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1.
BMJ Open ; 11(2): e039079, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602699

RESUMO

OBJECTIVES: Calretinin and mesothelin are molecular markers for the detection of malignant mesothelioma at early stages. Our objective was the re-evaluation of factors influencing calretinin and mesothelin concentrations in plasma of cancer-free men in order to minimise false-positive tests when using commercial assays approved for clinical diagnostics. SETTING: This re-evaluation used data and archived blood samples of the population-based Heinz Nixdorf Recall Study (HNRS) collected from 2011 to 2014. PARTICIPANTS: The present analysis comprised of 569 cancer-free men at the time of blood sampling (median age 70 years) from HNRS. PRIMARY AND SECONDARY OUTCOMES: Mesothelin plasma concentration was determined using ELISA and CLEIA (chemiluminescent enzyme immunoassay). Calretinin plasma concentration was assessed using ELISA. RESULTS: Compared with the previous determination of concentrations, we detected less false-positive tests using the commercial assays. In this analysis, we found nine false-positive calretinin tests using the ELISA (specificity 98.4%, 95% CI 97.0% to 99.2%) and 24 false-positive mesothelin tests using both ELISA and CLEIA (specificity 95.8%, 95% CI 93.8% to 97.2%). We confirmed renal dysfunction as major predictor of elevated marker concentrations. Mesothelin was additionally affected by bronchitis. Furthermore, elevated inflammation values and hypertension only affected the mesothelin concentration determined by ELISA. CONCLUSIONS: The newly available assays of calretinin and mesothelin approved for clinical diagnostics showed high specificities in the population-based cohort of elderly men without a malignant disease. The current evaluation provides a basis to consider influencing factors in order to further improve the diagnostic procedure.

2.
Neurotoxicology ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33301826

RESUMO

The aim of this study was to evaluate the effect of exposure to manganese (Mn) on fine motor functions. A total of 48 welders and 30 unexposed workers as controls completed questionnaires, underwent blood examinations, and a motor test battery. The shift exposure of welders to respirable Mn was measured with personal samplers. For all subjects accumulations of Mn in the brain were assessed with T1-weighted magnetic resonance imaging. Welders showed normal motor functions on the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale part III. Furthermore welders performed excellent on a steadiness test, showing better results than controls. However, welders were slightly slower than controls in motor tests. There was no association between fine motor test results and the relaxation rates R1 in globus pallidus and substantia nigra as MRI-based biomarkers to quantify Mn deposition in the brain.

3.
Environ Res ; 189: 109913, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32980007

RESUMO

Welders have an increased susceptibility to airway infections with non-typeable Haemophilus influenzae (NTHi), which implicates immune defects and might promote pneumonia and chronic obstructive pulmonary disease (COPD). We hypothesized that welding-fume exposure suppresses Th1-lymphocyte activity. Non-effector CD4+ T-cells from blood of 45 welders (n = 23 gas metal arc welders, GMAW; n = 16 tungsten inert gas welders, TIG; n = 6 others) and 25 non-welders were ex vivo activated towards Th1 via polyclonal T-cell receptor stimulation and IL-12 (first activation step) and then stimulated with NTHi extract or lipopolysaccharide (LPS) (second activation step). IFNγ and IL-2 were measured by ELISA. In the first activation step, IFNγ was reduced in welders compared to non-welders and in the GMAW welders with higher concentrations of respirable particles compared to the lower exposed TIG welders. IFNγ was not influenced by tobacco smoking and correlated negatively with welding-fume exposure, respirable manganese, and iron. In the second activation step, NTHi and LPS induced additional IFNγ, which was reduced in current smokers compared to never smokers in welders as well as in non-welders. Analyzing both activation steps together, IFNγ production was lowest in smoking welders and highest in never smoking non-welders. IL-2 was not associated with any of these parameters. Welding-fume exposure might suppress Th1-based immune responses due to effects of particulate matter, which mainly consists of iron and manganese. For responses to NTHi this is strongest in smoking welders because welding fume suppresses T-cell activation towards Th1 and cigarette smoke suppresses the subsequent Th1-response to NTHi via LPS. Both effects are independent from IL-2-regulated T-cell proliferation. This might explain the increased susceptibility to infections and might promote COPD development.

