[Radiologic image of diffuse pulmonary infiltration. Diagnostic orientation].
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Biomedical subjects
Publications and source records attributed to B Wallaert.
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No single laboratory examination is diagnostic. On the other hand, such examinations support the diagnosis and aid in management of treated patients. In the serum, there is lymphopenia with a lowered CD4/CD8 ratio. An increase in beta 2-microglobulin and in the soluble IL-2 receptor reflect T lymphocyte activation. A classic observation is hypercalcaemia with hypercalciuria. The increase in angiotensin I converting enzyme reflects the body granulomatous mass. The results of bronchoalveolar lavage show the characteristics of the alveolitis associated with granulomatosis, accumulation of CD4+ T lymphocytes and activated alveolar macrophages. In practice, biochemical anomalies are of interest in the follow-up of treated patients.
The aim of this investigation was to assess the cytotoxic effect of nickel hydroxy carbonate (NiHC) on guinea pig alveolar macrophages (AMs) by studying ultrastructural modifications and by determining beta-glucuronidase (BG) and lactate dehydrogenase (LDH) activities, as well as cellular ATP content. The ultrastructural studies revealed phagocytosis of NiHC particles and a general vacuolisation of the cells, especially at high concentrations. X-ray microprobe analyses of these particles demonstrated the presence of Ni, P and Ca which suggests the formation of Ni-P-Ca complexes. In exposed cells, a biphasic change in intracellular ATP concentrations was observed which could indicate 'activation' of AMs at low concentrations and inhibition of energy generation at higher concentrations. As for enzymatic activities, a dose-dependent increase in LDH release was observed except at low doses which increased ATP. There was a good correlation between ATP decrease and LDH release, consistent with a dose-dependent cytotoxic effect of NiHC. However beta-glucuronidase activity remained unchanged at all NiHC concentrations. It has been concluded that NiHC undergoes an intracellular, biological transformation to form Ni-P-Ca. Further investigations are needed to determine the precise nature and importance of these complexes.
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Primary cold urticaria (PCU) characterized by the association of urticaria, angioedema, and sometimes a shock-like reaction after cold exposure, is usually considered to be linked with histamine and prostaglandin D2 release by mast cells. To determine the involvement of cytokines, we studied the release of tumor necrosis factor-alpha (TNF-alpha) in the blood of the efferent vein after immersion of the hand in chilled water. Five patients with PCU were compared with a control population (three patients with nonphysical urticaria and three healthy subjects). Among patients with PCU who underwent the cold immersion test, two exhibited a shock-like reaction with a large urticarial plaque (patients 1 and 2), one had only a mild cutaneous reaction, and two had no reaction. Patient 1 was reevaluated after 6 months of treatment with H1 and H2 antihistamines: he did not respond to this challenge. All controls were strictly negative. Histamine was released within the first minute after the challenge in the three patients with PCU, but at a higher level for the two patients who had a systemic reaction. TNF-alpha was undetectable in the blood of the patient with only a mild cutaneous reaction, whereas TNF-alpha release was observed for the two patients with a systemic reaction, 2 and 6 minutes after the end of the cold immersion test. The two other patients and the control subjects released neither histamine nor TNF-alpha. In parallel, pathologic and immunohistochemical (with a rabbit anti-TNF-alpha antibody) studies were performed on skin biopsy specimens collected 10 minutes after ice-cube test.(ABSTRACT TRUNCATED AT 250 WORDS)
In smoking subjects with obvious emphysema, the interaction between neutrophil-derived MPO and H2O2 produced by alveolar inflammatory cells (alveolar macrophages (AM) and polymorphonuclear neutrophils (PMN)) has the ability to spontaneously inactivate, in vitro, the alpha 1 proteinase inhibitor (alpha 1PI). This inactivation can induce a desequilibrium of the protease-antiprotease balance in the lungs. In this study, we investigated the ability of glutathione to protect alpha 1PI. In a cellular model of alpha 1PI inactivation mimicking the effects of alveolar inflammatory cells present in the lower respiratory tract of smoking patients with emphysema, we demonstrated that glutathione can protect alpha 1PI against the oxidative inactivation by these activated cells. This protection has been computed in a cellular experimentation (AM and MPO-system) with a 50% inhibitory concentration of 62 microM. Moreover, glutathione has an important inhibitory effect directly on H2O2 released by PMA-stimulated AM (IC50 = 30 microM) or PMA stimulated PMN (IC50 = 70 microM). The mechanism, which governs glutathione may be a result of a scavenging effect on H2O2 as demonstrated in a free cellular experiment. With this in vitro demonstrated effectiveness, glutathione as a therapeutic antioxidant, via the aerosol, has been proposed, in order to prevent tissue damage, inflicted by an excess of activated phagocytic cells, in some lung diseases such as smoking patients with emphysema.
