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Biomedical subjects

F B Michel

Publications and source records attributed to F B Michel.

At least 55 records · Page 3Linked to original sources
PubMed1997

Leukotriene E4 plasma levels in adult asthmatic patients with variable disease severity.

Cysteinyl leukotrienes (C-LTs) are local inflammatory mediators involved in bronchial asthma. Seventeen asthmatic patients (FEV1 ranging from 41 to 99.8% of predicted values) and 11 healthy subjects were studied. The clinical severity of asthma was assessed by the Aas score. Plasma C-LTs were measured by enzyme immunoassay (EIA) after sample purification by solid-phase extraction (SPE), to investigate whether differences may exist between asthmatic and control subjects and whether leukotriene E4 (LTE4) levels were related to the severity of disease. LT measurements showed that 87.6 +/- 1.2% was recovered as LTE4 and 9.4 +/- 1.3% as LTC4. In asthmatic subjects, LTE4 plasma levels were found to be significantly higher than those in the control group (1.073 +/- 0.133 and 0.53 +/- 0.19 ng/ml of plasma, respectively; P < 0.002). Moreover, there was a significant correlation between LTE4 plasma levels and the Aas clinical score (P < 0.005). These data suggest that plasma LTE4 levels might be used to assess the severity of asthma.

Adolescent↗
PubMed1997

Prostaglandin H synthase 1 and 2 immunoreactivities in the bronchial mucosa of asthmatics.

Prostaglandin H synthases or cyclooxygenases 1 (PGHS-1) and 2 (PGHS-2) catalyze the conversion of arachidonic acid to prostaglandin endoperoxides, leading to the formation of prostaglandin and thromboxane mediators of inflammation. The expression of these enzymes in the respiratory epithelium has not been determined, although they may be relevant to the pathophysiology of inflammatory disorders such as asthma and chronic bronchitis (CB). We studied PGHS-1 and PGHS-2 immunoreactivity in bronchial biopsies obtained from 22 patients with chronic stable asthma, seven patients with CB, and 12 normal subjects. Both types of PGHS were mainly expressed in the epithelium (basal and ciliated cells), and PGHS-1 and PGHS-2 were found in 21 of 41 and 34 of 41 biopsies, respectively. We did not find any differences in PGHS expression between the patient populations. There were no correlations between any of the clinical parameters studied or the pathologic patterns and the presence and characteristics of the PGHS immunoreactivities. Thus, both PGHS enzymes are expressed in normal human respiratory epithelium and are not quantitatively upregulated in the main bronchi in stable asthma and CB.

Adrenal Cortex Hormones↗
PubMed1997

Immunohistochemical detection of p53 protein and prognosis of surgically resected non-small-cell lung cancer.

We analyzed the survival of 89 surgically treated patients presenting non-small-cell lung cancer in regard to the accumulation of p53 protein as detected by indirect immunoperoxidase reactivity of PAb1801 anti-human p53 protein. Although the well-known factors such as stage grouping, tumor status, and nodal status were found to be prognostic determinants, the p53 protein accumulation had no effect on either univariate analysis or multivariate analysis of survival.

Adult↗
PubMed1997

[Current issues in respiratory allergology].

To summarise in a few lines our present understanding of respiratory allergies necessarily limits the number of topics which can be addressed. The role of aeroallergens in these diseases, both those which were previously unknown or non-existent and those which were well characterised (cypress, ambrosia) but which are becoming more prevalent in the atmosphere has now been demonstrated. The understanding of the mechanisms of respiratory allergies, which are essentially derived from tissue inflammation, has undergone rapid progress and evolved towards the identification of transcription factors which regulate the genes coding for cytokines, enzymes and adhesion molecules. Specific immunotherapy should be heralded as one of the key elements in the global therapeutic strategy for respiratory allergies as long as the indications for it are rationally discussed. Our increasing our knowledge of the genetics of respiratory allergies should continue to stimulate research projects, but the results obtained so far underline the complexity of this domain and diagnosis and treatment via genetics remains in the future.

Air Pollutants↗
PubMed1997

[Specific immunotherapy of respiratory allergies].

Specific immunotherapy has been in routine use since 1911 for the treatment of respiratory allergic diseases. There is however a certain amount of controversies regarding its overall indications. Its efficacy has been demonstrated in double-blind placebo controlled studies in both allergic rhinoconjunctivitis and allergic asthma. The improvement of allergenic extracts (in particular by standardization), the better understanding of the mechanisms of action of immunotherapy, the recently proposed use of other administration routes and the publication of guidelines have legitimated its definite role to play in the therapeutic management of allergic respiratory diseases.

Child↗
PubMed1997

[Recent advances in the genetics of respiratory allergies].

