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Biomedical subjects

M Radermecker

Publications and source records attributed to M Radermecker.

At least 19 recordsLinked to original sources

Bronchial eosinophilic infiltration in Crohn's disease in the absence of pulmonary disease.

BACKGROUND: Immunological and functional bronchopulmonary abnormalities may be present in up to two-thirds of patients with Crohn's disease. Having recently described a mild increase in methacholine airways responsiveness in these patients, we investigated whether this physiological abnormality is associated with bronchial inflammation since it has previously been described in asthma. METHODS: Eighteen patients with Crohn's disease and 15 healthy controls matched for age, atopy and smoking habit, were studied. All the subjects underwent a bronchial methacholine challenge (1, 4 and 16 mg/mL) and a sputum induction by inhalation of hypertonic saline (NaCl 4.5%). The sputum samples were analysed for their cellular composition as well as for the levels of several mediators and proteins in the fluid phase, including eosinophil cationic protein (ECP), myeloperoxydase, albumin, alpha2-macroglobulin, interleukin-8 (IL-8), IgA and IL-8/immunoglobulin A complexes. RESULTS: When compared to control subjects, patients with Crohn's disease had significantly higher sputum eosinophil counts (14.5% [0-79.9%] vs 0.2% [0-2.3%]; P < 0. 001) and ECP levels (26.2 microg/L [4-124.2 microg/L] vs 9.8 microg/L [0-94.2 microg/L]; P < 0.05). However, patients with Crohn's disease had no sign of increased plasma exudation as reflected by sputum levels of albumin and alpha2-macroglobulin similar to those seen in control subjects. Furthermore the sputum levels of IL-8, IgA and IL-8/IgA complexes were not significantly different between the two groups. The magnitude of the fall in forced expiratory volume in 1 s after methacholine inhalation was significantly increased in Crohn's disease patients although it did not correlate with the extent of sputum eosinophilia or with the sputum ECP levels. CONCLUSIONS: Crohn's disease patients without any clinical respiratory involvement have airway eosinophilia without local increased plasma exudation. However, bronchial eosinophilia in Crohn's disease per se is not sufficient to induce clinically significant airway hyperresponsiveness, suggesting that other factors than bronchial eosinophilic infiltration are required for the clinical expression of an airway instability.

Adult

The effect of processing on inflammatory markers in induced sputum.

The effects of the mucolytic agent, dithioerythritol (DTE), and the temperature at which sputum processing is conducted on cellular and biochemical markers in induced sputum was assessed. Samples from healthy and atopic asthmatic subjects were treated with either DTE or phosphate-buffered saline (PBS) at 22 or 37 degrees C and compared for cell counts and concentrations of histamine, tryptase, eosinophil cationic protein (ECP), free interleukin (IL)-8, immunoglobulin (Ig)A, IL-8/IgA complexes and secretory component (SC). In addition, the influence of DTE on in vitro mediator release from blood eosinophils, basophils and bronchoalveolar lavage (BAL) mast cells was studied. Processing with DTE improved cytospin quality and increased the cell yield and measurable ECP, tryptase, IgA and SC, but reduced levels of histamine in PBS-treated samples and had no effect on IL-8. Cell counts or mediator levels were similar when sputum was processed at 22 or 37 degrees C, even though DTE induced blood basophils and BAL mast cells to release histamine at 37 degrees C. In spiking experiments, recovery of added ECP, tryptase, total IL-8 and histamine from sputum was similar in DTE- and PBS-processed sputum, but reduced for free IL-8 in PBS-treated samples. In conclusion, dithioerythritol improves cell and mediator recovery without causing cell activation when sputum processing is conducted at room temperature. The extent of recovery depends on the mediator studied.

Asthma

Usefulness of induced sputum analysis in pulmonary diseases.

In this study, we analysed the cellular component of induced sputum in healthy control subjects (n = 30), asthmatics (n = 44), patients suffering from COPD (n = 15), pulmonary tuberculosis (PTB) (n = 14) and healthy steel workers (HSW) (n = 14). Sputum was induced by inhalation of hypertonic saline (NaCl 5%) for 20 min. When compared to the healthy control group, all the disease groups as well as the one of healthy steelworkers exhibited significantly higher total sputum cell counts. Analysis of the differential cell counts showed that there was a significant increase in % eosinophils in asthmatics, in % neutrophils in COPD, asthmatics, tuberculosis and healthy steelworkers and in % lymphocytes in pulmonary tuberculosis. Our study illustrates the feasibility and the possible clinical application of induced sputum analysis in several pulmonary diseases and shows how this technique could be useful in assessing airway inflammatory processes in subjects exposed to industrial pollutants.

