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Biomedical subjects

F B Michel

Publications and source records attributed to F B Michel.

At least 109 records · Page 6Linked to original sources

Cyfra 21-1, a new marker of lung cancer.

The are few outstanding serous markers in the treatment of bronchial cancer. ACE lacks sensitivity and specificity and cannot be used as a diagnostic marker. It has been described as a marker of tumoral mass, although not in our study. Prognostic significance was observed, but only in a univariate analysis. Sensitivity of SCC TA4 varied between studies. In our population, the ROC curve for SCC TA4 showed poor discrimination potential. NSE was shown to be a useful marker in the treatment of patients with small cell cancers. Cytokeratins are expressed by all bronchial cancers. Cytokeratin 19 is a sub-unit detected in simple epithelia and their neoplastic counterparts. During tumoral cell lysis, certain fragments of this cytokeratin may be liberated. The immunoradiometric assay described here is able to detect fragments of cytokeratin 19 (called Cyfra 21-1) in serum. Our study established a correlation between Cyfra 21-1 levels and the cancer stage for NCPC, but not for CPC. In addition, Cyfra 21-1 concentration may be used as a tumoral mass marker. Patients with high Cyfra 21 levels must undergo special treatment to find remote tumors.

Antigens, Neoplasm↗

Quantification and localization of HLA-DR and intercellular adhesion molecule-1 (ICAM-1) molecules on bronchial epithelial cells of asthmatics using confocal microscopy.

An increased expression of HLA-DR and ICAM-1 molecules on bronchial epithelial cells has been observed in asthmatic patients. The aim of this study was to evaluate the localization and to quantify the spontaneous expression of HLA-DR and ICAM-1 on bronchial epithelial cells recovered by bronchial brushing of nine asthmatics and nine controls. Epithelial cells constituted over 95% of cells recovered as shown using an anti-cytokeratin MoAb. Expression of HLA-DR and ICAM-1 was studied using indirect immunofluorescence and confocal microscopy. The intensity of fluorescence of epithelial cells expressing HLA-DR and ICAM-1 was significantly (P < 0.003) increased in asthmatics. In asthmatics, but not in controls, the expression of both molecules was localized in the cytoplasm on the apicolateral portions of the cells. This study shows an up-regulation in the expression of HLA-DR and ICAM-1 molecules by bronchial epithelial cells from asthmatics and a localization of these molecules within the cell.

Adult↗

Psychology of the allergic patient.

Biological hypersensitivity is the fundamental feature of atopy, and patients suffering from this syndrome are characterized by their ability to produce high levels of IgE in response to low amounts of antigen. This hypersensitivity results in a range of acute and chronic diseases, such as asthma, rhinitis, allergic conjunctivitis and atopic dermatitis. In addition to their biological effects, these diseases may have psychological consequences in terms of stress, anxiety or depression. However, atopic patients, far from displaying a typical depressive psychological profile, are characterized by their increased emotional sensitivity. Atopic individuals alert us to the presence of allergens but perhaps they also indicate something about our way of life. Are the symptoms displayed by allergic patients, their wheezing, sneezing or itching skin, more than a simple biological response?

Asthma↗

Current trends in the management of allergic diseases.

Treatment strategies for allergic diseases are based on allergen avoidance, pharmacotherapy and immunotherapy. Allergen avoidance should always be attempted, even if it is rarely complete and needs several days or weeks to be effective. Pharmacotherapy is aimed at reducing symptoms arising from allergen triggers and inflammation. In seasonal allergic diseases, a short treatment course is sufficient to reverse nonspecific hyperreactivity and symptoms. In chronic allergic diseases, however, inflammation is of major importance and symptoms are not always readily controlled. Moreover, the treatment should be prolonged as proposed by Guidelines for the Management of Asthma and Rhinitis (1, 2). Effective and well-tolerated drugs are now available and some may be combined for rhinitis or asthma therapy. In rhinitis, first-line therapy is still based on non-sedating antihistamines and topical corticosteroids. Cromoglycate and other drugs may also be used. For asthma, anti-inflammatory therapy is the first-line treatment. In mild sufferers, cromoglycate, nedocromil or low-dose inhaled steroids can be used. For more severe disease, high doses of inhaled corticosteroids are proposed. Bronchodilators are used as 'rescue' medications, though many patients with severe symptoms need regular bronchodilator therapy. Long-acting beta 2-agonists have been introduced recently, but their exact place in the management of asthma is not yet fully established. Immunotherapy was first introduced in 1911 and was based on decades of physicians' experience, rather than on rational thought. Standardized allergens have improved the efficacy of immunotherapy, but the safety of this treatment needs to be improved.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗

Modulation of phenotypic and functional properties of normal human mononuclear phagocytes by granulocyte-macrophage colony-stimulating factor.

