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Biomedical subjects

P Godard

Publications and source records attributed to P Godard.

At least 109 records · Page 6Linked to original sources
PubMed1998

[Biological perspectives].

The tumour biology of non-small cell bronchial cancer integrates recent developments and a dynamic schema of the phenomena of tumour progression and diffusion of the metastatic disease. There is no leap of known biological disruption between Stage II and Stage III. The latter is defined by anatomical criteria and is a transition in the continuum of the natural history of these cancers. The moto for the tumour progression is the genotypic instability and phenotypic diversification. Metastatic microscopic disease constitutes the first cause of failure in the treatment of Stage III non-small cell bronchial cancer. Among prognostic factors for survival emphasis is placed on the alterations of p53 expression, different types of aneuploidy, anomalies of the expression of cellular adhesion molecules and finally, tumour diversification towards a metastatic phenotype.

Aneuploidy↗
PubMed1998

[New cytotoxics in the treatment of bronchial cancers].

This review presents a synthesis of published studies on the activity of the newer cytotoxic drugs in the treatment of bronchial cancer. It also touches on the early indications of recent results which until now have only been the subject of oral presentations. The taxanes form a new class of anti-cancer drug. Myelosuppression is their limiting factor. These are very active cytotoxic drugs but their toxological profile makes them difficult to use in polychemotherapy. The anti-tumour activity of docetaxel (Taxotere) has been shown. For non-small cell cancer (CNPC) the objective response (OR) is of the order of 26% in new patients and 21% in those who have been pre-treated with a combination of drugs based on Cisplatine. For paclitaxel (Taxol) the OR is around 25% in new patients. In association with a course of cisplatine the efficacy would be dose dependent. For small cell cancer (CPC) it enables a level of OR around 38% as monochemotherapy. Inhibitors of topoisomerase I (topotecan, irinotecan) form another new class of therapy. Myelosuppression again limits their toxicity. Diarrhoea is an additional toxicity of irinotecan (Campto). The inhibitors of topoisomerase I seem particularly active as monochemotherapy in the treatment of smal cell cancer. Haematological toxicity makes them difficult in association. The activity of topotecan (Hycantin) in the treatment of non-small cell carcinoma remains to be studied. For this indication irinotecan would enable an OR of 33% in new patients. The new anti-metabolite, gemcitabine (Gemzar) is characterised by a different mode of action from other cytotoxics used in the treatment of bronchial cancer. For non-small cell carcinoma it is active as monotherapy and in association with cisplatine. Its activity is more modest in the treatment of CPC but few studies are available for this indication. Its toxic profile makes it promising to be used in association. The new spindle drug vinorelbine (Navelbine) is active as monotherapy or associated with cisplatine in the treatment of non-small cell carcinoma. The limiting toxicity is haematological. Its neurotoxicity is moderate compared to agents in the same therapeutic class. These different cytotoxic drugs arouse a ligitimate interest but the optimal therapeutic schemas for their use remain poorly understood (with the exception of vinorelbine). Their place in the therapeutic arsenal remains to be defined whilst waiting for the results of Phase III studies, their routine use cannot be recommended.

Antineoplastic Agents↗
PubMed1998

[The value and limits of Palmaz's prosthesis in the treatment of tracheobronchial stenosis].

The use of endobronchial prosthesis may be indispensable to maintain patency of the airways. We report our experience using Palmaz's prosthesis in four patients. The results were satisfactory in one patient but we have been confronted with three failures and one grave complication. The failures were linked to unsuitable properties of this prosthesis which has led us limit its use whilst waiting for newer studies.

Adolescent↗
PubMed1997

[Leukotriene antagonists. A new therapeutic approach in asthma].

BRONCHIAL INFLAMMATION: Corticosteroids are currently the most important treatment for bronchial inflammation in asthma. SULFIDOPEPTIDE LEUKOTRIENES: These biologically active fatty acids play an important role in the inflammation process in asthma. A NEW THERAPEUTIC APPROACH: Some leukotriene receptor antagonists and synthesis inhibitors are effective and safe treatment for mild to moderate asthma. GLOBAL STRATEGY: The role of these new drugs in the management of asthma remains to be defined on the basis of comparative clinical trials with the standard reliever treatment: inhaled corticosteroids.

Asthma↗
PubMed1997

Concomitant brain radiotherapy and high-dose ifosfamide in brain relapses of lung cancer.

