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Biomedical subjects

F B Michel

Publications and source records attributed to F B Michel.

At least 19 recordsLinked to original sources

[Application of the WHO chronic respiratory diseases programme in Sub-Saharian Africa: problems in Senegal].

INTRODUCTION: To prevent and control chronic respiratory diseases, the WHO has outlined a programme to be applied in all the countries. In Sub-Saharan countries like Senegal, its application faces many barriers. METHODS: This work is a detailed analysis of the main areas of the programme based on the socio-economic, cultural and medical realities present in Sub-Saharan Africa countries, and particularly in Senegal. RESULTS: There is a lack of political engagement resulting from the precarious socio-economical situation. The demand for care is impaired because of the prevalence of illiteracy and the practice of traditional healing methods which is the first recourse for patients. The inaccessibility and lack of adequate health structures, technical equipment and qualified medical staff, and the high cost of medications for the majority of the population is the cause of this weakness of the healthcare system. These international recommendations are both not compatible with the local realities and not known to the majority of health providers. CONCLUSIONS: The mobilisation of international and national human and financial resources, the involvement of community-based structures, the adaptation and revision of the recommendations, the introduction of medications advocated by the Bamako Initiative, the training of health providers, the adaptation of regional and continental initiatives against tobacco and the creation of smoking cessation centres are needed if this chronic respiratory diseases programme is to be efficiently implemented.

Asthma↗

Specific immunotherapy in rhinitis and asthma.

OBJECTIVE: The primary objective of this review is to discuss the efficacy of immunotherapy on combined lung and nasal symptoms, as well as data suggesting that allergen-specific immunotherapy (SIT) may, by altering the natural course of allergic disease, have a preventive effect on rhinitis and asthma. DATA SOURCES: A review of literature published on allergen-specific immunotherapy in the treatment of allergic rhinitis and asthma was performed. The review represents a synthesis of these sources and the expert opinion of the author. STUDY SELECTION: The expert opinion of the authors was used to select the relevant data for the review. RESULTS: Epidemiologic studies have consistently shown that asthma and rhinitis often co-exist in the same patients, and rhinitis often precedes the onset of asthma. SIT has been shown to be effective as a curative treatment for these allergic diseases, but there is increasing evidence indicating that SIT also may have a preventive effect. A study of children monosensitized to house dust mites showed that immunotherapy altered the natural course of allergy in preventing the development of additional sensitizations. CONCLUSIONS: At present, SIT seems to be the only treatment that may modify the course of the disease, either by preventing the development of new sensitivities or by altering the natural history of asthma. When SIT is introduced to patients with only allergic rhinoconjunctivitis, it may stop the development of asthma. SIT should be started early in the disease process, as soon as allergy has been diagnosed, to modify the spontaneous long-term progress of the allergic inflammation and disease.

Asthma↗

[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↗

[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↗

[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↗

[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↗

[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↗

[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↗

[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↗

[Corticosteroid-resistant asthma: basic aspects].

A CONTROVERSIAL DEFINITION: The current definition of corticosteroid-resistant asthma is a spirometry definition. There is however, no consensus on dose, treatment duration, steroid administration route and the degree of FEV1 non-reversibility allowing the diagnosis of corticosteroid-resistant asthma. Finally, the beneficial effect of steroids in clinical terms (symptom frequency, number of hospitalizations, quality of life) is not taken into consideration, thus nearly one-half al all patients included in studies on corticosteroid resistance are taking long-term oral steroids. This subgroup of patients must be considered individually when examining these studies. COMPLEX PATHOGENESIS: There are a wide range of anomalies described in the literature involving: glucocorticoid pharmacokinetics, cytokine regulation, cell function (monocytes, lymphocytes, eosionophils), and transcription factors (glucocorticoid and AP-1 receptors). DIFFICULT THERAPEUTIC MANAGEMENT: There are several prerequisites before proposing exceptional regimens using cyclosporine, gold salts, methotrexate, or immunoglobulins: i) certain diagnosis of asthma (with CT scan and ultrasonographic explorations if needed, ii) proper control of environmental factors and good compliance, iii) proof of the absence of clinical benefit with long-term corticosteroids. These exceptional therapeutic schemes have their disadvantages and are only warranted by clinically patent corticosteroid resistance (whatever the "biological" cause).

