Cytokine gene polymorphisms and atopic disease in two European cohorts. (ECRHS-Basel and SAPALDIA)

BACKGROUND: Atopy and allergic phenotypes are biologically characterized by an imbalanced T helper cell response skewed towards a type 2 (TH2) immune response associated with elevated serum immunoglobulin E (IgE) levels. Polymorphisms in cytokine genes might modulate regulation of the TH1/TH2 balance. We thus aimed at reproducing our previous findings from a European study population on the association of various cytokine polymorphisms with self-reported hay fever as well as increased total and specific IgE levels in two comparable study populations. METHODS: Two prospective Caucasian cohorts were used. In the Basel center of the European Community Respiratory Health Survey (ECRHS, n = 418) ten distinct cytokine polymorphisms of putative functional relevance were genotyped. In the Swiss cohort Study on Air Pollution And Lung Disease In Adults (SAPALDIA, n = 6003) two cytokine polymorphisms were genotyped. The associations of these polymorphisms with atopy were estimated by covariance and logistic regression analysis. RESULTS: We confirmed IL4, IL10, IL6 and IL18 as candidate genes for atopic health outcomes. In the large, well-characterized SAPALDIA cohort the IL6(-174G>C) and IL18(-137G>C) polymorphisms were associated with circulating total IgE concentrations in subjects with hay fever. The IL18(-137G>C) polymorphism was also associated with the prevalence of hay fever. CONCLUSION: Comprehensive characterization of genetic variation in extended cytokine candidate gene regions is now needed. Large study networks must follow to investigate the association of risk patterns defined by genetic predisposing and environmental risk factors with specific atopic phenotypes

Prevalence of renal impairment and its association with cardiovascular risk factors in a general population: results of the Swiss SAPALDIA study

Background. Impaired renal function is evolving as an independent marker of the risk of cardiovascular morbidity and mortality. Little is known about the prevalence of impaired renal function and its relationship to cardiovascular risk factors in the Swiss general population. Methods. SAPALDIA comprises a random sample of the Swiss population established in 1991, originally to investigate the health effects of long-term exposure to air pollution. Participants were reassessed in 2002/3 and blood measurements were obtained (n = 6317). Renal function was estimated using the Cockcroft-Gault equation and the modified MDRD (four-component) equation incorporating age, race, gender and serum creatinine level. Results. The estimated prevalence of impaired renal function [estimated glomerular filtration rate <60 ml/min/1.73 m2] differed substantially between men and women, particularly at higher ages, and amounted to 13% [95% confidence interval (CI) 10-16%] and 36% (95% CI 32-40%) in men and women, respectively, of 65 years or older. Smoking, obesity, blood lipid levels, high systolic blood pressure and hyperuricaemia were all more common in men when compared with women. These cardiovascular risk factors were also associated independently with creatinine in both women and men. Women were less likely to receive cardiovascular drugs, in particular angiotensin-converting enzyme inhibitors and β-blockers, when compared with men of the same age. Conclusion. Moderate renal impairment seems to be prevalent in the general population, with an apparent excess in females which is not explained by conventional cardiovascular risk factors. The unexpected finding questions the validity of the prediction equations, in particular in female

Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population

BACKGROUND: Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes. OBJECTIVES: We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures. METHODS: For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV(1)), FEV(1) over forced vital capacity (FEV(1)/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF(25-75)) was regressed on interval exposure to particulate matter >10 microm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (p(interaction)>0.05). Replication was attempted for SNPs with MAF<10% in 3320 SAPALDIA participants without GWAS. RESULTS: On the SNP-level, rs2035268 in gene SNCA accelerated FEV(1)/FVC decline by 3.8% (p(interaction) = 2.5x10(-6)), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml p(interaction) = 9.7x10(-8)) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (p(interaction) = 3.0x10(-4)) on FEV(1)/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful. CONCLUSIONS: Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobac smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challengin

