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Biomedical subjects

F B Michel

Publications and source records attributed to F B Michel.

At least 73 records · Page 4Linked to original sources
PubMed1996

Bronchial elastic fibers in normal subjects and asthmatic patients.

Elastic fibers required to maintain bronchial patency during ventilation may be damaged in asthma as a result of repair following inflammation or stretching during exacerbations. Fifteen normal subjects and 40 asthmatics of variable severity were studied. Bronchial biopsies were obtained from a subsegmental bronchus using a flexible bronchoscope. The elastic fibers were examined using orceine-eosine sustaining and/or immunohistochemistry with two monoclonal antibodies against elastin or transmission electron microscopy (six asthmatics and four control subjects). Orceine-eosine staining revealed that most normal subjects had normal fibers throughout the submucosa whereas of the 21 asthmatics analyzed only three had a normal superficial elastin network. In five patients, elastin had virtually disappeared. In the remaining patients, fibers appeared fragmented. The deeper layer of elastic fibers was abnormal in 17 asthmatics, fibers being patchy, tangled, and thickened. The fragmentation of the superficial network of elastic fibers shown in asthmatics was confirmed by immunohistochemistry. Electron microscopy studies suggested that the elastinolytic process and fragmentation of elastic fibers occurred in asthmatics. Elastinolysis occurs in the airways of asthmatics possibly as a result of repair elicited by chronic inflammation. Mechanical stretch induced by breathing and edema may lead to the fragmentation of fibers in asthmatic airways.

Adult↗
PubMed1996

Cytokeratins as serum markers in lung cancer: a comparison of CYFRA 21-1 and TPS.

We examined two recently described cytokeratin markers, CYFRA 21-1 (cytokeratin fragment recognized by KS 19-1 and BM 19-21 antibodies) and TPS (specific M3 epitope of the tissue polypeptide antigen), in 405 lung cancer patients (91 small-cell and 314 non-small-cell lung cancers) and 59 patients presenting with nonmalignant pulmonary disease. Sensitivity-specificity relationship, as analyzed by receiver operating characteristic curves, demonstrated a higher accuracy of CYFRA 21-1 in comparison with TPS in both small-cell and non-small-cell lung cancers. Thresholds of 3.6 ng/ml and 140 U/L for CYFRA 21-1 and TPS respectively gave a 90% to 95% specificity. Sensitivity of CYFRA 21-1 was the highest in squamous-cell carcinomas (0.61) and the lowest in small-cell lung cancers (0.36), whereas sensitivity of TPS did not vary significantly according to histology (overall sensitivity, 0.40). In non-small-cell lung cancers, both serum CYFRA 21-1 and serum TPS distributions varied significantly according to Mountain's stage of the disease, nodal status, tumor status, and performance status, inasmuch as the worse each above-mentioned variable became, the higher the median and interquartile serum marker level was. Neither CYFRA 21-1 nor TPS was able to accurately discriminate between stage IIIa (marginally resectable) and stage IIIb (unresectable) non-small-cell lung cancers, however. In both small-cell and non-small-cell lung cancers, univariate survival analyses demonstrated that either a CYFRA 21-1 level over 3.6 ng/ml or a TPS level over 140 U/L significantly indicated a poor survival rate. In the whole population, taking into account other significant variables, Cox's model analysis demonstrated that a poor performance index, an advanced stage of the disease, the presence of metastases, elevated serum lactate dehydrogenase, and high serum CYFRA 21-1 (odds ratio, 1.74; 95% confidence interval, [1.33-2.27] were independent prognostic variables. We concluded that CYFRA 21-1 is a significant determinant of survival. Other applications of cytokeratin markers in lung cancer are still limited.

Adult↗
PubMed1996

Comparison of an expert system with other clinical scores for the evaluation of severity of asthma.

"Asthmaexpert" was produced at the special request of several clinicians in order to obtain a better understanding of the medical decisions taken by clinical experts in the management of asthmatic patients. In order to assess the severity of asthma, a new score called Artificial Intelligence score (AI score), produced by Asthmaexpert, was compared with three other scores (Aas, Hargreave and Brooks). One hundred patients were enrolled prospectively in the study during their first consultation in the out-patient clinic. Distribution of severity level according to the different scores was studied, and the reliability between AI and other scores was evaluated by Kappa and MacNemar tests. Correlations with functional parameters were performed. The AI score assessed higher levels of severity than the other scores (Kappa = 18, 28 and 10% for Aas, Hargreave and Brooks, respectively) with significant MacNemar test in all cases. There was a significant correlation between AI score and forced expiratory volume in one second (FEV1) (r = 0.73). These data indicate that the AI score is a severity score which defines higher levels of severity than the chosen scores. Correlations for functional parameters are good. This score appears easy to use for the first consultation of an asthmatic patient.