PURPOSE: To investigate the role of computed tomography (CT) in determining disease activity and functional impairment and in predicting the prognosis of lung involvement in patients with sarcoidosis. MATERIALS AND METHODS: Two groups of patients underwent CT, pulmonary function tests, and bronchoalveolar lavage. Disease activity was based on serum angiotensin converting enzyme activity and/or lymphocytosis at bronchoalveolar lavage. CT findings in group 1 were correlated with indexes of disease activity and functional parameters at diagnosis. In group 2, evaluation initially and at follow-up led to investigation of correlations between initial CT findings and evolution of disease activity and functional impairment. RESULTS: CT abnormalities in group 1 were nodules, air-space consolidation, lung distortion, septal and nonseptal linear areas of high attenuation, ground-glass attenuation, and honeycombing. Profusion of septal lines was the only CT finding that correlated with disease activity. Statistically significant (P < .05) but low correlation (r < .48) was observed between the extent of abnormalities at CT and impairment of lung function, except for nodules. CONCLUSION: Profusion of lung changes reflects functional impairment but not disease activity. CT findings cannot help predict the evolution of lung changes over time.
Various studies have suggested the involvement of immunoglobulin G4 (IgG4) antibodies (Ab) in the physiopathology of allergic disorders. Recently, an abnormal IgG4 Ab production in response to immunization has been reported in some atopic patients. Thus, in order to evidence in allergic patients, a potential abnormal IgG4 Ab response to aeroallergens following natural exposure, we compared, in 34 patients sensitive to Dermatophagoides pteronyssinus and in 16 healthy subjects, the IgG4 Ab response to D. pteronyssinus, grass pollen and cat dander, using a solid-phase radioimmunoassay. Since some patients were also sensitive to grass pollen and/or to cat dander, we analyzed, in all patients, the IgG4 Ab responses both towards the allergen(s) they were sensitive to (sensitizing allergen) or not (unrelated allergen). The results showed that 90% of the patients produced levels of antisensitizing allergen(s) IgG4 Ab significantly higher than the controls; this IgG4 Ab response was correlated with the corresponding specific IgE Ab level. In addition, among these patients, around 40% presented high levels of IgG4 Ab to the unrelated allergen(s). Thus, in allergic patients, while specific IgE Ab define the nature of the sensitizing allergen, the presence of IgG4 Ab directed against various allergens seems in relation with an abnormal isotype regulation associated with atopic disorders.
