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Biomedical subjects

A Magnan

Publications and source records attributed to A Magnan.

At least 55 records · Page 3Linked to original sources

[Role of leukotriene inhibitors in the treatment of childhood asthma].

Leukotriene inhibitors are new pharmacological agents for the treatment of mild to moderate persistent asthma and exercise-induced asthma (EIA). Studies concerning their use in children remain scarce. Available data in the treatment of persistent asthma in children suggest that they could be an alternative to long-acting beta 2-agonists when asthma control cannot be obtained with inhaled steroids alone. Their main advantages are first that they are given orally once daily; second, that they do not induce tachyphylaxis to bronchoprotection against EIA, unlike long-acting beta 2-agonists. Studies specifically conducted in children are necessary to best describe their place in pediatric asthma treatment.

Administration, Oral↗

Relationships between natural T cells, atopy, IgE levels, and IL-4 production.

BACKGROUND: Th2 cells govern allergic disorders. Mechanisms leading to the Th2 commitment are dominated by the requirement of IL-4. A potential source of this triggering IL-4 could be the CD4 + subset of a small population of T cells, natural T (NT) cells. Indeed, this subset is involved in IgE responses in mice and produces promptly high amounts of IL-4 in both mice and man. METHODS: NT cells were identified in peripheral blood by flow cytometry with antibodies against Valpha24 and Vbeta11, recognizing the T-cell receptor specific for NT cells. Simultaneous staining with anti-CD3, anti-CD4, or anti-CD8 antibodies was performed. The frequency of NT cells in man was studied according to the presence of atopy defined by the positivity of skin tests, according to total IgE levels in serum, and according to IL-4 concentration of whole-blood culture supernatants determined by a flow cytometer microsphere-based assay. RESULTS: Seventy subjects were included, of whom 30 were atopic. The number of CD4+ NT cells was higher in atopics than in nonatopics (P=0.009). This number was correlated to the total IgE levels (r = 0.34, P = 0.03). In addition, the number of CD4 + NT cells, but also of CD8 + NT cells, was correlated to the levels of IL-4 (r=0.71, P=0.01, and r=0.6, P=0.03, respectively). CONCLUSIONS: These results show that the number of NT cells, particularly the CD4+ subset, is related to atopy, IL-4 production, and IgE levels. Therefore, this population of T cells is likely to play a role in the Th2 commitment initiating atopic diseases.

Adolescent↗

Fel d 1 production in the cat skin varies according to anatomical sites.

BACKGROUND: Fel d 1 is the major cat allergen, inducing asthma in sensitized individuals. It is produced by the skin and lies on fur. Recently, it was established that the amount of Fel d 1 on fur varies among anatomical sites. However, it is not known whether the allergen production by skin varies in parallel. The objective was to compare the Fel d 1 production by male cat skin in two anatomical sites, the face and the chest, in order to correlate it with Fel d 1 amounts on fur, and to assess the reaccumulation of Fel d 1 after washing. METHODS: Ten intact male cats were shaved under general anesthesia at both areas, and the fur was collected. The skin was washed and the washing fluid collected for Fel d 1 assays. Fel d 1 levels were measured in microg/g fur and ng/cm2 skin by ELISA before and after washing and 48 h later. RESULTS: In skin washing, the mean Fel d 1 level was significantly higher in the face (1015.2 +/- 821.6 ng/cm2) than the chest (115.2 +/- 66.8 ng/cm2). In the fur, the respective levels were 63.6 +/- 34 and 29.6 +/- 13.6 microg/g. In the skin sample taken after skin washing, the level of Fel d 1 dropped to 25.1 +/- 25.7 ng/cm2 on the face and to 22 +/- 17.4 ng/cm2 on the chest. After 2 days, skin Fel d 1 levels returned to basal values, with higher values on the face than the chest. CONCLUSIONS: This study shows that Fel d 1 levels on the skin are dramatically higher on the facial area than chest. This anatomical variation is concordant with the levels of Fel d 1 found on fur. Washing reduces levels of major allergen on cat skin and fur, but the accumulation on skin is restored within 2 days.

