[Bronchial anthracosis and pulmonary mica overload]. / Anthracose bronchique et surcharge pulmonaire en micas.

INTRODUCTION: The discovery of anthracotic plaques generally suggests either a history of tuberculosis or occupational exposure to dust. Other etiologies should, however, be considered. CASE REPORTS: A 60-year-old Iranian woman presented with a history of dyspnoea and with chest radiography demonstrating calcified hilar lymph nodes and interstitial lung disease. Pulmonary function tests revealed airway obstruction. A diffuse bronchial inflammatory appearance accompanied by anthracotic plaques was found at bronchoscopy, which prompted transmission electron microscopy analysis of non-fibrous mineral particles in the bronchoalveolar lavage fluid (BALF). This demonstrated the presence of an alveolar particle count greater than 10(7) particles/ml (p/ml), significantly more than that found in 42 BALF samples taken from controls without a history of occupational dust exposure (4,4.10(5) p/ml). Furthermore, the analysis also revealed an abnormally elevated proportion of mica particles (64%). Two other individuals, a 68 year-old Moroccan woman and a 70-year-old Algerian woman, who had anthracotic plaques, but no radiological evidence of interstitial lung disease, also underwent mineral analysis of BALF. Neither were found to have a raised alveolar particle count, but the mineral profile showed an abnormally elevated proportion of micas (62%) for one patient, and silica crystalline (40%) as well as micas (32%) for the other patient. CONCLUSIONS: Even if mica is present in 30 to 90% of the BALF, the results observed in these three patients raises the possibility of non-occupational environmental exposure and that anthracotic plaques might be associated with domestic pollution.

Role of fibre characteristics on cytotoxicity and induction of anaphase/telophase aberrations in rat pleural mesothelial cells in vitro: correlations with in vivo animal findings.

Thirteen samples of natural fibres and five samples of man-made fibres (MMF) were tested to determine their cytotoxicity and ability to produce chromosome missegregation in cultures in rat pleural mesothelial cells (RPMC). The natural samples included attapulgite, two amphiboles (amosite and crocidolite); seven consisted of chrysotile from various origins and three were obtained after chemical treatment of chrysotile. MMF included three refractory ceramic fibres (RCF) and two vitreous fibres (MMVF). All fibre samples were characterized by electron microscopic measurement of the fibre dimensions. Cytotoxicity was assayed on the basis of determination of mitochondrial integrity and chromosome missegregation by light microscopy examination of anaphases/telophases. The carcinogenic potency of 10 natural samples has been previously investigated using intrapleural inoculation in rats. It was therefore possible to establish correlations between in vitro and in vivo data obtained with the same set of samples. The various samples of chrysotile produced different in vitro effects, in agreement with the dispersion of response also observed in vivo. Cytotoxicity appears to be dependent on both fibre length and fibre diameter, as the longest or thickest fibres were the most toxic. The production of abnormal anaphases/telophases appears to depend on the presence of fibres of selected size, such as those previously defined by Stanton et al. (L > 8 micrograms; D < or = 0.25 microns); a threshold values was determined below which no abnormal anaphases/telophases were detected. This non-observable effect level was estimated to be 2.5 x 10(5) 'Stanton' fibres per cm2. There was no correlation between cytotoxicity and mesothelioma induction; in contrast, a correlation was found between the ability of a sample to produce chromosome missegregation in vitro and mesothelioma in vivo.

Pleural plaques, asbestos exposure, and asbestos bodies in bronchoalveolar lavage fluid.

The profiles of occupational asbestos exposure were investigated in a series of 66 hospital patients in whom pleural plaques constituted the only asbestos-induced abnormality. The relationship between a radiological semiquantitative score of pleural plaques and indices of asbestos exposure was also examined. On the basis of a standardized occupational questionnaire, four classes of asbestos exposure were distinguished in our study population: no evidence of exposure, low-level exposure, sporadic exposure at higher levels, and a remaining group of individuals with substantial exposure. Asbestos body count in bronchoalveolar lavage fluid (BALF) was used as an objective indicator of cumulative lung retention of asbestos. Our results support the data indicating that pleural plaques may occur in subjects with low-level or sporadic asbestos exposure. Although it is admitted that pleural plaques are strongly associated with past asbestos exposure, our data suggest that the stage of pleural plaques was not correlated to the level, frequency, duration of exposure nor to the amount of asbestos bodies in the BALF in subjects free of any lung parenchymal abnormalities on high resolution computerized tomography.

