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Biomedical subjects

P Brochard

Publications and source records attributed to P Brochard.

At least 37 records · Page 2Linked to original sources

SV40-like DNA sequences in pleural mesothelioma, bronchopulmonary carcinoma, and non-malignant pulmonary diseases.

Pleural and pulmonary malignancies are usually associated with well-known carcinogen exposure. Recently, the presence of simian virus 40 (SV40)-like DNA sequences has been detected in brain and bone-related human cancers and in pleural mesothelioma. In order to determine whether SV40-like DNA sequences are also present in bronchopulmonary carcinoma and non-malignant lung samples, 125 frozen pleural and pulmonary samples (including 21 mesotheliomas, 63 bronchopulmonary carcinomas, 8 other tumours, and 33 non-malignant samples) and 38 additional samples distant from tumours were studied for the occurrence of SV40-like DNA sequences by polymerase chain reaction (PCR) amplification followed by hybridization with specific probes. Sequences related to SV40 large T antigen (Tag) were present in 28.6 per cent of bronchopulmonary carcinomas, 47.6 per cent of mesotheliomas, and 16.0 per cent of cases with non-neoplastic pleural and pulmonary disease. No statistically significant difference in the occurrence of these DNA sequences was found between malignant mesothelioma and bronchopulmonary carcinoma, but a significantly higher number of mesothelioma cases exhibited SV40-like DNA sequences in comparison with cases of non-malignant pleural or pulmonary disease (P < 0.04). Among cases positive for SV40-like DNA sequences, a history of asbestos exposure was found in 3 out of 12 bronchopulmonary carcinomas and 8 out of 10 mesotheliomas. Immunohistochemistry using monoclonal antibodies directed against Tag did not demonstrate nuclear staining. The DNA sequences were not related to BK virus sequences, but three samples were positive with probes hybridizing with JC virus DNA sequences. In conclusion, this study demonstrates the presence of SV40-like DNA sequences in pulmonary neoplasms and in non-malignant lung tissues. It appears that the presence of SV40-like DNA is not unique to cancer.

Adult↗

[Occupational exposure to cadmium and renal cancer. Apropos of a case].

INTRODUCTION: Cadmium is a carcinogenic substance and bronchial and prostatic cancer may be readily identified as professional diseases. It is also a nephrotoxic substance but renal carcinoma are rarely imputed to this kind of intoxication. CASE REPORT: We report the observation of a 59-year-old woman with a long unprotected professional exposure to cadmium. She developed an epidermoid carcinoma of the kidney and later of the lung. Levels of cadmium in blood samples were abnormally high, confirming the existence of a chronic impregnation. CONCLUSION: We have judged cadmium to be responsible for her renal disease: the fact of a long unprotected professional exposure, the scarcity of renal epidermoid carcinoma, the well established nephrotoxicity of this substance and the association with other cancers, appear to us as convincing evidence, and the kidney cancer of our patient has been considered a professional disease.

Cadmium↗

Guidelines for mineral fibre analyses in biological samples: report of the ERS Working Group. European Respiratory Society.

Microscopic techniques for analysing asbestos fibres in lung tissue and bronchoalveolar lavage have provided major information in the understanding of asbestos-related diseases. These analyses are increasingly applied for clinical work and medicolegal problems. Differences in sampling, preparation and counting techniques, definitions of reference populations and expression of results have caused major difficulties in comparing results from different laboratories. Therefore it appeared necessary to set a goal to harmonize these analyses between the European laboratories active in this field. This article summarizes the work of a European Respiratory Society working group with participation from nine European laboratories. The five main issues touched upon are: 1) definitions of control populations and reference levels; 2) sampling, preparation and analytical techniques; 3) asbestos fibres in lung tissues in different pathologies; 4) asbestos bodies in lung tissue, bronchoalveolar lavage and sputum; and 5) basis for the interpretation of fibres and asbestos bodies in biological samples. These guidelines indicate the crucial importance of several factors for the interpretation of the results; namely, adequate sampling, comparable analytical procedures and expression of the results, the use of well-defined reference populations, and a comprehensive understanding of the factors affecting the fibre retention and the dose-responses associated with the different asbestos-related diseases.