Administration, Inhalation

Correlation between bronchoalveolar lavage (BAL) fluid cell lysate histamine content and BAL fluid eosinophil count in atopic and nonatopic asthmatics.

We have compared the bronchoalveolar lavage fluid (BAL) cellular composition and the BAL cell lysate histamine content (fluorometric assay) in 28 stable mild to moderate asthmatics (atopic n = 18 and intrinsic n = 10) and 11 control subjects. When compared to control subjects, the whole group of asthmatics had a higher proportion of BAL eosinophils (p < 0.01) and metachromatic cells (p < 0.05). The BAL cell lysate histamine was increased in atopic (p < 0.05) and intrinsic asthmatics (p < 0.05) in comparison with control subjects. In the whole group of asthmatics, the BAL cell lysate histamine content correlated with the percentage of BAL eosinophils (r = 0.58, p < 0.01). This relationship was significant in both atopic (r = 0.48, p < 0.05) and intrinsic (r = 0.70, p < 0.05) asthmatics. For the whole group of asthmatics, both the BAL cell lysate histamine and the percentage of BAL eosinophils inversely correlated with the percent predicted FEV1 (r = -0.42, p < 0.05; r = -0.51, p < 0.05). We conclude that an increased BAL cell lysate histamine content correlates with airway eosinophilic infiltration and lung function impairment in mild to moderate atopic and intrinsic asthmatics. This suggests that BAL mast cells play a key role in recruiting eosinophils in the airways of asthmatics irrespective of the presence of an atopic status.

Adult

Whole-body 18FDG positron emission tomography in the staging of non-small cell lung cancer.

Despite advances in morphological imaging, some patients with lung cancer are found to have nonresectable disease at surgery or die of recurrence within yr of surgery. We performed a prospective study in 109 patients to compare the accuracy of whole-body positron emission tomography (PET) using fluorine-18 deoxyglucose (18FDG) and conventional imaging (CI) methods for the staging of non-small cell lung cancer (NSCLC). When CI or PET study suggested metastatic disease, confirmation was obtained by biopsy or follow-up information. As compared to CI, 18FDG-PET correctly changed the N stage in 22 patients (33%) and the M stage in 15 patients (14%). For the detection of distant metastases, PET study showed five false-positive sites and no false-negative cases. Currently, the accuracy of PET in the detection of M stage is 96%. Our study shows that visual interpretation of whole-body fluorine-18 deoxyglucose-positron emission tomography images can improve the diagnostic accuracy in the staging of non-small cell lung cancer. Further experience is needed to establish if metabolic imaging would be a cost-effective tool in the future management of lung cancer.

Carcinoma, Non-Small-Cell Lung

High neuron specific enolase levels in bronchoalveolar lavage fluid of patients with lung carcinoma: diagnostic value, relation to serum neuron specific enolase, and staging.

BACKGROUND: High levels of neuron specific enolase (NSE) have recently been described in the bronchoalveolar lavage (BAL) fluid of patients with lung carcinoma. Although its value in serum has been extensively studied, its diagnostic value in BAL fluid in terms of sensitivity, specificity, and predictive value have not been evaluated. In addition, its value in staging and relation to serum NSE are yet unknown. METHODS: NSE levels were determined on the same day in the BAL fluid and the sera of two groups of patients: those with newly diagnosed lung carcinoma and those with smoking related chronic obstructive pulmonary disease (COPD). Clinical TNM staging was also performed. Levels of NSE in BAL fluid were expressed as nanograms per 100 international units of lactate dehydrogenase. BAL fluid NSE levels of the two groups were compared with staging and serum NSE. RESULTS: A highly significant difference exists in BAL NSE in the two groups. For diagnostic purposes, the simultaneous measurements of serum NSE increases its sensitivity, but specificity remains unchanged. No correlation exists between BAL NSE and serum NSE, tumor size, nodal status, or the presence of metastases. BAL NSE is a better predictor of malignancy than serum NSE. CONCLUSION: BAL fluid measurements of NSE may have diagnostic value, specially if it is simultaneously measured in the serum. However, our study does not show any value for this technique in staging of lung carcinoma. Also it has no correlation with serum NSE. Studies will have to be performed to determine if BAL NSE can predict chemotherapeutic sensitivity.

