Contractile Responses and Structure of Small Bronchi Isolated from Rats after 20 Months' Exposure to Ozone

Short-term exposure to high concentrations of ozone has beenshown to increase airway responsiveness in normal humans andin all laboratory animal species studied to date. While ourknowledge concerning the pulmonary effects of single exposuresto ozone has increased rapidly over recent years, the effectsof repeated exposures are less understood. The goal of the presentstudy was to determine whether airway responsiveness is increasedafter near-lifetime exposure to ozone. Airway segments representingapproximately eighth generation airways were isolated from Fischer344 rats of both genders that had been exposed for 6 hr perday, 5 days per week for 20 months to 0, 0.12, 0.5, or 1.0 partsper million (ppm) ozone. Circtimferential tension developmentwas measured in isolated airways in response to bethanechol,acetylcholine, and electrical field stimulation. Responsivenessof the airways to the contractile stimuli was described by theeffective dose or frequency that elicited half-maximum contraction(ED50) and the maximum response. Since ozone exposure is associatedwith remodeling of peripheral airways, smooth muscle area wasdetermined and tension responses were normalized to the areameasurements. Before normalization of tension data to smoothmuscle area, neither the ED50 nor maximum response of smallbronchi to the contractile stimuli was altered after chronicozone exposure. Smooth muscle area was greater in airways isolatedfrom animals that had been exposed to 0.5 ppm ozone. After accountingfor smooth muscle area, maximum responses of the small bronchiisolated from male rats were significantly reduced after 0.12and 0.5 ppm ozone. Although not significant statistically, asimilar trend was observed in airways isolated from female rats.These results suggest that the increase in airway responsivenessassociated with acute ozone exposure does not persist duringnear-lifetime exposure. Although the mechanism responsible forthe adaptation to the effects of 03 on airway responsivenessis unknown, the results indicate that smooth muscle cell functionwas compromised by the chronic exposure. The mechanism(s) responsiblefor mediating this effect and the relevance of these resultsto humans remains to be determined.     

Apolipoprotein E alleles in nonagenarian subjects in the Belfast Elderly Longitudinal Free-living Ageing Study (BELFAST)

The ApoE gene has three alleles coding for the proteins apoE2, apoE3 and apoE4. E4 has been reported to be associated with hypercholesteraemia, ischaemic heart disease, age-related cognitive decline and Alzheimer's disease. Conversely, the E2 allele has been associated with longevity in French centenarians and their siblings. In this study, we have assessed any shift in the ApoE genotypes in nonagenarian subjects from Belfast where there is a high intrinsic incidence of cardiovascular disease. ApoE phenotypes were determined by electrofocusing and immunoblotting in 114 Senieur-approximated subjects >90 years old and compared with 2071 subjects, 30--65 years of age, recruited from the same geographical area by the MONItoring of CArdiovascular trends study group in Belfast (MONICA). The E4 allele was reduced in the nonagenarian group (X(2)=11.1; P=0.0006), the E3 unchanged and E2 frequency was increased (X(2)=4.0; P=0.047). These results suggest that longevity is negatively associated with the E4 allele and may be associated with carriage of E2.     

Shades of gray matter: Noninvasive optical images of human brain reponses during visual stimulation

Recent theories about human brain function emphasize the need for imaging methods that allow the study of dynamic interactions among different structures. In this paper, we report on a new technique, based on the measurement of parameters of migration of near-infrared photons, that yields functional images of the human occipital cortex, combining a spatial resolution of 0.5 cm and a temporal resolution of 50 ms. This technique appears to be suitable for studying the dynamics of cortical activation.     

Binding of 14C-spermidine to melanin in vivo and in vitro

It has been shown that melanin has the properties of a polyanion and may in vivo and in vitro bind inorganic cations and drugs which are positively charged at physiological pH by a cation-exchange mechanism. In the present study, we explored if the organic aliphatic polycation spermidine would bind to melanin in vivo after administration of ¹⁴C-spermidine to pigmented mice and in vitro at incubations with pigment from beef-eyes. The results showed a high labelling of the pigmented tissues in the mice after the administration of ¹⁴C-spermidine. At long survival intervals, the radioactivity in the melanin was higher than in any other tissue. A strong melanin affinity of ¹⁴C-spermidine was found in vitro. An analysis of the binding by the method of Scale hard showed that the data could be best fitted by the assumption of two classes of binding sites. The in vivo bound material could be displaced by in vitro incubation in solutions containing inorganic cation-chloride salts or HCI and HC1 was also very effective in inhibiting the melanin-binding of ¹⁴C-spermidine in vitro. The results indicate that an electrostatic interaction between spermidine and melanin will occur both in vivo and in vitro.     

Effect on Trend Estimates of the Difference between Survey Respondents and Non-respondents: Results from 27 Populations in the WHO MONICA Project

Introduction: In the World Health Organization (WHO) MONICA (multinational MONItoring of trends and determinants in CArdiovascular disease) Project considerable effort was made to obtain basic data on non-respondents to community based surveys of cardiovascular risk factors. The first purpose of this paper is to examine differences in socio-economic and health profiles among respondents and non-respondents. The second purpose is to investigate the effect of non-response on estimates of trends. Methods:Socio-economic and health profile between respondents and non-respondents in the WHO MONICA Project final survey were compared. The potential effect of non-response on the trend estimates between the initial survey and final survey approximately ten years later was investigated using both MONICA data and hypothetical data. Results: In most of the populations, non-respondents were more likely to be single, less well educated, and had poorer lifestyles and health profiles than respondents. As an example of the consequences, temporal trends in prevalence of daily smokers are shown to be overestimated in most populations if they were based only on data from respondents. Conclusions: The socio-economic and health profiles of respondents and non-respondents differed fairly consistently across 27 populations. Hence, the estimators of population trends based on respondent data are likely to be biased. Declining response rates therefore pose a threat to the accuracy of estimates of risk factor trends in many countries.     

