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Biomedical subjects

P Godard

Publications and source records attributed to P Godard.

At least 145 records · Page 8Linked to original sources
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

Fos immunoreactivity assessment on human normal and pathological bronchial biopsies.

The transcription factor Fos is involved in cell proliferation and differentiation. Its expression in normal and pathological adult human tissues and cells has rarely been studied. We therefore studied bronchial biopsies obtained from 14 normal subjects (NS), 18 non-steroid-treated asthmatics, 10 corticosteroid-treated asthmatics and 10 patients with chronic bronchitis (CB), in addition to 34 patients with lung cancer (LC), by immunofluorescence for Fos immunoreactivity, using a highly specific polyclonal antibody. Bronchial tissue of 0/10 NS, 11/18 non-steroid-treated asthmatics, 1/10 steroid-treated asthmatics, 0/10 CB and 1/34 LC expressed Fos. In asthmatic patients, the expression was heterogeneous, localized to epithelial cells and correlated with the epithelium shedding (tau = 0.45, P = 0.0001). Corticosteroid-treated patients rarely expressed Fos, suggesting a role for this proto-oncogene in asthmatic bronchial inflammation. Fos was rarely expressed in the normal and pathological (CB, LC) proliferative compartment of the human bronchi, suggesting its low role in cell proliferation of the large airways.

Adenocarcinoma↗
PubMed1995

Protein content in bronchoalveolar lavage fluid of patients with asthma and control subjects.

BACKGROUND: Secretory component (SC), Clara cell protein (CC10) and to some extent, IgM are proteins locally synthetized in airways. Albumin, alpha 2-macroglobulin and alpha 1-antitrypsin are mainly plasma proteins. In patients with asthma, blood proteins may occur in greater amounts in bronchoalveolar lavage fluid (BALF) than in control subjects because of plasma extravasation. These proteins were measured in BALF to define markers of local synthesis and plasma exudation. METHODS: Twenty-four patients with asthma (mean age, 40 +/- 3.1 years) and 24 control subjects (mean age, 29 +/- 11 years) were tested. Five aliquots of saline solution (50 ml) were instilled, and the recovered BALF was stored. Clara cell protein was measured by a sensitive immunoassay technique based on the agglutination of latex particles. SC, immunoglobulins, alpha 2-macroglobulin, alpha 1-antitrypsin, and albumin were measured by an immunoradiometric assay. Protein concentrations were normalized to albumin. RESULTS: In BALF from patients with asthma there was a significant increase in alpha 2-macroglobulin and IgM and a significant decrease of SC, alpha 1-antitrypsin, and Clara cell protein compared with control subjects. Also, the ratio to albumin was significantly increased for alpha 2-macroglobulin and IgM and decreased for SC. There was no correlation between the severity of asthma and the amount of proteins. CONCLUSIONS: BALF protein content is significantly different in patients with asthma and control subjects, for proteins produced locally and derived from plasma.

Adolescent↗
PubMed1995

Evaluation of atopy through an expert system: description of the database.

BACKGROUND: In order to understand the medical decisions taken during the initial visit of a new asthmatic patient, a group of experts designed an expert system which provides conclusions about severity, precipitating factors and treatment. Rules for atopy and the assessment of allergic factors have been discussed and implemented in the expert system. Conclusions about severity have been yet validated using an appropriate methodology. OBJECTIVE: The aim of this study was to investigate a sample of 471 patients according to conclusions regarding atopy. METHODS: A total of 471 cases report forms (CRF) was filled in for adult asthmatic outpatients, seen for the first time in our clinic without emergency situations. Data of each CRF were used by the expert system to draw conclusions. The expert system discerns three patterns for atopy, yes, possible or no. The variables known to reflect different features according to the classification of asthma as atopic or not have been studied. The variables used in the rules for atopy, obviously linked to the conclusion, were not compared. For many medical problems no unique objective solution exists and this is why a group of patients with possible atopy was introduced. RESULTS: Patients with atopy had less severe asthma (P = 0.01), a better FEV1 value (P = 0.0007) and showed their first symptoms of asthma earlier (P = 0.00001) than patients without atopy. CONCLUSIONS: The characteristics of the group studied here are consistent with the literature. This could be considered as an indirect validation of the expert system. Moreover, patients with possible atopy show intermediate findings for these variables and it is possible to suggest a 'dose-effect' relationship.

Adolescent↗
PubMed1995

Increased expression of heat shock protein 70 on airway cells in asthma and chronic bronchitis.

