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Biomedical subjects

P Godard

Publications and source records attributed to P Godard.

At least 91 records · Page 5Linked to original sources
PubMed1998

[Drug allergies: management and current aspects].

UNLABELLED: ALLERGIC AND PSEUDOALLERGIC REACTIONS: Adverse drug reactions occur in 1 to 3% of hospitalized patients and 10% are due to allergic and pseudoallergic reactions. Allergic reactions are unpredictable reactions related to immunologic mechanism. Pseudoallergic reactions mimic allergic reactions but no drug-specific antibody or T cell proliferation can be demonstrated. PREVENTION: We are lacking clinical and biological tools and the available ones still need to be validated. However, a precise diagnosis is required in order to set up prevention measures. We focus here on some basic and new data concerning these reactions, in particular epidemiological studies, mechanisms and diagnostic methods.

Cross-Sectional Studies↗
PubMed1998

Generation of eicosanoids from 15(S)-hydroxyeicosatetraenoic acid in blood monocytes from steroid-dependent asthmatic patients.

The aim of this study was to investigate eicosanoid metabolism by human peripheral blood monocytes (PBM) from steroid-dependent asthmatic patients as compared to control subjects and untreated asthmatic patients. Eicosanoid biosynthesis by PBM isolated from venous blood using Percoll gradient centrifugation was evaluated following stimulation of 5 x 10(6) cells with calcium ionophore A23187, with or without exogenous 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), and analyzed by reverse phase high performance liquid chromatography (RP-HPLC). Without 15(S)-HETE, PBM synthesized leukotriene B4 (LTB4) only (40 +/- 12 ng and 59 +/- 11 ng for untreated and steroid-dependent asthmatics, respectively). In the presence of 15(S)-HETE, PBM produced six-fold smaller amounts of leukotriene B4 (P < 0.0001). They also released 5(S),15(S)-dihydroxyeicosatetraenoic acid (5(S),15(S)-diHETE) in similar amounts for all the populations, whereas low amounts of lipoxins (LXs) were produced by PBM from asthmatics only (2.7 +/- 0.7 ng and 4.6 +/- 2.8 ng for untreated and steroid-dependent asthmatics, respectively). Moreover, PBM were also able to release an unknown compound containing conjugated triene chromophore. Cells from steroid-dependent asthmatic patients synthesized this unknown metabolite in higher amounts than controls and untreated asthmatics (133 +/- 18 ng vs 52 +/- 19 ng and 68 +/- 15 ng, respectively, P < 0.02). This work shows for the first time that human PBM are able to metabolize 15(S)-HETE and lead to lipoxins and to an unknown metabolite, with the amounts of the latter being enhanced by long-term corticosteroid treatment.

Adrenal Cortex Hormones↗
PubMed1998

Six-hour trimethoprim-sulfamethoxazole-graded challenge in HIV-infected patients.

BACKGROUND: Hypersensitivity reactions to trimethoprim-sulfamethoxazole (TMP-SMX) are very common in HIV-infected patients, leading to drug discontinuation. However, it is the drug of choice as prophylaxis for Pneumocystis carinii pneumonia. OBJECTIVES: We sought to determine the safety and long-term efficacy of a 6-hour TMP-SMX-graded challenge in a group of hypersensitive HIV-infected patients. METHODS: Forty-four consecutive HIV-infected patients with documented TMP-SMX hypersensitivity were seen in our outpatient allergy department. They ingested 12 doses of increasing amounts of TMP-SMX at half-hour intervals. Thereafter, they took 80/400 mg TMP-SMX daily and were advised to "treat through" every nonbullous cutaneous adverse reaction. RESULTS: All 44 patients tolerated the procedure without any adverse reactions during the day of challenge. Eleven of the 44 patients experienced mild hypersensitivity reactions on days 1 to 2 (8 patients) and 8 to 10 (3 patients), consisting mainly on a 1-day pruritic maculopapular eruption. Two patients stopped TMP-SMX at day 1, and 2 stopped it at days 10 and 15, giving an overall success rate at 1 month of 91% (40 of 44). Two were successfully rechallenged late. After a median follow-up of 10 months, 42 patients were taking TMP-SMX without any adverse reaction, giving an overall success rate of 95%. CONCLUSIONS: A 6-hour graded challenge with cautious "treating through" of mild reactions enables more patients to take TMP-SMX and is safe and effective.

Administration, Oral↗
PubMed1998

The use of home nebulizers in adult asthma.

Nebulization therapy is an approach for the treatment of respiratory diseases such as asthma which was not anticipated in the international recommendations for the treatment of asthma and which merits study. Even if the place of nebulizers in the treatment of asthma exacerbations has been validated, this is not the case for adult asthmatic subjects with chronic asthma. While asthma control for most patients can be achieved using metered-dose inhaler and dry powder inhaler therapy, some patients may require regular home nebulized therapy. Before determining the objectives and therapeutic characteristics of nebulization in the treatment of chronic asthma in the adult patient, we shall first describe the pathophysiological elements involved in the treatment of asthma and of the couple 'nebulized substance-nebulizer' leading to an optimal nebulization.