Animals↗

[Response to IgE].

Over the last three decades, a good deal of work has focused on the IgE response due to the implication of these antibodies in allergic diseases. IgE antibodies, mediators of immediate hypersensitivity reactions, bind to specific high or low affinity receptors which are distributed on cell surfaces throughout the organism. Activation of receptors contributes to the different aspects of allergic inflammation. Regulation of the IgE response is complex and involves different factors modulating isotype synthesis, low-affinity receptor FcERII:CD23 and its soluble portion, and the Th1/Th2 balance. Allergic diseases are characterized by a dysregulated IgE response, probably related to an imbalance favoring Th2 leading to exaggerated reaction. The advent of anti-IgE treatments can be seen as a notable progress in the management of atopic diseases. Their contribution will depend on the exact role of the IgE response in inflammatory allergic reactions.

Antigens↗

[Natural history of atopy].

Atopy is defined by an individual propensity to develop IgE-dependent reactions against environmental allergens. It could be now defined by a propensity to develop a Th2 response against such allergens, which takes into account not only the IgE production but also the eosinophil activation and the pivotal role of T lymphocytes in this process. A number of factors are determinants of atopy: some of them precede birth, such as genetic factors and some peculiarities of the immune system during pregnancy, in relation to maternal atopy, to in utero allergen exposure or to pregnancy itself. After birth, car pollution could modify the response to allergens by enhancing the IgE production. Food habits, by favoring intake of omega-6 polyunsaturated fat acids contained in some vegetal fat instead of omega-3 polyunsaturated acids from fish, could facilitate IgE dependent sensitization. Viral infections could, depending on their nature and their circumstances of occurrence protect from atopy inversely induce some sensitizations. Finally the degree of exposure to allergens themselves is proportional to the probability of sensitization. Together, these determinants of atopy could account for the higher prevalence of atopy in developed countries. The clinical expression of atopy varies during life from atopic dermatitis to rhinitis and asthma. Infancy is the time for dermatitis and sensitization to food allergens. Sensitization to airborne allergens occurs thereafter. Asthma, sometimes introduced by one or several bronchiolitis episodes follows to dermatitis or can be associated to it. Rhinitis appears in children or young adults. Seasonal, it is due to pollens and is rarely associated with asthma. In contrast, perennial, it is due to indoor allergens and leads to bronchial hyperreactivity and asthma.

Adult↗

[Role of desensitization in the treatment of respiratory allergies].

Most authors consider immunotherapy as an efficient and safe treatment for pollen and mite allergic rhinitis. Recent meta-analyses showed that immunotherapy brings a significant benefit to some asthmatic patients depending on the type of allergen used, the severity of the disease, the number of allergenic sensitivities. Nevertheless everybody agrees that pharmacological treatment of asthma and immunotherapy must be complementary when indications of desensitization are given. All precautions to avoid adverse systemic effects or to cure them immediately must be taken. More work is needed as concerning the duration of the treatment, the efficacy of some local allergen administrations, the indications in the young child. The future is based on the use of antigenic peptides and of recombinant allergens.

Allergens↗

Aggressive form of pleural epithelioid haemangioendothelioma: complete response after chemotherapy.

Epithelioid haemangioendotheliomas are rare tumours of endothelial origin. They can develop in any tissue but occur principally in the lung and liver. Their usual course is a slow progression, so that they can be treated by surgery. In aggressive forms, no treatment has proved efficient to date. This study, describes a case of bilateral pleural epithelioid haemangioendothelioma that extended to the peritoneum. The histological diagnosis was confirmed by both conventional examination and immunohistochemistry. After six courses of carboplatine plus etoposide, a complete response was obtained. The complete remission is still lasting at 18 months after the diagnosis and the patient is healthy.

Antineoplastic Combined Chemotherapy Protocols↗

[Modes of administration of inhaled corticosteroids in mild to moderate persistent asthma].