Adrenal Cortex Hormones↗

Comparison between nasal provocation tests and skin tests in patients treated with loratadine and cetirizine.

BACKGROUND: The effect of H1-blockers may differ depending on the target organ. OBJECTIVE: A double-blind, placebo-controlled study was carried out to compare the effect of a 7-day treatment with loratadine (10 mg daily) or cetirizine (10 mg daily) on nasal challenge with grass pollen grains and skin tests with allergen or histamine. METHODS: Twenty-four patients were enrolled, but the analysis was carried out on 23. Nasal challenge was carried out by using 5-fold increasing numbers of pollen grains. Skin prick tests were done with serial concentrations of allergens and 1 concentration of histamine. Patients were tested in a cross-over design, with each treatment being administered for the previous 7 days and with a 2-week washout period. RESULTS: By comparison with placebo, loratadine and cetirizine increased significantly the threshold number of pollen grains required to induce a positive nasal challenge (P <.001). There was no difference between loratadine and cetirizine. Skin test responses to allergen were significantly reduced by loratadine and cetirizine by comparison with placebo. Skin test responses to histamine were significantly decreased by the 2 H1-blockers, but they were more profoundly decreased by cetirizine than by loratadine. CONCLUSIONS: Both H1-blockers reduced similarly allergen-induced skin test and nasal challenge responses. Cetirizine was more effective on histamine skin test responses.

Adult↗

Concomitant brain radiotherapy and vinorelbine-ifosfamide-cisplatin chemotherapy in brain metastases of non-small cell lung cancer.

AIM: To determine whether or not brain radiotherapy and concomitant three-drug chemotherapy is feasible and yields anti-tumour activity in patients with non-small cell lung cancer and brain metastases at time of presentation. PATIENTS AND METHODS: Twenty-three previously untreated patients suffering from non-small cell lung cancer and brain metastasis were prospectively included in this feasibility study. Most of the patients had neurological symptoms and an Eastern Collaborative Oncology Group (ECOG) performance index over 2. Treatment consisted of three courses of whole brain radiotherapy (18 Gy in 10 fractions) and vinorelbine, 30 mg/m2 on days 1 and 8, ifosfamide, 1.5 g/m2 daily from day 1 through day 3 with uromitexan uroprotection, and cisplatin, 100 mg/m2 on day 2. A cycle restarted every 28 days. RESULTS: Eighteen patients completed the three-cycle programme. All patients were affected by a grade 4 neutropenia and 14 of them experienced a febrile episode. Other toxicities were mild to moderate and manageable. Received-dose intensities of vinorelbine, ifosfamide and cisplatin were 80, 90 and 90%, respectively. Overall response rate was 30%. Specific evaluation of brain response demonstrated complete response for seven patients, and partial response in six (objective brain response rate, 56%). All responders benefited by a remission of symptoms and improvement of performance index. Median survival from start of protocol was 7.6 months. CONCLUSION: Although the high rate of toxicity requiring re-admission, concomitant brain radiotherapy plus vinorelbine, ifosfamide and cisplatin chemotherapy is feasible in patients suffering from brain metastasis, and demonstrates an anti-tumour activity for this particular subset of stage IV non-small cell lung cancer. The development of such an aggressive approach needs further comparative evaluation.

Adult↗

Neoadjuvant etoposide, ifosfamide, and cisplatin followed by concomitant thoracic radiotherapy and continuous cisplatin infusion in stage IIIb non-small cell lung cancer.