In asthma, alveolar macrophages (AMs) are hyperreactive releasing large amounts of mediators and expressing high levels of surface markers. Granulocyte-macrophage colony-stimulating factor (GM-CSF) upregulates monocytes and AMs, and may be involved in the hyperreactivity of AMs. The effects of GM-CSF were tested on monocytes and AMs from normal subjects by examining the expression of factors thought to be upregulated in asthma. After various incubation times of GM-CSF, the expression of CD23 and beta 2-integrins (CD11a, CD11b, CD11c) was studied by FACS and the release of sCD23 was measured by ELISA. The priming and stimulatory effects of GM-CSF were tested on monocytes and AMs and the release of leukotriene B4 (LTB4) was measured by ELISA. GM-CSF induced the expression of CD11c and CD23 and the release of sCD23. GM-CSF primed and stimulated monocytes and AMs to release LTB4. The effects of GM-CSF may explain partly the hyperreactivity of AMs in asthma.

Adult↗

Quality of life in asthma. I. Internal consistency and validity of the SF-36 questionnaire.

Asthma is a chronic disease in which social life is altered. The importance of restrictions on social life may be greater in severe asthma or when symptoms are not adequately controlled. General scales of quality-of-life (QOL) may be used to detect the importance of social life impairment, but it is not yet known whether the scores of such QOL measures are reliable and valid in asthmatic patients. A study was carried out in 252 patients with asthma of variable severity (FEV1 ranging from 25 to 131% of predicted) to assess the validity of a general QOL scale, the first French version of the SF-36 health status questionnaire (SF-36). This is based on 36 items selected to represent nine health concepts (physical, social, and role functioning; mental health; health perceptions; energy or fatigue; pain; and general health). All nine SF-36 category scores were highly significantly correlated with the severity of asthma assessed by the clinical score of Aas (p < 0.0007 to p < 0.0001). Eight SF-36 category scores were highly significantly correlated with FEV1 (p < 0.003 to p < 0.0001). A high internal reliability of SF-36 was found using the alpha coefficient of Cronbach (0.91 for the whole questionnaire). The SF-36 questionnaire is valid and reliable in asthma and can therefore be used to examine QOL in asthmatic and nonasthmatic patients and to determine to what extent asthma impairs social life.

Adult↗

Cell proliferation in the bronchial mucosa of asthmatics and chronic bronchitics.

In chronic inflammatory diseases, cells are recruited but may also derive from local proliferation. In normal bronchial epithelium, under 5% of cells are in cycle but in asthma and chronic bronchitis, proliferation may occur. Cycling cells can be identified by immunohistochemistry using PC10 monoclonal antibody (Proliferating Cell Nuclear Antigen, PCNA). We enumerated PCNA-positive cells (labeling index = LI) in bronchial biopsies of 11 healthy non-smokers (HNS), seven healthy smokers (HS), 30 non-smoking asthmatics (NSA), six smoking asthmatics (SA) and 18 chronic bronchitics (CB). Twenty non-small cell lung cancer patients were used as positive control subjects. Ciliated and secretory cells were PCNA-negative. Basal cells were PCNA-positive in one of the 11 HNS (LI = 0.18 +/- 0.60), none of the seven HS, two of the 30 NSA (LI = 0.05 +/- 0.20), two of the six SA (LI = 2.4 +/- 4.3) and 11 of the 18 CB (LI = 12 +/- 20). In smokers, PCNA positivity correlated with tobacco consumption (Rho = 0.62, p < 0.0008) and in patients with chronic bronchitis, with the degree of metaplasia (tau = 0.815, p < 0.0001). The submucosa of most subjects showed no PCNA immunoreactivity. These findings suggest that the bronchial mucosa of nonsmokers is not hyperproliferative, even in asthmatics. Tobacco smoking increases PCNA immunoreactivity, possibly leading to the metaplasia of chronic bronchitis.

Adolescent↗

Measurement of the internal size of bronchi using high resolution computed tomography (HRCT)

Computed tomography (CT) of the lungs makes it possible to study individual airways. A technique using high-resolution-CT (HRCT) has been developed to measure the internal size of the bronchi. Five normal subjects had a conventional HRCT scan at full, deep inspiration. The internal size of the airways from segmental to the sixth generation bronchi was measured using an original method of data analysis. The size of the airways ranged 0.5-50 mm2 (approximately 0.8-8 mm in diameter. The technique was found to be highly reproducible, making it possible to study the variation in airways calibre after provocative challenge or administration of bronchodilator in asthma.

