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Biomedical subjects

J Bignon

Publications and source records attributed to J Bignon.

At least 109 records · Page 6Linked to original sources

High frequency chest wall oscillation in patients with chronic air-flow obstruction.

In order to assess high frequency chest wall oscillation (HFCWO) as a way to assist spontaneous breathing in obstructive lung disease, we studied 12 patients with severe and stable COPD. HFCWO at 5 Hz were applied by means of an inflatable vest. In order to avoid any discomfort, oscillations were applied only during the expiratory phase of the spontaneous breathing cycle. We compared gas exchange and pattern of breathing during control and HFCWO periods, each lasting 15 min. Minute ventilation did not change, but the pattern of breathing was markedly altered during HFCWO: breathing frequency decreased (p less than 0.001) from 18 +/- 6/min during control to 14 +/- 5/min, whereas tidal volume increased (p less than 0.01) from 600 +/- 200 ml during control to 860 +/- 400 ml. Secondary to this change in the pattern of breathing, arterial PO2 increased slightly (p less than 0.01) from 54 +/- 7 mm Hg during control to 57 +/- 8 mm Hg during HFCWO, and arterial PCO2 significantly (p less than 0.01) decreased from 46 +/- 6 mm Hg during control to 43 +/- 7 mm Hg during HFCWO. In addition, duty cycle (Ti/Ttot) decreased (p less than 0.001) from 0.37 +/- 0.03 s during control to 0.29 +/- 0.05 s during HFCWO. Such a decrease in duty cycle suggest that inspiratory muscle work was facilitated under HFCWO. In 8 patients, we obtained the tension-time index (TTdi), or the product of duty cycle and Pdi/Pdimax, and found that this index significantly decreased (p less than 0.05) from 0.06 +/- 0.03 during control to 0.04 +/- 0.02 during HFCWO.(ABSTRACT TRUNCATED AT 250 WORDS)

Dyspnea↗

Pleural carcinogenic potency of mineral fibers (asbestos, attapulgite) and their cytotoxicity on cultured cells.

The carcinogenicity of several samples of mineral fibers was tested following injection of 20 mg in the pleural cavity of noninbred Sprague-Dawley rats. Three samples of chrysotile asbestos (mean length: 3.2, 2.1, and 1.2 micron) induced mesotheliomas at a rate of 48, 52, and 19%, respectively. The first sample was acid leached prior to intrapleural injection; in that group, the percentage of mesotheliomas was reduced to 25%. Treatment with amosite and crocidolite resulted in the occurrence of 57 and 56% of mesotheliomas. Acid-treatment of amphiboles did not significantly modify the percentage of mesotheliomas. When the Stanton's fiber dimensions were taken into consideration to correlate with mesothelioma incidence, the observed number of mesotheliomas in the chrysotile-treated animals was much lower than that expected, suggesting that other fiber parameters (chemistry, physicochemistry) play a role in the carcinogenicity. Attapulgite fibers (mean length: 0.77 micron) did not induce tumor, and the mean survival time was of the same order as that observed in the control groups. The injection of quartz resulted in no mesothelioma but did result in 6 malignant histiocytic lymphomas (17%) and 2 malignant schwannomas (6%). In vitro experiments did not show strong correlation between cytotoxicity and the carcinogenic potency of these minerals, but the qualitative cellular responses might give some indications on the fiber's potency. In addition, the in vitro effects of the fibers seem to be modulated by their size.

Animals↗

[Obstructive bronchiolitis].

The term "obstructive bronchiolitis" used in this review covers different clinicopathological aspects. On the one hand, it refers to "small airways disease", where bronchiolar narrowings are widespread, secondary to post inflammatory fibrotic changes linked to tobacco smoke or fibrogenic dust inhalation. These obstructive changes at the level of small airways are responsible for a fixed airflow limitation. The specificity and sensibility of functional tests designed for early detection of such an obstruction (the frequency dependence of compliance, the nitrogen slope and the density dependence of the flow-volume curve) are still controversial. On the other hand, the entity covers a disease described at the beginning of the century under the name "bronchiolitis obliterans". It usually appears as a consequence of various causes: viral infection, toxins acting either inhalation or by systemic route, immunological mechanisms as in connective tissue diseases or in graft versus host reactions. A special emphasis is put on idiopathic bronchiolitis obliterans associated with organizing pneumonia. Some clinicopathologic correlations are of basic interest in relation to etiological factors: bronchiolitis obliterans due to viral infection in children involving mainly membranous bronchioles; by contrast, bronchiolitis obliterans related to other causes seems to extend further down from the terminal bronchioles to the respiratory bronchioles. Lymphoid bronchiolitis appears non specific and is mostly observed in association with systemic connective tissue diseases, such as rheumatoid arthritis.

