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Biomedical subjects

B Wallaert

Publications and source records attributed to B Wallaert.

At least 127 records · Page 7Linked to original sources

[Interstitial lung disease linked to fluoxetine].

Fluoxetine (Prozac) is a new anti-depressant introduced on the marked in France since 1989. We report a case of a patient who developed progressive dyspnea without any other symptoms who had been treated with Prozac for nine months. Clinical examination found bilateral basal crepitations. Laboratory assessments showed evidence of inflammation (ESR: 50 mm per hour; CRP 8.9 mg/l), the pulmonary radiograph and thoracic CT scan showed evidence of bilateral diffused interstitial disease. There was also a restrictive ventilatory defect (TLC 59 per cent predicted; FEV1 79 per cent predicted; FVC 70 per cent predicted), effort hypoxaemia and alveolar hyperlymphocytosis (35 per cent). The clinical, radiological and pulmonary function improved and the bronchoalveolar lavage became normal three months after stopping Prozac suggesting a role for this drug in the genesis of this interstitial pneumonia.

Aged↗

An in vivo model of allergic inflammation: pulmonary human cell infiltrate in allergen-challenged allergic Hu-SCID mice.

CB.17 severe combined immunodeficient (SCID) mice were used to establish a model of allergic pulmonary inflammation. SCID mice were intraperitoneally reconstituted with 10(7) peripheral blood mononuclear cells (PBMC) from patients sensitive to Dermatophagoides pteronyssinus (Dpt) and 2 weeks later were exposed to Dpt aerosols. After Dpt nebulization, SCID mice engrafted with PBMC from Dpt-sensitive patients developed a specific human IgE response as well as an intense pulmonary infiltrate of human cells. In contrast, SCID mice reconstituted with PBMC from patients allergic to grass pollen or from non-allergic donors failed to produce IgE or to exhibit a similar inflammatory response. The level of the IgE production was dependent on the IgE level of the allergic donor. In the lungs of the same allergic SCID mice, 2 months after Dpt inhalation, the cell infiltrate contained CD45+, CD45RO+, CD20+ and HLA-DR+ human cells. They were located in perivascular and peribronchial areas and disseminated in the mouse lung parenchyma. Moreover, mRNA IL-5+ cells and eosinophils were found in peribronchial infiltrates. The observations indicate that humanized allergic SCID mice may develop, after nebulization with the relevant allergen, immune reactions similar to those observed in man and suggest that SCID mice may represent a useful model to analyze the regulatory mechanisms of IgE-associated allergic diseases.

Administration, Inhalation↗

In vitro assessment of environmental toxicology using alveolar cells as target.

Biphasic culture of alveolar cells (alveolar macrophages and type II cells) has been widely developed and permits a precise evaluation of the toxic effects of air pollutants. Clearly, in vitro exposure of alveolar cells to high concentrations of oxidant gases is responsible for a loss of cell viability. In contrast, when exposed to realistic concentrations of gases (NO2, O3), cell viability is not altered and various proinflammatory mediators are released. This in vitro model has proved to be sensitive at levels of gas exposure of ambient air quality standards and appears a sensitive biological indicator of air pollutant cell toxicity.

Air Pollutants↗

Increased intestinal permeability in bronchial asthma.

T lymphocytes are a major component of bronchial inflammatory processes in asthma. Because lymphocytes have the ability to migrate from one mucosal site to another, we initiated this prospective study to demonstrate mucosal abnormalities of the digestive barrier in asthma. To establish this we studied intestinal permeability in a group of 37 patients with asthma (21 allergic and 16 nonallergic) by measuring chromium 51-labeled ethylenediaminetetraacetatic acid (CrEDTA) urinary recovery. The results were compared with those obtained in a group of 13 nonasthmatic patients with chronic obstructive pulmonary disease and 26 healthy control subjects. Urinary recovery of CrEDTA was significantly higher in patients with asthma (2.5% +/- 1.95%) than in patients with chronic obstructive pulmonary disease (1.16% +/- 0.48%) and healthy control subjects (1.36% +/- 0.14%). There was no significant difference in intestinal permeability between patients with allergic asthma (2.94% +/- 2.4%) and those with nonallergic asthma (1.92% +/- 0.9%). Intestinal permeability was not correlated with the severity of asthma as measured by FEV1. Similarly, intestinal permeability did not significantly vary according to Aas score or steroid treatment. Serum IgE values and eosinophil blood count were not correlated with intestinal permeability. Intestinal permeability was evaluated sequentially in seven patients with asthma (4 allergic and 3 nonallergic) with a mean interval of 7.6 months (range, 2 to 13 months) and did not significantly change. Our results support the hypothesis that a general defect of the whole mucosal system is present as a cause or a consequence of bronchial asthma.