Asbestos↗

[Delayed health effects of pesticides: review of current epidemiological knowledge].

The use of pesticides has extensively grown in the last decades, regardless of the economic level of the countries. This led to great improvements in agriculture but also a threat for human health. Short term effects are quite well known through approval procedures for pesticides. On the other hand, long term effects are not properly assessed. A review of epidemiologic knowledge is presented here. Epidemiologic studies on pesticides have found associations with long-term effects on health mainly in three fields: cancer (especially hematological cancer), neurotoxic effects (polyneuropathy, neuro-behavioral hazards, Parkinson's disease), and reproductive disorders (infertility, birth defects, adverse pregnancy outcomes, perinatal mortality). These conclusions have been obtained despite difficulties in exposition assessment due to the retrospective nature of the studies. But the continuous development of pesticide use in agriculture, and also in domestic environment, emphasizes the need for epidemiologic studies on long-term effects of pesticides relying on accurate exposure assessment.

Environmental Exposure↗

[Mineral analysis and study of asbestos pathology].

Several tools are available for the evaluation of the exposure to asbestos, particularly occupational questionnaire and mineralogical analysis of biological samples. These analysis allow quantification of the level of retention of asbestos fibres in the respiratory tract. Two groups of analysis may be used: quantification of asbestos bodies in sputum, bronchoalveolar lavage fluid or lung tissue samples using light microscopy; quantification and identification of asbestos fibres in bronchoalveolar lavage fluid or lung tissue using analytical electron microscopy. Profiles of lung retention of asbestos bodies or asbestos fibres have been described in various asbestos-related disorders, and reference values are available in control populations mainly for asbestos bodies using light microscopy. Mineralogical analysis of biological samples is not required for compensation of occupational asbestos-related diseases. However, this type of analysis may prove to be useful to the chest physician when looking for the etiology of some nonspecific respiratory diseases (interstitial pulmonary fibrosis, lung cancer), particularly when the occupational questionnaire is not contributive. As they are quite easier and less expensive, analysis using light microscopy will be performed first.

Asbestos↗

[Rolled atelectasis and asbestosis. Apropos of 26 patients].

Round atelectasis (AE) is a benign form of respiratory problem which develops due to fixing of the visceral pleura. This lesion for which the principal cause is exposure to asbestos may pose problems of differential diagnosis with bronchopulmonary cancer. In a cohort of 286 patients suffering from benign asbestos related pleural disease the diagnosis of round atelectasis was made on computerized tomography in 26 patients (31 AE) on the following criteria: rounded opacities of less than 7 cm in diameter situated at the periphery of the lung in contact with a thickened pleura with an acute angle linking the pleura and the opacity, a reduction of lung volume on the side of the atelectasis and the presence of a "comet tail sign". These patients were investigated to specify the circumstances of the occurrence, including their symptomatology, the changes in lung function, the topography of the round atelectasis and the associated radiological signs. Intense exposure to asbestos either continuous or discontinuous was found in 19 patients; 20 patients presented with some respiratory symptoms (dyspnoea 15/26, cough 11/26 and chest pain 9/26) but the reduction in lung function was moderate (7 had restrictive ventilatory trouble, 4 obstructive problems and a mixed problem in 1). The preferred localisation for round atelectasis was in the inferior lobes in the posterior basal lateral vertebral area (26/31) which may explain their being frequently missed on the standard radiograph (only one case of round atelectasis was visible on the straight chest radiograph in our study). An understanding of the pathology and the computered tomographic characteristics are now well defined and should enable an unnecessary diagnostic thoracotomy to be avoided which besides has no justification from the functional point of view.

Asbestosis↗

Detection of SV40-like DNA sequences in pleural mesothelioma, bronchopulmonary carcinoma and other pulmonary diseases.