Aged

Staging of non-small-cell lung cancer by whole-body fluorine-18 deoxyglucose positron emission tomography.

Positron emission tomography (PET) using fluorine-18 deoxyglucose (FDG), showing increased FDG uptake and retention in malignant cells, has been proven useful to differentiate malignant from benign tissue. We undertook a prospective study in 61 patients to compare the accuracy of whole-body FDG PET and conventional imaging (CI) methods for the staging of non-small-cell lung cancer (NSCLC). CI included chest and abdomen computed tomographic scanning and bone scintigraphy. When CI or PET study suggested metastatic disease, confirmation was obtained by biopsy or clinical or radiological follow-up. As compared to CI, PET correctly changed the N stage in 13 patients (21%) and the M stage in six patients (10%). There were three false-positive and no false-negative distant PET findings. Our preliminary results show that whole-body FDG PET can improve the diagnostic accuracy in the staging of NSCLC.

Aged

Gastrin levels in serum and bronchoalveolar lavage fluid of patients with lung cancer: comparison with patients with chronic obstructive pulmonary disease.

BACKGROUND: The gastrin gene is known to be expressed in all classes of bronchogenic carcinomas. Furthermore, high levels of gastrin have been reported in both the bronchoalveolar lavage (BAL) fluid and serum of patients with lung cancer. Based on these preliminary data a study was conducted to evaluate the usefulness of gastrin measurements in the diagnosis and staging of lung cancer. METHODS: Thirty-five patients with lung cancer (26 non-small cell (NSCLC) and nine small cell (SCLC)) and 25 patients with chronic obstructive pulmonary disease underwent fibreoptic bronchoscopy and BAL. Gastrin levels were determined in both BAL fluid and the serum and compared with each other and with staging. RESULTS: No difference was found between the gastrin levels in the BAL fluid or serum of the study groups. There was no correlation with the stage in NSCLC and no correlation was found between the gastrin levels in the serum and the BAL fluid. A significant difference was seen in gastrin levels in BAL fluid between extensive and limited SCLC (p < 0.05). CONCLUSION: There is no evidence of clinical usefulness for gastrin measurements in lung cancer.

Adult

Evaluation of the solitary pulmonary nodule by positron emission tomography imaging.

Current noninvasive imaging methods are not sufficiently reliable for accurate detection of malignancy in most solitary pulmonary nodules (SPNs). Positron emission tomography (PET) using 18-fluorodeoxyglucose (FDG), showing increased FDG uptake and retention in malignant cells, has proved useful to differentiate malignant from benign tissue and could, therefore, contribute to the evaluation of the SPN. We performed a prospective study of 50 patients referred to the Pneumology Department with unclear diagnoses of SPN after conventional radiological screening. PET study was performed on each subject before an invasive procedure was proposed. Thirty three patients had a malignant nodule and 17 had a benign nodule. The mean size of malignant nodule was 3 cm (range 1.5-4.5 cm). All showed a marked increase in 18-FDG uptake. The mean size of benign nodule was 1.8 cm (range 0.5-3.5 cm). PET imaging showed the absence of 18-FDG uptake and correctly identified 15 of 17 benign nodules. There was two false-positive cases with a moderate increase in 18-FDG uptake (1 postprimary tuberculosis; and 1 anthracosilicotic nodule with nonspecific inflammation). At present, the sensitivity and specificity of the method are 100 and 88%, respectively. The positive and negative predictive values of PET imaging for SPNs are 94 and 100%, respectively. Our preliminary results demonstrate that PET-FDG imaging is a noninvasive technique, which appears highly accurate in differentiating malignant SPN from benign SPN.

Aged

Staging of the mediastinum: value of positron emission tomography imaging in non-small cell lung cancer.