4.
Am J Respir Crit Care Med ; 202(3): 412-421, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32330394

RESUMO

Rationale: Millions of workers around the world are exposed to respirable crystalline silica. Although silica is a confirmed human lung carcinogen, little is known regarding the cancer risks associated with low levels of exposure and risks by cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by cancer subtype.Objectives: We aimed to address current knowledge gaps in lung cancer risks associated with low levels of occupational silica exposure and the joint effects of smoking and silica exposure on lung cancer risks.Methods: Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of silica exposure and smoking on risk of lung cancer. Stratified analyses by smoking history and cancer subtypes were also performed.Measurements and Main Results: Our study included 16,901 cases and 20,965 control subjects. Lung cancer odds ratios ranged from 1.15 (95% confidence interval, 1.04-1.27) to 1.45 (95% confidence interval, 1.31-1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative silica exposure was associated (P trend < 0.01) with increasing lung cancer risks in nonsilicotics and in current, former, and never-smokers. Increasing exposure was also associated (P trend ≤ 0.01) with increasing risks of lung adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. Supermultiplicative interaction of silica exposure and smoking was observed on overall lung cancer risks; superadditive effects were observed in risks of lung cancer and all three included subtypes.Conclusions: Silica exposure is associated with lung cancer at low exposure levels. An exposure-response relationship was robust and present regardless of smoking, silicosis status, and cancer subtype.


Assuntos
Adenocarcinoma de Pulmão/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Dióxido de Silício , Silicose/epidemiologia , Adulto , Idoso , Canadá/epidemiologia , Fumar Cigarros , Europa (Continente)/epidemiologia , Feminino , Humanos , Exposição por Inalação , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade
5.
Urol Oncol ; 38(12): 886-895, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32199755

RESUMO

BACKGROUND: Follow-up recommendations for patients with nonmuscle invasive bladder cancer (NMIBC) are largely based upon expert opinion. A growing body of evidence suggests that current follow-up strategies for bladder cancer patients with low and intermediate risk represent overdiagnosis and may lead to overtreatment. The goal of this study is to explore the options of a noninvasive follow-up in patients with pTa G1-2/low-grade NMIBC. METHODS: The risks and options for a urine marker-guided, noninvasive follow-up of patients with pTa G1-2/low-grade NMIBC were defined and the study design for a prospective randomized trial (UroFollow) was developed based upon the current literature. RESULTS: The investigators postulated that follow-up of patients with pTa G1-2/low-grade NMIBC requires a high sensitivity of urinary tumor markers. However, data from prospective studies with prediagnostic urine samples are scarce, even for approved markers, and cross-sectional studies with symptomatic patients overestimate the sensitivity. So far, cell-based markers (e.g., uCyt+ and UroVysion) in urine appeared to have higher sensitivities and specificities in low-grade NMIBC than urine cytology and markers analyzing soluble tumor-associated antigens. Marker panels are more sensitive than single-marker approaches at the expense of a lower specificity. Given a prospective randomized comparison with a marker sensitivity of 80% compared to usual care with cystoscopy, the sample size calculation yielded that 62 to 185 patients under study per arm are needed depending on different recurrence rates. CONCLUSIONS: Based upon these findings the UroFollow trial has been designed as a prospective randomized study comparing a noninvasive marker-based (UroVysion, NMP22, urine cytology, and ultrasound) follow-up with the current standard of care over a period of 3 years.

6.
Am J Epidemiol ; 188(11): 1984-1993, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504103

RESUMO

To investigate the risk of lung cancer after exposure to welding fumes, hexavalent chromium (Cr(VI)), and nickel, we analyzed 3,418 lung cancer cases and 3,488 controls among men from 2 German case-control studies (1988-1996). We developed a welding-process exposure matrix from measurements of these agents, and this was linked with welding histories from a job-specific questionnaire to calculate cumulative exposure variables. Logistic regression models were fitted to estimate odds ratios with confidence intervals conditional on study, and they adjusted for age, smoking, and working in other at-risk occupations. Additionally, we mutually adjusted for the other exposure variables under study. Overall, 800 cases and 645 controls ever worked as regular or occasional welders. Odds ratios for lung cancer with high exposure were 1.55 (95% confidence interval (CI): 1.17, 2.05; median, 1.8 mg/m3 × years) for welding fumes, 1.85 (95% CI: 1.35, 2.54; median, 1.4 µg/m3 × years) for Cr(VI), and 1.60 (95% CI: 1.21, 2.12; median, 9 µg/m3 × years) for nickel. Risk estimates increased with increasing cumulative exposure to welding fumes and with increasing exposure duration for Cr(VI) and nickel. Our results showed that welding fumes, Cr(VI), and nickel might contribute independently to the excess lung cancer risk associated with welding. However, quantitative exposure assessment remains challenging.


