Reproducibility of allergen,endotoxin and fungi measurements in the indoor environment

Measurements of biocontaminants in settled house dust once a year are commonly used to assess long-term exposure. To examine stability over time and seasonal variation, we measured concentrations of mite and cat allergens, endotoxin and mold spores in living room floor dust in 745 German homes collected twice a year in two different seasons. The study population consisted of adults and children living in five different areas in Germany. All dust samples were collected in a standardized manner from the living room floor and taken during the years 1995 to 1998. The median interval between the two dust samplings was approximately 7 months. Mite and cat allergens were measured in settled house dust by monoclonal antibodies, endotoxin by the limulus amebocyte lysate method, and total spore counts by cultural methods. Crude Pearson's correlation coefficients between log-transformed concentrations in the first and second dust samples ranged between 0.65 and 0.75 for allergens, 0.59 for endotoxin and only 0.06 for total spore counts. The strongest and most consistent seasonal effects were observed for fungi with highest levels in July-September. Cat allergen concentrations were found consistently to be increased in January-March. Mite allergens did not show a strong and consistent seasonal pattern. We conclude that repeated measurements of mite and cat allergens and endotoxin in settled house dust improve the estimate for annual mean concentrations. However, even a single observation of these biocontaminants may be a good proxy for a 1-year exposure since repeated measures were highly correlated. However, repeated measurements of fungi levels were only weakly correlated and thus repeated observations for assessment of annual means of total spore counts are needed.     

Residential radon and risk of lung cancer in Eastern Germany

BACKGROUND: There is suggestive evidence that residential radon increases lung cancer risk. To elucidate this association further, we conducted a case-control study in Thuringia and Saxony in Eastern Germany during 1990-1997. METHODS: Histologically confirmed lung cancer patients from hospitals and a random sample of population controls matched on age, sex and geographical area were personally interviewed with respect to residential history, smoking, and other risk factors. One-year radon measurements were performed in houses occupied during the 5-35 years prior to the interview. The final analysis included a total of 1,192 cases and 1,640 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. RESULTS: Measurements covered on average 72% of the exposure time window, with mean radon concentrations of 76 Bq/m3 among the cases and 74 Bq/m3 among the controls. The smoking- and asbestos-adjusted ORs for categories of radon (50-80, 80-140 and >140 Bq/m*3, compared with 0-50 Bq/m3) were 0.95 (CI = 0.77 to 1.18), 1.13 (CI = 0.86 to1.50) and 1.30 (CI = 0.88 to 1.93). The excess relative risk per 100 Bq/m? was 0.08 (CI = -0.03 to 0.20) for all subjects and 0.09 (CI = -0.06 to 0.27) for subjects with complete measurements for all 30 years. CONCLUSIONS: Our data indicate a small increase in lung cancer risk as a result of residential radon that is consistent with the findings of previous indoor radon and miner studies.     

Temporal changes in blood lead levels of children in east Germany

This analysis investigates the temporal changes in blood lead levels (BLL) in repeated cross-sectional surveys of 5-7 year old children conducted in 1992-93, 1995-96 and 1998-99 and in a prospective cohort from a smelter town and an agricultural control region in east Germany. The region of Hettstedt has a long history of mining and smelting resulting in high levels of heavy metal pollution whereas the region of Zerbst has no known industrial sources of heavy metals. In the region of Hettstedt lead content in ambient dust fall declined since the early 1990s due to the closure of many factories, whilst in Zerbst lead in ambient dust fall was constantly low in the 1990s. Blood lead levels decreased during the observation period both in children from the smelter town and in children from the agricultural control region. From 1992-93 to 1998-99 the mean BLLs of school entrants fell by 20% (41.6 to 33.3 micrograms/l) in Hettstedt and by 30% (34.2 to 23.8 micrograms/l) in Zerbst. In the same observation period mean BLLs of cohort children declined by 35% (41.9 to 27.3 micrograms/l) in Hettstedt and by 39% (32.3 to 19.8 micrograms/l) in Zerbst. At the beginning of the observation period cohort children were 5-7 years of age and were followed up to the age of 11-14. Adjustment for sociodemographic factors, city area and environmental uptake of lead did not influence the percentage changes in BLL of school-entrants. It seems that the decline in ambient lead fall had an impact on the body burden of lead, but the overall decrease in BLL in these two regions is caused by the overall decrease of lead in gasoline and thus in food.     

