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Biomedical subjects

P Godard

Publications and source records attributed to P Godard.

At least 163 records · Page 9Linked to original sources
PubMed1994

Clinical evaluation of serum tissue polypeptide-specific antigen (TPS) in non-small cell lung cancer.

M3 is an epitope of the tissue polypeptide antigen detectable in the serum by immunoradiometric assay. This epitope is referred to as tissue polypeptide-specific antigen (TPS). We examined the pretreatment TPS level of 160 non-small cell lung cancer (NSCLC) patients and 71 patients who suffered from non-malignant pulmonary diseases. The upper limit of normal values was 140 U/l. Using this cutoff, the sensitivity and specificity were 36 and 90%, respectively. The TPS was significantly higher in NSCLC patients with an advanced stage, a mediastinal lymph node involvement or a poor performance status. This level was significantly higher in the group of patients for whom the disease proved to progress during chemotherapy. In univariate analysis, patients with a high TPS level proved to have a shorter survival than patients with a TPS < or = 140 U/l. In Cox's model analysis, performance status, stage of the disease and serum TPS were the only significant prognostic variables. The low sensitivity of TPS precludes its use for diagnosis. However, the pretreatment TPS level adds information to the management of NSCLC inasmuch as it predicts a low sensitivity to chemotherapy and a poor prognosis.

Adult↗
PubMed1994

Release of cytokines by blood monocytes during strenuous exercise.

During strenuous exercise in endurance athletes, monocytes are activated and there is an acute inflammation and hypoxemia possibly due to lesional pulmonary edema. IL-6 and TNF-alpha released by monocytes may be implicated in the acute phase of lesional pulmonary edema. A study was carried out to determine whether TNF-alpha and IL-6 are released during strenuous exercise, and, if adrenalin released during exercise alters their generation. Ten young and six master athletes underwent an incremental exercise test. Arterial blood was drawn at rest, at the end of the exercise, and 20 minutes afterwards. Monocytes were isolated and incubated for 18 hours in the presence or absence of adrenalin. Il-6 and TNF-alpha were measured in monocyte supernatants. The spontaneous release of IL-6 or TNF-alpha was increased in young athletes when compared to older subjects. The spontaneous release of TNF-alpha was increased, but not significantly, by exercise and there was no correlation between the release of IL-6 and TNF-alpha and lung function measured during hypoxemia. Adrenalin inhibited the release of IL-6 or TNF-alpha. Correlations were observed between the in vitro release of IL-6 or TNF-alpha and age, VO2max, maximal ventilation and maximal power output of the subjects.

Adult↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Phenotypic and functional modulation of normal human alveolar macrophages by histamine.

Alveolar macrophages (AM) play a regulatory role in asthma. AM from asthmatics are activated, release increased amounts of cytokines, and express higher levels of the low affinity receptor for IgE (Fc epsilon RIIb/CD23b) and receptors for adhesion molecules. The bronchial microenvironment may modulate the phenotypic and functional characteristics of AM. On AM from normal subjects, the effects of histamine were studied on the expression of adhesion molecules (LFA-1, ICAM-1) and CD23b as well as on the release of fibronectin. The expression of LFA-1, ICAM-1, and CD23b was examined by immunocytochemistry using the alkaline phosphatase-anti-alkaline phosphatase technique. The expression of CD23b mRNA was studied by in situ hybridization. The release of fibronectin was measured by enzyme immunoassay. We found that histamine induced in a dose- and time-dependent fashion a significant increase of AM expressing the three membrane markers and a significant increase in the release of fibronectin. The maximum effect of histamine was observed after an incubation of 12 to 24 h and a dose of 1 microM. The histamine effects were specific, since they were significantly inhibited by an H1-blocker, pyrilamine, used at a concentration of 10 microM. The effect of an H2-blocker (ranitidine, concentration of 10 microM) was inconstant. Cycloheximide blocked the histamine effects, suggesting that it requires protein synthesis for its action. This study provides an in vitro model of cellular interaction between mast cells and AM, which might be relevant in the airway inflammation in asthma.

Adult↗
PubMed1994

Enhancement of reactive oxygen species formation in stable and unstable asthmatic patients.