Inhaled corticosteroids are the treatment of choice for asthma. However, poor compliance by patients is one of the principal difficulties forced by clinicians. Thus, it seems important to propose the minimal daily number of doses. This study has compared the various modes of administration of inhaler corticosteroids and was carried out in patients with mild to moderate persistent asthma. Thus, comparing two to four doses per day shows an identical efficacy if the dose is less than 800 micrograms per day. At higher doses only two studies have been carried out and there are discordant results. The studies compare two doses versus one single dose per day and equally disagree with numerous works in favor of a single daily dose. In the single study carried out for at least twelve months the twice daily dose was the most effective. Thus it seems reasonable to suggest a single dose for mild persistent asthmatics. For moderate persistent asthmatics the choice between a single or twice daily dose would depend on the therapeutic compliance of the patient.

Administration, Inhalation↗

[Acute pleurisy revealing post-myocardial infarction syndrome].

We report a case of Dressler's syndrome in which the diagnosis was made following an investigation of pleurisy which the laboratory data revealed as inflammatory. A myocardial infarction which had occurred two months earlier had passed unnoticed. The principal value of this case was to draw attention to the syndrome which may initially be a pleurisy but also clinically the picture may mimic pneumonia, both alone or together may be associated with classical pericarditis. Pleurisy occurs in Dressler's syndrome but it is rarely the presenting diagnosis as the cardiac picture tends to predominate.

Acute Disease↗

Alveolar macrophage interleukin (IL)-10 and IL-12 production in atopic asthma.

Inflammation in asthma is characterized by a Th2 response. In many experimental systems, this response can be regulated by interleukin (IL)-10 and IL-12. IL-10 deactivates T cells, and IL-12 reorients the response toward a Th1 pattern. Alveolar macrophages (AM) can secrete both of these cytokines, and thus regulate T-cell behavior in asthma. They can enhance the Th2 response by turning off their secretion of IL-10 and IL-12, or tend to downregulate it by producing these cytokines. To elucidate that point, we assayed the AM IL-10 and IL-12 from 11 asthmatic patients and four controls. Six asthmatics were treated by inhaled corticosteroids. AM were recovered by bronchoalveolar lavage (BAL). They were isolated and cultured for 24 h without stimulation or in the presence of lipopolysaccharide (LPS). IL-10 and the p40 subunit of IL-12 were assayed in the BAL fluid and in AM culture supernatants by ELISA. Spontaneous AM IL-10 production was higher in asthmatics, particularly in the treated group. The AM IL-10 production after stimulation by LPS was also elevated in asthmatics, but was mainly so in untreated patients. IL-12 levels were higher in BAL fluids from untreated patients than from controls. The IL-12 production of LPS-stimulated-AM from these patients was increased. These results show that AM are at least primed for the production of IL-10 and IL-12 in asthma, and suggest that these cells could be involved in the resolution of the asthmatic inflammation.

Administration, Inhalation↗

Rhinitis alone or rhinitis plus asthma: what makes the difference?

This paper examines the clinical expression of asthma in a group of patients displaying rhinitis according to age, sex, associated symptoms, smoking, familial history of asthma, atopy, type of sensitization to aeroallergens (pollens and/or indoor allergens), total serum immunoglobulin E (IgE), and blood eosinophils. A total of 117 adults with rhinitis were analysed on the basis of symptoms. Among them, 51 also displayed asthma, defined as a history of recurrent episodes of dyspnoea with a reversible airflow obstruction or a positive methacholine challenge. The logistic regression analysis carried out in a stepwise approach, combining several factors, showed that various parameters affected the risk of having asthma associated with rhinitis. A further analysis was made in 74 rhinitis patients comparing 42 subjects without nonallergic airway hyperresponsiveness (NAAH) to 32 patients with asthma and NAAH. Atopy, high total serum IgE levels, elevated blood eosinophil count and maternal asthma were associated with asthma. Furthermore, in atopic patients, pollen sensitization was more closely related to rhinitis alone, whereas sensitization to indoor allergens was a major determinant for the association of asthma with the symptoms of rhinitis. The same risk factors as those found in the clinical part of the study discriminated the patients with rhinitis without NAAH from those with rhinitis, asthma and NAAH. In conclusion, this study gives new insights into the relationships between asthma and rhinitis.

