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M Demedts

Publications and source records attributed to M Demedts.

At least 19 recordsLinked to original sources
PubMed1992

The role of thiol oxidation in Cobalt(II)-induced toxicity in hamster lung.

Exposure of lung tissue to Co(II) ions both in vivo and in vitro results in toxicity, a relatively early event of which is the oxidation of cellular glutathione. In this study we have attempted to delineate the relationship between this oxidation of glutathione and the subsequent development of cellular dysfunction. Simultaneous incubation with H2O2 potentiated Co(II)-induced increases in both levels of oxidized glutathione (GSSG) and the activity of the pentose phosphate pathway in hamster lung slices. This effect was initially synergistic and, thereafter, both parameters were maintained at significantly greater levels than with either treatment alone throughout the incubation period until the onset of detectable cellular dysfunction. When dysfunction occurred, however, it was not quantitatively increased by the co-treatment over that occurring with CoCl2 alone. Similarly, pretreatment of slices with the glutathione reductase inhibitor 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) potentiated the Co(II)-induced increase in levels of GSSG. However, this effect was again not associated with an enhancement of cell dysfunction. Since the Co(II)-induced cell damage appeared not to be related directly to the oxidation of glutathione, the quantitative significance of the latter was investigated by comparison with the known oxidant tert-butyl hydroperoxide (t-BOOH). At a concentration of 100 microM, t-BOOH caused an increase in the concentration of GSSG in BCNU-pretreated lung slices which was comparable to that after treatment with Co(II)/H2O2 or CO(II)/BCNU. None of these treatments resulted in a loss of protein thiols. Furthermore, in contrast to Co(II), t-BOOH/BCNU treatment did not result in impaired cell functions. However, at a t-BOOH concentration of 250 microM, t-BOOH/BCNU treatment caused a significantly greater increase in the level of GSSG than that caused by the previous treatments and was associated with both a loss of protein thiols and increased cell dysfunction. We have concluded from these data that under our experimental conditions, Co(II)-induced cell dysfunction is not a consequence of oxidation of cellular glutathione. The reason for this appears to be that the extent of glutathione oxidation by Co(II) even at a concentration which induces cell dysfunction is not of sufficient magnitude to result in the oxidation of protein thiol groups, an event which is likely to constitute the critical consequence of glutathione oxidation in the toxic process.

Animals↗
PubMed1992

Lung injury induced by paraquat, hyperoxia and cobalt chloride: effects of ambroxol.

The effects of the surfactant stimulating drug ambroxol were studied in rats given paraquat (PQ, 15 mg/kg, s.c.), intratracheal cobalt chloride (CoCl2, 2.5 or 1.25 mg Co/kg) or exposed for 2 days to oxygen (greater than 95% O2). Ambroxol (50 mg/kg, i.p., twice daily) was given as a pretreatment for 4 days, or up to 7 days following pneumotoxic administration. Besides body weight evolution and lethality, various pulmonary indices were measured 2 days (O2) or 3 days (PQ and CoCl2) and 7 days after pneumotoxic treatment: wet and dry lung weight, total cell count, distribution of inflammatory cells and lactate dehydrogenase in bronchoalveolar lavage fluid, and histological damage assessed by a semiquantitative injury score. Neither form of ambroxol treatment prevented the toxicity of any of the pneumotoxic agents. The use of a combination of different indices of lung damage showed that different pneumotoxic agents may cause quite distinctive patterns of injury.

Ambroxol↗
PubMed1992

Relationship between axial motion and volume displacement of the diaphragm during VC maneuvers.

During semistatic inspiratory and expiratory vital capacity (VC) maneuvers, axial motion of the diaphragm was measured by lateral fluoroscopy and was compared with diaphragmatic volume displacement. Axial motion was measured at the anterior, middle, and posterior parts of the diaphragm, and the mean of these measurements was used. The volume displacement was calculated in two ways: first, from respiratory inductive plethysmograph-(Respitrace) derived cross-sectional area changes of rib cage and abdomen (Vdi,RIP) by means of a theoretical analysis described by Mead and Loring (J. Appl. Physiol. 53: 750-755, 1982) and, second, from fluoroscopically measured changes in position and anteroposterior surface of the diaphragm (Vdi,F). A very good linear relationship was found between Vdi,RIP and Vdi,F during inspiration as well as expiration (r greater than 0.95), indicating that the analysis of Mead and Loring was valid in the conditions of the present study. The diaphragmatic volume displacement (active or passive) accounted for 50-60% of VC. A very good linear relationship was also found between mean axial motion and volume displacement of the diaphragm measured with both methods during inspiration and expiration (r greater than 0.98). Our data suggest that, over the VC range, diaphragmatic displacement functionally can be represented by a pistonlike model, although topographically and anatomically it does not behave as a piston.