PATIENTS AND METHODS: Twenty patients with lung cancer and brain metastasis were prospectively included in this feasibility study (four small-cell and 16 non-small-cell lung cancers). There were two previously untreated patients and 18 pretreated patients for whom brain metastases constituted the first relapse after a treatment-free interval following chemotherapy for the primary lung cancer. Most of the patients had neurological symptoms and an ECOG performance index over 2. Treatment consisted of three courses of whole brain radiotherapy (18 Gy in 10 fractions) and ifosfamide: 3 g/m2 daily from day 1 through day 4, i.e., during the first four days of radiotherapy with uromitexan uroprotection and haematopoietic support (r-HuG-CSF). RESULTS: Seventeen patients completed the three-cycle programme. Sixteen patients had grade 4 neutropenia and six of them experienced a febrile episode. Other toxicities were mild to moderate and manageable. The received dose-intensity of ifosfamide was 90%. Response evaluation demonstrated stable disease for two patients, partial response for eight, complete response for six and progression for four. All responders benefited by a remission of symptoms and improvement of performance index. Median survival from start of protocol was 13 months. CONCLUSION: Brain radiotherapy plus high-dose ifosfamide is feasible in patients suffering from brain recurrences of lung cancer.

Adult↗
PubMed1997

Gene therapy strategies for asthma.

Asthma is a disease which is increasing in frequency and severity despite the incontestable advances in the understanding of its physiology and treatment. New therapeutic strategies are therefore required and at the time when a new treatment, that of gene therapy, is giving hope for the treatment of so far incurable illnesses, it would seem to us to be useful to discuss the possible use of this treatment in severe asthma and in particular in the case of the most severe asthmatic patients requiring continuous oral steroid treatment (referred to as steroid-dependent). These patients are those who require particular medical attention, they often need to be admitted to hospital and they represent over 50% of the total costs associated with asthma. No satisfactory alternative therapy is currently available. In this regard, a variety of gene-based strategies have recently been proposed for inflammatory and immunologic disorders. It is thus the purpose of this review to consider its application to asthma therapy, although there are very few published works that directly bear on gene therapy linked to asthma. After a brief outline of the epidemiology of asthma, its genetics and the available animal models, we will focus on its immunopathology slanting the discussion towards the possibility of a gene-based treatment.

Asthma↗
PubMed1997

Leukotriene E4 plasma levels in adult asthmatic patients with variable disease severity.

Cysteinyl leukotrienes (C-LTs) are local inflammatory mediators involved in bronchial asthma. Seventeen asthmatic patients (FEV1 ranging from 41 to 99.8% of predicted values) and 11 healthy subjects were studied. The clinical severity of asthma was assessed by the Aas score. Plasma C-LTs were measured by enzyme immunoassay (EIA) after sample purification by solid-phase extraction (SPE), to investigate whether differences may exist between asthmatic and control subjects and whether leukotriene E4 (LTE4) levels were related to the severity of disease. LT measurements showed that 87.6 +/- 1.2% was recovered as LTE4 and 9.4 +/- 1.3% as LTC4. In asthmatic subjects, LTE4 plasma levels were found to be significantly higher than those in the control group (1.073 +/- 0.133 and 0.53 +/- 0.19 ng/ml of plasma, respectively; P < 0.002). Moreover, there was a significant correlation between LTE4 plasma levels and the Aas clinical score (P < 0.005). These data suggest that plasma LTE4 levels might be used to assess the severity of asthma.

Adolescent↗
PubMed1997

Prostaglandin H synthase 1 and 2 immunoreactivities in the bronchial mucosa of asthmatics.

Prostaglandin H synthases or cyclooxygenases 1 (PGHS-1) and 2 (PGHS-2) catalyze the conversion of arachidonic acid to prostaglandin endoperoxides, leading to the formation of prostaglandin and thromboxane mediators of inflammation. The expression of these enzymes in the respiratory epithelium has not been determined, although they may be relevant to the pathophysiology of inflammatory disorders such as asthma and chronic bronchitis (CB). We studied PGHS-1 and PGHS-2 immunoreactivity in bronchial biopsies obtained from 22 patients with chronic stable asthma, seven patients with CB, and 12 normal subjects. Both types of PGHS were mainly expressed in the epithelium (basal and ciliated cells), and PGHS-1 and PGHS-2 were found in 21 of 41 and 34 of 41 biopsies, respectively. We did not find any differences in PGHS expression between the patient populations. There were no correlations between any of the clinical parameters studied or the pathologic patterns and the presence and characteristics of the PGHS immunoreactivities. Thus, both PGHS enzymes are expressed in normal human respiratory epithelium and are not quantitatively upregulated in the main bronchi in stable asthma and CB.