Adult↗
PubMed1998

Glucocorticoid insensitive asthma: a one year clinical follow up pilot study.

BACKGROUND: Glucocorticoid resistant or insensitive asthmatic subjects are usually defined as patients whose baseline pre-bronchodilation forced expiratory volume in one second (FEV1) of less than 70-80% predicted improves significantly in response to beta 2 agonists but by less than 15% following 1-2 weeks of 40 mg prednisolone daily. Since there is little long term clinical information on these patients, a one year prospective study was performed to assess whether glucocorticoid sensitivity may vary over time. METHODS: Nineteen severe asthmatic subjects were studied and received 40 mg prednisolone daily for seven days. Prednisolone was given for a further seven days in glucocorticoid insensitive asthmatics and then stopped. Patients were followed up for one year and the glucocorticoid test was repeated on five patients in each group six months later. RESULTS: Eleven patients were classified as glucocorticoid insensitive and eight as glucocorticoid sensitive on day 7. The demographic characteristics of the patients were similar in both groups. Four glucocorticoid insensitive patients became responsive after one further week of prednisolone treatment. Six months later, four of five glucocorticoid sensitive patients and three of five previously glucocorticoid insensitive patients were glucocorticoid sensitive. CONCLUSIONS: Glucocorticoid sensitivity varies over time.

Adult↗
PubMed1998

Safety of inducing sputum in patients with asthma of varying severity.

Inducing sputum using hypertonic saline is a noninvasive method to investigate airway inflammation in people with asthma. However, hypertonic saline may also induce bronchoconstriction in some patients. The aim of the study was to examine whether the overall safety of using hypertonic saline to induce sputum in patients with mild to moderate asthma could be extended to patients with severe and/or uncontrolled asthma. Nine control subjects and 64 asthmatic patients with varying severity of the disease (FEV1 40-126% predicted values) were studied. Twenty-one of those patients had uncontrolled asthma. Sputum was induced in a standardized manner using hypertonic saline. The safety of the procedure was evaluated by assessing the clinical response and measuring FEV1 just before and during sputum induction. The procedure was well tolerated in most patients, but it had to be stopped due to side effects in 11.6% of patients with severe asthma. None of the side reactions were severe. Few patients with uncontrolled (17.3%) or severe asthma (18.6%) had a drop in FEV1 of 10-20%. The fall in FEV1 was significantly greater in patients with severe asthma than those with mild disease (p < 0.02 Mann-Whitney U test). We conclude that hypertonic saline-induced sputum is a safe technique even in patients with severe asthma.

Adult↗
PubMed1998

Bronchial mucosal immunoreactivity of sensory neuropeptides in severe airway diseases.

Neuropeptides act on most of the components of the bronchial environment. They influence bronchomotor tone and bronchial vascular caliber and permeability. To investigate the nonadrenergic, noncholinergic system within the airways in asthma and chronic bronchitis, we performed endobronchial biopsies in 16 normal human volunteers, 49 patients with asthma of varying severity, including 16 patients treated with oral corticosteroids, and 13 patients with chronic bronchitis. Frozen sections of biopsies stained with specific antibodies against the neural marker PGP 9.5, vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), and neuropeptide Y (NPY) were analyzed for the presence of nerves through indirect immunofluorescence. Nerves were present in most of the biopsies and were found within and below the epithelium and adjacent to smooth muscle, glands, and blood vessels. By comparison with those in normal subjects, the numbers of VIP-immunoreactive nerves were not significantly decreased in patients with asthma and chronic bronchitis, but NPY-immunoreactive nerves were significantly decreased in the smooth muscle of these latter two groups of patients (p < 0.005). There was no correlation between disease severity and the number of nerves found in the biopsies. This study does not confirm previous findings in autopsy material of some defects in sensory and VIP-containing nerves in severe asthma.

Administration, Oral↗
PubMed1998

Glucocorticoid receptors in bronchial epithelial cells in asthma.

The expression of the glucocorticoid receptor (GR) in untreated or in steroid-dependent asthmatic patients is poorly understood. We therefore studied GR mRNA and protein levels in bronchial biopsies obtained from seven untreated asthmatic patients, seven control volunteers, and seven patients with chronic bronchitis. We also studied in bronchial epithelial cells obtained by brushing from 13 untreated asthmatics, 18 steroid-dependent asthmatics, 11 control volunteers, and 12 patients with chronic bronchitis, GR and heat shock protein 90 kD (hsp90) mRNA as well as the immunoreactivity of GR, intercellular adhesion molecule (ICAM-1), and granulocyte macrophage-colony-stimulating factor (GM-CSF). GR mRNA and protein level was similar in all subject groups in both biopsies and bronchial epithelial cells. Hsp90 mRNA level was also similar in all subject groups. ICAM-1 expression was significantly increased in bronchial epithelial cells from untreated asthmatics, but ICAM-1 was not expressed in those from steroid-dependent asthmatic patients. GM-CSF expression was significantly increased in bronchial epithelial cells from untreated and steroid-dependent asthmatic patients. GR expression within the airways is unaltered by oral long-term steroid treatment in asthma, but the expression of some but not all specific markers for asthma is modified by oral steroid.