There is increasing evidence to suggest that human blood polymorphonuclear neutrophils (PMNs) and monocytes play an important role in the inflammatory processes of asthma. In asthmatic patients, PMNs and monocytes were shown to be activated more than in healthy subjects. We investigated the capacity of these two cell populations to generate reactive oxygen species (ROS) in stable and unstable asthmatic patients. The two populations of asthmatic patients were identified by asthma activity, as expressed by clinical events occurring within 2 weeks prior to the study. Oxygen species formation was analysed for isolated purified PMNs and monocytes (Mos) by chemiluminescence (CL) using lucigenin and luminol as luminescent probes. CL was determined on nonstimulated and on phorbol myristate acetate (PMA)-stimulated cells. The stimulatability coefficient (PMA-stimulated/nonstimulated cell ratio) of each cell population was then calculated. Resting PMNs and Mos generated significantly greater amounts of ROS in stable asthmatic patients, and much more in unstable asthmatic patients, as compared to healthy subjects, both in lucigenin and luminol enhanced CL. Non O2.- ROS production from PMA-stimulated PMNs and Mos was identical in unstable asthmatic patients and in healthy subjects, whereas a significant decrease was observed in stable asthmatic patients, as assessed by luminol enhanced CL. PMA-stimulated cells showed no difference in O2.- generation, as assessed by lucigenin enhanced CL. However, the stimulatability coefficient of all asthmatic patients was always significantly lower than that of healthy subjects. These results suggest that there are differences in priming and stimulation of Ros production from PMNs and Mos between stable and unstable asthmatic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acridines↗
PubMed1994

Enoximone vs nicardipine during the early postoperative course of patients undergoing cardiac surgery. A prospective study of two therapeutic strategies.

The hemodynamic effects of enoximone and nicardipine were compared during the early postcardiac surgery period in 40 patients with systemic hypertension and moderate cardiac dysfunction. Patients were prospectively randomized into two groups. Mean right atrial pressure was maintained above 7 mm Hg. The drug infusion rate was adjusted to maintain mean systemic artery pressure (SAP) within the 65 to 80 mm Hg range. Complete hemodynamic evaluations were performed before any drug infusion and during the following 24 h with special attention to O2-related variables. Oxygen consumption, cardiac index, and stroke index improved significantly and similarly in the two groups. The SAP and systemic vascular resistance decreased more rapidly in the enoximone group but whole body lactate level increased after the second hour of infusion. Furthermore, this was paralleled by an arteriovenous O2 contents difference deficit. In our study, nicardipine was found superior over enoximone in terms of recovery from intraoperative tissue hypoxia. Furthermore, enoximone's inotropic effects were not found to be clinically relevant.

Cardiac Surgical Procedures↗
PubMed1994

[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↗
PubMed1994

Low-affinity receptor for IgE on human bronchial epithelial cells in asthma.

Bronchial epithelial cells are activated in asthma but the mechanisms underlying this activation are poorly understood. We tested the possibility that bronchial epithelial cells recovered by brushing from 15 asthmatic and 11 control subjects may be activated by an IgE-dependent mechanism. The expression of the low-affinity IgE receptor (CD23) was studied by immunocytochemistry using the alkaline phosphatase anti-alkaline phosphatase technique and immunofluorescence using confocal microscopy. Four of eight allergic asthmatic patients and none of the seven non-allergic asthmatic or control subjects had a positive expression of CD23. The functional activity of CD23 was examined in the cells recovered from these subjects by stimulating them with IgE/anti-IgE. 15-HETE was not released but endothelin was released in the three or four asthmatic patients who had a positive expression of CD23. None of the other subjects released any endothelin. This study suggests that bronchial epithelial cells of asthmatic patients may be directly activated by an IgE-mediated mechanism.

Adult↗
PubMed1994

[Mechanisms of bronchial hyperreactivity. Role of the epithelium].

Bronchial epithelial cells are present all along the airways. They play a role of barrier and protect the airways against inhaled pollutants. However it is known to day that they could play an active role, through synthesis and release of mediators which modulate the airway muscles, the epithelium permeability and the vascular tone. Shedding of the epithelium is a constant feature of the asthmatic airways as can be observed directly on the bronchial biopsies and indirectly through and increased number of epithelial cells in the bronchoalveolar lavage fluid. The epithelial shedding is well correlated to the bronchial hyperreactivity. In vitro, bronchial epithelial cells release higher quantities of 15 HETE, endothelin and PGE2 in asthmatics than in normal control subjects. They express HLA-DR and ICAM-1 in higher quantities in asthmatic patients. Bronchial epithelial cells might play an important role in inflammatory lesions which are observed in asthmatic patients. They could be a good target for new therapeutic approaches in asthma.