Bronchiolitis↗

[Mineralogical study of non-fibrous particles in bronchoalveolar lavage fluid].

A chemical and mineral analysis of non-fibrous particles was performed using transmission electron microscopic analysis in 77 broncho-alveolar lavages (BAL) requested as an aid to diagnosis. A qualitative mineral analysis of the BAL defined the ubiquitous elements (iron, silicates, silica) or frequent (titanium, aluminium, nickel, chromium, calcium) for which a semi-quantitative analysis of the BAL was shown to be necessary in the interpretation of the results. On the other hand a qualitative analysis was generally sufficient for rare particles, their presence being evidence of occupational or environmental exposure. A study of the correlation between the doctors' assessments and the qualitative results of the BAL shows that, with the exception of silica, exposure to ubiquitous or common particles is poorly estimated. Better orientated mineralogical studies will occur with requests for BAL by the medical staff. Greater knowledge of the background exposure in control non-exposed subjects will enable better utilisation of the results of this technique.

Bronchoalveolar Lavage Fluid↗

The interactions between asbestos fibers and metaphase chromosomes of rat pleural mesothelial cells in culture. A scanning and transmission electron microscopic study.

Rat pleural mesothelial cells (PMCs) in culture at the exponential growing phase were exposed to 5 micrograms/ml of chrysotile (CH) or crocidolite (CR) asbestos fibers: the cells and their chromosomes were studied 48 hours thereafter by light, scanning, and transmission electron microscopy (LM, SEM, TEM). PMCs phagocytized both CH and CR. Mild vacuolar cytoplasmic changes by LM and a few small surface blebbings by SEM were present, mainly in cells treated with CH. Metaphase chromosomes were well separated and retained surface details by SEM in the control group. Chromosomes were frequently entangled with, adherent to, and severed or pierced by long and thin curvilinear CH with occasional chromatin fibers threading over the partly severed asbestos. Similar chromosomal changes were much less frequently found in CR-treated cells; TEM confirmed the same findings. CH and CR have different physicochemical properties and also appear to have direct, intricate, but different interactions with chromosomes, as well as the cytoplasm, of PMCs.

Animals↗

Chromosomal changes induced by chrysotile fibres or benzo-3,4-pyrene in rat pleural mesothelial cells.

The induction of chromosomal aberrations in rat pleural mesothelial cells (RPMC) following in vitro treatment with chrysotile fibres has been demonstrated. The production of chromosomal aberrations was also observed after treatment of the cells with benzo-3,4-pyrene (BP). The yield of abnormal metaphases was dose-dependent and reached 58% at a BP dose of 2 micrograms/ml. Chrysotile fibres at 7 micrograms/ml induced 21% abnormal metaphases and the frequency decreased with further increases in fibre concentration. Their decline is possibly related to a lethal effect. Chrysotile-induced chromosomal aberrations were primarily of the chromatid type and included breaks and fragments. BP induced chromosome exchanges which were not seen following chrysotile treatment. Minutes and double minutes were detected in BP-treated RPMC and occasionally found after chrysotile application. These results confirm that chrysotile fibres are clastogenic for some cultured cells and demonstrate that the fibres induce chromosome damage in target RPMC.

Animals↗

In vitro growth characteristics of rat mesothelioma cells in culture.

The study reports morphological growth characteristics and chromosome analysis of neoplastic rat pleural mesothelial cells (RPMC) isolated from a mesothelioma-bearing rat. The pleural mesothelioma was induced by intrapleural injection of chrysotile fibers. Neoplastic RPMC were cultured by the standard methods used for normal RPMC. Neoplastic RPMC cultures had a population doubling time of 19 hr versus 30 hr for the normal cells. Plating efficiency in liquid medium was almost 100%. Cultures of neoplastic RPMC were anchorage-independent since 70% of the seeded cells formed colonies after one week; after the second week, colony size was enhanced but colony recovery was not. The serum dependence of neoplastic cells was less than that of the normal cells. 79 out of 100 metaphase cells analyzed had 41 to 43 chromosomes, and the modal number was 42 (38%). A large metacentric chromosome was observed in 77 of the 100 neoplastic metaphase cells analyzed, but not in any normal metaphase cells. In nude mice, the neoplastic RPMC were tumorigenic.