Adult↗
PubMed1996

Overview of allergic mechanisms. Ebastine has more than an antihistamine effect.

Histamine antagonists together with topical steroids are the treatment of choice in allergic rhinitis. Many of these histamine antagonists exhibit effects in addition to blockade of the histamine receptor. In this study we have investigated the effects of ebastine and carebastine on the release of eicosanoids and cytokines from human dispersed polyp cells and the effect of these compounds on the release of inflammatory mediators into nasal lavage fluid after allergen challenge. Ebastine was shown to block the release of anti-IgE-induced prostaglandin D2 (PGD2) and leukotriene C4/D4 from human nasal polyp cells (IC30 values of 2.57 and 9.6 mumol/L, respectively) and to inhibit the release of cytokines. Carebastine inhibited the release of PGD2 (IC30 8.14 mumol/L) but had little effect on cytokine release. When patients underwent nasal provocation tests with allergen, ebastine significantly increased the mean number of pollen grains required to induce an allergic response. In addition, the drug inhibited the release of granulocyte-macrophage colony-stimulating factor but had no effect on any other mediators measured.

Adolescent↗
PubMed1996

[Value of imaging in asthma].

While the definition of asthma is based on clinical manifestations and respiratory function, imaging is widely used in acute asthma. We attempted to exploit the resources of high-resolution computed tomography to better study the fine structure of the airways. In acute asthma and at the first consultation for asthma, standard radiograms provide little precise information on the bronchi excepting cases with major lesions. High-resolution computed tomography can identify persistent bronchial and lung lesions which significantly correlate with clinical expression. These lesions are more frequent in non-allergic persons. We were able to obtain dynamic images demonstrating the anatomic variations in bronchial obstruction occurring after a provocation test. These applications are now in the clinical research stage. High-resolution computed tomography may soon play a role in clinical management of patients with asthma.

Asthma↗
PubMed1996

[Vectors of gene transfer. Applications in pneumology].

Human gene therapy in 1996 is a reality with almost 100 trials world-wide involving nearly 450 patients. The stakes are enormous. To assure the efficacy and safety of such a regime is mainly a problem of vector to carry the chosen nucleotide sequences. The ideal vector should have as a unique function that of the transport of the gene of therapeutic interest to the desired area at the proper quantity. The ideal vector does not currently exist and each system, viral or non-viral has both advantages and inconveniences.

Base Sequence↗
PubMed1996

[The epidemiology and genetics of asthma. I. Descriptive epidemiology and analysis of environmental factors].

Asthma is regarded as a disease with a complex interaction between genetic and environmental factors. Since the end of the 1970s and during the 80s the world has seen an increase in the prevalence, morbidity and mortality linked to asthma. The rapidity of progress of this phenomenon means that it cannot be explained only by modification of genetic factors and stresses the preponderance of exogenous factors. The purpose of this review is to examine the epidemiological knowledge of these environmental factors and of the genetic factors in asthma in order to underline how these genetic and exogenous factors interact and modulate the occurrence of the asthmatic disease. In the first part of this general review we will discuss the epidemiology of asthma in terms of prevalence, incidence, mortality, cost and socio-professional and scholastic repercussions and will underline for each environmental factor its causal role and/or exacerbation in asthma as well as its contribution in the increased prevalence and severity of asthma. In the second part of this general view we touch on the epidemiological knowledge of the genetics of asthma and of atopy.

Absenteeism↗
PubMed1996

[The epidemiology and genetics of asthma. II. Genetic aspects of the epidemiology of asthma and atopy].