Assuntos
Cromo/toxicidade , Neoplasias Pulmonares/epidemiologia , Níquel/toxicidade , Doenças Profissionais/epidemiologia , Soldagem , Adulto , Idoso , Estudos de Casos e Controles , Alemanha/epidemiologia , Humanos , Neoplasias Pulmonares/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/induzido quimicamente
7.
Lung ; 197(5): 641-649, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31267149

RESUMO

PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal cancer caused by exposure to asbestos. Currently, the diagnosis is a challenge, carried out by means of invasive methods of limited sensitivity. This is a case-control study to evaluate the individual and combined performance of minimally invasive biomarkers for the diagnosis of MPM. METHOD: A study of 166 incident cases of MPM and 378 population controls of Mestizo-Mexican ethnicity was conducted. Mesothelin, calretinin, and megakaryocyte potentiating factor (MPF) were quantified in plasma by ELISA. The samples were collected from 2011 to 2016. RESULTS: Based on ROC analysis and a preset specificity of 95%, the combination of the three biomarkers reached an AUC of 0.944 and a sensitivity of 82% in men. In women, an AUC of 0.937 and a sensitivity of 87% were reached. In nonconditional logistic regression models, the adjusted ORs in men were 7.92 (95% CI 3.02-20.78) for mesothelin, 20.44 (95% CI 8.90-46.94) for calretinin, and 4.37 (95% CI 1.60-11.94) for MPF. The ORs for women were 28.89 (95% CI 7.32-113.99), 17.89 (95% CI 3.93-81.49), and 2.77 (95% CI 0.47-16.21), respectively. CONCLUSIONS: To our knowledge, this is the first study evaluating a combination of mesothelin, calretinin, and MPF, and demonstrating a sex effect for calretinin. The biomarker panel showed a good performance in a Mestizo-Mexican population, with high sensitivity and specificity for the diagnosis of MPM.


Assuntos
Biomarcadores Tumorais/sangue , Calbindina 2/sangue , Proteínas Ligadas por GPI/sangue , Neoplasias Pulmonares/sangue , Mesotelioma/sangue , Neoplasias Pleurais/sangue , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Incidência , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Masculino , Mesotelioma/diagnóstico , Mesotelioma/epidemiologia , México/epidemiologia , Pessoa de Meia-Idade , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/epidemiologia , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Fatores Sexuais
8.
Eur J Popul ; 35(2): 329-346, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31105502

RESUMO

Collecting life course data is increasingly common in social and epidemiological research, either through record linkage of administrative data or by collecting retrospective interview data. This paper uses data on employment histories collected through both strategies, compares the attained samples, and investigates levels of agreements of individual histories. We use data from the German Heinz Nixdorf Recall Study with information on employment histories collected retrospectively from 2011 until 2014 (N = 3059). Administrative data from the German Institute for Employment Research (IAB) were linked to the survey data. After comparing respondents who provide self-reported histories with the subsample of the ones for which administrative data were available, we investigate the agreement of individual employment histories from the two sources (between 1975 and 2010) using sequence analyses. Almost all participants provided survey data on employment histories (97% of the sample), linkage consent was given by 93%, and administrative data were available for 63% of the participants. People with survey data were more likely to be female, to have a higher education, and to work self-employed and in the tertiary sector. The agreement of individual employment histories is high and similar across time, with a median level of agreement of 89%. Slightly lower values exist for women and people working in the tertiary sector, both having more complex histories. No differences exist for health-related factors. In conclusion, it is likely that missing consent and failed record linkage lead to sample differences; yet, both strategies provide comparable and reliable life course data.