Animals↗

Bronchoalveolar lavage fluid and serum complement activity in pulmonary sarcoidosis.

In this work, using bronchoalveolar lavage fluids (BALF), we demonstrated the presence of complement within airways by assaying hemolytic activity of the whole classical pathway (CH50) and by measuring the complement component C2 (C2H50). Patients with sarcoidosis, patients with idiopathic pulmonary fibrosis (IPF), and healthy control subjects were compared. No CH50 activity was found in BALF from healthy control subjects (n = 9), but some activity (mean, 20 CH50) was associated with IPF (n = 7). Complement activities ranged from 40 to 554 CH50 in patients with sarcoidosis (n = 27). During the treatment, complement activity decreased in BALF from the few patients in our series who received corticotherapy. C2 hemolytic activity was detected in BALF from the normal control group (in the absence of CH50 activity). In the sarcoidosis and IPF groups when CH50 was present, the variations in the C2/CH50 ratio were studied. The high ratio observed in BALF from patients with sarcoidosis and a chronic derangement of alveolar structure suggests either an increased C2 production or an alternative complement pathway (C2-independent) activation within their lungs.

Adult↗

An enzyme immunoassay for auto-antibodies to keratin in normal human serum and in pleural fluids from patients with various malignant or non-malignant lung diseases.

An enzyme-linked immunosorbent assay (ELISA) for anti-keratin antibodies was prepared by coating microplates with epidermal keratin purified from the stratum corneum from human foot. Naturally occurring auto-antibodies bind keratin via their f(ab')2 fragment. They were assayed in the serum from 65 healthy people. The serum titer increased significantly with aging. Auto-antibodies stained all the layers of a normal human epidermis whereas an immune serum, prepared by injecting a rabbit with pure human keratin proteins, stained more efficiently the outer layers of the human skin; pre-immune rabbit serum did not stain human skin at all. The lowest anti-keratin activities were observed in serum from patients with squamous cell lung carcinoma and with mesothelioma. The activity was lower in pleural fluid from patients with pleural mesothelioma than in pleural fluid from other types of cancer. This is possibly due to the fixation of autoantibodies onto the pleural tumor or on cell debris arising from the tumor.

Animals↗

[Results of bacteriological technics and demonstration of pneumococcal antigens by counterimmunoelectrophoresis in 40 cases of Streptococcus pneumoniae pneumonia].

This study is conducted on 45 patients with Streptococcus pneumoniae pneumonias. Counter-immunoelectrophoresis (CIE) (detection of pneumococcal polysaccharides antigens in serum and/or urine and/or pleural fluid) and conventional bacteriological technics (blood culture and/or thoracentesis and/or transtracheal function) have been performed in all cases. Streptococcus pneumoniae has been identified with conventional bacteriological technics in 27 patients. Pneumococcal antigens have been identified in 28 patients. Both technics have been positive in 10 patients. The detection of antigens has been positive in 7 on 8 pleural fluids. The CIE is very useful in patients who has been treated by antibiotics before bacteriological examination of samples (6 CIE + and 1 bacteriological technic +). The association of the two technics is very useful. The percentage of cases with CIE / and bacteriology - is 40% (18 cases). The percentage of cases with bacteriology + and CIE - is 37.7% (17 cases).

Adult↗

Alternating radiotherapy and chemotherapy schedules in small cell lung cancer, limited disease.

Sixty-three evaluable patients with limited small cell lung carcinoma were entered into two pilot studies alternating 6 cycles of combination chemotherapy (Doxorubicin 40 mg/m2 d 1; VP16213 75 mg/m2 d 1, 2, 3; Cyclophosphamide 300 mg/m2 d 3, 4, 5, 6; and Methotrexate 400 mg/m2 d 2--plus folinic acid rescue--or Cis-Platinum 100 mg/m2 d 2) with 3 courses of mediastinal radiotherapy as induction treatment. The first course of radiotherapy started 10 days after the second cycle of chemotherapy; there was a 7 day rest between chemotherapy and radiotherapy courses. This 6 month induction treatment was followed by a maintenance chemotherapy. The total mediastinal radiation dose was increased from 4500 rad in the first study to 5500 rad in the second. Both protocols obtained a complete response (CR) rate of greater than 85% (with fiberoptic bronchoscopy and histological verification). Local control at 2 years was 61% in the first study and 82% in the second. Relapse-free survival at 2 years was 32 and 37%, respectively. Toxicity was acceptable. We conclude that our results justify further clinical research in alternating radiotherapy and chemotherapy schedules.