Adult↗
PubMed1992

Ventilatory effects of acetazolamide in cats during hypoxemia.

In normoxemic cats, acetazolamide (ACTZ) has been shown to cause a large rise in ventilation (VE) but a decrease in peripheral chemoreceptor activity. The relative contribution of the peripheral chemoreceptors to ventilation is higher during hypoxemia than during normoxemia. Therefore, what are the effects of ACTZ during steady-state hypoxemia? The aims of this study in anesthetized cats were 1) to study the effect of ACTZ (50 mg/kg iv) on mean hypoxemic [arterial PO2 (PaO2) approximately 6 kPa] ventilation and 2) to study the effect of ACTZ on the isocapnic hypoxic ventilatory response. In the first study, in six cats with an inspiratory CO2 fraction of 0, ACTZ led to an insignificant rise in mean VE of 119 ml.min-1.kg-1 after 1 h. In five other cats maintained at an inspiratory CO2 fraction of 0.015, ACTZ resulted in a significantly larger response in VE (268 and 373 ml.min-1.kg-1 after 1 and 2 h, respectively). In the second study, before infusion in five cats, an isocapnic fall in mean PaO2 from 13 to 4.7 kPa led to a significant rise in mean VE of 385 ml.min-1.kg-1; 1 h later, the response (at the same mean alveolar PCO2) was reduced to an insignificant rise of 38 ml.min-1.kg-1. Before infusion four other cats showed a significant rise in mean VE of 390 ml.min-1.kg-1 when mean PaO2 was lowered isocapnically from 12.4 to 6.8 kPa; 2 h after infusion, an isocapnic fall in mean PaO2 from 13.9 to 7.2 kPa led to an insignificant rise of 112 ml.min-1.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗
PubMed1992

Survey of cobalt exposure and respiratory health in diamond polishers.

This cross-sectional study was undertaken after the discovery of cobalt-related fibrosing alveolitis and bronchial asthma in diamond polishers occupationally exposed to cobalt. A total of 194 workers from 10 diamond polishing workshops and 59 workers from three other workshops from the diamond industry (control subjects) were studied; a questionnaire was administered and spirometry was performed. Cobalt exposure was assessed by environmental air sampling using both area and personal sampling and by measuring urinary cobalt concentration. When considered on a workshop basis, these environmental and biologic indices of exposure correlated well with each other. These measurements led to the definition of three cobalt exposure categories: a no exposure group, a low exposure group, and a high exposure group. The high exposure was, however, still below the present threshold limit value for cobalt (50 micrograms/m3). Spirometry showed that indices of ventilatory function (FVC and FEV1) were significantly (p less than 0.05) lower in the group with the highest exposure to cobalt. These differences were not due to differences in smoking habits. The results were confirmed when the data were analyzed by covariance analysis of lung function indices against smoking status, taking mean cobalt exposure in each workshop as a covariate, and when the data were analyzed by multiple regression analysis. This analysis showed that cobalt exposure correlated with decreased pulmonary function. Our results suggest that, during diamond polishing, exposure to cobalt at levels below the current threshold limit value is associated, on a group basis, with measurable effects on lung function parameters. The relationship between these cross-sectional epidemiologic findings and the occurrence of overt lung disease in diamond polishers remains to be established.

Air Pollutants, Occupational↗
PubMed1992

Four-stage tuberculin testing in elderly subjects induces age-dependent progressive boosting.

We administered four sequential tuberculin skin tests (5 TU, PPD) with intervals of one week to 223 subjects older than 65 years of age to evaluate whether elderly subjects demonstrated progressive boosting. Indurations of at least 10 mm with increases of at least 6 mm (over the previous test) were considered significant reactions, and these were found in 29 percent of the subjects after test 1, in 43 percent after test 2, in 53 percent after test 3, and in 57 percent after test 4 (p less than 0.05), ie, only about 50 percent of all the positives were detected after the first test. The percentage of positive reactors was inversely related to age (p less than 0.001), yet this age-dependent difference decreased with increasing number of tests. For the 65- to 74-year-old age group, 44 percent reacted positively after the first test and after three tests almost a plateau of 65 to 70 percent positive reactors was reached, suggesting that a minority only of about 30 to 35 percent of these geriatric patients might have outlived their bacilli or were never infected. For the 75- to 84-year-old age group, 24 percent reacted after the first test and 55 percent reacted after the fourth one. For the older than 85-year-old age group, 19 percent positive reactors were found after the first test and 46 percent were found after the fourth test, without clear-cut leveling off toward a plateau value, suggesting that additional tests would induce further boosting. Mean diameters of positive reactions were 15 to 24 mm, and were mostly at least 12 mm larger than in the previous tests. These data support the hypothesis that the negative tuberculin reaction, which is often found in elderly subjects, is mainly due to the failing immune response to tuberculin antigen that can be restored progressively by repeated administrations. These findings, furthermore, emphasize that especially in elderly, care should be taken not to interpret a boosting reaction as a conversion and especially that neither a two-step testing as recommended by the ATS and CDC (Am Rev Respir Dis 1990; 142:723-35) nor even a four-step testing may suffice to detect all positives in this type of population.