Mesotheliomas are pleural-based tumours mainly associated with asbestos exposure (70% of cases) and the incidence is still raising. Recently, a possible viral connection was reported and 60% of mesotheliomas were demonstrated to contain and express SV40-like DNA sequences. In this study, the presence of SV40-like DNA sequences were investigated in mesotheliomas (15 tissue samples and six cell lines) and in 63 additional bronchopulmonary carcinomas, one parietal osteosarcoma and non-malignant lung samples as well as in organizing pleuritis (8). Finally, 163 samples were analysed by the polymerase chain reaction (PCR) with a set of primers PYV.for and PYV.rev to amplify a 173 bp region of the SV40 Tag. and a 179 bp region JC virus (JCV) as well as a 182 bp region BK virus (BKV). PCR amplification and hybridization with a probe specific for SV40 Tag revealed that 47.6% of mesotheliomas, 28.6% of primary bronchopulmonary carcinomas and 16% of non-neoplasic lung diseases contained SV40-like DNA sequences. No statistically significant difference in the occurrence of these DNA sequences was found between malignant mesothelioma and bronchopulmonary carcinoma. However, a significantly higher number of mesothelioma cases exhibited SV40- like DNA sequences in comparison with non-malignant pleural and pulmonary tissues. The DNA sequences were not related to BK and JC virus sequences. These results indicate that SV40-like DNA sequences are present in mesotheliomas as well as in bronchopulmonary carcinomas and non-malignant pleuropulmonary diseases.

Antigens, Polyomavirus Transforming↗

[Asbestos-associated occupational lung diseases. Role of the pneumology unit in screening and compensation].

The application of new decrees concerning the protection of individuals against sanitary risks linked to the various possible expositions to asbestos dusts is leading to a growing involvement of pulmonologists in diagnosis procedures not only for active workers regularly examined via the occupational medicine healthcare system, but also for those who are no longer, the unemployed or retired previously exposed to asbestos fibres. The present chapter presents and comments the revised guidelines about the compensation procedures for occupational diseases, and provides useful recommendations for establishing the records leading to their medical assessment. It emphasises the importance of a close cooperation between pulmonologists and radiologists in order to avoid radiation overdosing, which could increase the risk of lung cancer, as much as possible.

Asbestos↗

[Epidemiological approach to mesothelioma].

Mesothelioma, the primitive cancer of pleura, peritoneum or pericardium, is a tumor for which many etiologic studies have been conducted, because of close relations with environment. If asbestos remains the essential risk factor, many uncertainties persist on extent of phenomena in next decades. Furthermore, emergence of new etiologies, confirmed on human (erionite, ionizing radiations) or only suspected in experimentation (some biopersistent synthetic fibers, some virus as the SV40), ask new questions which are susceptible to modify our view of mesothelioma epidemiology.

Asbestos↗

Consequences of occupational asthma on employment and financial status: a follow-up study.

The aim of this study was to describe changes in employment and income following a diagnosis of occupational asthma, and to determine what factors might affect these changes. Two hundred and nine patients with occupational asthma were reviewed on average 3.1 yrs after the diagnosis had been made. They were contacted by telephone or were sent a self-administered questionnaire by post. Multiple logistic regression models were constructed to determine which variables were associated with loss of employment after the diagnosis. At the time of review, 44% of patients had left their previous job and 25% were currently unemployed. Remarkably, 32% remained exposed to the offending agents in the same job. Forty six percent of the patients had suffered a reduction of income (84% of those who had left their employer versus 19% of those still employed in the same company (p < 0.001)). Claims for compensation, size of the company, level of education, and age at the time of diagnosis were significantly associated with a risk for becoming unemployed or having a new employer after the diagnosis of occupational asthma. Occupational asthma results in severe socioeconomic consequences. The French compensation system for occupational asthma should be revised, as the criteria currently used to determine compensation for this disease largely underestimate the social and occupational damages.

Adolescent↗

The use of a new static device based on the collection of the thoracic fraction for the assessment of the airborne concentration of asbestos fibres by transmission electron microscopy.

A new static device, the CATHIA sampling head, based on the collection of the thoracic fraction is proposed for the assessment of the airborne concentration of asbestos fibres by transmission electron microscopy. By comparison with a standard aerosol sampling head, it has been shown that this sampler reduces the total mass concentration, but does not introduce any change in the most common index used to characterize an asbestos aerosol fibre, that is the concentration of fibres with length greater than 5 microns, diameter less than 3 microns and length to diameter ratio greater than 3. The homogeneity of the deposited dust on the collection filter favours the use of this sampling head with both the indirect and direct preparation methods.