Asthma is regarded as a disease with a complex interaction between genetic and environmental factors. Since the end of the 1970s and during the 80s the world has seen an increase in the prevalence, morbidity and mortality linked to asthma. The rapidity of progress of this phenomenon means that it cannot be explained only by modification of genetic factors and stresses the preponderance of exogenous factors. The purpose of this review is to examine the epidemiological knowledge of these environmental factors and of the genetic factors in asthma in order to underline how these genetic and exogenous factors interact and modulate the occurrence of the asthmatic disease. In the first part of this general review we discussed the epidemiology of asthma in terms of prevalence, incidence, mortality, cost and socio-professional and scholastic repercussions and underlined for each environmental factor its causal role and/or exacerbation in asthma as well as its contribution in the increased prevalence and severity of asthma. In the second part of this general view we touch on the epidemiological knowledge of the genetics of asthma and of atopy.

Asthma↗
PubMed1996

[Bronchial cancer: from epidemiology to treatment].

The quest for an effective treatment for lung cancer is a major preoccupation for the medical community as it is now the leading cause of cancer mortality worldwide and its incidence continues to increase particularly in developing countries, in women and in patients under the age of 45 due to the high incidence of tobacco smoking. The major form of treatment for lung cancer is surgery whenever possible followed by chemotherapy either alone or in association with radiotherapy. The treatment of non-operable tumours can today be justified both by the slight but undeniable amelioration of survival rates and more importantly by an increase in the quality of life. Our experience, based on the treatment of 640 patients, suggests that the use of chemotherapy, which is legitimized by the high incidence of metastatic spread associated with the disease, leads to chemoresistant relapses in the case of small cell cancers and primary resistances in non-small cell cancer. Recent advances in the treatment of bronchial cancers are worth underlining as they have led to radical changes in daily practice. The efficacity of chemotherapy in the treatment of small cell cancers is based on a dose-effect relationship which justifies the use of induction therapy which, even if not particularly intensive, should be given at an optimal level. Moreover, thoracic radiotherapy is beneficial in the early stages of the disease. Chemotherapy increases the survival rates for patients with non small cell cancers and although this was difficult to demonstrate the effect is, today, widely accepted. Certain types of chemotherapy are oriented towards the optimisation of initial treatment with the aim of eradicating the microscopic metastatic disease (this is the case for chemotherapy intensification for small cell cancers and neo-adjuvant chemotherapy for non small cell cancers). Other strategies are aimed at maintaining a chemotherapy-induced tumoral response: possibly involving the use of interferons. Whilst thoracic oncology cannot promise exciting breakthroughs in the short-term, present phase III trials with new cytostatic drugs and new therapies give rise to real hopes for the future.

Bronchial Neoplasms↗
PubMed1995

[Community acquired pneumonias in the region of Montpellier. Increase of pneumococci with reduced sensitivity to penicillins].

OBJECTIVES: Bacteriological data indicate that there is an increased incidence of Streptococcus pneumoniae strains with an intermediate sensitivity to penicillin. The goals of the present study was i) to investigate the profile of sensitivity of Streptococcus pneumoniae isolated from patients with bacterial pneumonia in the area of Montpellier and ii) to compare this profile with the findings of the national center registry to better appreciate geographical specificity. METHODS: Fifty-six patients with bacterial pneumonia were enrolled into the study. From September 1989 to March 1994, we performed bacterial sampling including blood cultures, protected brushes and bronchoalveolar lavage specimens. We examined the antibiotic sensitivity of the germs which were isolated. All patients were followed using clinical and radiological criteria. RESULTS: A precise bacteriological diagnosis was established in 83.6% of the population. Streptococcus pneumoniae was found in 47.2% of the samples. In 19%, the strains displayed an intermediate sensitivity to penicillin. All patients recovered. CONCLUSION: We found a higher rate of resistance to penicillin in Montpellier than the common rate of the national reference center in France. The location of Montpellier closed to the Spanish border might, at least in part, explain this difference.

Adolescent↗
PubMed1995

5-15-diHETE and lipoxins generated by neutrophils from endogenous arachidonic acid as asthma biomarkers.

5-Lipoxygenase (5-LO) activation of human blood polymorphonuclear cells (PMN) from healthy subjects (HS) and from asthmatic patients (AP) was investigated comparing their respective capacities to produce lipoxins, 5,15-dihydroxyeicosatetraenoic acid (5,15-diHETE) and leukotrienes, under in vitro stimulation by ionophore A23187. PMN from AP were able to generate higher leukotriene levels from endogenous sources than PMN from HS. Moreover they produced 5,15-diHETE (from 50 to 280ng/10(7) cells) and lipoxins (from 1 to 30ng/10(7) cells), in a linear manner, whereas in the same experimental conditions no detectable amounts of these compounds appeared in PMN from HS. The enhanced 5-LO activation of blood PMN may reflect transcellular signalisation priming indicating that lipoxins and 5,15-diHETE could be much more specific inflammatory state biomarkers than leukotriene B4.

