Search PubMed⌕ Search

Biomedical subjects

P Godard

Publications and source records attributed to P Godard.

At least 55 records · Page 3Linked to original sources
PubMed2001

Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs inversus and primary ciliary dyskinesia (Kartagener syndrome).

Kartagener syndrome (KS) is a trilogy of symptoms (nasal polyps, bronchiectasis, and situs inversus totalis) that is associated with ultrastructural anomalies of cilia of epithelial cells covering the upper and lower respiratory tracts and spermatozoa flagellae. The axonemal dynein intermediate-chain gene 1 (DNAI1), which has been demonstrated to be responsible for a case of primary ciliary dyskinesia (PCD) without situs inversus, was screened for mutation in a series of 34 patients with KS. We identified compound heterozygous DNAI1 gene defects in three independent patients and in two of their siblings who presented with PCD and situs solitus (i.e., normal position of inner organs). Strikingly, these five patients share one mutant allele (splice defect), which is identical to one of the mutant DNAI1 alleles found in the patient with PCD, reported elsewhere. Finally, this study demonstrates a link between ciliary function and situs determination, since compound mutation heterozygosity in DNAI1 results in PCD with situs solitus or situs inversus (KS).

Alleles↗
PubMed2001

Rhinosinusitis in severe asthma.

BACKGROUND: Chronic rhinosinusitis is a common comorbidity of asthma. However, sinonasal involvement in severe steroid-dependent asthma is still undefined. OBJECTIVE: The aim of the study was to evaluate chronic rhinosinusitis in 35 patients with severe steroid-dependent asthma by using a clinical score and coronal computed tomography (CT) scanning. METHODS: Thirty-five subjects (16 female subjects) with severe asthma requiring daily doses of oral corticosteroids were compared with 34 patients (19 female patients) with mild-to-moderate asthma. Sinonasal involvement was studied by using clinical and CT scores. Airflow obstruction, therapy requirement, and asthma triggering factors were carefully assessed. RESULTS: The proportion of patients with symptoms of rhinosinusitis was similar in both groups of asthmatic subjects (74% in patients with severe steroid-dependent asthma and 70% in patients with mild-to-moderate asthma). All subjects with steroid-dependent asthma versus 88% of subjects with mild-to-moderate asthma had abnormal CT scan results. The clinical (P <.05) and CT scan (P <.0005) severity scores were higher in the subjects with severe steroid-dependent asthma. In both groups the CT scan scores were correlated to the clinical scores (P <.0001 and P <.006), but only in the mild-to-moderate group were both scores correlated with high significance (P <.002 and P <.0005) to the absolute number of blood eosinophils. CONCLUSION: Frequency of rhinosinusitis in patients with mild-to-moderate or severe steroid-dependent asthma is similar; however, sinonasal involvement, as evaluated by clinical symptoms and CT scan imaging, is significantly greater in the patients with severe steroid-dependent asthma than in those with mild-to-moderate asthma.

Adolescent↗
PubMed2001

Effects of glucocorticoids on endogenous and transcellular metabolism of eicosanoids in asthma.