[Osteoarthritis with rice bodies rich in calcium microcrystals. 4 cases with ultrastructural study]. / Arthropathies mécaniques avec grains de riz riches en microcristaux calciques. Quatre cas avec étude ultrastructurale.

Rice bodies are often found in inflammatory joint fluid specimens, especially from rheumatoid arthritis patients, but have rarely been reported in osteoarthritis. We found rice bodies in knee joint fluid specimens from four of 88 patients with osteoarthritis. There were three males and one female. Age ranged from 61 to 86 years. Three patients had slowly progressive knee osteoarthritis and one had rapidly destructive disease. Abundant, recurrent effusions occurred in all four patients despite one to five local corticosteroid injections per patient and radiation synovectomy in two patients. The joint fluid specimens contained 120 to 320 cells/mm3 and large numbers of rice bodies that stained with alizarin red S. Transmission electron microscopy studies showed that the rice bodies were composed of fibrin and contained numerous intra- and extra-cellular calcium crystals composed of apatite alone in two cases and of a combination of apatite and calcium pyrophosphate dihydrate in the two others. Collagen fibers and fragments of bone and cartilage were present in a few rice bodies. Phagocytic cells, type C synoviocytes, chondrocytes and a few inflammatory cells were also seen. These rice bodies composed mainly of fibrin and apatite may have played a role in the pathogenesis of the recurrent joint effusions in our patients.

Lung retention of cerium in humans.

A retrospective study was conducted to evaluate lung retention of particles containing cerium in subjects with and without previous occupational exposure to mineral dusts. Analytical transmission electron microscopy was performed on 459 samples of bronchoalveolar lavage (BAL) fluid and 75 samples of lung tissue. Study of the distribution of mineralogical species in human samples showed that particles containing cerium were encountered in less than 10% of subjects. The proportion of subjects with particles containing cerium in their biological samples was not different between controls and subjects with previous occupational exposure to fibrous or nonfibrous mineral dusts. This was considered as the background level of lung retention of cerium in the general population. By contrast, determination of the absolute concentration of particles containing cerium in BAL fluid and lung tissue samples showed that 1.2% (from BAL fluid) and 1.5% (from lung tissue) of subjects with previous exposure to mineral particles had high lung retention of particles containing cerium. This study is believed to be the first one in which lung retention of cerium was estimated in the general population.

Non-fibrous dust load and smoking in dental technicians: a study using bronchoalveolar lavage.

A study was conducted with transmission electron microscopy to find whether bronchoalveolar lavage could be used to identify subjects with occupational exposure to mineral particles. Non-fibrous mineral particles in bronchoalveolar lavage (BAL) fluid from 46 dental technicians and 41 white collar controls with lung diseases but free from occupational exposure to dusts were analysed. The total particle concentration in BAL fluid was significantly higher in dental technicians than in controls (12.18 x 10(5) particles/ml of BAL fluid, v 2.03 x 10(5) particles/ml, p < 0.001). Dental technicians had significantly more crystalline silica, aluminium, and alloys containing nickel and chromium. There was a non-significant twofold increase of total particle concentration in the lungs of dental technicians who were smokers compared with non-smokers. The results strongly support the use of BAL fluid analysis to assess dust accumulation in workers in heavily exposed occupations such as dental technicians. This is a valid method to evaluate occupational exposure to non-fibrous mineral particles, and may be useful to determine the occupational aetiology of some respiratory diseases.

Induction of metaphase and anaphase/telophase abnormalities by asbestos fibers in rat pleural mesothelial cells in vitro.