Adult↗

[Role of eosinophilia in atopic pathology].

Atopy corresponds to a heightened predisposition to develop an IgE-mediated reaction to allergens in the environment. Symptomatic manifestations of atopy include skin disorders, rhinitis, and allergic asthma. Tissue infiltration by polynuclear eosinophils is a shared feature of all atopic diseases. In asthma, eosinophilic infiltration is considered as a pathognomonic finding, proportional to severity. Eosinophils have been linked directly to epithelial damage responsible for asthma symptoms as a result of massive production of basic proteins which are toxic for the mucosa. Eosinophils also produce fibrosis-inducing cytokines and contribute to remodeling of the airway. Activation of Th2 lymphocytes accounts for the influx of eosinophils into the airway via production not only of IL-5 but also of chemokines such as RANTES, MCP-3, and, above all, eotaxine. Resolution of airway inflammation in asthma is related to eosinophil apoptosis occurring spontaneously or therapeutically in response to anti-inflammatory agents. Based on current data, eosinophils can be considered as a pivotal factor in the occurrence of atopic manifestations and thus constitute a prime target for future immunotherapies.

Anti-Inflammatory Agents↗

Long-acting beta-2 agonists. An attempted response to various questions which can be posed by pneumonologists.

The use of long acting beta 2 agonists is an undeniable improvement in the treatment of certain types of asthma. It enables better control of unstable asthma, improves and gives a superior quality of life. Current work confirms however that when used in the long term they ought to be associated with anti-inflammatory treatment. If they do not produce any important secondary effects, even when used for a long period, it is not currently possible to confirm that their prolonged use does not change the intensity of their bronchodilator effect and/or the intensity of the bronchodilator effect of the short acting beta 2 stimulants. Some studies have shown that their addition to basic treatment with inhaled steroids is more effective than increasing the inhaled steroids. Other studies are necessary to know if they may enable the reduction in inhaled corticosteroids and how far.

Administration, Inhalation↗

Platelet-derived growth factor expression in primary pulmonary hypertension: comparison of HIV seropositive and HIV seronegative patients.

Primary pulmonary hypertension (PPH) is characterized by intimal fibrosis and cell proliferation (including fibroblasts, smooth muscle and endothelial cells) in the distal pulmonary arterial tree. Considerable interest has been generated by recent reports of PPH in human immunodeficiency virus (HIV)-1-infected individuals. Although the lack of evidence for a pulmonary artery infection has suggested that in such cases HIV may act through mediator release rather than by direct endothelial infection, the mechanisms underlying HIV-associated PPH remain poorly defined. Platelet-derived growth factor (PDGF) has the ability to induce smooth muscle cell and fibroblast proliferation and migration. Given these considerations, we have attempted to document a possible role for PDGF in PPH occurring in HIV seropositive and seronegative patients. Using semiquantitative polymerase chain reaction (PCR), PDGF A-chain messenger ribonucleic acid (mRNA) expression was analysed in surgical lung biopsies from 13 HIV seronegative patients and one HIV seropositive patient, all displaying severe PPH. In parallel, lung samples from two patients with HIV-1-associated PPH were studied by immunohistochemistry and in situ hybridization. Results were compared to those obtained in three HIV-1-infected individuals with no pulmonary complication (as demonstrated by clinical, radiological, bacteriological, and necropsy findings) and five control lung biopsies. As compared to controls, PDGF A-chain mRNA expression is elevated in lung biopsies from patients displaying PPH (p=0.029). In HIV-1-associated PPH, interstitial perivascular cells expressing PDGF A-chain mRNA and protein could be detected by in situ hybridization and immunohistochemistry, respectively. Platelet-derived growth factor expression is elevated in lung biopsies of patients displaying primary pulmonary hypertension. Growth factors such as platelet-derived growth factor may play a part in the initiation and/or progression of primary pulmonary hypertension.

Adult↗