Differences in Heart Rate Variability Associated with Long-Term Exposure to NO2

BACKGROUND: Heart rate variability (HRV), a measure of cardiac autonomic tone, has been associated with cardiovascular morbidity and mortality. Short-term studies have shown that subjects exposed to higher traffic-associated air pollutant levels have lower HRV. OBJECTIVE: Our objective was to investigate the effect of long-term exposure to nitrogen dioxide on HRV in the Swiss cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA). METHODS: We recorded 24-hr electrocardiograms in randomly selected SAPALDIA participants >or= 50 years of age. Other examinations included an interview investigating health status and measurements of blood pressure, body height, and weight. Annual exposure to NO2 at the address of residence was predicted by hybrid models (i.e., a combination of dispersion predictions, land-use, and meteorologic parameters). We estimated the association between NO2 and HRV in multivariable linear regression models. Complete data for analyses were available for 1,408 subjects. RESULTS: For women, but not for men, each 10-microg/m3 increment in 1-year averaged NO2 level was associated with a decrement of 3% (95% CI, -4 to -1) for the standard deviation of all normal-to-normal RR intervals (SDNN), -6% (95% CI, -11 to -1) for nighttime low frequency (LF), and -5% (95% CI, -9 to 0) for nighttime LF/high-frequency (HF) ratio. We saw no significant effect for 24-hr total power (TP), HF, LF, or LF/HF or for nighttime SDNN, TP, or HF. In subjects with self-reported cardiovascular problems, SDNN decreased by 4% (95% CI, -8 to -1) per 10-microg/m3 increase in NO2. CONCLUSIONS: There is some evidence that long-term exposure to NO2 is associated with cardiac autonomic dysfunction in elderly women and in subjects with cardiovascular disease

Circulating alpha1-antitrypsin in the general population: Determinants and association with lung function

BACKGROUND: Severe alpha1-antitrypsin (AAT) deficiency associated with low AAT blood concentrations is an established genetic COPD risk factor. Less is known about the respiratory health impact of variation in AAT serum concentrations in the general population. We cross-sectionally investigated correlates of circulating AAT concentrations and its association with FEV1. METHODS: In 5187 adults (2669 females) with high-sensitive c-reactive protein (CRP) levels < or = 10 mg/l from the population-based Swiss SAPALDIA cohort, blood was collected at the time of follow-up examination for measuring serum AAT and CRP. RESULTS: Female gender, hormone intake, systolic blood pressure, age in men and in postmenopausal women, as well as active and passive smoking were positively, whereas alcohol intake and BMI inversely correlated with serum AAT levels, independent of CRP adjustment. We observed an inverse association of AAT with FEV1 in the total study population (p < 0.001), that disappeared after adjustment for CRP (p = 0.28). In addition, the AAT and FEV1 association was modified by gender, menopausal status in women, and smoking. CONCLUSION: The results of this population-based study reflect a complex interrelationship between tobacco exposure, gender related factors, circulating AAT, systemic inflammatory status and lung function

Decreased PM10 exposure attenuates age-related lung function decline: genetic variants in p53, p21, and CCND1 modify this effect.