Administration, Oral↗
PubMed1998

Expression of the high-affinity receptor for IgE on bronchial epithelial cells of asthmatics.

Bronchial epithelial cells are the first cells to come into contact with inhaled pneumoallergens. It has been suggested that these cells may play an important role in the allergic response, and indeed bronchial epithelial cells of some atopic asthmatic subjects have been shown to express the low-affinity receptor for IgE on their surface. In this report we demonstrate, using bronchial biopsies, that bronchial epithelial cells of some asthmatic subjects express both the alpha and gamma chains of the high-affinity receptor for IgE (Fcepsilon RI) on their surface and that they are capable of fixing IgE. Second, using reverse transcription-polymerase chain reaction, we show that both control and asthmatic subjects have messenger RNA for Fcepsilon RI. Finally, we demonstrate that this receptor may be functional since stimulation of the cells with the antibody to the alpha chain of Fcepsilon RI results in the liberation of 15-hydroxyeicosatetraenoic acid from epithelial cells of asthmatic, but not control, subjects or subjects suffering from chronic bronchitis. These data suggest that bronchial epithelial cells from at least some asthmatic subjects express a functional high-affinity receptor for IgE and it is therefore possible that these cells may be able to interact directly with inhaled allergens.

Adolescent↗
PubMed1998

Superoxide anion production by monocytes of corticosteroid-treated asthmatic patients.

Reactive oxygen species play an important role in promoting inflammation. Blood monocytes have been described to release higher amounts of superoxide anion in uncontrolled and untreated asthmatics. Corticosteroids are widely used in asthma, but little is known about their molecular mechanism of action. The aim of our study was to analyse the ex vivo effect of corticosteroid treatments on superoxide anion release by blood monocytes. Superoxide anion release was measured by a spectrophotometric method based on the superoxide dismutase (SOD) -inhibitable reduction of ferricytochrome C by blood monocytes from untreated patients and asthmatics treated with i.v., inhaled and oral corticosteroids. Monocytes from uncontrolled and untreated asthmatics, released high amounts of superoxide anions. After short-term treatment with i.v., corticosteroids, this release was found to decrease significantly (1.410 versus 0.340 nM, p<0.05). Cells from asthmatics who had undergone long-term treatment with inhaled or oral steroids presented low amounts of superoxide anion production, with a significant difference as compared to untreated asthmatics (0.375 nM p<0.01 and 0.620 nM p<0.02 respectively). In general, patients with controlled asthma (treated with short-term oral steroids, or with long-term inhaled steroids) released lesser amounts of superoxide anion than uncontrolled and untreated asthmatics. In the case of steroid-dependent asthmatics there was no difference between patients with a controlled or uncontrolled disease.

Administration, Inhalation↗
PubMed1998

[Nose and sinus: anatomo-pathologic relations].

The relationship between rhinitis and chronic sinusitis is close and complex and may perhaps show many points of view, anatomical and physiological, epidemiological (by comparing the prevalence of an ailment in carriers of another ailment), experimental (by making nasal allergen provocation tests and studying the sinus anomalies induced) and physiopathological (by phenotyping and comparison of the inflammation present with one another and other ailments). If the results of these studies are convincing, there is still lack of formal proof that confirms the fundamental role of nasal inflammation in general and in particular allergic inflammation in the genesis of sinusitis.

Allergens↗
PubMed1998

[Corticoid therapy and bronchial inflammation in asthma. The use of bronchial biopsy].

The development of fibreoptic bronchoscopy has enabled significant progress in the understanding of the pathogenesis of asthma. It has brought to the fore the importance of bronchial inflammation even in asymptomatic patients and/or in patients who have only mild disease. The practice of bronchial biopsy in vivo is an excellent method of studying bronchial inflammation. The purpose of this general review is to recall the value of bronchial biopsies in the understanding of the effects of steroids on asthma: effects on the epithelium, the basement membrane and the blood vessels. Their cellular contents consist equally of cytokines, enzymes and adhesion molecules. At the level of the bronchial epithelium steroid therapy engenders a diminution in eosinophils, mast cells an lymphocytes. It restores the ratio of ciliated to other cells back to normal and increases the number of nerve synapses. Regarding the interstitium the corticoids diminish the number of eosinophils, mast cells and T lymphocytes. The effect on different lymphocyte subtypes is controversial, as is the effect of the basal membrane. Steroid therapy diminishes the proteins, GM-CSF.RANTES and IL-8 as well as the messengers IL-4, IL-13 and IL-5. It seems to increase the messengers for IFN-gamma and IL-12 and favourably modulates the vascular composition to inflammation in asthma. Nevertheless it is to be regretted that too few studies have looked at the correlations between histological changes and clinical and respiratory function improvement engendered by steroid therapy.

Adrenal Cortex Hormones↗