explanation for this finding is the reduction in exposure over the last 50 years. Our results strengthen the evidence that PAH may have a carcinogenic potential for the urothelium. Furthermore, our results indicate a urothelial cancer risk for the use of chlorinated solvents.

Airway diseases and allergies in East and West German children during the first 5 years after reunification: time trends and the impact of sulphur dioxide and total suspended particles.

BACKGROUND: East-West comparison studies in Europe find higher prevalences of infectious airway diseases and lower prevalences of allergies in eastern areas. Pollution from sulphur dioxide (SO2) or total suspended particles (TSP) are discussed as causes of this difference. METHODS: In four differently polluted areas of East Germany where pollution decreased dramatically between 1989 and 1995 cross-sectional studies in about 7-year-old children were repeated every year between 1991 and 1995. In two differently polluted areas of West Germany studies with the same design were done in 1991 and 1994. In all, 19090 children participated in the study. Thirteen different questions about airway diseases and allergies were evaluated. Logistic regression was used to adjust for confounding. RESULTS: With the exception of pneumonia, all infectious airway diseases and irritations of the airways show a steeper temporal decrease in East than in West Germany or are positively associated with either SO2 or TSP in East Germany. For allergies and related symptoms no differences in time trends could be detected or no association with SO2 or TSP could be seen in East Germany. CONCLUSION: Most airway diseases were more frequent in East than in West Germany in 1991 and were associated with SO2 or TSP. The decrease in these pollutants between 1991 and 1995 has already had a favourable effect. An effect of SO2 or TSP pollution on allergies and related symptoms could not be detected. This pollution does not protect against the development of allergies.

Pulsatile pattern of thyrotropin-release in normal men.

To evaluate the existence of a pulsatile secretion pattern of thyrotropin (TSH) the 24 h release profile of the hormone was investigated in 7 healthy male subjects by taking blood via an indwelling venous catheter at 10-min intervals. Thyrotropin levels were analysed with high precision by a recently developed immunoradiometric assay (IRMA) able to distinguish euthroid and hyperthyroid TSH-levels. Visual analysis (n = 10.4 peaks/24 h) and the computer assisted evaluation by the Santenprogramme (n = 9.9 peaks/24 h) as well as the Pulsar-programme (n = 7.7 peaks/24 h) revealed an episodic release pattern with a low amplitude of pulses. These preliminary results are highly suggestive of a pulsatile TSH secretion similar to other pituitary hormones.

Random field models in the textural analysis of ultrasonic images of the liver.

Conventional two-dimensional (2-D) texture parameters serve as the "gold standard" of texture analysis. The authors compared a new stochastic model, based on autoregressive periodic random field models (APRFM) with conventional texture analysts (CTA) parameter, which were defined as measures of the co-occurrence matrix, i.e., entropy, contrast, correlation, uniformity, and maximum frequency. By fitting the model to a given texture pattern, the estimated model parameters are suitable texture features. In 81 patients, divided into patients without (N=19) and with (N=62) microfocal lesions of the liver, a set of 24 CTA and 16 APRFM parameters were calculated from ultrasonic liver images. To ensure simple computation the APRFM parameters were based on the unilateral type of pixel neighborhood. Regenerated texture by APRFM was visually comparable with the original texture. Reclassification analysis using the classification and regression tree (CART) discriminant analysis system and the area under the receiver operating characteristic (ROC) curve was used to assess the texture classification potency of APRFM- and CTA-parameters. Discriminating between liver with and without microfocal lesions, the best results were seen for the APRFM parameter.

Challenges to environmental toxicology and epidemiology: where do we stand and which way do we go?

Modern toxicology investigates a wide array of both old and new health hazards. Priority setting is needed to select agents for research from the plethora of exposure circumstances. The changing societies and a growing fraction of the aged have to be taken into consideration. A precise exposure assessment is of importance for risk estimation and regulation. Toxicology contributes to the exploration of pathomechanisms to specify the exposure metrics for risk estimation. Combined effects of co-existing agents are not yet sufficiently understood. Animal experiments allow a separate administration of agents which can not be disentangled by epidemiological means, but their value is limited for low exposure levels in many of today's settings. As an experimental science, toxicology has to keep pace with the rapidly growing knowledge about the language of the genome and the changing paradigms in cancer development. During the pioneer era of assembling a working draft of the human genome, toxicogenomics has been developed. Gene and pathway complexity have to be considered when investigating gene-environment interactions. For a best conduct of studies, modern toxicology needs a close liaison with many other disciplines like epidemiology and bioinformatics.

Mercury concentrations in urine, scalp hair, and saliva in children from Germany.