T-lymphocytes are important components of the inflammatory cell infiltrate in bronchial mucosa in asthma. Because activated lymphocytes migrate through the thoracic duct and the general circulation to remote glandular and mucosal sites, we initiated this study to evaluate the histologic abnormalities of a minor salivary gland (MSG) associated with bronchial asthma. Fifty-eight asthmatic patients were prospectively studied (37 women, 21 men; mean age, 54 +/- 6 yr). Twenty-nine patients had allergic asthma (AA) and 29 had nonallergic asthma (NAA). Results were compared with those obtained from 15 healthy control subjects and 15 nonasthmatic patients with chronic obstructive pulmonary disease (COPD). MSG was normal in 14 of 15 patients with COPD and in 14 of 15 control subjects. Forty-three of 58 (74%) asthmatic patients presented MSG abnormalities. These were significantly more frequent in asthmatics (74%) than in patients with COPD and healthy control subjects (6%, p < 0.001 versus asthmatics) and in NAA (97%) than in AA (52%, p < 0.01). The main pathologic features of MSG in asthma were T-lymphocyte infiltration (57%: AA nine of 29; NAA 24 of 29), partly degranulated mast cells (64%: AA, 11 of 29; NAA, 26 of 29), basement membrane thickening (64%: AA, 11 of 29; NAA, 26 of 29), and endothelial cell changes (26%: AA, one of 29; NAA, 14 of 29). Eosinophils were found only in two cases. Expression of ICAM-1 was demonstrated in nine of 16 patients with NAA, whereas VCAM-1 and E-selectin were negative in all of them.(ABSTRACT TRUNCATED AT 250 WORDS)
To identify the clinical relevance of cytokines involved in the development of lung fibrosis observed in patients with coal workers' pneumoconiosis (CWP), we investigated the BAL fluid contents and AM secretions of three mediators that modulate fibroblast growth: platelet-derived growth factor (PDGF), Type I insulin-like growth factor (IGF-I), and transforming growth factor Type beta (TGF-beta). Our study population consisted of 25 patients with CWP (16 simple pneumoconiosis, SP, 9 progressive massive fibrosis, PMF, 9 control subjects, and 6 patients with idiopathic pulmonary fibrosis (IPF). The fibrotic potency of AM supernatants was also tested for their ability to promote the growth of a human lung fibroblast cell line appreciated by [3H]-thymidine incorporation. PDGF and IGF-I concentrations were increased in BAL fluids of patients with PMF compared with SP and control subjects, whereas TGF-beta concentration was significantly higher in BAL fluid of patients with SP compared with PMF and control subjects. PDGF, IGF-I, and TGF-beta concentrations in AM supernatants followed the same profile observed in BAL fluids, suggesting that AM is one of the main cell sources of PDGF, IGF-I, and TGF-beta in the lung of pneumoconiotic patients. After treatment by acidification, which activated the latent form of TGF-beta, AM from patients with SP induced an inhibition of [3H]-thymidine incorporation and fibroblast growth was restored after neutralization of TGF-beta by specific antibodies. In contrast, AM supernatants from patients with PMF and IPF promoted the proliferation of fibroblasts and treatment by acidification did not modify this effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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Chronic interstitial pneumonia (PIC) are rare in infants. We report a case of an infant who presented with a chronic interstitial pneumonia following an infection with a respiratory syncytial virus. The diagnosis was confirmed histologically (open lung biopsy). The failure of oral steroid therapy (Prednisolone 2 mg/kg/day) led to the use of boluses of methylprednisone (30 mg/kg/day, daily for three days in three series one month apart). The treatment led to a progressive improvement and thirty months after the last bolus the respiratory examination was normal as was the radiology. The efficacy of bolus steroid therapy observed by other authors should be confirmed in multicentre trials using surgical biopsy to precise the pulmonary lesions.