Adult↗

Expression of leucocyte-endothelial adhesion molecules is limited to intercellular adhesion molecule-1 (ICAM-1) in the lung of pneumoconiotic patients: role of tumour necrosis factor-alpha (TNF-alpha).

Coal workers' pneumoconiosis (CWP) is characterized by a chronic inflammatory lung reaction associated with macrophage accumulation in alveolar spaces. In this study, we investigated in CWP the implication of adhesion molecules such as E-selectin, ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) and the role of TNF-alpha which is one of the cytokines inducing their expression. Adhesion molecule expression was analysed by immunohistochemistry on lung biopsies from patients with CWP and from healthy subjects. In parallel, soluble adhesion molecules were detected in bronchoalveolar lavage fluids (BALF) from patients by specific ELISA. The involvement of TNF in the induction of these adhesion molecules was measured (i) by immunohistochemistry on sections from lung fragments, and (ii) by evaluating in vitro the expression of adhesion molecules on endothelial cells and on alveolar epithelial cells in the presence of alveolar macrophage supernatants. In control subjects, a weak staining of ICAM-1 was detected only in alveolar walls, while E-selectin and VCAM-1 were undetectable. In pneumoconiotic patients, ICAM-1 was expressed at a high level by endothelium, by alveolar and bronchial epithelial cells and by alveolar macrophages. E-selectin and VCAM-1 expression remained undetectable. Measurement of soluble adhesion molecule showed that only the concentration of sICAM-1 was significantly increased in BALF from patients with CWP compared with controls. The involvement of TNF in this ICAM-1 expression was shown by the in vitro effect of alveolar macrophage supernatants on adhesion molecule expression by endothelial cells and epithelial cells (this effect was neutralized by anti-TNF antibodies) and by the increased production of TNF in the lung of pneumoconiotic patients. These data provide evidence for the involvement of ICAM-1, induced at least in part by alveolar macrophage-derived TNF, in the development of the inflammatory reaction in CWP.

Aged↗

Venom immunotherapy modulates interleukin-4 and interferon-gamma messenger RNA expression of peripheral T lymphocytes.

The mechanism by which specific immunotherapy exerts its beneficial effect remains unclear. In order to evaluate the influence of venom immunotherapy on the T-cell cytokine pattern of allergic reactions, we studied interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) mRNA expression of peripheral T lymphocytes from 12 patients undergoing rush venom desensitization, before treatment at Day 0 (D0), at Day 15 (D15) and Day 90 (D90) after treatment, and from seven controls. Antigen-specific T-cell proliferation was also determined. Cytokine mRNA expression was evaluated using in situ hybridization, 24 hr after culture of peripheral T cells with medium, venom, or an unrelated allergen. Allergen-induced T-cell proliferation decreased at D15 and D90 of rush immunotherapy (P < or = 0.02). In venom-stimulated cultures of the patient group, there was a decrease in IL-4 mRNA-positive cells at D15 and D90 (P < or = 0.001). Before desensitization, IFN-gamma mRNA expression was lower in patients than in controls and did not increase after in vitro allergen stimulation. In contrast, after immunotherapy, spontaneous IFN-gamma mRNA expression increased, but only at D90 (P < or = 0.001). The cytokine pattern observed at D90 after immunotherapy was similar to that observed in control subjects. In conclusion, venom immunotherapy induced an altered cytokine mRNA pattern in allergen-stimulated T cells which was dissociated from the early changes of allergen-induced T-cell responsiveness.

Adolescent↗

Erdheim-Chester disease. Clinical and radiologic characteristics of 59 cases.