Spatial four-alternative forced-choice method is the preferred psychophysical method for naïve observers

H. R. Blackwell (1952) investigated the influence of different psychophysical methods and procedures on detection thresholds. He found that the temporal two-interval forced-choice method (2-IFC) combined with feedback, blocked constant stimulus presentation with few different stimulus intensities, and highly trained observers resulted in the "best" threshold estimates. This recommendation is in current practice in many psychophysical laboratories and has entered the psychophysicists' "folk wisdom" of how to run proper psychophysical experiments. However, Blackwell's recommendations explicitly require experienced observers, whereas many psychophysical studies, particularly with children or within a clinical setting, are performed with na?ve observers. In a series of psychophysical experiments, we find a striking and consistent discrepancy between na?ve observers' behavior and that reported for experienced observers by Blackwell: Na?ve observers show the "best" threshold estimates for the spatial four-alternative forced-choice method (4-AFC) and the worst for the commonly employed temporal 2-IFC. We repeated our study with a highly experienced psychophysical observer, and he replicated Blackwell's findings exactly, thus suggesting that it is indeed the difference in psychophysical experience that causes the discrepancy between our findings and those of Blackwell. In addition, we explore the efficiency of different methods and show 4-AFC to be more than 3.5 times more efficient than 2-IFC under realistic conditions. While we have found that 4-AFC consistently gives lower thresholds than 2-IFC in detection tasks, we have found the opposite for discrimination tasks. This discrepancy suggests that there are large extrasensory influences on thresholds--sensory memory for IFC methods and spatial attention for spatial forced-choice methods--that are critical but, alas, not part of theoretical approaches to psychophysics such as signal detection theory.     

Risk and spectrum of diseases in travelers to popular tourist destinations

BACKGROUND: Traveling to tropical regions is related to increased health risks. Travelers' diarrhea is the most frequent health problem, but the range of travel-related diseases also includes potential life-threatening diseases such as malaria. The actual risk of European travelers acquiring specific infectious diseases and other hazards in the tropics is to a large extent unknown and is therefore often adopted from that of the indigenous population. The objective of this study was to elucidate the risk for travel-related diseases, symptoms, and accidents in a population of Europeans who travel to popular tourist destinations. METHODS: From July 2003 to June 2004, 794 travelers consulting the travel clinic of the Berlin Institute of Tropical Medicine were recruited for a questionnaire-based observational study before traveling to Kenya, Tanzania, Senegal, the Gambia, India, Nepal, Thailand, or Brazil. RESULTS: Overall, illness was reported by 42.9% of travelers, with 10.2% reporting more than one adverse health event. Most frequently gastrointestinal symptoms were noted (34.6%), followed by respiratory symptoms (13.7%). More than 5% experienced an accident. Travel to the Indian subcontinent nearly doubled the risk of becoming ill; travel to Thailand significantly decreased the risk. Additional risk factors were a long duration of staying abroad, young age, and traveling under basic conditions. Of all travelers, 80% did not follow the traditionally recommended dietary restrictions. Among travelers visiting malaria-endemic areas, 20% did not carry any antimalarial drugs with them, not continuous chemoprophylaxis or standby medication. CONCLUSIONS: Because of the rising travel activity, especially to tropical countries, the importance of qualified pretravel advice consultation is increasing. To improve the travelers' health, attention needs to be paid to individual risk factors, the prevention and therapy of travelers' diarrhea, malaria prophylaxis, management of respiratory illness, and personal safety.     

Is the nociceptin (NOP) receptor involved in attenuation of the expression of sensitization to morphine-induced hyperlocomotion in mice?