Disease management programmes in Germany: first reactions by patients suffering from diabetes

The performance of health delivery for chronic diseases in Germany has been considered deficient for a long time and in need of improvement. The launch of Disease Management Programmes (DMP) for type 2 diabetes in the summer of 2002 can be seen as an attempt to optimise health care for the chronically ill. The aim of our study was to find out at an early stage of DMP development which factors, personal or otherwise, would have an influence on whether diabetic patients know of, and are willing to participate in, such a programme. The data of 679 diabetic patients, collected between late 2002 and the end of 2003, presented here have been extracted from a written follow-up study to the three baseline surveys S1 (1984/85), S2 (1989/90) und S3 (1994/95) in Augsburg as part of the WHO-MONICA project with more than 13,000 participants. The study population is characterised by a rather high age (mean: 67.4 years), a long duration of the disease (mean: 9.8 years) as well as a high intensity of contacts with physicians. Only 28 % of the diabetic patients had heard of the DMP, but a majority of the participants (54 %) stated their readiness to participate in DMP once offered. Higher age, low education as well as no participation in diabetes education have been identified in logistic regression models as impeding factors both for the knowing of and the participation in DMP. As a consequence, promotion of the DMP should be directed to those sections of the diabetic population outside the effective reach of the traditional diabetes care organisations.     

Distribution, determinants and reference values of left ventricular parameters in the general population--results of the MONICA/KORA echocardiography studies

For successful fighting against the burden of cardiovascular disease in the community a comprehensive knowledge about the prevalence and the impact of underlying risk factors is important. The present paper summarises some studies undertaken on more than 2000 persons from the MONICA/KORA-studies (parts of S1 and S3) where left ventricular mass (LVM) and other left ventricular parameters were determined by echocardiography. We especially investigated the associations of LVM with blood pressure and obesity. A special focus was on sex-specific factors in the determination of LVM and the influence of different indices of body size when normalising LVM. It could be shown that hypertension and obesity are major determinants of LV hypertrophy. Especially women with both hypertension and obesity on showed a high prevalence of concentric hypertrophy, significantly more than men. We also showed that the prevalence of LV hypertrophy in a representative sample of the general population (25 to 74 years) is 17.5 % for men, and 18.5 % for women. This underscores the need for primary and secondary prevention regarding the development of LV hypertrophy. Finally, our data in a selected group of normal subjects (reference sample) may be used for the development of reference values for left ventricular parameters in the general German population.     

KORA--a research platform for population based health research

KORA (Cooperative Health Research in the Region Augsburg) is a regional research platform for population-based surveys and subsequent follow-up studies in the fields of epidemiology, health economics, and health care research. KORA was established in 1996 to continue and expand the MONICA project in Augsburg, including the Acute Myocardial Infarction (AMI) Registry. The available pool of study participants allows for cohort, case-control and family studies. We present the KORA infrastructure, aspects of data management and quality control, and the concept of cooperative research. The increasing use of the MONICA/KORA cohorts for a variety of research topics, with a recent focus on genetic epidemiology, indicates the attractiveness of this concept.     

Allergies in adults

Only few epidemiological studies have assessed allergic diseases in adults. In a follow-up study of the MONICA survey S3 (1994/95), which was performed 1997-1999, a total of 1,537 persons were interviewed and tested by skin prick and patch test. Furthermore data of the MONICA survey (RAST, cholesterol, food diaries) could be used. Within survey S4 (1999/2001) a total of 4,261 subjects were interviewed concerning their personal history of atopic diseases and the corresponding history of their partners. In survey S3 the prevalence of allergic sensitisation was 20.5 % for persons without formal graduation from school and 48.1 % for those with a university degree. 20.8 % reported a hypersensitivity to food and about one quarter exhibited a positive reaction in skin prick test. Atopic eczema and hay fever increased over quartiles of HDL cholesterol. Similar, allergic sensitisation (RAST) increased over quartiles of uptake of unsaturated fatty acids in men. 40 % of those who were patch tested exhibited a positive reaction, with perfume mix, nickel, thimerosal and balsam of Peru being the most prominent allergens. Inhabitants of the City of Augsburg were sensitised more often (34.0 % overall, 23.9 % pollen) than inhabitants of villages with (29.4 %, 17.0 %). Full time farmers were sensitised less frequently (22.0 %, 8.4 %). In survey S4 the lifetime prevalence of atopic diseases diagnosed by doctors was 5.1 % for atopic eczema, 6.1 % for asthma and 13.7 % for hay fever. Subjects who lived together with a partner who suffered from hay fever were affected in 19.6 % whereas 13.1 % had hay fever when the partner was not affected. Future studies will offer an unique opportunity to analyse the incidence and remission of manifestations of atopy in adults.