The cytogenetic effects of asbestos fibers on rat pleural mesothelial cells were studied in vitro. Crocidolite UICC significantly enhanced aneuploidy and produced few structural chromosome aberrations, whereas anatase, an isomorphic particle, induced no numerical or structural changes. Mitomycin C (300 nM) produced a tenfold increase in abnormal anaphases compared with controls. Asbestos produced anaphase/telophase abnormalities in a concentration-dependent manner. The majority of the abnormalities involved lagging chromosomes. Crocidolite UICC induced abnormalities at a dose of 7.0 micrograms/cm2, whereas Canadian chrysotile did so at 1.0 to 2.0 micrograms/cm2. When the response was assessed by the number of long and thin fibers per cm2 (length > 8 microns; diameter < or = 0.25 microns), crocidolite UICC produced more abnormalities than Canadian chrysotile at all concentrations. On a per-weight basis, these findings differ from those obtained after intrapleural inoculation, as crocidolite induced more mesotheliomas than chrysotile; however, on a per-fiber basis, the in vitro and in vivo effects were similar. These results show that anaphase/telophase analysis is sensitive and complementary to metaphase analysis, and suggest that asbestos might produce cell transformation by inducing chromosome missegregation and aneuploidy.

In vitro response of rat pleural mesothelial cells to talc samples in genotoxicity assays (sister chromatid exchanges and DNA repair).

The genotoxicity of three samples of talc has been determined using in vitro cell systems previously developed for testing asbestos fibres. The talc samples used consisted of particles of respirable size in order to test the effect of particles likely to be deposited in the lung. Genotoxicity was tested in cultures of rat pleural mesothelial cells (RPMC) using genotoxicity assays for unscheduled DNA synthesis (UDS) and sister chromatid exchanges (SCEs). The effects were compared with those obtained with negative controls (attapulgite and anatase) and positive controls (chrysotile and crocidolite asbestos). In contrast to asbestos, none of the talc samples, nor the negative controls, induced enhancement of UDS or SCEs in treated cultures in comparison with the untreated cultures.

Mesothelioma in rats following intrapleural injection of chrysotile and phosphorylated chrysotile (chrysophosphate).

Pathological effects of asbestos are probably dependent on the size and surface properties of the fibers. Surface-modified chrysotile fibers were injected into the pleural cavity of rats to investigate the potency of the fiber to induce mesothelioma. Chrysotile fibers were modified by a phosphorylation process, resulting in the presence of phosphorus at the fiber surface. Phosphorylated samples were characterized by enhanced durability and reduced affinity for biological macromolecules. Five samples were tested: 1 untreated and 4 phosphorylated. ChrP1, ChrP2 and ChrP3 corresponded to phosphorylated samples obtained by first, second and third passages through an Alpine classifier; Pm was defibrillated ChrP1. The number of fibers per microgram and the size distribution were determined by transmission electron microscopy and classified in 4 size groups. Groups of 35 rats were inoculated with 20 mg of fibers suspended in 0.9% NaCl solution. No mesothelioma was found in the saline controls. All fiber samples were proficient in producing mesothelioma; the percentages were different between groups and untreated chrysotile but not significantly so. The differences may be explained on the basis of the number of fibers injected which were greater than 8 microns in length and less than 0.25 microns in diameter. The findings of a proficiency of long fibers to produce mesothelioma, previously reported by others for glass fibers, could be applied to chrysotile.

Sister chromatid exchanges in human lymphocytes treated with silica.

The abilities of Min U Sil quartz or tridymite particles to induce sister chromatid exchanges (SCEs) in cultures of human lymphocytes plus monocytes or of human purified lymphocytes were investigated. With cultures of lymphocytes plus monocytes the level of SCEs was significantly enhanced after treatment with tridymite at the highest dose tested (50 micrograms/cm2). No effect was observed with purified lymphocytes. Quartz did not give clear cut results. Complementary experiments with tridymite filtrates suggested that phagocytosis of tridymite particles by monocytes was a necessary step for the induction of SCEs in human lymphocytes.

Translocation of subcutaneously injected chrysotile fibres: potential cocarcinogenic effect on lung cancer induced in rats by inhalation of radon and its daughters.