Arachidonic Acid↗
PubMed1995

Evaluation of the effects of ambroxol on the ofloxacin concentrations in bronchial tissues in COPD patients with infectious exacerbation.

Infectious excerbations of COPD are generally due to Streptococcus pneumoniae, Haemophilus species, and other Gram-negative bacteria. Ofloxacin has potent activity against Gram-negative species but is less effective against Gram-positive species including Streptococcus pneumoniae. It has also been shown that the administration of ambroxol increases the concentration of some antibiotics in pulmonary tissues. The aim of the study was to determine whether ambroxol increases the bronchial tissue concentrations of ofloxacin to a level exceeding the MIC90 of the bacterial species less susceptible to ofloxacin. 24 patients with COPD were randomized in two groups. Drug regimens of ofloxacin alone (200 mg twice daily) or ofloxacin (200 mg twice daily)+ambroxol (30 mg thrice daily) were administered over 10 d. A fibroscopy was performed on day 10 with bronchial biopsies and broncho-alveolar lavage. At steady state, concentrations of drug in plasma and bronchial samples were assayed by HPLC with fluorometric detection. There was no significant difference in the bronchial levels of ofloxacin between the two groups; however, in alveolar cells, ofloxacin concentration was three times higher in the group with ambroxol. Ambroxol does not increase ofloxacin concentrations in bronchial tissue because high concentrations are already present in the lung.

Administration, Oral↗
PubMed1995

A multicenter clinical study of the efficacy and tolerability of azelastine nasal spray in the treatment of seasonal allergic rhinitis: a comparison with oral cetirizine.

A new topically administered intranasal antiallergic drug, azelastine, was investigated in a large randomized multicenter study that compared it with oral cetirizine from the aspects of efficacy and safety. Patients were treated for 14 days, and efficacy was assessed on days 7 and 14 by means of an investigator rating scale measuring the severity of eight nasal and ocular symptoms of seasonal rhinitis. In addition, patients recorded the extent of individual symptoms on a visual analogue scale (VAS). Tolerability was assessed on the basis of adverse events reported. Data from a total of 129 patients were included in the analysis of drug efficacy. Treatment groups had significant reductions in the investigators' total symptom score during treatment. These reductions were 47% and 55% for azelastine and cetirizine, respectively, at day 7 and 61% and 67% at day 14. There were no differences between the two groups whether they were analyzed overall or separately for nasal and ocular symptoms. Patients' daily VAS scores showed a significantly better resolution of nasal stuffiness and rhinorrhea in the azelastine-treated group than in the cetirizine-treated group. There were no differences for any other symptom. Adverse events were reported by 12 patients in the azelastine group and 20 patients in the cetirizine group. Drowsiness was the only frequently occurring event and this was reported by 9 patients in the cetirizine group and 2 patients in the azelastine group (P = 0.003).

Administration, Inhalation↗
PubMed1995

Neoadjuvant chemotherapy of locally advanced non-small cell lung cancer.

Neoadjuvant chemotherapy was tested in non-small cell lung cancer in an attempt to increase the resectability of the tumor and to treat the microscopic metastatic disease known to be responsible for the majority of failures in surgically treated patients. This review deals with published trials. Most of them are feasibility studies in Stage III NSCLC. Obviously, the heterogeneity of eligibility criteria from one study to another prevents general conclusions on the usefulness of neoadjuvant chemotherapy. However, it is possible to conclude that neoadjuvant chemotherapy has an antitumor activity; the majority of the studies report a 60% objective response rate including a significant number of complete responses and a 50% complete resection rate. Neoadjuvant chemotherapy does not increase morbidity after surgery except when it is combined with preoperative radiation therapy. At the time of writing, one Phase III randomized study comparing neoadjuvant chemotherapy followed by surgery with surgery alone has been published. This study concludes that the combined modality treatment improves the survival of patients with locally advanced non-small cell lung cancer. Taken as a whole, the literature deserves further studies to determine the place of neoadjuvant chemotherapy in lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