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Biomedical subjects

P Godard

Publications and source records attributed to P Godard.

At least 127 records · Page 7Linked to original sources
PubMed1996

5(S),15(S)-dihydroxyeicosatetraenoic acid and lipoxin generation in human polymorphonuclear cells: dual specificity of 5-lipoxygenase towards endogenous and exogenous precursors.

5-Lipoxygenase activation of human blood polymorphonuclear cells (PMN) from asthmatic patients (asthmatics) was studied to investigate whether differences may exist with healthy subjects (controls). The respective cell capacities to produce lipoxins (LXs), leukotrienes, and 5(S), 15(S)-dihydroxyeicosatetraenoic acid [5(S),15(S)-diHETE] were compared under in vitro stimulation by ionophore A23187, with or without exogenous 15(S)-hydroxyeicosatetraenoic acid [15(S)-diHETE]. Eicosanoids were analyzed by elution with an isocratic reverse-phase high performance liquid chromatography system, and their profiles, detected by simultaneous monitoring at 302, 280, and 246 nm, were evaluated on the basis of chromatographic behavior: UV spectral characteristics and coelution with synthetic standards. In the presence of exogenous 15(S)-HETE, human PMN were able to produce LXs and 5(S),15(S)-diHETE, PMN from asthmatics were able to produce 5(S), 5(S),15(S)-diHETE, and LXs from endogenous sources, whereas in the same experimental conditions, no detectable amounts of these compounds were released by PMN from controls. The levels of 5(S),15(S)-diHETE, and LXs biosynthesized from endogenous arachidonic acid were highly correlated. Two different LX patterns were observed involving two possible metabolic pathways: (a) via the intermediate 5,6-epoxytetraene alone for LXs generation from exogenous 15(S)-HETE; and (b) via 5,6- and/or 14,15-epoxytetraenes leading to the formation of an enzyme-bound delocalized carbocation for LXs generation from endogenous arachidonate, respectively. The enhanced 5-lipoxygenase activation of blood PMN from asthmatics and the metabolism of exogenous 15(S)-HETE may reflect a priming induced by various mediators released from environmental cells, and could be considered as a model of transcellular signalization between PMN and endothelial cells.

Arachidonate 5-Lipoxygenase↗
PubMed1996

Long-term oral corticosteroid therapy does not alter the results of immediate-type allergy skin prick tests.

BACKGROUND: Medications can modulate the results of skin prick tests (SPTs). Short-term corticosteroid therapy does not alter IgE-mediated skin tests, but the impact of long-term oral corticosteroid therapy on SPT results is unclear. A prospective study was carried out in patients with steroid-dependent asthma who received oral corticosteroids for a long period to determine whether this treatment reduced skin test reactivity. METHODS: Thirty-three patients with steroid-dependent asthma (median age, 59 years) were compared with 66 patients with asthma who served as a control group, matched for age, sex, and atopic status. SPTs with codeine phosphate and a screening battery of standardized allergen extracts were performed before commencement and after at least 1 year of daily oral prednisone treatment (median duration, 2 years; median daily dose, 20 mg). RESULTS: Fifteen patients with corticosteroid-dependent asthma were allergic before treatment, and their sensitization was not changed by long-term treatment with oral corticosteroids. The median wheal diameters induced by codeine phosphate were similar in both groups. The median wheal diameters induced by allergens, and more specifically, by Dermatophagoides pteronyssinus and D. farinae were similar in both groups and did not change in the steroid group after treatment. CONCLUSIONS: Systemic corticosteroid therapy (prednisone, 10 to 60 mg/day) for 2 or more years does not seem to alter SPT reactivity.

Adult↗
PubMed1996

Involvement of endothelin in mononuclear phagocyte inflammation in asthma.

BACKGROUND AND AIM: Endothelin has bronchoconstrictive, vasoactive, and inflammatory properties and may be involved in the pathogenesis of asthma. We have studied the involvement of endothelin in asthma by examining its expression and release by mononuclear phagocytes obtained from 56 patients with asthma and 32 control subjects and the activation of mononuclear phagocytes by endothelin. METHODS: Endothelin immunoreactivity was studied by using immunocytochemistry on monocytes and alveolar macrophages. Spontaneous and lipopolysaccharide-induced endothelin release from monocytes and alveolar macrophages was studied by radioimmunoassay. The proportion of intracellular endothelin was assessed after cell disruption by Triton (Union Carbide Corp., Bound Brook, N.J.). The release of fibronectin and tumor necrosis factor-alpha induced by endothelin was studied in alveolar macrophages by enzyme immunoassay. RESULTS: Endothelin immunoreactivity was significantly increased in cells from patients with asthma in comparison with those from the control group, but its release by alveolar macrophages was similar in both groups. Levels in the cell lysates and supernatants were similar for patients with asthma and normal subjects. Endothelin significantly increased the release of tumor necrosis factor-alpha and fibronectin by alveolar macrophages from normal subjects and patients with stable asthma, but it significantly decreased their release in patients with unstable asthma. CONCLUSION: This study suggests a role for endothelin in airway inflammation in asthma. Endothelin may act in a different fashion on alveolar macrophages, depending on the degree of stability of the disease.

Adult↗
PubMed1996

Glucocorticoids induced down-regulation of glucocorticoid receptor mRNA expression in asthma.

Although their precise mechanism of action remains to be elucidated, glucocorticoids represent the most effective therapy in the treatment of asthma. Interactions between the glucocorticoid receptor and the AP-1 complex have been shown to regulate the transcription of some genes, including glucocorticoid receptor itself. The aim of the present study was to compare the expression of mRNA for glucocorticoid receptor in human blood monocytes obtained from seven unstable untreated asthmatic patients who were subsequently treated with high doses of parenteral corticosteroid (methyl prednisolone 120 mg/day) for 10 days. mRNA expression was identified after RNA extraction using RNAzol and analysed after reverse transcriptase, by polymerase chain reaction using a semiquantitative competitive hybridization assay. All asthmatic patients showed an improvement in their FEV1 values after corticosteroid treatment (per cent of predicted value 68.28 +/- 4.93 versus 95.57 +/- 6.41, P < 0.02), and a significant decrease for glucocorticoid receptor mRNA expression (P < 0.02) was observed in their monocytes. This is the first report of an ex vivo down-regulation for the glucocorticoid receptor mRNA expression, following corticosteroid treatment.

Adult↗
PubMed1996

Interleukin 8 in bronchoalveolar lavage of asthmatic and chronic bronchitis patients.

Interleukin 8 (IL-8) is a chemoattractant cytokine having a distinct target specificity for the neutrophil. However, it was also found to be active on primed eosinophils. IL-8 was measured by enzyme immunoassay in the bronchoalveolar lavage fluid (BALF) of 9 control subjects, 19 asthmatics and 36 chronic bronchitis patients. Its levels were correlated with neutrophil and eosinophil counts as well as levels of myeloperoxidase (MPO) and eosinophil cationic protein in the BALF. Asthmatic and chronic bronchitis patients had elevated levels of IL-8 in comparison with normal subjects. There was no correlation between the severity of asthma or chronic bronchitis and IL-8 levels. In asthmatic subjects there was a correlation between IL-8 and MPO levels (p < 0.0001, Spearman test). There was no significant correlation between eosinophils and IL-8. In chronic bronchitis there was a correlation between IL-8 and MPO levels as well as between IL-8 and neutrophil counts (p < 0.004 and p < 0.0152, respectively, Spearman test). IL-8 is involved in neutrophilic inflammation in asthma and chronic bronchitis, but differences in the IL-8 regulation of neutrophils were observed in both diseases.

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↗
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

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

[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↗