Recent studies have shown limitations of morphological imaging in staging mediastinal lymph node involvement in lung cancer. In contrast to computed tomography (CT), which depends primarily on anatomical imaging features, positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) depends mainly on the metabolic characteristics of a tissue for the diagnosis of disease. We have performed a prospective study comparing FDG-PET and CT of the thorax in the presurgical assessment of the mediastinum in 50 patients with newly diagnosed non-small cell lung cancer (NSCLC). CT and PET scans were interpreted separately, and results were compared to pathological staging obtained during thoracotomy. Hilar or mediastinal lymph node involvement was present in 58%. In staging for lymph node involvement, CT had a sensitivity of 72% and specificity of 81%, whereas PET had a sensitivity and specificity of 90% and 86%, respectively. When the PET study was compared to histological results, there were four cases showing more advanced mediastinal involvement with PET and four cases showing less involvement with PET. From our preliminary results, we conclude that positron emission tomography with 18-fluorodeoxyglucose is significantly more accurate than computed tomography in the mediastinal staging of non-small cell lung cancer.

Aged

Regulation of histamine release from human bronchoalveolar lavage mast cells by stem cell factor in several respiratory diseases.

We investigated the effects of stem cell factor (SCF) on histamine release (HR) from human bronchoalveolar lavage (BAL) mast cells. BAL cells were recovered from lavage performed in patients undergoing clinical bronchoscopy. SCF (0.02-20 ng/ml), which is by itself a poor secretagogue (mean +/- SEM HR: 3.7 +/- 0.9%; n = 27), strongly enhanced HR induced by anti-IgE in a concentration-related manner. Significant potentiation began at 0.2 ng/ml (30 +/- 10%; p < 0.05; n = 12) and reached a plateau at 2 ng/ml (40 +/- 10%; P < 0.01 at 2 ng/ml and 45 +/- 10%; P < 0.01 at 20 ng/ml; n = 12). In contrast, SCF failed to enhance HR induced by calcium ionophore A23187. Among the BAL cell samples initially unresponsive to anti-IgE (55% of samples), 36% (10/28) were converted to responders if the cells were shortly preincubated with SCF. In 25% of samples (7/27), SCF (20 ng/ml) caused direct HR of 10 +/- 2.1%. The mast cells which released histamine when challenged with SCF also secreted higher levels of histamine in response to anti-IgE and calcium ionophore than those nonresponsive to SCF. While interleukin (IL)-3 and IL-5 (20 ng/ml) were unable to modulate immunologic HR, GM-CSF (20 ng/ml) produced significant potentiation (P < 0.05), which was, however, smaller than that observed with SCF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic

Increased frequency of bronchial hyperresponsiveness in patients with inflammatory bowel disease.

Although bronchopulmonary manifestations are rare in inflammatory bowel disease (IBD), subclinical abnormalities have been described in up to 50% of cases. The pathophysiology of these abnormalities remains unknown. However, a latent inflammation of the bronchial mucosa secondary to the inflammation of the intestinal mucosa has been suggested. This subclinical inflammation may lead to increased bronchial responsiveness. We studied the bronchial responsiveness in 38 inflammatory bowel disease (IBD) patients, using the methacholine test. Bronchial hyperresponsiveness was defined by a PC20M < 16 mg/ml. Twenty-four healthy controls were also studied. There was no significant difference in baseline FEV1 between IBD patients and controls. However, there was a significantly greater fall in FEV1 in the IBD patients at the concentrations of methacholine tested. The frequency of bronchial hyperresponsiveness was significantly higher in the IBD population (45%) than in controls (17%; P < 0.03). Atopy, defined by skin test, was more common in IBD patients (42%) than in controls (21%). Even when only nonatopic subjects were considered, the frequency of bronchial hyperresponsiveness was significantly higher in IBD patients (41%) than in controls (5%; P < 0.02). Thus, subclinical bronchial hyperresponsiveness is common in IBD, and may be considered a further extraintestinal manifestation.

Adolescent

[Therapeutic strategy in asthma: special cases and pseudo-asthma].

Therapeutic strategy of asthma such as that described by international consensus must sometimes be modified in certain situations, the triggering agent or subsequent complications. Account should also be taken of pseudo-asthmas, i.e. other illnesses accompanying the sibilant dyspnoea. The therapeutic principles of each of these conditions are set out and specially emphasize asthma in pregnancy and states of resistance to corticosteroids.

Adrenergic beta-Antagonists