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Allergen-specific immunotherapy is widely used to treat allergic diseases, and current research is now focusing on the development of therapeutic vaccines acting on the IgE immune response following allergen challenge. The IgE immune response is dependent on genetic and environmental factors; production of IgE results from complex interactions among B cells, T cells, mast cells, basophils, surface and adhesion molecules and various cytokines. New vaccination methods under investigation involve allergen-specific or nonspecific methodology. Allergen-specific methods currently being developed include allergoids, passive saturation of effector cells, plasmid DNA immunisation and antigen-antibody complexes. The mechanisms of immunotherapy using allergen-specific methods differ with the allergens and the route of immunisation used (parenteral, intranasal, sublingual, oral or bronchial). Many vaccines being developed at present comprise synthetic, recombinant or highly purified subunit antigens, which although they have increased safety may also be less immunogenic. It is hoped that the addition of adjuvants will overcome this drawback. Methods of increasing the dose of allergen while reducing the possibility of an anaphylactic reaction include the use of non-anaphylactic isoforms of the allergens, alteration of the tertiary structure of the allergens and construction of minimal allergen-derived T cell peptides. Nonspecific approaches include humanised anti-IgE antibodies, moderation of the T2 cytokine network and antisense oligodeoxynucleotide therapy. [ABSTRACT FROM AUTHOR]

Objective: To assess the type, frequency and potential clinical significance of medication-administration errors.Design: Prospective study using the observation technique as described by the American Society of HealthSystem Pharmacists but eliminating the disguised aspect.Setting: Medical intensive care unit (ICU) in a university hospital.Patients and Participants: 2009 medication administration interventions by nurses.Interventions: Pharmacist-performed observation of preparation and administration of medication by nurses, comparison with the original medical order and comparison with the data available in the literature.Measurements and Results: 132 (6.6% of 2009 observed events) errors were detected. Their distribution is as follows: 41 dose errors, 29 wrong rate, 24 wrong preparation technique, 19 physicochemical incompatibility, 10 wrong administration technique and 9 wrong time errors. No fatal errors were observed, but 26 of 132 errors were potentially life-threatening and 55 potentially significant.Conclusion: According to this first observation-based study of medication administration errors in a European ICU, these errors were due to deficiencies in the overall organisation of the hospital medication track, in patient follow-up and in staff training. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GC) are commonly used as anti-inflammatory drugs in asthma, but can produce serious secondary effects and, moreover, be inefficient in corticoresistant asthmatics. After binding to the glucocorticoid receptor (GR), they repress the synthesis of proinflammatory cytokines via inhibition of the transcription factors AP-1 and NF-κB. Since qualitative and quantitative defects of the GR have been reported in corticoresistant patients, the transfer of the GR gene in the lung epithelium, the primary site of inflammation in asthma, may restore sensitivity to GC in these patients. As a prerequisite to in vivo studies, we have transfected A549 human lung epithelial cells with a GR expression vector. Using AP-1 and NF-κB-dependent reporter gene assays and an immunoassay for the proinflammatory cytokine RANTES, we show that the overexpressed GR significantly repressed AP-1 and NF-κB activities in the absence of hormone and that the GC dexamethasone produced an additive inhibitory effect. The GC-independent repression of AP-1 and NF-κB activities was further demonstrated by overexpressing a ligand- binding deficient GR mutant. Our data suggest that delivery of the GR gene in vivo may reduce inflammation without recourse to GC and may constitute an alternative therapeutic approach for corticoresistant asthma. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The objective of this pilot study was to examine the relation between fluvoxamine (FVX) plasma concentrations, therapeutic response and side effects during a four-week treatment period. Twenty two patients who met the DSM IV criteria for major depression received 100 mg FVX during the first 2 days of treatment and then 150 or 200 mg/day. No clear relationship between plasma concentrations and side effects was detectable. A relationship between plasma concentrations and clinical efficacy was detectable after 21 days but not after 28 days of treatment. These preliminary results indicate that therapeutic drug monitoring might be useful for patients treated with FVX. [ABSTRACT FROM AUTHOR]