Methotrexate was suggested as a treatment in 1976 by Mullarkey for severe steroid-dependent asthma, in order to reduce the use of systemic steroids responsible for numerous undesired side-effects. The aim of this open trial was to study the efficacy and tolerance of Methotrexate in the short, medium and long term and after its cessation, in ten patients aged 49.2 (+/- 3.0) who were suffering from severe steroid-dependent asthma (18.5 +/- 4.8 mg of prednisone daily for at least one year). Methotrexate was given in a dose of 15-30 mg for 14.3 months (+/- 1.8) with a post-treatment follow-up for eight patients lasting 7.9 months (+/- 1.7). The efficacy was assessed on the daily dosage of prednisone and was also evaluated using the FEV1 (VEMS) (the variations expressed were a percentage of the variation from the predicted value). In the short term (six weeks) there was no significant change in the FEV1 nor in the dose of prednisone. In the medium term (12 weeks) there was evidence of a reduction in the average daily dosage of prednisone of 39.5% with an increase in the FEV1 of 14.1%. In the long term MTX was not found as effective in reducing the dose of prednisone (15.2 mg) as on the FEV1 (an increase of 5.1% on the theoretical values). There was a favourable outcome for two patients who maintained the benefit after stopping the MTX. Seven out of ten patients presented with side effects of MTX, in three of whom the drug has to be stopped.(ABSTRACT TRUNCATED AT 250 WORDS)
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Idiopathic pulmonary fibrosis (IPF) response to corticosteroids and cytotoxic medications appears to be the most important determinant of survival. The purpose of this retrospective study was to analyse the determinants of response to immunosuppressive therapy with prednisone alone, or prednisone and cyclophosphamide, in IPF. Twenty five consecutive patients were studied. Initial evaluation in untreated patients included clinical, biological and functional parameters. Sequential evaluation by pulmonary function tests (forced vital capacity (FVC) and transfer factor of the lungs for carbon monoxide (TLCO)) was performed at a 3 month interval. Response to therapy was defined as an improvement in FVC and/or TLCO of more than 10% after 12 months, with maintenance of this improvement for at least another 12 months. Twelve of the 25 patients were classified as responders. A symptomatic disease of less than 12 months duration before onset of therapy related to response. FVC was more impaired in the group of responders when the comparison was limited to patients with an FVC of less than 90%. Bronchoalveolar lavage cell counts were not significantly different between responders and non-responders. Assessment of pulmonary function after 3 months of treatment was predictive of maintenance of the response or of even further improvement. Patients with improved FVC after 3 months of therapy had a significantly shorter symptomatic disease before onset of treatment (7.6 +/- 7.1 vs 20.2 +/- 18.6 months). A beneficial effect of addition of cyclophosphamide was observed only in patients who demonstrated an early but short-lived improvement to steroids. Adverse reactions of immunosuppressive therapy were noticed in 10 patients, and required discontinuation of treatment in six of them.(ABSTRACT TRUNCATED AT 250 WORDS)
Iatrogenic pneumonias to sulphasalazine are most usually seen during the course of a haemorrhagic proctocolitis (RCH). We report a case in which a young woman was treated with 5-aminosalicylate (Pentasa) and prednisolone during an exacerbation of RCH. After 3 months of treatment the steroid therapy was stopped and the Pentasa was continued at the same dose (3 g per day). She presented with increasing dyspnoea on effort. Clinical examination was normal but a CT scan of the chest showed interstitial micro nodules; there was also a restrictive ventilatory disorder, hypoxaemia on effort and an alveolar eosinophilia (1.8%) The clinical progress, respiratory and blood gases all improved rapidly after stopping the Pentasa with the disappearance of the interstitial nodule over 5 months, suggesting that the role of the Pentasa was causal in the genesis of the pneumonia.
Erdheim-Chester's disease is a rare form of visceral xanthogranulomatosis. We report a case of a patient aged 50 presenting with a diffuse interstitial pneumonia which revealed Erdheim-Chester's disease with localisation in the bones, peri-aortic region and also with neurological involvement. The diffuse interstitial pneumonia which progressed chronically was characterised by a diffuse thickening of the septa with subpleural cysts and bilateral apical bullae with thickening of the pleura. Respiratory function tests showed a restrictive ventilatory defect with resting hypoxaemia which was aggravating by exercise. Broncho-alveolar lavage showed a lymphocytosis (26%) also with polymorpho neutrophils (11%). The pathological diagnosis was confirmed by transbronchial lung biopsy showing an excess of foamy histiocytes in the interstitium which are characteristic of the disease. The progress of this interstitial pneumonia is stabilised without immunosuppressive drugs.