We made a retrospective evaluation of clinical and radiologic features, treatment, and outcome of Erdheim-Chester disease, a rare non-Langerhans cell histiocytosis. We had 7 patients coming from 3 French teaching hospitals and reviewed 52 cases from the literature. These cases were considered to have Erdheim-Chester disease when they had either typical bone radiographs (symmetrical long bones osteosclerosis) and/or histologic criteria disclosing histiocytic infiltration without features for Langerhans cell histiocytosis (no S-100 protein, no intracytoplasmic Birbeck granules). Ages at diagnosis ranged from 7 to 84 years (mean +/- SD = 53 +/- 14 yr) with a male/female ratio of 33/26. Bone pain was the most frequent clinical sign (28/59), mostly located in the lower limbs. Exophthalmos and diabetes insipidus were found in respectively 16/59 and 17/59 patients. General symptoms (fever, weight loss) and "xanthomas" (mainly located on the eyelids) were present in 11/59 patients. Retroperitoneal involvement was found in 17/59 patients. Skeletal X-ray showed typical osteosclerosis of the diaphysis of the long bones in 45/59 patients. Bone radiographs showed osteolytic lesions of the flat bones (skull, ribs) in 8 patients. Histologic diagnosis was performed after a bone biopsy (28 patients), a retroorbital biopsy (9 patients), and/or a biopsy of the retroperitoneal infiltration or the kidney (11 patients). Six of our 7 patients but only 5 of 52 patients from the literature had the complete histologic criteria, disclosing no Birbeck granules or S-100 immunostaining. In other cases, histologic results usually described a xanthogranulomatous infiltration by foamy histiocytes nested in fibrosis. Treatment was corticotherapy (20/59), chemotherapy (8/59), radiotherapy (6/59), surgery (3/59) and immunotherapy (1 patient). Twenty-two patients died after a mean follow-up of 32 +/- 30 mo (range, 3-120 mo). In conclusion, Erdheim-Chester disease may be confused with Langerhans cell histiocytosis as it sometimes shares the same clinical (exophthalmos, diabetes insipidus) or radiologic (osteolytic lesions) findings. However, it also appears to have distinctive features. Patients are older and have a worse prognosis than those with Langerhans cell histiocytosis, and the diagnosis relies on the association of specific radiologic and histologic findings.

Adolescent↗

Inspiratory muscle strength and endurance in steroid-dependent asthma.

The adverse effect of long-term steroid treatment on respiratory muscle function remains controversial. We evaluated inspiratory muscle strength and endurance in steroid-dependent asthmatics in comparison with other asthmatics or with patients with chronic obstructive pulmonary disease exhibiting a comparable level of lung hyperinflation. Inspiratory muscle function was assessed by maximal inspiratory pressure (Pimax) and by an incremental inspiratory threshold loading test in 19 patients who had had steroid-dependent asthma (SDA) requiring a mean daily dose of 20.7 +/- 0.8 mg prednisone for 5 +/- 1.4 yr. They were compared with 16 healthy control subjects, 30 patients with COPD, and 16 patients with non-steroid-dependent asthma (NSDA). Pimax as percentage of predicted values (%Pimax) was not significantly different in patients with SDA (77 +/- 5%) or NSDA (83 +/- 6%) than in control subjects (93 +/- 4%). In contrast, %Pimax was lower in patients with COPD (59 +/- 4.4%) than in those with SDA or NSDA (p < 0.05) or the control subjects (p < 0.0001). A significant correlation was found between %Pimax and hyperinflation assessed by the FRC/TLC ratio (r = 0.42; p < 0.001). Inspiratory endurance, defined as the ratio of maximal peak inspiratory pressure sustained for 2 min to individual Pimax (Plim2/Pimax), was significantly lower in the SDA (43 +/- 3%; p < 0.0001), NSDA (65 +/- 4%; p = 0.01), and COPD (55 +/- 3%; p < 0.0001) groups than in the control group (76 +/- 2%). Plim2/Pimax was also lower in patients with SDA than in those with COPD (p = 0.0073) or NSDA (p < 0.0001). Hyperinflation plays a major role in inspiratory muscle dysfunction associated with obstructive lung disorders, but the finding of a significantly decreased endurance in patients with SDA when compared with patients with COPD, despite a lower level of hyperinflation in the former group, points to a deleterious effect of long-term corticosteroid treatment on inspiratory muscle function in asthmatics.

