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Biomedical subjects

P Demoly

Publications and source records attributed to P Demoly.

At least 19 recordsLinked to original sources
PubMed2001

Correlation between different gene expression assays designed to measure trans-activation potencies of systemic glucocorticoids.

The glucocorticoids (GC) betamethasone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone and triamcinolone acetonide are currently used in the treatment of inflammatory diseases. Through a process called trans-activation, GC activate gene expression and produce various physiological and pharmacological effects. In particular, by inducing gluconeogenic enzymes, long-term GC treatment may cause diabetes. Using three different assays, we have extensively compared the capacity of the above GC to activate gene expression. trans-Activation of a GC inducible luciferase gene was assessed in HeLa and A549 cells after stable and transient transfection, respectively. In hepatoma tissue culture cells, we measured trans-activation of the endogenous gene encoding tyrosine aminotransferase, a gluconeogenic enzyme. Half-maximal effective concentrations of GC were determined by dose-response analyses. Results obtained with these assays were highly correlated and GC were ranked in three groups according to their trans-activation potency: betamethasone, dexamethasone, and triamcinolone acetonide > methylprednisolone and prednisolone > hydrocortisone. Potencies were not strictly related to receptor binding affinities and not significantly affected by the amount of endogenous GC receptor.

Dose-Response Relationship, Drug↗
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

[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

JLP5B9: new monoclonal antibody against polysialylated neural cell adhesion molecule is of value in phenotyping lung cancer.

Non-small-cell lung cancer (NSCLC) is currently one of the most prevalent malignant tumors. It displays a wide variety of phenotypes which includes neuroendocrine markers commonly found on small-cell lung cancers (SCLC) such as the neural cell adhesion molecule (NCAM) and in particular its highly polysialylated isoform, embryonic NCAM (eNCAM). NSCLC with neuroendocrine differentiation may represent a subset of tumors whose cells have a more aggressive biological behavior. A tumor marker that distinguishes this latter sub-type could be of clinical relevance. Accordingly, we have raised a monoclonal antibody of the IgM type (JLP5B9) directed against capsular polysaccharides of N. meningitidis B which bears polysialic acid groups. We have demonstrated that JLP5B9 recognizes eNCAM with high affinity and that it is specifically directed against the polysialic acid moieties of NCAM. JLP5B9 was also found to react with human SCLC, NSCLC and neuroblastoma cell lines. We then used JLP5B9 as a specific probe for the detection of tissue eNCAM and found that it was expressed on up to 20% of tumor cells obtained from 5 out of 13 patients with NSCLC. This mAb deserves further investigation to evaluate its potential as a tool for serodiagnosis of lung cancer.

Adult↗
PubMed2000

In vitro diagnosis of cypress pollen allergy by using cytofluorimetric analysis of basophils (Basotest).

BACKGROUND: Cupressaceae pollen allergy is a worldwide pollinosis, but its in vitro diagnosis is notoriously difficult. The Basotest is a newly available in vitro test for the detection of allergen-specific IgE based on the level of cellular activation of basophils by using flow cytometry. OBJECTIVES: The Basotest was compared with the measurement of cypress pollen-specific IgE in highly selected patients. METHODS: We analyzed 34 patients allergic to cypress pollen selected on the basis of a suggestive clinical history and positive skin test and nasal challenge responses to cypress pollen extract. We also analyzed 8 patients with positive skin test responses to cypress pollen extract who did not present symptoms during the pollen season (intermediate group) and 33 control subjects. Sensitivity, specificity, and efficiency of the Basotest and serum-specific IgE levels measured by using the CAP System were determined in patients allergic to cypress pollen. Histamine release was studied in a selected group of patients. RESULTS: The Basotest was more sensitive (91.2%) than the CAP System (76%) for the in vitro diagnosis of cypress pollen allergy. A dose-response curve was observed in basophils obtained from patients allergic to cypress pollen. There were no false-positive results with either test (specificity 100%). The results of the Basotest or those of the CAP System did not correlate with the patients' in vivo threshold sensitivity assessed by skin tests and nasal challenge. CONCLUSIONS: The Basotest was found to be an effective diagnostic test in patients allergic to cypress pollen.

Adult↗
PubMed2000

Epidemiologic evidence for asthma and rhinitis comorbidity.

Asthma and rhinitis are often comorbid conditions, and the overall characteristics of the diseases and the treatment options for the disorders are similar. Several recent epidemiologic studies in the general population have provided evidence to strongly associate the development of asthma with a previous history of either allergic or perennial rhinitis. Additional links between asthma and rhinitis include a description of increased aspirin intolerance in both disorders and the observation that most subjects with occupational asthma experience rhinitis. Further, the likelihood of the development of asthma is much higher in individuals with both perennial and seasonal rhinitis than for individuals with either condition alone. Asthma and rhinitis were found to be comorbidities regardless of atopic state, and perennial rhinitis has been associated with an increase in nonspecific bronchial hyperresponsiveness. Several studies have identified rhinitis as a risk factor for asthma, with the prevalence of allergic rhinitis in asthmatic patients being 80% to 90%. These studies and others demonstrate that the coexistence of asthma and allergic rhinitis is frequent, that allergic rhinitis usually precedes asthma, and that allergic rhinitis is a risk factor for asthma. Finally, studies that have examined the age of onset of atopy as a confounding factor for the development of asthma and allergic rhinitis have suggested that early age atopy may be an important predictive factor for respiratory symptoms that continue into late childhood. In conclusion, rhinitis and asthma are strongly associated, and rhinitis has been identified as a risk factor for asthma.

Asthma↗
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↗
PubMed2000

[Genetics of asthma and atopy].

The genetics of asthma and atopy has made tremendous progresses over the last couple of years. It has been known for ages that allergies and asthma are concentrating within families. Modern genetics has pinpointed some gene areas such as 5q31.1, 6p21.3, 11q13, 12q15, 14q11.1 and 16p12. Much of the information available today has been fragmentary and not always confirmed. Alleles at multiple loci are likely to be involved and the ultimate picture is most likely determined by many genetic and environmental factors.

Alleles↗
PubMed2000

[From allergic rhinitis to sinus diseases (sinusitis/nasal polyps): epidemiologic and experimental links].

The relationships between rhinitis and chronic sinusitis are close and complex, those between allergic rhinitis and nasal polyposis are controversial. These relationships can be demonstrated not only in terms of anatomy, physiology and epidemiology (by comparing the prevalence of one disease in patients suffering from the other disease), but also experimentally (by studying the sinus involvement following nasal allergen provocations), and pathophysiologically (by phenotyping and comparing the inflammation present in both diseases). Results of such studies are convincing and have confirmed the fundamental role of nasal inflammation in general and allergic inflammation in particular in the genesis of sinusitis (it is now therefore recommended to utilize the term 'rhinosinusitis'). The importance of allergy in the etiologic development of nasal polyps remains controversal and doubtful. Because the diagnosis of allergic rhinitis provides useful therapeutic options, an appropriate evaluation for underlying allergies in indicated in any patient with chronic upper respiratory tract symptoms.

Diagnosis, Differential↗