Air Pollutants, Occupational↗

Mineralogical analysis of the respiratory tract in aluminium oxide-exposed workers.

A retrospective study was conducted in order to characterize the retention of fibrous and nonfibrous mineral particles in the respiratory tract in subjects with previous occupational exposure in the aluminium industry. Bronchoalveolar lavage (BAL) fluid (three samples) or lung parenchyma (two samples) were studied using analytical transmission electron microscopy in five patients. A high concentration of aluminium fibres (> 10(7) fibres.g-1 dry lung) was identified in two lung tissue samples, and aluminium fibres were also identified in BAL fluid in three patients. All fibres were short (mean length: 1-2 microns), with no fibre longer than 5 microns. Some biopersistence of these fibres in the respiratory tract is suggested from these observations, since fibres were identified in biological samples collected more than 4 yrs after cessation of exposure in four out of five patients. Occupational physicians should be aware of possible exposure to short, thin aluminium fibres during primary aluminium production. Further studies are needed to assess the potential health effects of these fibres. Industrial hygiene measurements should also be performed to document the potential sources of exposure to aluminium fibres in this industry.

Adult↗

Ubiquitous fiber exposure in selected sampling sites in Europe.

OBJECTIVES: This study evaluates personal exposure to respirable inorganic and organic fibers during normal human lifetimes and assesses the order of magnitude of the contribution of inorganic fibers other than asbestos to total fiber exposure from man-made and natural sources. METHODS: Four groups (suburban schoolchildren, rural retired persons, office workers, and taxi drivers), with five persons per group, were monitored for 24 h four times during one year. Personal sampling pumps collected airborne dust on gold-precoated Nuclepore filters. The fibers were analyzed for fiber sizes specified by the World Health Organization. RESULTS: The geometric mean concentrations ranged from 9000 fibers.m-3 (office workers) to 20000 fibers.m-3 (schoolchildren) for organic fibers, and from 600 fibers.m-3 (taxi drivers) to 4000 fibers.m-3 (schoolchildren) for gypsum fibers. For other inorganic fibers the concentrations were around 5000 fibers.m-3. The contribution of fibers with an elemental composition similar to that of man-made vitreous fibers (MMVF) was less than about one-quarter of the content of other inorganic fibers. The fiber size distributions were uniform across the groups, and the organic fibers were the longest and thinnest nonasbestos fibers. CONCLUSIONS: Lifetime exposure to fibers can be ranked as organic fibers > other inorganic fibers > fibers with an elemental composition similar to MMVF > MMVF. Information on the biological effects of fibers is difficult to interpret for use in assessing the health risk from exposure to low levels of ubiquitous fibers, and there is a lack of knowledge on the effects of organic fibers.

Adolescent↗

Respiratory symptoms, ventilatory impairment, and bronchial reactivity in oil mist-exposed automobile workers.

Studies concerning the respiratory effects of oil mists are sparse and contradictory. The aim of this study was to determine the respective effects of occupational exposure to straight cutting oils and soluble mineral oils on the prevalence of respiratory symptoms, ventilatory impairment, and bronchial reactivity. The population study consisted of 308 male workers of a large French car-making plant, including 40 subjects chronically exposed to straight cutting oils (group S), 51 subjects chronically exposed to soluble mineral oils (group E), 139 subjects with chronic dual exposure to straight cutting oils and soluble mineral oils (group D), and 78 unexposed assembly workers used as a control group (group C). Worker evaluation included a standardized questionnaire, measurement of pulmonary function, and a methacholine challenge. Oil mist concentration at the work place was determined by gravimetric analysis. The arithmetic mean concentration was 2.6 +/- 1.8 mg/m3. The geometric mean concentration was 2.2 +/- 1.9 mg/m3. The prevalence of respiratory symptoms did not differ significantly among the four groups. However, the subjects exposed to straight cutting oils (group S + group D) had a significantly higher prevalence of chronic cough and/or phlegm than the others (group E + group O): 25.7% vs. 16.3% (p = 0.048). Furthermore, the prevalence of cough and/or phlegm increased significantly (p = 0.03) with increasing duration of exposure to straight cutting oils after adjustment on smoking categories. Lung function tests did not differ significantly among the four groups but we observed a significant decrease of forced expiratory volume in 1 sec (FEV1), forced expiratory flow during the middle half of forced vital capacity (FEF25-75), and maximal flow rate at 50% and 25% of exhaled forced vital capacity (V50 and V25) according to duration of exposure among smokers exposed to straight cutting oils, suggesting a synergistic effect of tobacco and insoluble oils. No effect of exposure to mineral oils on bronchial reactivity was demonstrated. It is concluded that despite low levels of pollution by oil mists, the present study has shown tenuous adverse chronic effects of straight cutting oils on respiratory symptoms and lung function. However, no adverse effect of soluble mineral oils was demonstrated. These results suggest that threshold limit values for mineral oils should be reassessed.