Asthma↗

Nongranulomatous interstitial lung disease in Crohn's disease.

Crohn's disease is a granulomatous systemic disorder of unknown aetiology. Obvious pulmonary involvement is exceptional. We report the case of a 33 year old woman treated with mesalazine for Crohn's disease and presenting with dyspnoea. Pulmonary function tests showed a restrictive ventilatory pattern with hypoxaemia on exertion. Chest radiography disclosed an interstitial pattern with ground glass on high resolution computer tomography. Clinical and radiological abnormalities progressed after withdrawal of mesalazine. Corticosteroids led to a partial regression but were stopped because of severe side-effects. Because of worsening of the clinical situation, open lung biopsy was performed and showed a histopathological aspect of nongranulomatous interstitial diffuse lung disease with an inflammatory lymphoid infiltration associated to some mild interstitial collagen fibrosis. Addition of cyclophosphamide to high-dose pulse steroid therapy induced a significant and sustained improvement.

Adult↗

Perindopril-associated pneumonitis.

We report two cases of perindopril-associated pneumonitis with typical drug-induced clinical features. In the first case, biopsies showed granulomatous sarcoid-like lesions; in the second, bronchial wall eosinophil infiltratf2p4was reported with increased blood eosinophil count. In these two cases, improvement was obtained by withdrawal of the drug and was completed with steroids. All other causes were ruled out. Angiotensin-converting enzyme inhibitor (ACEI)-induced pneumonitis is still rare but has to be recognized as a real side-effect.

Aged↗

Pulmonary hypertension associated with POEMS syndrome.

Pulmonary hypertension (PH) is an uncommon but lethal complication of some connective tissue diseases. We describe two cases of PH associated with plasma cell dyscrasia, with polyneuropathy (P), organomegaly (O), endocrinopathy (E), M protein (P) and skin changes (S) described as POEMS syndrome. Two patients, one female and one male, were hospitalized for dyspnoea. Both had a history of POEMS syndrome a few years previously. PH was diagnosed from cardiac catherization, and complete investigations did not reveal other underlying disease. In Case No. 1, mean pulmonary artery pressure was 40 mmHg and pulmonary vascular resistance was 775 dyne x s x cm-5 x m2, with a significant reversibility to vasodilators. Nifedipine and fluindrone treatment was initiated. The patient was still alive 18 months later. In Case No. 2, mean pulmonary artery pressure was 28 mmHg and pulmonary vascular resistance was 243 dyne x s x cm-5x m2, with a slight reversibility to vasodilators. The patient died 6 months later. Our observations suggest that pulmonary hypertension (PH) may be associated with the POEMS syndrome, and that patients suffering from the POEMS syndrome and dyspnoea should be tested for PH.

Aged↗

Determinants of survival in pulmonary Langerhans' cell granulomatosis (histiocytosis X). Groupe d'Etude en Pathologie Interstitielle de la Société de Pathologie Thoracique du Nord.

The course of pulmonary Langerhans' cell granulomatosis (pulmonary LCG) is variable, difficult to predict and ranges from spontaneous remission to progressive respiratory insufficiency and death. To identify the determinants of survival, we performed a survival analysis on 45 patients with pulmonary LCG. The patients were aged 28 +/- 10 yrs (mean +/- SD) (range 12-62 yrs), 32 males and 13 females, almost exclusively current smokers (96%), and 78% presented symptoms at the time of diagnosis. Diagnosis was made by lung biopsy in 25 patients (56%) and by bronchoalveolar lavage (BAL) analysis in 20 patients (44%). The patients were followed for a median period of 6 yrs (range 1-29 yrs) after the diagnosis. During the period of observation, 33 (73%) patients survived (median follow-up period = 5.8 yrs; range, 1-29 yrs) and 12 (27%) died or underwent lung transplantation (median follow-up period = 8.4 yrs; range 1.4 - 16.1 yrs). The median survival was approximately 13 years. A univariate analysis demonstrated that diminished survival was significantly associated with: an older age at diagnosis (p = 0.0001); a lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio at diagnosis (p = 0.005); a higher residual volume/total lung volume (RV/TLC) ratio at diagnosis (p = 0.02); and steroid therapy during follow-up (p = 0.03). Additional predictive information on mortality was: age > 26 yrs (sensitivity 83%, specificity 64%); FEV1/FVC ratio < 0.66 (sensitivity 75%, specificity 86%); and a RV/TLC ratio > 0.33 (sensitivity 75%, specificity 63%). In multivariate Cox analysis, the combination of factors which gave the best prognostic value was FEV1/FVC ratio and age (p < 0.01). The present findings suggest that adverse prognosis factors at diagnosis in pulmonary Langerhans' cell granulomatosis include older age, lower FEV1/FVC ratio and higher RV/TLC ratio, with additional predictive information on mortality if aged > 26 yrs, FEV1/FVC ratio < 0.66, and RV/TLC ratio > 0.33.