The genetics of atopy and asthma is a fascinating area of research which has made tremendous progresses over the last couple of years. It has been known for ages that allergies and asthma are concentrating within families. Modern genetics has pintpointed some gene areas such as 5q31.1, 6p21.3, 11q13, 12q15 and 14q11.1. To do so, a crucial step is the definition of the phenotypes. Once the phenotype is set up (which is not an easy task), familial aggregation and segregation studies can be performed. These familial studies allow molecular genetics and linkage analysis. Both candidate gene approach and genome-wide search have been utilized in the genetic of atopy and asthma. Much of the information available today has been fragmentary and not always confirmed. Alleles at multiple loci are likely to be involved and the ultimate picture is most likely determined by many genetic and environmental factors.

Genetic Markers↗
PubMed1996

[Pharmacological specificities and modalities of prescriptions for corticoids for asthmatic adults].

The efficacy of corticosteroids in asthma has been recognized over 40 years ago. Since that time, the advent of inhaled forms has further improved the therapeutic of these drugs which are now recognized as the fundamental treatment for asthma, and described in detail by national and international consensus. Based on a large body of literature, it can now be recommended to prescribe inhaled corticosteroids for symptomatic asthma patients. Long-term treatment is required and dosage not exceeding 1000 micrograms/d (beclometasone dipropionate equivalent) in adults are safe. Differences in the pharmacological characteristics of the various systematic and inhaled corticosteroids can be used to adapt treatment and administration route to each patient and achieve good patient compliance with optimal therapeutic efficacy.

Administration, Inhalation↗
PubMed1996

[Bronchial asthma: current concepts].

Asthma, a chronic inflammatory disease of the airways, involves activation of various cell types and development of various degres of post-inflammatory lealing and repair processes which remodel the airways. The short duration of the severe episodes is clearly related to the degree of inflammation, but the natural history of the disease itself remains unclear. Treatment must take into account the fact that clinical expression varies, associating short episodes which can be prevented or attenuated with bronchodilatators and severe acute episodes which should be treated or prevented by anti-inflammatory drugs (inhaled corticosteroids are the most effective) preferably given in the early stages of the disease and used for a prolonged period. Long-term use of inhaled corticosteroids may limit airway remodeling, but there have been few long-term studies to date. Further data is required.

Acute Disease↗
PubMed1996

[Nebulization for basic treatment of asthma in adults].

Many different forms of nebulizer treatment for asthma have been developed over the last few years, including several which have reached international concensus. Nevertheless, there are no widely recognized recommendations concerning the role of nebulization in the treatment of asthma in adults. We present here the main elements on the pathophysiological basis of nebulization treatment of asthma, the physical and chemical parameters of nebulization, the different nebulizers and the substances which can be administered and their costs. The indications for home nebulizer treatment of asthma in adults include asthma with chronic sinusitis or nasosinus polyposis, asthma with hypersecretion with or without bronchial dilatation, severe poorly controlled asthma, corticodependent asthma. The aim of this discussion on nebulizer administration is to reduce the amount of systemic corticosteroid delivery and underline the need for quality research in this area.

Administration, Inhalation↗
PubMed1996

[Asthma and corticotherapy].

There has been a considerable amount of progress in the treatment of asthma providing a highly acceptable quality of life for the majority of patients. Cortisone remains the main medication in severe asthma. But despite the effective reduction in bronchial inflammation provided by cortisone, it is somewhat disappointing that nothing better has been found after a half-century of use. Actually, we have done better. Inhaled cortisone allows application of the active substance in situ, avoiding the inconvenience of systemic administration. In addition, doses can be given in micrograms instead of milligrams. Corticodependency and corticoresistance are the two main problems encountered. Corticodependency is a very heterogeneous highly individual phenomenon. In some corticodependent patients, respiratory function is nearly normal and stable while in others, respiratory function cannot be controlled readily and frequent hospitalizations in the intensive care unit are required. Weaning is a long-term process which must be planned as part of an overall management program. Corticoresistance, in our experience a rather rare condition, involves abnormal cell response to corticoids with abnormal or impaired production of cytokins, interleukin 4 and interleukin 5. A decrease in the number and binding capacity of corticosteroid receptors may also be involved. Cytoplasmic regulation rather than the receptor gene itself would be implicated. By modifying the corticosteroid receptors it would theoretically be possible to override corticorestistance and, by targeting the bronchial epithelium, disassociate the local anti-inflammatory effects of cortisone and the deleterious systemic effects. Understanding the mechanism of action of corticosteroids in patients with severe asthma is one of the challenges facing medicine in the 21st century.

Asthma↗
PubMed1996

r-metHuG-CSF support to ifosfamide, cisplatin, etoposide chemotherapy in non-small cell lung cancer.