9.
J Epidemiol Community Health ; 73(6): 489-495, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30804047

RESUMO

BACKGROUND: Associations of socioeconomic status (SES) and smoking-related diseases depend on uniform validity of self-reported smoking habits in different SES groups. We investigated the influence of SES on validity of self-reported smoking status by means of urinary cotinine. METHODS: We determined total urinary cotinine in the baseline population of the Heinz Nixdorf Recall Study. Participants with cotinine>200 µg/L were potential current smokers. We defined upper and lower 20% of the gender-specific distribution of the International Socio-Economic Index (ISEI) as high and low SES, respectively, else as intermediate. We analysed the association of self-reported smoking status and cotinine by ISEI and additional SES measures, stratified by gender. In self-reported non-smokers, we estimated age-adjusted ORs with 95% CI to detect differences by SES in the validity of self-reported smoking status. RESULTS: In 2004 men and 1887 women, 78% and 80%, respectively, reported to be non-smokers. Median cotinine concentrations were 2 µg/L in non-smokers, and 3651 µg/L in male and 3127 µg/L in female smokers. Based on cotinine in non-smokers, 2.0 % of men (n = 32) and 1.8 % of women (n = 27) were potential smokers, with lower proportions in the subgroup of never-smokers (men: 0.7%, women: 0.5%). The validity of self-reported smoking status did not substantially differ by SES. Tendencies for increased underreporting were indicated for women with low ISEI (OR 1.35; 95% CI 0.54 to 3.39) and men in blue-collar jobs (OR 1.39; 95% CI 0.67 to 2.87). CONCLUSION: Validity of self-reported smoking status in this elderly German cohort was high and did not depend on SES.

10.
Cells ; 8(2)2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30699914

RESUMO

We took advantage of magnetic resonance imaging (MRI) and spectroscopy (MRS) as non-invasive methods to quantify brain iron and neurometabolites, which were analyzed along with other predictors of motor dysfunction in Parkinson's disease (PD). Tapping hits, tremor amplitude, and the scores derived from part III of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS3 scores) were determined in 35 male PD patients and 35 controls. The iron-sensitive MRI relaxation rate R2* was measured in the globus pallidus and substantia nigra. γ-aminobutyric acid (GABA)-edited and short echo-time MRS was used for the quantification of neurometabolites in the striatum and thalamus. Associations of R2*, neurometabolites, and other factors with motor function were estimated with Spearman correlations and mixed regression models to account for repeated measurements (hands, hemispheres). In PD patients, R2* and striatal GABA correlated with MDS-UPDRS3 scores if not adjusted for age. Patients with akinetic-rigid PD subtype (N = 19) presented with lower creatine and striatal glutamate and glutamine (Glx) but elevated thalamic GABA compared to controls or mixed PD subtype. In PD patients, Glx correlated with an impaired dexterity when adjusted for covariates. Elevated myo-inositol was associated with more tapping hits and lower MDS-UPDRS3 scores. Our neuroimaging study provides evidence that motor dysfunction in PD correlates with alterations in brain iron and neurometabolites.


Assuntos
Encéfalo/metabolismo , Ferro/metabolismo , Metaboloma , Atividade Motora , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Idoso , Estudos de Casos e Controles , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
11.
BMC Res Notes ; 12(1): 77, 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30744695

RESUMO

OBJECTIVE: Malignant mesothelioma is an aggressive cancer of the serous membranes. For the detection of the tumor at early stages non- or minimally-invasive biomarkers are needed. The circulating biomarkers miR-132-3p, miR-126-3p, and miR-103a-3p were analyzed in a nested case-control study using plasma samples from 17 prediagnostic mesothelioma cases and 34 matched asbestos-exposed controls without a malignant disease. RESULTS: Using prediagnostic plasma samples collected in median 8.9 months prior the clinical diagnosis miR-132-3p, miR-126-3p, and miR-103a-3p revealed 0% sensitivity on a defined specificity of 98%. Thus, the analyzed miRNAs failed to detect the cancer in prediagnostic samples, showing that they are not feasible for the early detection of malignant mesothelioma. However, the miRNAs might still serve as possible markers for prognosis and response to therapy, but this needs to be analyzed in appropriate studies.


Assuntos
Biomarcadores Tumorais/sangue , MicroRNA Circulante/sangue , Detecção Precoce de Câncer/normas , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , MicroRNAs/sangue , Adulto , Asbestose/sangue , Estudos de Casos e Controles , Humanos , Neoplasias Pulmonares/sangue , Masculino , Mesotelioma/sangue , Pessoa de Meia-Idade , Sintomas Prodrômicos , Sensibilidade e Especificidade
12.
Aging Ment Health ; 23(11): 1478-1486, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30621439