In the present study we investigated whether synthetic agonists of the nociceptin (NOP) receptors, Ro 64-6198 [(1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4,5]decan-4-one] and Ro 65-6570 (8-acenaphthen-1-yl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one), influence the expression of sensitization to the locomotor stimulant effect of morphine in mice. Sensitization was produced by five repeated administrations of morphine (10 mg/kg, s.c.) at 3-day intervals. Seven days after the last morphine injection, Ro 64-6198 (1 and 3 mg/kg, i.p.) and Ro 65-6570 (3 and 6 mg/kg, i.p.) were given immediately before the challenge dose of morphine (10 mg/kg, s.c.). Both substances inhibited the expression of sensitization to the locomotor stimulant action of morphine. However, the selective NOP receptor antagonist, [Nphe1]NC(1-13)NH2 (30 nmol, i.c.v.) did not reverse the inhibitory effect of the Ro-compounds. Therefore, our results suggest that the NOP receptor may not be critical for the influence of Ro-compounds on the morphine-induced sensitization, or the observed effect may be attributed to one functional subset of this receptor, stimulation of which is not blocked by [Nphe1]NC(1-13)NH2.     

Inflammation and type 2 diabetes: results from KORA Augsburg

Type 2 diabetes is associated with a systemic low-grade inflammation. First data provided by cross-sectional studies from as early as the 1960s demonstrated elevated systemic levels of glycoproteins and acute-phase reactants and increased leukocyte counts in type 2 diabetes patients. Subsequently, prospective studies showed that elevated concentrations of several acute-phase proteins and cytokines are predictive of later type 2 diabetes. Immune gene variants in man and in animal models were found to affect insulin resistance and diabetes incidence. Antidiabetic treatment by medication, diet or physical activity results in a significant decrease of systemic immune mediator concentrations. Immunological analyses of the KORA Survey S4 (1999/2001) allowed us to show that levels of circulating acute-phase proteins like CRP and of IL-6 are highly correlated and associated not only with overt type 2 diabetes, but already with impaired glucose tolerance (IGT) pointing out a role of these mediators in the pathogenesis of type 2 diabetes. On the contrary, TNFalpha was neither coregulated with CRP nor associated with diabetes status. Our study therefore shows that type 2 diabetes is accompanied by a non-random and differential upregulation of components of the innate immunity and suggests that this inflammatory condition is involved in the aetiology of the disease. Future work will extend the range of analysed immune mediators to chemokines and will also investigate the association of immune markers with indices of obesity to elucidate the relevance of this traditional risk factor for low-grade inflammation.     

Genetic diversity in german and European populations: looking for substructures and genetic patterns

A classical case-control study is a powerful and cost-efficient approach to detect association of genetic markers with complex disease phenotypes. However, only a small fraction of significant association results has been replicated by other studies. Undetected genetic substructures in the population may be one of the reasons for spurious or biased results. The German "Genomic Control" study aims at detecting genetic differentiation between one Southern German population, represented by the KORA study (KORA Survey S4 (1999/2001)), and two Northern German populations (SHIP, Greifswald, and POPGEN, Schleswig-Holstein). Relevant population-substructures will be assessed, as well as their influence on case-control studies. Since KORA samples are used as controls for different German genetic association studies, the knowledge gained through this Genomic Control project will influence the planning of further genetic association studies. A second project, the European LD study, deals with the detection and comparison of linkage disequilibrium (LD) patterns in the human genome for eight distinct European populations. In general, a conservation of LD patterns across European samples can be observed for most gene regions. However, there are chromosomal regions with variable LD structure which may have implications on the fine-mapping of genes in different populations.     

The orphanin receptor agonist RO 64-6198 does not induce place conditioning in rats

The abuse liability of Ro 64-6198, an orphanin FQ (OFQ) receptor full agonist that exhibits anxiolytic properties, was evaluated using an unbiased conditioned place preference (CPP) paradigm in rats. As OFQ is structurally related to opioid peptides and also exhibits anxiolytic-like properties, the effect of Ro 64-6198 on CPP was compared with those of morphine and alprazolam. We show here that neither Ro 64-6198 nor alprazolam exhibited rewarding or aversive properties, whereas morphine induced a pronounced CPP. These results strengthen the previous finding that Ro 64-6198 lacked abuse liability in a self-stimulation paradigm, suggesting that this new class of anxiolytic drugs is devoid of the risk for potential non-medical use and dependence.