Adult↗

Biopersistence of cerium in the human respiratory tract and ultrastructural findings.

For diagnostic purposes, mineralogical analysis was performed in bronchoalveolar lavage fluid and lung tissue from a 58-year-old patient previously exposed to asbestos and rare earth dusts. No significant retention of asbestos was demonstrated in lung tissue by light microscopy (asbestos bodies) or transmission electron microscopy analysis (uncoated fibers). Particles containing rare earth (cerium, lanthanum) and phosphorus were identified in alveolar macrophages in bronchoalveolar lavage fluid, and cerium-containing particles accounted for 70% of particles observed in the lung tissue. Ultrastructural analysis of lung tissue revealed the presence of particles containing cerium and phosphorus in interstitial macrophages and elastic fibers. These results suggest that rare earth is metabolized and should be considered as biopersistent in the human respiratory tract, since occupational inquiries revealed that exposure to cerium oxide abrasive powder had ceased at least 15 years earlier.

Asbestos↗

Proposal of a tiered approach to assessing and classifying the health risk of exposure to fibres.

The basis of a preventative health policy for humans against potential risks from chemical products is based on risk assessment leading to the classification and labeling of substances. However, the different existing classifications do not give an homogeneous framework that can be used in every country. Therefore, a tiered approach to assessing and classifying the health risk of exposure to fibres is proposed based on the EU Directive on carcinogens. The aim of this paper is to propose an algorithm for the risk assessment of existing and future fibres. Clearly chemically defined respirable fibres should be classified according to an algorithm based on a step-by-step procedure: a priori criteria, screening tests, long-term inhalation tests and epidemiological data (for commercial fibres). Then fibre-containing products should be labelled according to the classification of each type of fibre it contains, on one hand, and the ability of the product to release fibre in the air, on the other. The different tests listed in this algorithm, extensively discussed during the Workshop, are presented in detail in the following paper.

Carcinogenicity Tests↗

Organic solvent exposure may increase the risk of glomerular nephropathies with chronic renal failure.

BACKGROUND: Several studies have suggested that exposure to organic solvents is associated with glomerular nephropathies (GN), but this relationship remains controversial. METHODS: A case-control study of 298 biopsy-proven cases and 298 hospital controls, matched for year of birth, sex, origin, and place of residence, was conducted between 1989 and 1991 in five hospitals in the Paris area: 82 cases of membranous glomerulopathy were included; 100, nephrotic syndrome with either minimal change nephropathy or focal and segmental hyalinosis (MCN/FSH); and 116, IgA nephropathy (IgA N). Subjects were interviewed about their lifelong occupational and non-occupational activities. A 'blind' assessment of type, level, and duration of solvent exposure was carried out by two industrial hygienists. Human leucocyte antigen (HLA) phenotypes were determined. RESULTS: Among males, a clear association, which was not explained by social class, was observed between chronic renal failure and high exposure to solvents for both MCN/FSH (OR = 7.7, 95% CI: 1.4-41.6) and IgA N (OR = 3.5, 95% CI: 1.0-11.8). The odds ratios increased with duration of exposure. No relationship was observed between such exposure and GN cases with normal renal function. No evidence was found that the HLA phenotype plays a role in the association between solvent exposure and the disease. CONCLUSIONS: These results support the hypothesis of a causal relationship between high solvent exposure, which concerned 15% of the males in this study, and the development of GN with chronic renal failure.

Adult↗