BACKGROUND: Human blood polymorphonuclear cells, which biosynthesize eicosanoids from the 5-lipoxygenase (5-LO) pathway, are likely to be involved in asthma, in which glucocorticoids represent the first line of therapy. Their effects on leukotriene release after a short course of treatment, which have been reported in several studies, are controversial. OBJECTIVE: We sought to investigate whether long-term oral glucocorticoids inhibit lipid mediators from the 5-LO pathway. METHODS: Twelve normal control subjects, 29 asthmatic subjects, and 50 glucocorticoid-dependent asthmatic subjects were included in the study. Polymorphonuclear cells were studied for endogenous and transcellular metabolism of eicosanoids. RESULTS: Total leukotriene B(4) production was significantly lower in cells from glucocorticoid-dependent asthmatic subjects (mean +/- SD, 177 +/- 26 ng/10(7) cells) than in control subjects (406 +/- 27), untreated asthmatic subjects (421 +/- 34), and asthmatic subjects treated with inhaled glucocorticoids (290 +/- 56). When incubated with arachidonic acid, these polymorphonuclear cells released very low amounts of 5(S)- and 12(S)-hydroxy-eicosatetraenoic acid (HETE), whereas endogenous 15(S)-HETE was found in substantial amounts. The transformation of exogenous 15(S)-HETE into 5(S),15(S)-diHETE and lipoxins was significantly more important in untreated asthmatic subjects than in control subjects and glucocorticoid-dependent asthmatic subjects. CONCLUSION: This study showed that long-term oral corticotherapy affects the 5-LO activity and leads to a decrease production of all metabolites in contrast to short-term or inhaled glucocorticoids. This study also questions the site of action of glucocorticoids in regulating the availability of arachidonic acid and potential eicosanoid regulation, as previously held in phospholipase A2 studies.

5-Lipoxygenase-Activating Proteins↗
PubMed2001

High or standard initial dose of budesonide to control mild-to-moderate asthma?

Guidelines on the use of inhaled steroids in asthma advocate that the daily dose should be chosen according to the severity of the disease. However, the question of the optimal starting dose remains to be properly addressed, as does the issue of the adjustment in dose required for a given patient. Whether a high initial dose of budesonide (800 microg b.i.d) was more efficacious than a standard dose (200 microg b.i.d) in controlling mild-to-moderate asthma was investigated, and whether the dose could be decreased, based on peak expiratory flow (PEF), symptom-score, beta2-agonist use in a double-blind, randomized, parallel-group 18-week study. One-hundred and sixty-nine patients (mean age 38 yrs, mean forced expiratory volume in one second 74% predicted) were enrolled. No difference was detected between the two groups in improvement in morning PEF (+61 L x min(-1) in the high-dose group, +60 L x min(-1) in the standard-dose group by 16 weeks). Morning and evening PEF values stabilized before the end of the first 4 weeks. No difference between groups was observed in symptom score, beta2-agonist use, number of exacerbation per interval and the best forced expiratory volume in one second achieved. The proportion of subjects being able to decrease the doses of budesonide was similar in both treatment strategies. It is concluded that both high and standard initial doses are equally effective in controlling symptoms and improving lung function in mild-to-moderate asthma.

Administration, Inhalation↗
PubMed2000

[Asthma and rhinitis medications: pregnancy precautions].

DRUG PRESCRIPTION: Many pregnant women have asthma and/or rhinitis. Particular attention is required when prescribing drugs in this situation. Medication can be prescribed during pregnancy when the apparent benefit is greater than the apparent risk. Usually at least one drug of each major class used to control these disease can be given safely. In addition, physiological changes associated with pregnancy could affect the upper and lower pathways. CAREFUL MANAGEMENT: Ideally, drug prescription for asthma and/or rhinitis in pregnant women should be part of a global process implicating obstetricians, primary care physicians, and allergy, rhinology or lung specialists. The only way to improve the mother's comfort and avoid complications for both mother and child is to perfectly control the disease. Indeed, it would be regrettable to be too prudent and deprive symptomatic patients of active treatments. Patients should be clearly informed of the benefits and risks of drug therapy.

Adult↗
PubMed2000

[Corticosteroid therapy of asthma].

UNLABELLED: BRONCHIAL INFLAMMATION AND GLUCOCORTICOIDS: Bronchial inflammation plays an important role in asthma and contributes to bronchoconstriction, hypersecretion and bronchial hyperreactivity. Glucocorticoids are the gold standard treatment in asthma affecting most of the components involved in bronchial inflammation. Inhaled steroids are recommended early in most countries. MECHANISM OF ACTION: The molecular and cellular mechanisms of glucocorticoids action are still better understood. However, it remains difficult to evaluate individual sensitivity when initiating treatment. Glucocorticoids have an effect on all inflammatory cells and bronchial structure cells. They bind to cytoplasmic receptors and then the complex links to DNA, inducing or inhibiting gene transcription in the target cell. DIFFERENT GLUCOCORTICOID SENSITIVITY: Very few patients are totally insensitive to the effect of glucocorticoids and require specific explorations for an identification. Although individual variability in corticosensitivity is similar in asthmatic patients and in the general population, the underlying mechanisms remain to be fully elucidated. The difference observed between responders and non-responders is not clearly identified and their definitions must be fully adapted.