RESUMO

Objectives: The paper identifies types of work-family trajectories of men and women and investigates their links with depression at older age. Method: We use data from the Heinz Nixdorf Recall study, with retrospective information on employment histories and parenthood between age 20 and 50 (1482 men and 1537 women, born between 1925 and 1955). We apply sequence analysis and group trajectories into six clusters for each gender. We test their association with two alternative measures of depression: self-reported depressive symptoms and intake of antidepressant medication. Multivariate models exclude participants with early life depression and adjust for age, marital status, education, and income. Results: We find clear differences of work-family trajectories between men and women, where women's trajectories are generally more diverse, and include family leaves and returns into full or part-time work. For men, work-family trajectories are neither related to depressive symptoms nor to medication intake. In contrast, women who returned into full-time work after family leave show more depression than those who return part-time, both in terms of depressive symptoms and intake of antidepressant medication. Conclusion: Our findings show gender differences in terms of work-family trajectories and their health-related consequences. In particular, findings suggest that mothers who return to full-time work are a vulnerable group for depression at older age and should be the focus of further research attention.


Assuntos
Depressão/etiologia , Equilíbrio Trabalho-Vida , Adulto , Fatores Etários , Idoso , Depressão/epidemiologia , Escolaridade , Feminino , Humanos , Renda , Masculino , Estado Civil , Pessoa de Meia-Idade , Fatores de Risco
13.
J Occup Environ Hyg ; 16(6): 400-409, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30625071

RESUMO

The International Agency for Research on Cancer classified welding fumes as carcinogenic to humans, and occupational exposure limits should be established to protect welders. The aim of this study is to estimate exposure levels to inhalable and respirable welding fumes by welding process to use them for exposure assessment in epidemiological studies and to derive occupational exposure limits. In total, 15,473 mass concentrations of inhalable and 9,161 concentrations of respirable welding fumes could be analyzed along with welding-related and sampling information, which were compiled in the German database MEGA between 1983 and 2016. In both particle-size fractions, model-based geometric means of the concentrations were estimated by welding process and material for frequently used welding processes adjusted for sampling time and median-centered for calendar years. The inhalable concentrations were approximately twice the respirable concentrations, with medians of 3 mg/m3 (inter-quartile range: 1.2-7.0 mg/m3) and 1.5 mg/m3 (inter-quartile range: < limit of detection -3.8 mg/m3), respectively. The adjusted geometric means of flux-cored arc welding, metal inert and active gas welding, shielded metal arc welding and torch cutting ranged from 0.9 to 2.2 mg/m3 for respirable welding fumes and from 2.3 to 4.7 mg/m3 for inhalable fumes. In both particle-size fractions, geometric means were between 0.1 and 0.9 mg/m3 when performing tungsten inert gas, autogeneous, resistance, laser, and plasma welding or spraying. Results derived from this large dataset are useful for a quantitative exposure assessment to estimate health risks of welders.


Assuntos
Exposição por Inalação/análise , Exposição Ocupacional/análise , Soldagem/métodos , Poluentes Ocupacionais do Ar/análise , Alemanha , Humanos , Metais/análise , Tamanho da Partícula
14.
Sci Rep ; 8(1): 14321, 2018 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-30254313

RESUMO

Malignant mesothelioma (MM) is strongly associated with a previous asbestos exposure. To improve timely detection of MM in asbestos workers, better screening tools - like minimally-invasive biomarkers - are desirable. Between 2008 and 2018 2,769 patients with benign asbestos-related diseases were recruited to participate in annual screens. Using a nested case-control design the protein markers calretinin and mesothelin were determined by enzyme-linked immunosorbent assays in prediagnostic plasma samples of 34 MM cases as well as 136 matched controls from the cohort. Conditional on a pre-defined specificity of 98% for calretinin and 99% for mesothelin the markers reached individual sensitivities of 31% and 23%, respectively, when including the incident cases with samples taken between one and 15 months before diagnosis. The combination of both markers increased the sensitivity to 46% at 98% specificity. Marker complementation increased with earlier sampling. The marker combination improves the sensitivity of the individual markers, indicating a useful complementation and suggesting that additional markers may further improve the performance. This is the first prospective cohort study to evaluate a detection of MM by calretinin and its combination with mesothelin up to about a year before clinical diagnosis. Whether an earlier diagnosis will result in reduced mortality has yet to be demonstrated.