Adult↗

Long-term results of neoadjuvant ifosfamide, cisplatin, and etoposide combination in locally advanced non-small-cell lung cancer.

Thirty-three patients with T3,N2,M0 or T4,N2,M0, non-small-cell lung cancer (NSCLC) took part in a phase 2 study in an attempt to evaluate the feasability of neoadjuvant chemotherapy followed by surgery and thoracic radiotherapy. Chemotherapy consisted of daily administration of the following treatment: etoposide, 100 mg/m2; cisplatin, 25 mg/m2; ifosfamide, 1.5 g/m2; and mesna, 1.8 g/m2 for 4 days. Three cycles were planned starting every 21 days. Responding patients underwent a thoracotomy in order to attempt a resection and then received a 45 Gy of thoracic radiotherapy. The results of response and resection rates have been published and the present final report deals with the long-term results. Chemotherapy induced a 55 percent partial response rate and a 15 percent complete response rate allowing a complete resection in 55 percent of the patients. Complete remission was histologically confirmed for the five complete responders. Although the median survival was short (10 months), six patients were long-term survivors (3-year survival rate: 19 percent). Survival was significantly influenced by the type of resection: patients for whom a complete resection was possible survived the longest with a median survival three times that of the other patients. Modalities of relapses differed according to the results of surgery: 8 of the 15 patients who did not undergo a complete surgical resection experienced a local relapse during the first 18 months of follow-up whereas in the complete resection group, central nervous system metastasis was the main site of relapse. We conclude that the neoadjuvants ifosfamide, cisplatin, and etoposide in patients with locally advanced NSCLC are feasible to use and allow a 19 percent 3-year survival rate. These results are the rationale of an ongoing randomized study comparing neoadjuvant chemotherapy followed by surgery and surgery alone. This study is designed to test whether neoadjuvant chemotherapy improves survival of patients with locally advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗

Safety considerations in assessing the role of immunotherapy in allergic disorders.

Specific immunotherapy (SIT) is accepted as an effective treatment of allergic diseases when high quality extracts are used. However, this form of treatment can cause untoward reactions among which systemic reactions are the most severe. Although life-threatening reactions are rare and deaths exceptionally reported, SIT should be prescribed by allergists to patients with well defined characteristics, and administered with care by (or under the close supervision of) physicians trained to deal rapidly with the reactions. Reactions with standardised extracts occur mostly during the dose increase phase but they can be prevented using adapted schedules and premedication. During maintenance injections or when vial batches are changed, standardised extracts of known shelf-life usually result in a low rate of systemic reactions. Patients with asthma are more prone to develop systemic reactions, and allergens should not be administered to patients with a forced expiratory volume in 1 second (FEV1) under 70% of predicted or in those who have unstable or symptomatic asthma. Systemic reactions may be observed with all allergens and allergenic preparations although it appears that high molecular weight extracts may be safer.

Allergens↗

[Neo-adjuvant chemotherapy of locally advanced non-small cell bronchial cancers].

Locally advanced non-small cell lung cancers have a poor prognosis following surgery alone when this has been possible, because of a high rate of local and metastatic relapses. Probability of five years survival for these patients ranges between 5 and 15%. Thus, locally advanced non small cell lung cancer for which resection is potentially possible but poorly curative are usually designated as marginally resectable. Adjuvant postoperative chemotherapy or radiation therapy hardly seem to improve survival. Therefore, other combined modality treatments might be proposed. Neoadjuvant chemotherapy may be used for non small cell lung cancer in an attempt (a) to improve complete resection rate and (b) to treat non-detectable metastatic disease. Numerous phase II studies have demonstrated the faisability of this combined modality in locally advanced non small cell lung cancers, particularly in stage N2 patients. Until the results of the ongoing phase III studies would be known, neoadjuvant chemotherapy might be considered as an investigational approach.

Antineoplastic Combined Chemotherapy Protocols↗

[Breath tests].

Explore the source record for details and available documents.

Humans↗

Differences in IL-4 release by PBMC are related with heterogeneity of atopy.