Twenty patients with locally advanced or metastatic non-small cell lung cancer entered a study of recombinant human methionyl G-CSF (r-metHuG-CSF) as an adjunct to ifosfamide, cisplatin and etoposide (IPE) regimen. Chemotherapy consisted of three courses of cisplatin 25 mg/m2, ifosfamide 1.5 g/m2 (with uroprotection) and etoposide 100 mg/m2 given on days 1-4 of a 21-day cycle. r-metHuG-CSF, 5 micrograms/kg, was administered subcutaneously from day 5 to day 14. Eighteen out of 20 patients completed the three courses (57 evaluable cycles). Grade 3-4 neutropenia affected 50, 42 and 22% of the patients during cycles 1, 2 and 3, respectively, whereas thrombocytopenia was observed in 25% of the patients throughout the chemotherapy protocol. Haematological toxic events requiring transfusions and/or antibiotics were responsible for 11 unplanned hospitalizations. Among these only three were exclusively devoted to febrile neutropenia care, the remaining eight being mainly required for blood transfusions. There were no deaths during the study duration. Dose reductions were needed in 65% of the patients and chemotherapy was delayed by thrombocytopenia in five patients. The total relative dose intensity was 84%. Eleven (55%) patients responded (one complete and 10 partial responses). Median survival was 9.5 months. We concluded that IPE combination chemotherapy can be administered safely with the support of r-metHuG-CSF inasmuch as neutropenia appears as mild to moderate and manageable. Optimal delivery of chemotherapy is still limited by other toxicities, mainly thrombocytopenia, but the successful relative dose intensity observed herein deserves further studies designed to analyze a dose intensity-survival relationship in non-small cell lung cancer.

Aged↗
PubMed1996

Undertreatment in a nonselected population of adult patients with asthma.

BACKGROUND AND AIM: The question of undertreatment has frequently been raised concerning the management of asthma but, to date, very few studies have been carried out. In those studies that have been performed, the methodology was inadequate because they were conducted on a selected population of patients with asthma or by interviewing doctors. As part of the European Community Respiratory Health Survey, nonselected patients with asthma (22 to 44 years old) in two French cities (Paris and Montpellier), were examined to assess possible undertreatment. METHODS: Patients with asthma were recruited according to a positive response to questions on asthma in a questionnaire and a positive methacholine challenge. The severity of asthma was assessed by a cumulative score, which has previously been shown to be significantly correlated with the validated clinical score of Aas. Patients were asked to attend the clinic and bring with them any medications that they regularly received. The optimal treatment of asthma was based on the International Consensus Report on the Management of Asthma. RESULTS: According to the international guidelines, among the patients who required antiinflammatory treatment, 86.4% were undertreated in Paris and 66.7% were undertreated in Montpellier (p < 0.03, chi square test). Moreover, among the patients with severe asthma, 85% and 60%, respectively, were not receiving an antiinflammatory treatment. CONCLUSION: This study is the first to highlight the magnitude of undertreatment of patients with asthma in a nonselected population.

Adult↗
PubMed1996

Hypodiploidy, Ki-67 growth fraction and prognosis of surgically resected lung cancers.

One hundred and thirty-seven lung cancer patients (123 non-small-cell lung cancers (NSCLC), 10 small-cell lung cancers (SCLC) and four carcinoid tumours) who underwent surgery in an attempt at complete resection were prospectively entered in a study whose aim was to determine the prognostic significance of a hypodiploidy or a multiploidy pattern of tumour cell DNA content and a high immunohistochemical reactivity of Ki-67, a nuclear antigen related to the cell cycle. Indirect immunoperoxidase reactivity of Ki-67 on frozen tumour tissue sections was evaluated both visually, using a classical semiquantitative scale, and by means of a computer-assisted image processor. Cell DNA content analysis was done using static computer-assisted cytometry on tumour cytological prints stained by the pararosaline Feulgen-Schiff technique. The ploidy was characterised for each tumour by DNA index (DI), percentage of hypodiploid cells and type of DNA content histogram (near diploid, hyperdiploid, hypodiploid and multiploid). Ki-67 immunostaining was negative in 64 tumours (48%) and positive in 69 (52%). DNA histogram classification disclosed 57 (42%) near diploid tumours. Among the 80 (58%) aneuploid tumours, 16 were hypodiploid, 44 hyperdiploid and 20 multiploid. The prevalence of both a positive Ki-67 immunostaining and an aneuploid DNA histogram differed according to histology as SCLC demonstrated a higher frequency of both features when compared with NSCLC and carcinoid tumours. On the other hand, Ki-67 immunostaining and ploidy did not significantly differ according to degree of differentiation, nodal status and Mountain's stage grouping. The percentage of cells in the hypodiploid modal DNA was significantly higher for tumours which demonstrated a high Ki-67 immunostaining, suggesting a link between growth fraction and DNA content abnormalities. In univariate analysis, survival did not differ significantly according to either the Ki-67 immunohistochemical reactivity or the DNA index. Patients with a hypodiploid tumour had a shorter survival than patients with other DNA histogram patterns but, owing to the low frequency of hypodiploidy, this difference did not reach statistical significance. In Cox's proportional hazard model, an SCLC histology, an advanced tumour status, a positive nodal status and a hypodiploid tumour (hazard ratio: 2.070; 95% confidence interval 1.041-4.116) were significant determinants of survival. We conclude that hypodiploidy in lung cancer is a distinct DNA content abnormality as it contributes significantly to prognosis. Neither visually assessed nor computer-generated Ki-67 immunostaining measurements significantly determine prognosis.