Assuntos
Asbestos/efeitos adversos , Calbindina 2/sangue , Proteínas Ligadas por GPI/sangue , Neoplasias Pulmonares/sangue , Mesotelioma/sangue , Exposição Ocupacional/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Incidência , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/diagnóstico , Masculino , Mesotelioma/induzido quimicamente , Mesotelioma/diagnóstico , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
15.
Neurotoxicology ; 68: 66-72, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30009858

RESUMO

Lead (Pb) is a recognized neurotoxin. Pb2+ can interfere with divalent metal transporters and ion channels and may thus affect other brain metals and cation signaling in neurons. Thereby, cognitive and sensory functions can be impaired. Whereas cognitive effects are well described less is known about olfaction and motor functions in the general population at currently lower exposure levels. The objective of this study was to evaluate the influence of Pb in blood (PbB) on odor identification and fine motor skills within the framework of the Heinz Nixdorf Recall Study (HNRS), a prospective cohort study among an elderly German population. Data on odor identification assessed with Sniffin' sticks and fine motor test results were collected during the second follow-up of HNRS (2011-2014) in 1188 elderly men aged 55 to 86 years. PbB was determined in 1140 blood samples archived at baseline (2000-2003) and in 796 samples from the second follow-up. The association between PbB and impaired odor identification (normosmia as reference) was estimated with proportional odds ratios (PORs) with 95% confidence intervals (CI). The odds ratios (OR) of substantially impaired dexterity (tapping hits <10th percentile, errors in aiming, line tracing, or steadiness>90th percentile) were estimated with mixed logistic regression models for test results with both hands, where PbB was adjusted for covariates. PbB at baseline (median 32.9 µg/L; 2.27% ≥90 µg/L) was higher than at follow-up (25.9 µg/L; 0.84% ≥90 µg/L). The individual concentrations were correlated (Spearman rs 0.59, 95% CI 0.54 - 0.63). PORs of an impaired odor identification in men with baseline PbB ≥90 µg/L were 1.96 (95% CI 0.94-4.11) and 1.57 (95% CI 0.47-5.19) with follow-up PbB. Fine-motor tests were not affected by elevated PbB with the exception of tapping in men with follow-up PbB ≥50 µg/L (OR 2.14, 95% CI 1.09-4.23). Increasing age had strong effects on all outcomes. Low education was associated with impaired odor identification, tapping, and aiming. Also, alcohol consumption and current smoking affected the test results, particularly steadiness. In this community-based cohort of elderly men, we could confirm indication of an influence of elevated PbB on odor identification. Small numbers of men with elevated PbB due to an on-going trend of decreasing PbB in the general population, strong covariates and multiple comparisons hamper the evaluation of adversity of these effects of PbB on olfaction and dexterity.


Assuntos
Chumbo/sangue , Destreza Motora , Olfato , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
16.
Int J Med Sci ; 15(9): 883-891, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30008600

RESUMO

Background: Diagnosis of malignant pleural mesothelioma (MPM) remains a challenge, especially when resources in pathology are limited. The study aimed to evaluate cost-effective tumor markers to predict the probability of MPM in plasma samples in order to accelerate the diagnostic workup of the tissue of potential cases. Methods: We conducted a case-control study stratified by gender, which included 75 incident cases with MPM from three Mexican hospitals and 240 controls frequency-matched by age and year of blood drawing. Plasma samples were obtained to determine mesothelin, calretinin, and thrombomodulin using enzyme-linked immunosorbent assays (ELISAs). We estimated the performance of the markers based on the area under the curve (AUC) and predicted the probability of an MPM diagnosis of a potential case based on the marker concentrations. Results: Mesothelin and calretinin, but not thrombomodulin were significant predictors of a diagnosis of MPM with AUCs of 0.90 (95% CI: 0.85-0.95), 0.88 (95% CI: 0.82-0.94), and 0.51 (95% CI: 0.41-0.61) in males, respectively. For MPM diagnosis in men we estimated a true positive rate of 0.79 and a false positive rate of 0.11 for mesothelin. The corresponding figures for calretinin were 0.81 and 0.18, and for both markers combined 0.84 and 0.11, respectively. Conclusions: We developed prediction models based on plasma concentrations of mesothelin and calretinin to estimate the probability of an MPM diagnosis. Both markers showed a good performance and could be used to accelerate the diagnostic workup of tissue samples in Mexico.