Adrenal Cortex Hormones↗
PubMed1997

Cellular protein kinase C activity in asthma.

Protein kinase C (PKC) is a primary group of enzymes mediating signal transduction for a wide variety of functions in many different cell types. Its activation has been implicated in various inflammatory diseases. In asthma, inflammatory cells, such as alveolar macrophages (AM) and polymorphonuclear neutrophils (PMN), are primed and activated compared with those obtained from control subjects. In particular, they release higher amounts of reactive oxygen species. PKC has been known to play an important role in the respiratory burst of human leukocytes. In this study, the PKC activity was measured in blood neutrophils and alveolar macrophages from control (n = 16) and asthmatic subjects (n = 28). In PMN, the total PKC activity was significantly lower in PMN from stable (182.00 +/- 27.20) and unstable (108.40 +/- 14.15) asthmatic patients, compared with control subjects (257.35 +/- 29.70 pmol/10(7) cells/min with p < 0.05 and p < 0.0005, respectively). In AM, PKC activity was 479.50 +/- 71.80 for controls and 254.00 +/- 25.90 pmol/10(7) cells/min for asthmatic patients. Moreover the percentage of membrane PKC was significantly higher in stable asthmatic patients in both cell types. After stimulation of neutrophils with PMA, a significant decrease in total PKC activity was observed in both control and asthmatic subjects. We have found an abnormal regulation of PKC activity in both blood PMNs and AM in asthmatic patients. These findings are consistent with the functional hyperreactivity of inflammatory cells observed in asthma.

Adult↗
PubMed1996

[Pharmacological specificities and modalities of prescriptions for corticoids for asthmatic adults].

The efficacy of corticosteroids in asthma has been recognized over 40 years ago. Since that time, the advent of inhaled forms has further improved the therapeutic of these drugs which are now recognized as the fundamental treatment for asthma, and described in detail by national and international consensus. Based on a large body of literature, it can now be recommended to prescribe inhaled corticosteroids for symptomatic asthma patients. Long-term treatment is required and dosage not exceeding 1000 micrograms/d (beclometasone dipropionate equivalent) in adults are safe. Differences in the pharmacological characteristics of the various systematic and inhaled corticosteroids can be used to adapt treatment and administration route to each patient and achieve good patient compliance with optimal therapeutic efficacy.

Administration, Inhalation↗
PubMed1996

[Bronchial asthma: current concepts].

Asthma, a chronic inflammatory disease of the airways, involves activation of various cell types and development of various degres of post-inflammatory lealing and repair processes which remodel the airways. The short duration of the severe episodes is clearly related to the degree of inflammation, but the natural history of the disease itself remains unclear. Treatment must take into account the fact that clinical expression varies, associating short episodes which can be prevented or attenuated with bronchodilatators and severe acute episodes which should be treated or prevented by anti-inflammatory drugs (inhaled corticosteroids are the most effective) preferably given in the early stages of the disease and used for a prolonged period. Long-term use of inhaled corticosteroids may limit airway remodeling, but there have been few long-term studies to date. Further data is required.

Acute Disease↗
PubMed1996

[Nebulization for basic treatment of asthma in adults].

Many different forms of nebulizer treatment for asthma have been developed over the last few years, including several which have reached international concensus. Nevertheless, there are no widely recognized recommendations concerning the role of nebulization in the treatment of asthma in adults. We present here the main elements on the pathophysiological basis of nebulization treatment of asthma, the physical and chemical parameters of nebulization, the different nebulizers and the substances which can be administered and their costs. The indications for home nebulizer treatment of asthma in adults include asthma with chronic sinusitis or nasosinus polyposis, asthma with hypersecretion with or without bronchial dilatation, severe poorly controlled asthma, corticodependent asthma. The aim of this discussion on nebulizer administration is to reduce the amount of systemic corticosteroid delivery and underline the need for quality research in this area.

Administration, Inhalation↗