Mercury levels measured in urine, hair, and saliva of 245 German children (8-10 years old) are reported. Mercury concentrations in urine ranged between <0.1 and 5.3 microg/l [geometric mean (GM) 0.26 microg/l or 0.25 microg/g creatinine; median for both, 0.22 in microg/l and microg/g, respectively]. Using multiple linear regression analysis, two predictors have been found accounting for 25.3% of the variance of mercury levels in urine: the number of teeth with amalgam fillings (23.2%) and the number of defective amalgam fillings (2.1%). The mercury content in hair ranged from <0.06 to 1.7 microg/g (GM 0.18 microg/g; median 0.18 microg/g). The frequency of fish consumption, the smoking habits of the parents, and the age of the children accounted for 20.4% of the variance of mercury levels in hair. The correlation between the hair mercury content and urine mercury concentration was low (r=0.297). Mercury levels in saliva ranged between <0.32 and 4.5 microg/l (median 0.16 microg/l). The mercury concentration in saliva was below the limit of quantification of 0.32 microg/l in more than 70% of the samples. Mercury analysis in urine is suitable to estimate mercury exposure due to amalgam fillings, whereas hair mercury better reflects mercury intake by fish consumption. Up to now, saliva does not seem to be a suitable tool to monitor the mercury burden, at least not at low exposure levels.

Assessment of environmental arsenic levels in Prievidza district.

A coal-burning power station in the Nitra Valley in central Slovakia annually emitted large quantities of arsenic (up to 200 tonnes) between 1953 and 1989. Since then, pollution-control measures have reduced arsenic emissions to less than 2 tonnes a year. However, the power station was still a source of airborne arsenic pollution. As part of an EU-funded study on exposure to arsenic and cancer risk in central and Eastern Europe we carried out a study of environmental levels of arsenic in the homes and gardens of residents of the district. Garden soil samples (n=210), house dust samples (n=210) and composite house dust samples (n=109) were collected and analysed using inductively coupled plasma atomic absorption spectroscopy (ICP-AES) at Imperial College. The mean arsenic content of coal and ash in samples taken from the plant was 519 microg/g (n=19) and 863 microg/g (n=22), respectively. The geometric mean (GM) arsenic concentration of garden soils was 26 microg/g (range 8.8-139.0 microg/g), for house dust 11.6 microg/g (range 2.1-170 microg/g) and for composite house dust 9.4 microg/g (range 2.3-61.5 microg/g). The correlation between the arsenic levels in soil and in house dust was 0.3 (P<0.01), in soil and composite house dust 0.4 and house dust and composite house dust 0.4 (P<0.01 for both), i.e., were moderate. Arsenic levels in both house dust and soil decreased with distance from the power station. Overall, levels in both fell by half 5 km from the point source. Weak correlations were seen between the total urinary arsenic concentrations and arsenic concentrations in composite house dust.

Value of acoustic rhinometry in environmental medicine.

It is a weak point of environmental medicine that health disturbances, e.g. functional affections of the upper respiratory tract, cannot be objectively judged by physicians resp. researchers. In this study, the validity of acoustic rhinometry, a method giving information on cross-sectional areas of the upper airways by means of ultrasound probing, was tested in 40 volunteers seven times during one year. Furthermore, using a simplified model of the nose the accuracy of this method to measure the minimal cross-sectional area (MCA) in the nose was tested. The measurements were extremely confounded by the mode of connection to the nose (e.g. selected adapter, direction of application) and by the MCA in the nasal cavity. Statistical analyses showed a good reproducibility of measurements repeated within minutes, but suggested an intrapersonal variability over the analyzed examination phases due to apparatus independent factors. However, this variability could not be explained by influencing and confounding factors obtained by questionnaire, medical history, and physical examination. The test model showed little to great errors (1.5 to 568.5%) between the actual and the measured MCA, depending on the diameter. It is concluded that the method of acoustic rhinometry has to be standardized before it's value for environmental medicine can finally be judged. Further studies are necessary that should focus among others on factors influencing the variability of MCA and the effect of MCA on the measurement of the area behind the MCA. So far, the use of acoustic rhinometry for the evaluation of nasal function cannot be recommended.

Concentrations of lead in blood, hair and saliva of German children living in three different areas of traffic density.