Assuntos
Biomarcadores Tumorais/análise , Calbindina 2/sangue , Proteínas Ligadas por GPI/sangue , Mesotelioma/diagnóstico , Neoplasias Pleurais/diagnóstico , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Pulmonares , Masculino , Mesotelioma/sangue , México , Pessoa de Meia-Idade , Neoplasias Pleurais/sangue
17.
Int Arch Occup Environ Health ; 91(8): 937-950, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29971594

RESUMO

PURPOSE: Radon is a risk factor for lung cancer and uranium miners are more exposed than the general population. A genome-wide interaction analysis was carried out to identify genomic loci, genes or gene sets that modify the susceptibility to lung cancer given occupational exposure to the radioactive gas radon. METHODS: Samples from 28 studies provided by the International Lung Cancer Consortium were pooled with samples of former uranium miners collected by the German Federal Office of Radiation Protection. In total, 15,077 cases and 13,522 controls, all of European ancestries, comprising 463 uranium miners were compared. The DNA of all participants was genotyped with the OncoArray. We fitted single-marker and in multi-marker models and performed an exploratory gene-set analysis to detect cumulative enrichment of significance in sets of genes. RESULTS: We discovered a genome-wide significant interaction of the marker rs12440014 within the gene CHRNB4 (OR = 0.26, 95% CI 0.11-0.60, p = 0.0386 corrected for multiple testing). At least suggestive significant interaction of linkage disequilibrium blocks was observed at the chromosomal regions 18q21.23 (p = 1.2 × 10-6), 5q23.2 (p = 2.5 × 10-6), 1q21.3 (p = 3.2 × 10-6), 10p13 (p = 1.3 × 10-5) and 12p12.1 (p = 7.1 × 10-5). Genes belonging to the Gene Ontology term "DNA dealkylation involved in DNA repair" (GO:0006307; p = 0.0139) or the gene family HGNC:476 "microRNAs" (p = 0.0159) were enriched with LD-blockwise significance. CONCLUSION: The well-established association of the genomic region 15q25 to lung cancer might be influenced by exposure to radon among uranium miners. Furthermore, lung cancer susceptibility is related to the functional capability of DNA damage signaling via ubiquitination processes and repair of radiation-induced double-strand breaks by the single-strand annealing mechanism.


Assuntos
Carcinógenos Ambientais/toxicidade , Neoplasias Pulmonares/genética , Neoplasias Induzidas por Radiação/genética , Proteínas do Tecido Nervoso/genética , Doenças Profissionais/genética , Radônio/toxicidade , Receptores Nicotínicos/genética , Estudos de Casos e Controles , Dano ao DNA/efeitos da radiação , Feminino , Marcadores Genéticos/efeitos da radiação , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Mineração , Exposição Ocupacional/efeitos adversos , Fatores de Risco , Ubiquitinação/efeitos da radiação , Urânio
18.
Ann Work Expo Health ; 62(3): 351-361, 2018 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-29444199

RESUMO

Objectives: Exposure to hexavalent chromium (Cr(VI)) has been primarily studied in chromate production. Here, we measured personal exposure to respirable Cr(VI) together with airborne and urinary Cr and Ni in welders to explore levels and associations between various measures of exposure. Methods: Shift concentrations of Cr(VI), Cr, and Ni were measured in respirable welding fumes in 50 men who used either gas metal arc welding (GMAW) (n = 24) or tungsten inert gas welding (TIG) (n = 19) as their major technique. Cr and Ni were determined in pre- and post-shift urine samples. Concentrations below the limit of quantification (LOQ) were multiply imputed. Spearman correlation coefficients (rs) were calculated with 95% confidence intervals (CIs) to explore associations between the exposure variables, and regression models were applied to estimate the effect of the parent metal on the urinary concentration. Results: Regarding the respirable Cr(VI), 62% of the measurements were below the LOQ, the 75th percentile was 0.50 µg m-3, and 8 out of 50 (16%) welders exceeded 1 µg m-3. The highest shift concentration that occurred as a result of shielded metal arc welding (SMAW) was 180 µg m-3. The Cr(VI) content in total Cr ranged from 4 to 82% (median 20%), although the concentration correlated with total Cr (rs 0.55, 95% CI 0.46; 0.64). The correlation between Cr(VI) and Ni was weaker (rs 0.42, 95% CI 0.34; 0.51) than that between total Cr and Ni in welding fumes (rs 0.83, 95% CI 0.74; 0.92). Both Cr(VI) and total Cr influenced the urinary Cr concentrations in post-shift samples (P = 0.0008 and P ≤ 0.0001, respectively). The airborne shift exposure was a weaker determinant than the Cr content in pre-shift urine samples, which strongly correlated with post-shift urinary Cr (rs 0.78, 95% CI 0.69; 0.87). Conclusions: The Cr(VI) content in total Cr varied considerably in welding fumes. The majority of welders using GMAW or TIG presented with shift concentrations of respirable Cr(VI) below 1 µg m-3. However, very high Cr(VI) concentrations may occur, for example in SMAW. The urinary concentration of total Cr, cannot be used to precisely determine the shift concentration of respirable Cr(VI) in welders.