OBJECTIVE: To determine the applicability and safety of an ifosfamide, cisplatin, and etoposide (VIP) regimen as a neoadjuvant chemotherapy to a concomitant thoracic radiotherapy and cisplatin continuous infusion in locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-four patients (stage IIIb in 43 and stage IIIa in 1) entered a study of VIP, followed by concomitant thoracic radiotherapy and cisplatin continuous infusion. Chemotherapy consisted of three courses of cisplatin 25 mg/m2, ifosfamide 1.5 g/m2 (with uroprotection), and etoposide 100 mg/m2 given on days 1 to 4 of a 21-day cycle with hematopoietic support using recombinant human methionyl granulocyte colony stimulating factor. Patients who achieved a response or a stabilization were planned to receive a split-course normofractionated thoracic radiotherapy (first course: 30 Gy/10; 4-week rest period; second course: 25 Gy/10). A continuous cisplatin infusion of 6 mg/m2 daily was administered using an autonomous chemotherapy delivery device. Total plasma platinum titration was performed daily during the two courses in five of the patients. Analyses were done on an intent-to-treat basis. RESULTS: Thirty-nine of the 44 patients received the three-cycle chemotherapy program. Received dose intensity was 82%. Thirty-eight patients received the radiotherapy and, among them, 35 received the complete concomitant continuous cisplatin infusion. Objective (complete) response rates were 48% (7%) at the end of chemotherapy and increased up to 61% (16%) by the end of radiotherapy. At the end of the first radiotherapy cycle, the mean total plasma platinum concentration was twice as high as that of the residual postinduction chemotherapy concentration. During induction chemotherapy, myelosuppression was the limiting toxicity requiring hospital readmission in 23 patients. During radiotherapy, the main toxicity was acute esophagitis. A relatively high rate of pulmonary fibrosis was observed using the subjective objective management analytic--late effects of normal tissue score without life-threatening pulmonary function impairment. None of the patients died from toxic reactions. Probability of survival at 1, 2, and 3 years was 49%, 19%, and 5%, respectively. Primary cause of failure was a local relapse in 63% of the patients, brain metastases in 24%, and hematogeneous metastases to other sites in 13%. CONCLUSION: Neoadjuvant VIP followed by concomitant radiotherapy-chemotherapy is feasible, but the split-course radiotherapy did not prevent a high rate of local recurrences. The high rate of toxic reactions requiring hospital readmission limits further development of such an aggressive regimen in NSCLC.

Adult↗

[Immunobiology of respiratory allergy].

Respiratory allergies are frequent and the etiological diagnosis is not always easy. Most often, the allergy assessment is vital. For the allergist, this assessment begins with skin tests which must be complemented by measurement of the level of specific IgE in case of doubt. For the generalist or physician who does not have special competence in allergy, an alternative to a specialist consultation at once is a multi-allergen test of detection. This assessment is necessary to set out the etiological diagnosis and facilitate the responsibility of the therapy.

Allergens↗

[Mechanism of action of glucocorticoids in asthma].

While on the basis of clinical studies glucocorticoids (GC) became the first-line therapy for asthma, the molecular basis of GC action has been extensively studied. Glucocorticoids exert their effects by binding to the glucocorticoid receptor (GR), which then inhibits or increases gene transcription through processes known as transrepression and transactivation, respectively. Transrepression results from the inhibitory interaction between the GR and other transcription factors like AP-1 and NF-kappa B. Since AP-1 and NF-kappa B DNA binding sites have been mapped to the promoter regions of many genes coding for proinflammatory mediators (IL-1, 2, 5, 6, 8, 13, TNF-alpha, RANTES, Eotaxin, GM-CSF, metalloproteinases, ICAM-1 ...), this interaction may be an important aspect of the GC anti-inflammatory properties. Transactivation is mediated through binding of the GC-activated GR to a DNA sequence called glucocorticoid response element (GRE) and may result in some benefits and side effects since GRE has been mapped to the promoter regions of genes coding for lipocortin, beta 2-adrenergic receptor, and for genes involved in the onset of metabolic effects (diabetes, hypokaliemia, hydrosodic retention) and glaucoma. Other molecular mechanisms may also be involved like the binding to the GR to a negative GRE (nGRE), the interaction with the basal transcriptional machinery, and the post transcriptional modulation of mRNA stability. In asthma, the relative importance of each mechanism remains to be studied, but both mechanisms may probably be involved.

Asthma↗