Exposure to radon 222 and its daughters has been shown to induce lung cancer in rats. The cocarcinogenic effect of intrapleurally injected mineral fibres in rats which have previously inhaled radon has also been established. The aim of this work was to establish whether a similar process could be induced at a distance from the lungs by subcutaneous injection of chrysotile fibres. Three groups of animals were used: (1) 109 rats which inhaled radon only (dose: 1600 working-level months (WLM]; (2) 109 rats given a subcutaneous injection in the sacrococcygeal region of 20 mg of chrysotile fibres after inhalation of the same dose of radon; and (3) 105 rats injected with fibres only. No mesotheliomas occurred in any of the 3 groups. The incidence of lung cancer was 55% in group 2, 49% in group 1 and 1% in group 3. Statistical analysis using Pike's model showed that the carcinogenic insult was slightly higher in group 2 than in group 1. Electron microscopy analysis of fibre translocation from the injection site showed that less than 1% of injected fibres migrated to the regional lymph-nodes and only about 0.01% to the lungs. After injection, the mean length of the fibres recovered in lung parenchyma increased with time, suggesting that short fibres are cleared by pulmonary macrophages whereas long fibres are trapped in the alveolar walls. Although the high tumour incidence observed in group 1 might have masked the cocarcinogenic effect induced by the fibres, it is possible that this effect can occur only at short distances.(ABSTRACT TRUNCATED AT 250 WORDS)

[The metrology of mineral fibres in thoracoscopic lung and pleural biopsies. Preliminary results (author's transl)]. / Métrologie des fibres minérales dans des biopsies thoracoscopiques pulmonaires et pleurales. Résultats préliminaires.

Metrology of mineral fibres by electron microscopy was carried out in thoracoscopy specimens ("normal" parietal pleura, pleural plaque, tumour, lung) obtained from different sites in 19 patients: 9 exposed to asbestos and 10 non-exposed controls. With regard to results concerning the parietal pleura, the differences in exposure of the patients (as revealed by history) were not reflected by metrological characteristics (nature and number of fibres, size, topographical distribution) and it was impossible to distinguish the exposed cases from the controls. The number of fibres ("non-measurable presence" being 130.10(3) fibres/g) did not differ significantly between the two "exposed" and "non-exposed" groups. By contrast, the number of fibres found in lung biopsies was in general very high in exposed patients (up to 379.10(3) fibres/g.) In 3 non-exposed patients, there was no asbestos in the lung. Broadly speaking, metrological data were similar to those previously obtained in other cases and using surgical or autopsy specimens. This reinforces the validity of the method of metrology in thoracoscopic specimens and confirms the complexity and difficulties of assessment of pleural involvement. The advantages of study of early pleural specimens obtained under thoracoscopic control in comparison with surgical or autopsy specimens remains to be determined in a larger number of cases. The safety of the method should be emphasized, no complications having been seen in this series.

Asbestos retention in human respiratory tissues: comparative measurements in lung parenchyma and in parietal pleura.

Asbestos fibres in respiratory tissues from 29 cases diversely exposed to asbestos dusts have been characterized, sized and counted using a transmission electron microscope. Comparison of data obtained by measurement of fibres in lung parenchyma and in parietal pleura samples showed the following: -- In each case, the proportion of chrysotile fibres (as opposed to amphiboles) was higher in parietal pleura than in lung parenchyma. (The proportion of chrysotile in pleura was greater than 90% in 30 of the 40 samples.) -- Fibres encountered in parietal pleura were shorter than those in the parenchyma. -- There was no evident correlation between numerical concentrations of fibres in lung parenchyma and those in parietal pleura. This study has shown that characteristics of asbestos retention in parietal pleura cannot be derived from measurements in lung parenchyma. On the basis of the cases analysed here, who were exposed to mixed types of asbestos dust, chrysotile seems to be the asbestos type retained almost exclusively in parietal pleural tissues. These findings might be taken into account when assessing the risk of pleural diseases (especially mesothelioma) attributable to each type of asbestos fibre.