Heat shock proteins (HSPs) appear to be involved in inflammation. Because asthma is an inflammatory disease, HSPs may be expressed. We studied the expression of HSP-70 by immunohistochemistry using the alkaline-phosphatase anti-alkaline phosphatase technique on epithelial cells and alveolar macrophages (AMs) from 19 patients with asthma, eight patients with chronic bronchitis (CB), and 13 control subjects and in bronchial biopsies from 15 asthmatics, 15 CB patients, and nine control subjects. The specificity of the antibody was confirmed by Western blotting on heated AM. The specificity of the immunostaining was confirmed by inhibition experiments. The expression of HSPs in the asthmatics in comparison with the CB patients and control subjects was significantly increased on epithelial cells (P < 0.002 and P < 0.007, respectively) and AMs (P < 0.0004 and P < 0.0002, respectively) and was significantly correlated with the severity of asthma (P < 0.005 for AMs) and the percentage of eosinophils in bronchoalveolar lavage fluid (P < 0.004). In biopsies from the asthmatics but not from the CB patients or control subjects, a positive staining for HSP-70 was observed on epithelium, mononuclear cells, and basement membrane and was correlated with the severity of asthma (P < 0.0005, P < 0.002, and P < 0.007, respectively). This study demonstrates that bronchial inflammation in asthma but not in CB may be linked to the production of HSPs.

Adult↗
PubMed1995

IFN-gamma activates superoxide anion production in blood monocytes from allergic asthmatic patients.

BACKGROUND: Peripheral blood monocytes may participate in allergic diseases by releasing inflammatory mediators. We have recently shown enhancement of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activity in adherent human peripheral blood monocytes from allergic patients when immunoglobulin E (IgE) binds to its low affinity receptor. Interferon-gamma (IFN-gamma), a monocyte-activating lymphokine, has been shown to prime monocytes for superoxide anion release. OBJECTIVE: We hypothesized that IFN-gamma could directly activate blood monocyte superoxide anion release and evaluated its modulatory effect on IgE-induced superoxide anion release from those cells. METHODS: Seven patients with allergic asthma, 6 patients with allergic rhinitis, and five nonallergic controls were studied. We measured superoxide anion release from their blood monocytes using a chemiluminescence assay. Cells were either nonstimulated, or stimulated for 30 minutes with IFN-gamma and/or serum IgE. RESULTS: We found that IFN-gamma stimulated superoxide anion production and decreased the IgE-induced superoxide anion production after 30 minutes of IFN-gamma preincubation only in blood monocytes from patients with allergic asthma. CONCLUSIONS: These data suggest that IFN-gamma receptors may be increased and/or coupled to NADPH oxidase in allergic asthmatic patients.

Adult↗
PubMed1994

[Oncogenes and anti-oncogenes in lung cancer].

In all normal cells, two type of genes, oncogenes and anti-oncogenes, are expressed and control cell proliferation and differentiation. Cell growth is stimulated by oncogenes and inhibited by anti-oncogenes. Cancerization involves loss of control due to defective gene expression either by overexpression of a normal protein (loss of quantitative control) or expression of an abnormal protein (loss of qualitative control). Several oncogenes have been identified. They include three oncogenes, c-myc, N-myc and L-myc, known to be overexpressed in small-cell carcinomas of the lung. Point mutations of the oncogene K-ras is found in 15 to 30% of adenoma carcinomas, especially in smokers. Loss of anti-oncogene function has also been described in processes leading to lung cancer. Chromosome abnormalities, for example the 3p14-23 deletion described in 1982, are found in 100% of small-cell carcinomas and in 50% of non-small-cell carcinomas. This deletion is never found in normal tissue. The gene involved has not yet been cloned. Other mutations or deletions include the RB gene, necessary for neuroendocrine differentiation, and the p53 gene which has undergone mutation in 50% of the non-small-cell carcinomas and 70% of the small-cell carcinomas. These acquired mutations are strongly associated with tobacco smoking. Oncogenes and anti-oncogenes play an important role in the complex step-wise process leading to cancerization. As tumour characterization becomes more precise and precancerous states better controlled, future treatments may relief on inhibiting tumoural growth by using drugs which would substitute for the lost effect of anti-oncogenes or inhibit activation of an oncogene. But at the present time, it is still difficult to define criteria predicting high risk of postoperative relapse or resistance and further studies investigating the correlation between genetic abnormalities and clinical staging and survival curves are required.

Cell Transformation, Neoplastic↗
PubMed1994

Modulation by interleukin-4 of cytokine release from mononuclear phagocytes in asthma.