Adolescent↗

Acute respiratory failure due to tracheobronchial involvement in Crohn's disease.

We present a case of tracheobronchial involvement in Crohn's disease, associated with respiratory failure leading to mechanical ventilation. Bronchoscopy revealed small, diffuse, whitish granulations and erythematous mucosa. Histopathology disclosed ulcerative bronchitis and noncaseating tuberculoid granuloma. The patient improved under a 6 week oral corticosteroid treatment followed by inhaled corticotherapy, without relapse of pulmonary symptoms.

Acute Disease↗

[MRI aspect and course of supra-tentorial sarcoidosic lesions].

Central nervous system lesions resulting from sarcoidosis occur in 5% of cases, but supratentorial mass lesions are uncommon. We report 3 cases of intracranial pseudo-tumoral lesions, due to sarcoidosis: 1 woman and 2 men. Clinical features included left facial myoclonus, headache and vertigo, right hemiparesis and unique general seizure. Sarcoidosis was diagnosed upon conjonctival biopsy in the first case, infiltrative lesions of the lungs and mediastinal lymph nodes in the second case, and intracerebral lesion plus lymph nodes biopsies in the last case. In the first case, CT scan and MRI images showed diffuse subcortical high signal, suggesting pachymeningitis with vasogenic oedema. In the second case, GT scan and MRI revealed numerous small granuloma in the left rolandic area, and one in the striatum. In the third case, CT scan showed an enlargement of the left temporal horn, due to an enhanced left periventricular lesion. MRI with gadolinium showed that the lesion encircled the ventricle horn. In all cases, clinical and radiological improvement was obtained after corticoid therapy.

Adult↗

[Drug-induced pleurisy].

Drug induced pleurisy is often a diagnosis of elimination because the clinical presentation, paraclinical features and anatomicopathological aspect are relatively non-specific. The pleural effusions are typically chronic and somewhat torpid, most often bilateral but may be unilateral. Two types of lesion are found: effusion or thickening and these may be associated. The peculiarity of these pleural diseases are the frequent coexistence of accompanying signs: for example pulmonary, cutaneous, ocular, hepatic, peritoneal, pericardial as well as evidence of inflammation and depending on the medicaments hypereosinophilia, cytolysis, cholestasis or antinuclear antibodies. Anatomicopathogically there is dense fibrosis which is diffuse, pauci-cellular and with little inflammation. The progress is variable according to the drug either going on to complete regression on the cessation of the medication or the persistence of a degree of pleural thickening. The causative drugs are essentially the derivatives of Ergotamine and amongst others bromocryptine and dantrolene.

Bromocriptine↗

[Treatment of pulmonary lymphangioleiomyomatosis using a GnRH agonist].

Pulmonary lymphangioleiomyomatosis is a rare and exclusively female disease which is oestrogen dependent and has a serious prognosis. We present two cases of young women aged 30 and 33 with the same clinical history of renal angiomyolipomas and recurring pneumothoraces. The computerised tomographic scans of the lung were strongly suggestive of LAM (there were fine wall cysts which were disseminated throughout both lung fields). The histological proof was provided by lung biopsy which was carried out during a thoracotomy for pleurectomies. The first patient who is currently asymptomatic and in excellent general health, was treated for three months with tamoxifen (Nolvadex), then for 20 months with 3.75 mg per month of triptoline (Decapeptyl), an agonist of GnRH. The second patient received triptoline in the same dose. After 40 months of treatment this patient was asymptomatic with satisfactory lung function tests. Agonists of GnRH (gonadotropic release hormone) seem to provide a useful alternative in the treatment of LAM.

Adult↗