Antineoplastic Combined Chemotherapy Protocols↗

In vitro transformation of rat pleural mesothelial cells by chrysotile fibres and/or benzo[a]pyrene.

Rat pleural mesothelial cells (RPMC) were treated, in vitro, in a two-stage model of carcinogenesis. RPMC obtained from passage 12th were treated once with 1 microgram/ml of benzo-[a]pyrene (BP) and from passage 13th to 40th with 0.4 microgram/cm2 of chrysotile fibres (Chr). Transformation was determined by the observation of the colonies formed when the cells were plated at low density. Colonies were classified into four classes according to the level of lack in contact inhibition between cells (0 to III). BP as well as chrysotile fibres were potent in inducing a high proportion of type III colonies which were not observed in control series. In addition, there was no synergistic effect between BP and Chr. These results would indicate that chrysotile fibres do not act as a promoter on rat pleural mesothelial cells in culture, but induce morphologically transformed colonies.

Animals↗

[Chronic obstructive bronchopneumopathies. What should be measured? When and how?].

Tobacco smoking, which is the main cause of chronic obstructive lung disease, produces two different disorders, each following an independent course: hypersecretion of mucus and impairment of ventilation. The most significant as regards prognosis is the latter. Its early detection requires fine respiratory function tests, notably flow-volume loops. At the chronic lung obstruction stage, conventional spirometry provides information on the degree of obstruction, and other additional tests can be used to investigate for possible emphysema. The potential repercussions of the disease on gas exchanges must be assessed by measuring arterial blood gases. Such measurements are usually performed on subjects awake and at rest, but they can be supplemented by exercise tests or examinations during sleep. A critical analysis of the values obtained is useful to decide whether oxygen therapy is needed and to follow up this treatment in patients with chronic respiratory failure.

Bronchi↗

In vitro biodegradation of chrysotile fibres by alveolar macrophages and mesothelial cells in culture: comparison with a pH effect.

The modification of the chemistry of asbestos chrysotile fibres (Mg3(Si2O5)(OH)4) after their ingestion by cultured cells has been studied. Two types of cells involved in asbestos related pulmonary disease were used, rabbit alveolar macrophages (AM), recovered by bronchoalveolar lavage, and pleural mesothelial cells (PMC) obtained from the rat parietal pleura. Chemical characterisation of intracellular fibres was performed on unstained ultrathin sections by electron probe microanalysis. The results showed a progressive leaching of Mg, characterised by a time dependent decrease of Mg/Si. AM were more efficient than PMC at leaching intracellular chrysotile fibres since it took longer to obtain the same proportion of leached fibres with PMC than with AM. As in vitro Mg-leaching can be obtained by acid treatment, chrysotile fibres were incubated, either untreated or pretreated with cell membranes, at pH 4 or 7 for various times. The data show that the kinetic of leaching by AM was comparable with leaching at pH 4. The leaching by PMC was of the same order as leaching at pH 7. When membranes were adsorbed on to the fibres, a delayed leaching was observed. The results indicate that the solubilisation of chrysotile by AM could be an intraphagolysosomal event due to a pH effect. With PMC, however, it is not possible to draw this conclusion since nothing is known about the intracellular pH.

Animals↗

Role of pleural mesothelial cells in the production of the submesothelial connective tissue matrix of lung.

The pleura is comprised of a single layer of mesothelial cells resting on a complex layer of connective tissue. The ability of mesothelial cells to produce the components of this connective tissue was investigated using cultured rat mesothelial cells. These cells produced several components of extracellular matrix, including 6.8 +/- 0.2 X 10(5) collagen pro-alpha-chains per cell per hour, which represented 3.09 +/- 0.05% of all proteins synthesized by these cells. Chemical and immunologic criteria were used to demonstrate that these collagen chains included those of collagen types I, III, and IV. In addition, these cells produced elastin, as well as the connective tissue glycoproteins laminin and fibronectin. Moreover, electron microscopic studies revealed that lung mesothelial cells were capable of organizing these components into complex structures that resembled components of the extracellular matrix (thick collagen fibers, the amorphous component of elastic fibers, and basement membranelike structures), and restricted the formation of these structures to the basal region below the cells in culture. Thus, pleural mesothelial cells are active sources of a variety of connective tissue macromolecules found beneath mesothelial cells in situ, and can assemble these components into structures resembling the pleural extracellular matrix.

Animals↗