Adult↗
PubMed1996

Pathophysiology of allergic rhinitis.

Allergy rhinitis results from an IgE-mediated allergy associated with nasal inflammation of variable intensity. The mechanisms of allergic rhinitis have been clarified using nasal challenge with allergen or proinflammatory mediators and measuring cells and mediators released during the early- and late-phase allergic reaction. However, the priming effect of the nasal mucosa is of importance since a single challenge does not perfectly mimic the ongoing allergic reactions induced by repeated allergen exposure. In seasonal and chronic allergic rhinitis, the same cells and mediators are of importance but nonspecific nasal hyperreactivity develops. The regulation of the inflammation of allergic rhinitis is dependent on adhesion molecules and cytokines.

Humans↗
PubMed1996

Computed tomography of the lungs in asthma: influence of disease severity and etiology.

Airways remodelling is a feature of longstanding asthma, but may differ in persons with allergic and nonallergic asthma. To assess airways remodelling indirectly, we compared permanent CT-scan abnormalities in 70 subjects with allergic (median age: 30 yr) and 56 with nonallergic asthma (median age: 54.5 yr) who had had asthma of similar duration. None of the subjects were smokers. Asthma severity was assessed by Aas score and FEV1. Permanent high-resolution computed tomographic (HR-CT) scan abnormalities were characterized. In comparison with allergic asthmatic subjects, those with nonallergic asthma had a significantly greater frequency of cylindric (p < 0.0007, Mann-Whitney U test) and varicose (p < 0.004) bronchiectasis, emphysema (p < 0.0003), bronchial recruitment (p < 0.0001), and sequellar linear shadows (p < 0.0001). There was a significant correlation between Aas score and emphysema (p < 0.0001 for nonallergic and p < 0.0005 for allergic asthma; Kendall's test method) or Aas score and sequellar linear shadows (p < 0.007, nonallergic asthma). There was a significant increase in the extent of permanent abnormalities with increasing severity and duration of asthma in both groups. Patients with brittle asthma had few permanent abnormalities. This study confirms that after a similar course of the disease, patients with nonallergic asthma have a more extensive remodelling of the airways than those with allergic asthma.

Adolescent↗
PubMed1996

Lung cancer chemotherapy. Response-survival relationship depends on the method of chest tumor response evaluation.

In a previous study we found that tumor responses as assessed by CT scan and fiberoptic bronchoscopy are sometimes discordant. We hypothesize that the response-survival relationship might vary according to the method of tumor response assessment. In a multivariate analysis of survival using the landmark method, we evaluated the prognostic significance of tumor response assessed by CT scan or fiberoptic bronchoscopy together with bronchial tumor location and histology of bronchial biopsies at restaging. A total of 133 lung cancer patients (50 small cell lung cancers and 83 non-small cell lung cancers) were entered in controlled chemotherapy trials and prospectively evaluated for chest tumor response by CT scan and fiberoptic bronchoscopy (FOB). Only 106 patients were fully evaluable for response by both methods. For these patients, a statistical concordance was observed between the two tests (kappa = 0.271; p < 0.001). There was a significant correlation between response and survival whatever the test used. However, only CT scan evaluation resulted in a classification showing that the more unfavorable the response stage was, the worse the survival became with no intersection between survival curves. Cox's hazard model demonstrated that CT-evaluated progression, proximal bronchial location at second FOB (intermediate, main bronchus or trachea) and positive histologic status at restaging were all prognostic determinants of poor survival. In conclusion, CT-evaluated response led to the best response-survival relationship as this method classified patients into four groups with different outcomes. Fiberoptic bronchoscopy should be avoided in patients who were found to have no endobronchial lesion during the pretreatment staging. For patients with pretreatment assessable endobronchial lesions, the decision of a second FOB depends on the results of CT restaging: FOB is probably unnecessary in patients for whom progression is disclosed by CT scan. In patients for whom CT scan discloses tumor response or stabilization, bronchial tumor location and histology of bronchial biopsies at second FOB are independent prognostic factors.

Adenocarcinoma↗