Lead contents in hair, whole blood and saliva were determined for 245 healthy children (121 male, 124 female, age: 8-10 years) from three residential areas of Düsseldorf (North-Rhine-Westphalia, Germany) with different traffic densities. The geometric mean for the lead content in hair was found to be 0.87 microg/g (range: 0.2-9.9 microg/g) for the entire test group. While the levels of lead in hair in the suburban population were significantly lower than in the two city centre populations, no significant difference concerning the lead content in hair could be detected in the latter. The geometric mean for lead concentration in whole blood amounted to 25.0 microg/l (range: 8.0-154 microg/l). There was no significant difference between the sub-groups. The lead concentrations found in saliva were rather low (range: < 1.5-47.0 microg/l). Of the values, 89% were below the detection limit of 1.5 microg/l. Due to reduced levels of lead in fuel, the present study exposes that the amount of lead in the children examined has further decreased compared to preceding surveys. The correlation between the lead content in hair and the road traffic density was not corroborated by the findings with regard to amounts of lead found in blood, indicating that residual lead from fuel does not result in a substantial burden of lead found in the whole body. In contrast to levels of lead found in blood, levels of lead found in hair may be influenced more by environmental conditions. Saliva is not a suitable material for biological monitoring with respect to lead exposure in children.

Availability and comparability of human biomonitoring data across Europe: a case-study on blood-lead levels.

Recently, it has become clear that the complexity of environmental health issues requires an approach that takes into account the complexities, interdependencies and uncertainties of the real world. An urgent issue that has surfaced is the need for accurate tools to better describe exposure characterization to environmental chemicals. By including human biomonitoring (HBM) data, a greater precision in exposure and associated risk estimates and more accurate dose-response relationships may be achieved. A restricting issue still is the availability of reliable and comparable HBM data. The aim of the current study was twofold: (1) to find out whether it is practically feasible to collect raw, individual HBM data across Europe; and (2) to evaluate the comparability and use of these HBM data for environmental health impact assessment at a European scale. Blood-lead (B-Pb) was selected as the chemical of choice because of its long history as an environmental pollutant in HBM programs and its known public health relevance. Through literature search and identification of HBM experts across Europe, HBM programs that measured B-Pb were identified and asked to share individual data on age, gender and B-Pb levels. Following this request, more than 20,000 individual data points from 8 European countries were collected. Analysing these data made clear that it is difficult to use disparate data collections because of the inherent variability with respect to the gender and age of participants and calendar-years sampled. When these confounders were taken however, there was no additional variability in B-Pb distributions among different countries. It was concluded that while it is possible to collect HBM data from different sources across Europe, the need to get data from comparable (sub-)populations is essential for appropriate use and interpretation of HBM data for environmental health impact assessment.

Emergence of hantavirus in South Germany: rodents, climate and human infections.

Human hantavirus (serotype Puumala) infections are prevalent throughout Europe. The bank vole is the main reservoir of the Puumala virus (PUUV). Between 2001 and 2006, the annual incidences in Germany ranged from 0.1 to 0.5 per 100,000 inhabitants. About half of the cases were reported from the state of Baden-Württemberg (BW) in southwest Germany. In 2007, 1,089 PUUV infections were reported from BW. This reflects an incidence of 10.1:100,000, which is more than 11 times higher than the mean incidence of the previous 6 years. Spatial analysis highlights incidences up to 90:100,000 in the most affected district. The winter season 2006/2007 showed an all time high in reported mean temperature. The previous summer and autumn led to a beech mast year, resulting in favourable feed conditions for bank voles in the winter season 2006/2007. The causes of the observed increase in PUUV infections in 2007 cannot be restricted to known cycles in the bank vole population. Favourable feed conditions, a mild winter and an early onset of spring may have influenced bank vole population size as well as human exposure to infectious rodent excretions. Further epidemiologic studies are necessary to better understand the interaction between environmental factors, occurrence of Puumala virus in bank voles and the risk for human disease.

[The regulation of feed intake and selection with special reference to poultry]. / Zur Regulation von Futteraufnahme und-auswahl unter besonderer Berücksichtigung des Geflügels.

Feed intake is regulated in a dialogue between the animal and the feed, which is influenced by numerous factors. The hypothalamus has a central integrative function. Furthermore, caudal brain areas (medulla oblongata, pons) are of importance because these areas are relays of peripheral signals and gustatory afferents. All peripheral informations are integrated by various neurotransmitters and neurohormones. The function of this neuronal system is not exactly known yet. Sensorial informations, mechano-, chemo- and osmoreceptors of the gastrointestinal tract and gastrointestinal hormones are discussed as influences of the periphery. The physiological satiety function of cholecystokinin is questionable in poultry. Hepatic chemoreceptors, which are activated by various metabolites, influence the amount of feed ingested. The feed choice appears to be regulated by the same mechanisms. Our knowledge about the translation of peripheral signals into choice behaviour by changes of neurotransmitter systems is limited.