Administration, Inhalation↗
PubMed2000

[Allergy to macrolides. 21 cases].

OBJECTIVE: Allergic drug reactions to macrolides are extremely rare and there is little information in the literature concerning relevant diagnostic tests. PATIENTS AND METHODS: Twenty-one patients were recently seen for assumed allergies (principally urticaria) to diverse macrolides. Skin tests (prick and intradermal tests) were performed with injectable forms of spiramycin and erythromycin. Seventeen out of 21 patients were provoked under strict hospital surveillance. RESULTS: Only 3 patients had a positive provocation test and were thus truly allergic (to spiromycin). They had positive skin tests to both macrolides tested. CONCLUSION: Most hypersensitivity reactions to macrolides are therefore diagnosed with provocation tests.

Adolescent↗
PubMed2000

[Allergy to macrolide antibiotics. Review of the literature].

MACROLIDE CLASSES: Macrolides are characterized by their basic structure made up of a lactonic cycle with 2 osidic chains. They are classified according to the number of carbon atoms in the cycle: 14-membered macrolides (erythromycin, troleandomycin, roxithromycin, dirithromycin, clarithromycin), 15-membered macrolides (azithromycin) and 16-membered macrolides (spiramycin, josamycin, midecamycin). MACROLIDE ALLERGY: Allergy to macrolides is extremely rare (0.4% to 3% of treatments). The little information available in the literature is insufficient to establish the usefulness of diagnostic tests. An immediate IgE-dependent hypersensitivity has been shown with erythromycin in some cases but the mechanism remains unknown and skin tests are quite often negative. Clinical manifestations are the same as those encountered with beta-lactams. It would appear that macrolide allergies are unlikely to be class allergies. This is important as eviction advice could be limited to the single causal macrolide.

Anti-Bacterial Agents↗
PubMed2000

Structural consequences of airway inflammation in asthma.

Asthma represents a chronic inflammatory process of the airways followed by healing, the end-result of which is an altered structure referred to as a remodeling of the airways. Repair usually involves 2 distinct processes: regeneration (which is the replacement of injured tissue by parenchymal cells of the same type) and replacement by connective tissue and its eventual maturation into scar tissue. In many instances both processes contribute to the healing response and inflammation. In asthma the processes of cell dedifferentiation, migration, differentiation, and maturation and connective tissue deposition can be followed either by complete or altered restitution of airway structure and function, the latter often seen as fibrosis and increase in smooth muscle and mucus gland mass. These features result in an increased resistance to airflow, particularly when there is bronchial contraction and bronchial hyperresponsiveness. The effect on airflow is compounded by the presence of increased mucous secretion and inflammatory exudate, which not only blocks the airway passages but also causes an increased surface tension that favors airway closure.

Animals↗
PubMed2000

Transcriptional potencies of inhaled glucocorticoids.