Atopy is heterogeneous and the IgE immune response of patients allergic to a single allergen (monosensitized) differs from that of those allergic to multiple allergens (polysensitized). Since interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) regulate human IgE synthesis in vitro, we determined whether cytokines may be involved in the heterogeneity of atopy by comparing the serum IgE and sCD23 titres to the cytokine profile of T lymphocytes from 44 atopic patients (13 mono- and 31 polysensitized) and seven non-atopic subjects. Monosensitized patients were allergic to grass or cypress pollens or house dust mites, and polysensitized ones to many pollen species (n = 5) or many allergens (n = 26). Total serum IgE was lower in the control group than in both atopic groups and in the monosensitized group than in the polysensitized one. IgE immunoblots to orchard grass pollen and house dust mites were less heterogeneous in the monosensitized group than in the polysensitized one. IL-4 production by in vitro-activated peripheral blood mononuclear cells (PBMC) was significantly higher in the polysensitized group than in the monosensitized, and marginal in the control group. In contrast, IFN-gamma production was strongly reduced in both atopic groups, and IL-2 production comparable in the three groups. IgE and soluble CD23 (sCD23) release was higher in the atopic groups than in the control, and higher in the polysensitized group than in the monosensitized one. This study shows that PBMC of mono- and polysensitized subjects have a different IL-4 and sCD23 profile and suggests that human beings may be classified into high and low IgE responders on the basis of IL-4 production.

Adolescent↗

[Maintenance treatment of asthma].

Taking charge of asthmatic patients can only be conceived in the long term. The objective of treatment is to obtain a quality of life that is as close as possible to the norm. Pretherapeutic evaluation is of paramount importance to assert the diagnosis, taking into account the multiple facets of asthma. It is widely agreed that the therapeutic pressure depends on the severity of the disease. The triggering factors may vary with time; it is essential to assess their responsibility and treat them. Asthma is a complex syndrome with multiple factors. To improve the therapeutic compliance needed for a good result time must be spent informing and teaching each patient.

Adrenal Cortex Hormones↗

[CYFRA 21-1: a new marker of epidermoid cancer of the bronchi. Comparison with 3 other markers].

Cytokeratins are intermediate filaments of the cytoskeleton that are expressed by bronchial epithelium and its neoplastic counterpart, lung cancer. A new immunoradiometric assay referred to as CYFRA 21-1 makes it possible to titrate in the serum a cytokeratin 19 fragment. This study deals with the sensitivity, specificity and applicability of this serum marker in squamous cell carcinoma. Sera from non malignant pulmonary diseases were taken as controls. In comparison with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC T-A4) and neuron specific enolase (NSE), CYFRA 21-1 was the most accurate marker. The area under the CYFRA 21-1 ROC curve was significantly greater than those of CEA, SCC T-A4 and NSE. Using a 3.6 ng/ml threshold, as determined by the ROC curve, CYFRA 21-1 was significantly correlated with tumor mass.

Antigens, Neoplasm↗

[The gene or genes of allergic asthma?].

Asthma is a multifactorial disease in which the hereditary component has been demonstrated by familial and identical twin studies. Allergy is important in the aetiology of asthma and is characterized by a hyperreaction to allergens triggering predominantly the immunoglobulines E. The levels of these antibodies are found to be elevated even in non allergic asthmatics. The majority of genetic research in this area is focused on either the genes of the specific immune response or that of the non allergic response. These are the genes of the class II MHC, and the APY gene on chromosome 11q respectively. The modern techniques of molecular genetics and in particular those of inverse genetics have recently contributed to a more comprehensive understanding of this disease.

Animals↗

[The effect of adrenergic beta agonists on morbidity and mortality of asthma].

The frequency and severity of asthma are increasing, and since 1960 two "epidemics" of deaths have occurred. During the first one, in the 1960's, a beta-adrenergic agonist with low specificity administered in high doses was blamed and usually exonerated. During the second epidemics, in the 1975-85 period, fenoterol (a moderately selective beta-adrenergic agonist) administered in high doses was also blamed, but its noxious effects have not yet been definitely confirmed. The hypotheses concerning the potential hazards of beta-adrenergic agonists inhaled for long periods are interesting, as they incite us to think and possibly to revise our therapeutic approach, but they should not lead to an unfounded panic. These drugs may exert their potential noxious effects at several levels. They might increase the inflammation of the bronchi and result in tachyphylaxis, but these mechanisms do not seem to be responsible. When given in very high doses beta-adrenergic agonists produce hypokalaemia which is a cause of arrhythmias; this mechanism may explain some of the noxious effects of these drugs, but it has never been confirmed in clinical practice. Thus, the suggested causes of the increase in severity of asthma are multifactorial. From the data now available no firm conclusion can be drawn concerning the effects of this class of drugs, but they should incite physicians to caution and, above all, to a better prescription of anti-asthma treatments.

Adrenergic beta-Agonists↗