Assuntos
Poluentes Ocupacionais do Ar/análise , Cromo/análise , Monitoramento Ambiental/métodos , Exposição Ocupacional/análise , Soldagem , Adulto , Cromo/urina , Gases , Humanos , Masculino , Pessoa de Meia-Idade , Níquel/urina , Aço Inoxidável
19.
PLoS One ; 13(2): e0192999, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29462211

RESUMO

BACKGROUND: An association between low socioeconomic status (SES) and lung cancer has been observed in several studies, but often without adequate control for smoking behavior. We studied the association between lung cancer and occupationally derived SES, using data from the international pooled SYNERGY study. METHODS: Twelve case-control studies from Europe and Canada were included in the analysis. Based on occupational histories of study participants we measured SES using the International Socio-Economic Index of Occupational Status (ISEI) and the European Socio-economic Classification (ESeC). We divided the ISEI range into categories, using various criteria. Stratifying by gender, we calculated odds ratios (OR) and 95% confidence intervals (CI) by unconditional logistic regression, adjusting for age, study, and smoking behavior. We conducted analyses by histological subtypes of lung cancer and subgroup analyses by study region, birth cohort, education and occupational exposure to known lung carcinogens. RESULTS: The analysis dataset included 17,021 cases and 20,885 controls. There was a strong elevated OR between lung cancer and low SES, which was attenuated substantially after adjustment for smoking, however a social gradient persisted. SES differences in lung cancer risk were higher among men (lowest vs. highest SES category: ISEI OR 1.84 (95% CI 1.61-2.09); ESeC OR 1.53 (95% CI 1.44-1.63)), than among women (lowest vs. highest SES category: ISEI OR 1.54 (95% CI 1.20-1.98); ESeC OR 1.34 (95% CI 1.19-1.52)). CONCLUSION: SES remained a risk factor for lung cancer after adjustment for smoking behavior.


Assuntos
Neoplasias Pulmonares/epidemiologia , Fatores Etários , Idoso , Canadá , Europa (Continente) , Feminino , Humanos , Modelos Logísticos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional , Razão de Chances , Fatores de Risco , Fatores Sexuais , Fumar/epidemiologia , Classe Social
20.
Eur J Epidemiol ; 33(4): 369-379, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29464445

RESUMO

Night shift work has been suspected to increase breast cancer risk but epidemiological studies have been inconsistent due to heterogeneous assessment of exposure to night work. To overcome this limitation, we pooled data of five population-based case-control studies from Australia, Canada, France, Germany, and Spain into a single harmonized dataset using a common definition of night work including 6093 breast cancer cases and 6933 population controls. The odds ratio for breast cancer in women who ever worked at night for at least 3 h between midnight and 5 a.m. as compared to never night workers was 1.12 (95% CI 1.00-1.25). Among pre-menopausal women, this odds ratio was 1.26 [1.06-1.51], increasing to 1.36 [1.07-1.74] for night shifts ≥ 10 h, 1.80 [1.20-2.71] for work ≥ 3 nights/week, and 2.55 [1.03-6.30] for both duration of night work ≥ 10 years and exposure intensity ≥ 3 nights/week. Breast cancer risk in pre-menopausal women was higher in current or recent night workers (OR = 1.41 [1.06-1.88]) than in those who had stopped night work more than 2 years ago. Breast cancer in post-menopausal women was not associated with night work whatever the exposure metric. The increase in risk was restricted to ER+ tumors, particularly those who were both ER+ and HER2+ . These results support the hypothesis that night shift work increases the risk of breast cancer in pre-menopausal women, particularly those with high intensity and long duration of exposure. Risk difference between pre- and post-menopausal women deserves further scrutiny.


Assuntos
Neoplasias da Mama/etiologia , Ritmo Circadiano , Jornada de Trabalho em Turnos/efeitos adversos , Tolerância ao Trabalho Programado , Feminino , Humanos , Medição de Risco
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