Aged↗
PubMed1992

Measurement of lung density by means of quantitative CT scanning. A study of correlations with pulmonary function tests.

In recent years, much attention has been given to the role of CT in detecting and quantitating pulmonary emphysema. We measured CT lung density in 45 patients undergoing a diagnostic work-up and compared this with pulmonary function tests. The CT lung densities measured with the sector method and with the whole lung method were very highly correlated with each other (r = 0.96, p less than 0.001), and measurements at TLC systematically gave a lower density than those at FRC (p less than 0.001). Also, CT density measurements at TLC and even more so at FRC correlated well with pulmonary function indices of airway obstruction and of hyperinflation, but not with indices that are considered more specific for emphysema (single breath DCO, static lung compliance) We conclude that CT lung-density gives a good reflection of the degree of hyperinflation, ie, enlargement of distal airways, but is not sensitive to detect whether or not this is associated with emphysema.

Female↗
PubMed1992

Pleuropulmonary changes during treatment of Parkinson's disease with a long-acting ergot derivative, cabergoline.

A patient with Parkinson's disease, initially treated with bromocriptine and subsequently with cabergoline, developed progressive pleuropulmonary abnormalities during the latter therapy. These lesions even worsened for some weeks after interruption of cabergoline, which may possibly be related to the prolonged action of this drug. Thus cabergoline may cause similar pleuropulmonary abnormalities to bromocriptine.

Bromocriptine↗
PubMed1991

Endobronchial tuberculosis mimicking lung cancer in elderly patients.

We report four elderly patients with cough who were referred with the presumptive diagnosis of bronchial carcinoma based on chest X-ray and the macroscopic view on fibreoptic bronchoscopy, but whose final diagnosis was endobronchial tuberculosis. Chest X-ray showed atypical pulmonary infiltrates in three patients, but was normal in one. Bronchoscopic examination revealed ulcerative and/or stenotic lesions. Endobronchial tuberculosis should be considered in differential diagnosis, especially in the elderly.

Aged↗
PubMed1991

Circulating immune complexes in chronic eosinophilic pneumonia.

In 9 out of 14 patients with chronic eosinophilic pneumonia (CEP), followed-up in our department, circulating immune complexes (CIC) and other immunologic indices were investigated. The diagnosis of CEP was based on the typical clinical and radiographic findings and on the demonstration of eosinophilia in serum, bronchoalveolar lavage (BAL), fiberoptic transbronchial biopsies and surgical lung biopsies. CIC measured by solid-phase monoclonal RF binding were always strongly positive during a flare-up of CEP, and CIC measured by solid-phase C1q binding were also positive in most cases. Remissions of CEP were accompanied by lowering or disappearance of CIC. CIC were significantly correlated with eosinophilia (p less than 0.001 for RF and p less than 0.02 for C1q). Other immunologic indices were normal except for increased IgE in two thirds of the patients, and a slightly positive rheumafactor without rheumatic disease in half of the patients. The CIC are thus related to disease activity, and can be used as one of the markers of it, in addition to the classical markers such as eosinophilia and chest X-ray. However, this does not imply that the CIC have a pathogenetic role in CEP; these CIC can, indeed, be an epiphenomenon only.

Adult↗
PubMed1991

Evaluation of the clinical usefulness of capnography curves during a hyperventilation provocation test in the diagnosis of hyperventilation syndrome.

We evaluated the diagnostic usefulness of capnography curves during and following a hyperventilation provocation test (HVPT) in the hyperventilation syndrome (HVS). The diagnosis of HVS was based on the Nijmegen questionnaire and on the reproduction of symptoms during HVPT. Capnography curves of 40 HVS patients, 40 non-HVS patients with psycho-somatic complaints and 26 healthy controls were analyzed. There was no difference in baseline end-tidal CO2-level (FETCO2) between the 3 groups. The spontaneous fall of FETCO2 during the adaptation phase was clearly different in HVS patients versus non-HVS patients or controls: -0.12 mmol/l (95% confidence limits -0.18 to -0.06) versus +0.01 mmol/l (95% confidence limits -0.04 to +0.16) (p = 0.002). The 3 minutes FETCO2 recovery ratio and the 5 minutes ratio were not significantly different between the groups. In conclusion, in this study the spontaneous fall of FETCO2 during the adaptation phase of the HVPT was the only valuable part of the capnography test to discriminate between HVS and non-HVS patients.