Animals↗
PubMed1994

[Mechanisms of bronchial hyperreactivity: role of airway inflammation and atopy].

The mechanisms of airway hyperresponsiveness are numerous and complex. The inflammatory process is one of the most important. It is characterized by epithelial damage and sloughing, by cellular infiltration of the bronchial mucosa and submucosa and by anatomical modifications of the bronchial wall. The cellular infiltrate is characterized by the presence of eosinophils, lymphocytes, monocytes-macrophages and mast cells. These cells are activated and release bronchoconstrictor and proinflammatory mediators. Eosinophils have toxic effects on the bronchial epithelium through the release of basic proteins, while lymphocytes play a central role through the release of cytokines, which can activate and recruit other cells. Mast cells have an important role of starter of the reaction but may also maintain it. Allergen inhalation in the laboratory, when a late response occurs, is responsible for an inflammatory reaction comprising eosinophil influx and activation and T lymphocyte activation. The intensity of the reaction is related to the transient increase in airway hyperresponsiveness confirming the important role of atopy and allergic reactions in airway hyperresponsiveness. However the same kind of inflammatory reaction can be present without atopy and antiinflammatory treatments, even if they reduce airway hyperresponsiveness, may not completely abolish it. This emphasises the complex mechanisms involved in persistent airway hyperresponsiveness.

Asthma↗
PubMed1993

[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↗
PubMed1993

[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↗
PubMed1993

[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↗
PubMed1993

Effect of nedocromil sodium on sulfidopeptide leukotrienes-stimulated human alveolar macrophages in asthma.

Alveolar macrophages (AM) may take part in the amplification of the inflammatory mechanism involved in asthma. During an asthma attack, mast cells and eosinophils release arachidonic acid derivative mediators of inflammation such as sulfidopeptide leukotrienes. Among them, LTC4 has been shown to be present in bronchoalveolar fluid. In asthmatic patients, we showed that the ability of AM to transform LTC4 into its derivatives LTD4 and LTE4 was related to the intensity of the local inflammation observed during endoscopy. AM from asthmatics incubated in the presence of LTC4 or LTE4, generated LTB4 and 5-HETE, which are potent chemoattractants. Nedocromil sodium (10(-4) M) decreased LTB4 releasability and intracellular 5-HETE concentrations in zymosan-stimulated AM from asthmatic patients, and was shown to decrease the LTC4 or LTE4-promoted formation of LTB4 and 5-HETE.

Adolescent↗
PubMed1993

Airway macrophages from patients with asthma do not proliferate.

BACKGROUND: Macrophages are involved in asthma, but their pulmonary turnover is unknown. We compared the ability of bronchoalveolar lavage (BAL) and bronchial macrophages to proliferate in normal subjects and patients with asthma. METHODS: BAL cells from eight patients with asthma and eight normal volunteers were separated with a discontinuous Percoll gradient (Pharmacia Fine Chemicals, Uppsala, Sweden). In a first experiment, nuclei of each alveolar macrophage (AM) fraction, stained with propidium iodide, were analyzed for DNA content with a flow cytometer, and the proportions of cells in the G0/G1, S, and G2 + M phases were determined. In a second experiment, expression of Ki-67-related antigen was sought on AMs by immunocytochemistry. Macrophages from 10 patients with asthma and 10 normal volunteers were studied in biopsy specimens by means of immunohistochemistry with a panmacrophage monoclonal antibody (HAM-56) and a monoclonal antibody against proliferating cell nuclear antigen. RESULTS: The proportions of BAL AMs in the different phases of the cell cycle were similar in normal subjects and patients with asthma for all fractions, and the percentage of cells in S and G2 +/- M phases ranged from 7.3% to 11.3%. Under 1% of BAL AMs expressed Ki-67-related antigen. None of the macrophages present in the biopsy specimens expressed proliferating cell nuclear antigen. CONCLUSIONS: This study does not indicate that an important source of airway macrophages is local proliferation.

Adolescent↗