BACKGROUND: Interleukin (IL)-4 is involved in IgE upregulation and downregulates cytokine release by mononuclear phagocytes. Mononuclear cells release greater amounts of IL-1, tumor necrosis factor-alpha, and IL-6 in patients with asthma than in control subjects, but the effect of IL-4 on cells from patients with asthma is unknown. The effects of IL-4 on the release of IL-1, tumor necrosis factor-alpha, and IL-6 by monocytes and alveolar macrophages were compared in 19 patients with asthma and 18 control subjects. METHODS: The release of IL-1, tumor necrosis factor-alpha, and IL-6 from unstimulated and lipopolysaccharide stimulated monocytes and alveolar macrophages was measured by ELISA. The effect of 30 U of IL-4 on the release of these cytokines was studied. RESULTS: Lipopolysaccharide-stimulated monocytes released significantly fewer cytokines in patients with asthma than in control subjects. IL-4 significantly inhibited cytokine release by monocytes of both groups. Unstimulated alveolar macrophages from patients with asthma released more cytokines than those of control subjects. Lipopolysaccharide induced a significantly greater increase in cytokine release in alveolar macrophages of control subjects in comparison with asthmatic subjects. IL-4 abolished the release of cytokines in alveolar macrophages from control subjects and had a minimal inhibitory effect on alveolar macrophages from patients with asthma. CONCLUSIONS: Alveolar macrophages from patients with asthma are hyperreactive but less prone to lipopolysaccharide stimulation and IL-4-downregulation than those from normal subjects.

Adolescent↗
PubMed1994

IgE produces monocyte superoxide anion release: correlation with CD23 expression. Comparison of patients with asthma, patients with rhinitis, and normal subjects.

Allergic inflammation involves many different cell types among which mononuclear cells, such as macrophages and monocytes, play an important role. These cells release numerous chemical mediators, including superoxide anion (O2.-). We evaluated the capacity of atopic serum to stimulate peripheral blood monocyte O2.- release. Thirteen untreated allergic patients (seven with asthma and six with rhinitis), and five nonallergic control subjects were studied. O2.- was measured in a photon-counting camera with Lucigenin-enhanced (Sigma Chemical Co., St. Louis, Mo.) chemiluminescence. Results were expressed (mean +/- SEM) in relation to basal values (peak/basal chemiluminescence values). Spontaneous production of O2.- was greater in allergic patients. Moreover, atopic serum stimulated O2.- production of blood monocytes in all subjects, but this was greater in subjects with allergic asthma than in subjects with allergic rhinitis and normal subjects. Anti-IgE immunoadsorption of atopic serum completely abrogated this effect, which was restored by the IgE-rich eluted fraction. IgE-induced O2.- release decreased as adherence duration increased and was correlated with surface CD23 expression. These results indicate that monocytes from allergic patients are in an activated state and that binding of IgE to their receptors generates O2.-, possibly by direct activation of blood monocyte reduced nicotinamide adenine dinucleotide phosphate oxidase.

Adult↗
PubMed1994

Detection of lymph node metastases in lung cancer: comparison of 131I-anti-CEA-anti-CA 19-9 immunoscintigraphy versus computed tomography.

Mediastinal lymph node metastasis is one of the most important prognostic variables of lung cancer. We designed a study to compare immunoscintigraphy (IS) using iodine-131 anti-carcinoembryonic antigen (CEA) and anti-carbohydrate 19-9 (CA 19-9) monoclonal antibody and computed tomography (CT-scan), in the setting of mediastinal staging. Seventeen patients were involved in a prospective, blind study, to compare IS with CT-scan imaging of the mediastinum. Sensitivity and specificity of both methods were analyzed with reference to pathological staging by mediastinal lymph node sampling. IS imaging was not possible in two patients owing to a thyroid uptake and one patient refused surgery. Among the 14 evaluable patients, sensitivity and specificity were 0.83 and 0.12 for IS, and 0.66 and 0.50 for CT-scan, respectively. We used different thresholds of positivity for both methods in order to evaluate the sensitivity-specificity relationship. When compared with that of IS, the area under the receiver operating characteristic (R.O.C.) curves of the CT-scan was bigger. Although one patient had pathologically confirmed N2 with negative CT-scan and positive IS, the results of IS were hampered by a very high level of false positivity. Finally, there was no relationship between positivity of IS and a high serum CEA level. Lack of specificity and the insufficient sensitivity of the iodine-131 anti-CEA-anti-CA 19-9, lead to the conclusion that IS adds weak information to a CT-scan, in the non-invasive mediastinal staging of lung cancer. More efficient radionuclides and markers are needed in the setting of lung cancer staging.

Adult↗