Glucocorticoids (GC) are the most effective anti-inflammatory drugs used in asthma. By a process called trans-activation, they increase the transcription of genes involved in either beneficial processes or certain side effects. Through trans-repression, they inhibit the transcription factors nuclear factor kappa B (NF-kappaB) and activator protein-1 (AP-1), thereby decreasing the expression of many genes encoding inflammatory mediators such as the cytokine RANTES. We have measured the trans-activation and trans-repression potencies of the five currently available inhaled GC using reporter gene assays. The rank order of trans-activation potencies in HeLa cells stably transfected with a GC-inducible luciferase gene was fluticasone propionate > budesonide and triamcinolone acetonide > beclomethasone dipropionate and flunisolide. For all GC except beclomethasone dipropionate, there was a highly significant correlation between their potency to trans-activate in HeLa cells and their capacity to induce the gluconeogenic enzyme tyrosine aminotransferase in hepatoma tissue culture (HTC) cells. The rank order of trans-repression potencies in A549 lung cells transiently transfected with an AP-1- or NF-kappaB-dependent luciferase gene was fluticasone propionate > budesonide > beclomethasone dipropionate, triamcinolone acetonide, and flunisolide. The same rank order was found for inhibition of RANTES release. Thus, determination of trans-repression and trans-activation potencies of GC may help to predict their capacity to produce anti-inflammatory and side effects, respectively.

Administration, Inhalation↗
PubMed2000

Glucocorticoid receptor alpha and beta in glucocorticoid dependent asthma.

Patients with glucocorticoid (GC)-dependent asthma present an ongoing inflammation of the airways despite chronic long-term treatment with oral GC. Interleukin (IL)-8 and granulocyte/macrophage colony-stimulating factor (GM-CSF) have been implicated in airway inflammation in severe asthma and their synthesis is normally repressed by GC. To further characterize the inflammatory process in GC-dependent asthma, we measured the release of IL-8 and GM-CSF by peripheral blood mononuclear cells (PBMC) of eight normal subjects, six untreated controlled asthmatics, six untreated uncontrolled asthmatics, and nine GC-dependent asthmatics. We show that PBMC from GC-dependent asthmatics released high amounts of these cytokines despite chronic in vivo exposure to GC (p < 0.001 versus normal subjects). In contrast, when untreated uncontrolled asthmatics were given a short course of oral GC, IL-8 and GM-CSF production was inhibited (p = 0.0078). Release of IL-8 and GM-CSF by PBMC of GC-dependent asthmatics was reduced after in vitro GC treatment (p < 0.002). We investigated whether the incapacity of GC to inhibit production of these cytokines in vivo was the result of a dysregulation of the glucocorticoid receptor (GR) in GC-dependent asthma. GRalpha and GRbeta are, respectively, the functional receptor and a putative dominant negative form of the receptor. Western blot and polymerase chain reaction (PCR) analyses indicated that GRalpha was expressed at similar level in all groups and was largely predominant over GRbeta. Thus, persistent release of IL-8 and GM-CSF in GC-dependent asthma is not associated with low expression of GRalpha or overexpression of GRbeta.

Adult↗
PubMed2000

[Drug allergies: a public health problem].

Adverse drug reactions occur in 10 to 20% of hospitalized patients and up to one third are due to allergic and pseudoallergic reactions. Allergic reactions are unpredictable reactions related to immunologic mechanisms. Pseudo-allergic reactions mimic allergic reactions but no drug specific antibody or T cell proliferation can be demonstrated. A true diagnosis is rarely set up and the tools for it are lacking. In this review, we will focus on some epidemiological data concerning these reactions, including data on incidence, mortality and cost.

Drug Hypersensitivity↗
PubMed2000

[Update on drug allergies induced by antibiotics and anti-retroviral agents].

Allergic reactions to antibiotics have raised considerable concerns, and are still underevaluated. It is a daily problem for general practitioners and allergologists. Their clinical manifestations are numerous, ranging from mild maculo-papular eruptions to sometimes deadly anaphylactic shocks or epidermal necrolisis. Atopy is not a risk factor, but concomitant viral infections, including Epstein-Barr virus and HIV infections are. HIV-infected patients indeed suffer more frequently from drug-induced hypersensitivity reactions than immunocompetent subjects or even non-HIV immunodeficient patients. 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. In some cases, graded challenges (desensitization when an IgE mechanism is involved) is possible and efficacious (quinolones for cystic fibrosis, sulfonamides for HIV-infected patients).

Anti-Bacterial Agents↗