BACKGROUND: Decreasing exposure to airborne particulates was previously associated with reduced age-related decline in lung function. However, whether the benefit from improved air quality depends on genetic background is not known. Recent evidence points to the involvement of the genes p53 and p21 and of the cell cycle control gene cyclin D1 (CCND1) in the response of bronchial cells to air pollution. OBJECTIVE: We determined in 4,326 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) whether four single-nucleotide polymorphisms in three genes [CCND1 (rs9344 [P242P], rs667515), p53 (rs1042522 [R72P]), and p21 (rs1801270 [S31R])] modified the previously observed attenuation of the decline in the forced expiratory flow between 25% and 75% of the forced vital capacity (FEF(25-75)) associated with improved air quality. METHODS: Subjects of the prospective population-based SAPALDIA cohort were assessed in 1991 and 2002 by spirometry, questionnaires, and biological sample collection for genotyping. We assigned spatially resolved concentrations of particulate matter with aerodynamic diameter &lt; or = 10 microm (PM(10)) to each participant's residential history 12 months before the baseline and follow-up assessments. RESULTS: The effect of diminishing PM(10) exposure on FEF(25-75) decline appeared to be modified by p53 R72P, CCND1 P242P, and CCND1 rs667515. For example, a 10-microg/m(3) decline in average PM(10) exposure over an 11-year period attenuated the average annual decline in FEF(25-75) by 21.33 mL/year (95% confidence interval, 10.57-32.08) among participants homozygous for the CCND1 (P242P) GG genotype, by 13.72 mL/year (5.38-22.06) among GA genotypes, and by 6.00 mL/year (-4.54 to 16.54) among AA genotypes. CONCLUSIONS: Our results suggest that cell cycle control genes may modify the degree to which improved air quality may benefit respiratory function in adults

Prise de position en faveur du dépistage mammographique du cancer du sein en Suisse

En janvier 2000, la revue The Lancet a publié un article signé par Gøtzsche et Olsen [1] contestant l'efficacité de la mammographie de dépistage. La Ligue suisse contre le cancer, dans le cadre de laquelle sont élaborés les programmes nationaux de lutte contre le cancer, a chargé un groupe de travail de procéder à une expertise épidémiologique de cet article. Après avoir pris connaissance de cette expertise et après un nouvel examen approfondi de la littérature disponible sur l'efficacité de ce dépistage, les responsables ou experts des instituts de santé publique et des principaux organismes suisses en charge de la lutte contre le cancer ont pris position en faveur de l'efficacité de ce dépistage. [Auteurs]]]> Breast Neoplasms ; Mammography ; Mass Screening fre oai:serval.unil.ch:BIB_4B0DF71B2532 2022-11-26T02:22:31Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_4B0DF71B2532 Transponder and an infrared-videocamera as methods in a fieldstudy on the social behaviour of Bechstein's bats (Myotis bechsteinii). Kerth G, König B. info:eu-repo/semantics/article article 1996 Myotis, vol. 34, pp. 27-34 oai:serval.unil.ch:BIB_4B0E8B70E047 2022-11-26T02:22:31Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_4B0E8B70E047 Hamodynamische Eigenschaften der Hamopumpe. [Hemodynamic properties of the hemopump] info:eu-repo/semantics/altIdentifier/pmid/7875998 Mihaljevic, T. Leskosek, B. von Segesser, L. K. Tonz, M. Turina, M. info:eu-repo/semantics/article article 1994-12 Helvetica Chirurgica Acta, vol. 60, no. 6, pp. 1159-62 info:eu-repo/semantics/altIdentifier/pissn/0018-0181 <![CDATA[The hemopump HP 31 is an improved version of a catheter-mounted, transvalvular, left ventricular assist device, which can be placed into the left ventricle through the ascending aorta. The purpose of this study was to examine the influence of hematocrit and afterload on the pump flow. The hemopump was tested using a flow bench model filled with heparinized bovine blood. The measurements were performed at four various hematocrit values: 16%, 24%, 32%, and 40%. The pump flow was measured at each hematocrit value under increasing afterload pressures (40-120 mm Hg), by all pump speed levels (n = 7). The average pump flow at highest pump speed and lowest afterload was 5.1 +/- 0.3 l/min (mean +/- standard deviation). The influence of afterload on the pump flow was statistically significant (p &lt; 0.001). The highest afterload pressure of 120 mm Hg caused a reduction in pump flow of 24 +/- 5%. The alterations of hematocrit values caused no statistically significant influence on the pump flow (p = 0.72). The results of our study enabled the construction of the nomogram for the in vivo determination of the pump flow. The in vivo performances of the hemopump can be improved through the afterload reduction, especially in the weaning phase of treatment. The oxygen delivery can be improved through the increase in hematocrit values without significant impairment of the pump flow