Carbon Dioxide↗
PubMed1991

Pitfalls of transthoracic needle aspiration biopsy.

Four cases are presented in whom transthoracic aspiration biopsy with the rotex needle provided a specific diagnosis, which, on thoracotomy was proved incomplete or wrong. Two cases of abscess were in fact excavated squamous cell carcinomas, one case of tuberculosis was in fact accompanied by a scar-adenocarcinoma, and a fourth case of supposed small cell carcinoma was found to be a muco-epidermoid carcinoma. In all cases, the final diagnosis after thoracotomy led to a change in therapy.

Adenocarcinoma↗
PubMed1991

Clinical spectrum of pulmonary tuberculosis in older patients: comparison with younger patients.

We compared the clinical-radiographic presentations of bacteriologically proven tuberculosis in 72 elderly (mean age: 71 yr) and 73 younger patients (mean age: 39 yrs). The tuberculin test (2 TU PPD) was positive in 55% and 92%, respectively. The prevalence of cough, dyspnea, anorexia, and weight loss was higher in the elderly (p less than .05), and night sweats were more prevalent in the younger patients (p less than .01). The radiographic pattern was not different between both groups (p greater than .10): "usual" apicoposterior lesions (with or without other abnormalities) were found in more than 70% of both groups; isolated "unusual" lesions consisted in both groups mainly of anterobasal infiltrations and sometimes of pleural effusions, rounded nodules, or miliary patterns. Yet, initially a wrong diagnosis was made more often in the elderly (p = .05). Malignancy, chronic pulmonary disease, and immunosuppression were more frequently encountered in the elderly (p less than .05), whereas alcoholism and smoking were more frequent in the younger patients (p less than .001). Tuberculosis-related mortality occurred in 6 elderly and 1 younger patient.

Adolescent↗
PubMed1991

Total respiratory resistance and reactance in patients with asthma, chronic bronchitis, and emphysema.

A comparison was made of total respiratory resistance (Rrs) and reactance (Xrs) determined between 6 and 26 Hz by means of a forced oscillation technique in 27 patients with asthma (group A), 28 patients with chronic bronchitis (group B), and 20 patients with emphysema (group E) to examine whether the method can provide data capable of distinguishing among these diseases. The three groups demonstrated a similar reduction in the FEV1. In addition, static and dynamic lung volumes, maximal expiratory flows, diffusing capacity for CO, airway resistance (Raw), and elastic lung recoil were measured. The observed alterations of Rrs and Xrs consisted of an increase in Rrs, a decrease in Rrs with frequency, and a decrease in Xrs. However, significant differences were found between the three groups: Rrs at 6 Hz and average Rrs were most increased in group A, whereas the negative frequency dependence of Rrs and the decrease in Xrs were least pronounced in group E. In all groups Rrs at 6 Hz, the average slope of Rrs, and the average level of Xrs were tightly interrelated and showed in addition a high correlation with airway resistance; the correlations with FEV1 were less satisfactory. Discriminant analysis performed on the complete set of data, excluding diffusing capacity and elastic lung recoil, which were used as selection criteria, demonstrated that forced oscillation parameters were the most important factors discriminating among the groups.

Adult↗
PubMed1991

Indices of oxidative stress in hamster lung following exposure to cobalt(II) ions: in vivo and in vitro studies.

Cobalt, a metal with numerous industrial applications, has been associated with lung disease, an extreme form of which is an interstitial fibrosis. The biochemical mechanisms underlying this toxicity are not understood. In vitro studies have suggested that cobalt(II) ions are able to generate reactive oxidant species (possibly hydroxyl radical) in a reaction with hydrogen peroxide, and we have hypothesized that the occurrence of such an event in lung tissue, and the subsequent development of oxidative damage, may contribute to this pulmonary toxicity. The intratracheal instillation of CoCl2 into hamster lungs resulted after 3 h in decreased levels of reduced glutathione and increases in levels of oxidized glutathione and in the activity of the pentose phosphate pathway. These changes, which are compatible with the generation of oxidative stress, were reversed by 48 h at low Co2+ doses (1.0 to 1,000 micrograms/kg). Irreversible changes at higher doses coincided with the onset of pulmonary edema. Incubation of lung slices with CoCl2 (0.1 to 10 mM) resulted in time- and Co2+ concentration-dependent increases in levels of oxidized glutathione and protein-mixed disulfides and a decrease in reduced glutathione. A concentration-dependent stimulation of the pentose phosphate pathway was also observed. These changes preceded the detection of overt cell toxicity, as assessed by various biochemical parameters. These data indicate that thiol oxidation constitutes an early event in the pulmonary toxicity of cobalt(II) ions and are compatible with the hypothesis that the generation of oxidative stress may be of significance to the toxic process.

Animals↗