BioDrugs

Beedle, Alan S.

doi: 10.1007/bf03259303pmid: N/A

Chen, Minhu

doi: 10.1007/bf03259304pmid: N/A

SummaryHelicobacter pylori is now accepted as the aetiological agent in peptic ulcer disease and has been characterised as a grade 1 carcinogen. The development of an effective vaccine is therefore desirable, although effective therapies for the eradication of the organism are available. The first step towards the development of an anti-H. pylori vaccine was initiated by the demonstration that a sonicate of H. felis can protect mice against infection with H. felis. Urease has been identified in the mouse model as a protective antigen. Other virulence factors, such as vacuolate cytotoxin and a heat shock protein of H. pylori, have been investigated as candidate vaccine components by the development of a new H. pylori mouse model. Vaccine adjuvants, delivery systems and therapeutic vaccination are likely to be the areas of major progress in the future.

Schroeder, Timothy J.; First, M. Roy; Gaber, A. Osama

doi: 10.1007/bf03259305pmid: N/A

SummaryThere is substantial evidence for a heightened immune response in paediatric transplant recipients when compared with adults. This is most important in very young children, who have a larger number of functional T cells, stronger mixed lymphocyte reactivity and increases in expression of some cytokines. Although corticosteroids have been a mainstay of immunosuppressive protocols for decades, many paediatric transplant programmes are attempting steroid withdrawal in order to minimise adverse effects and maximise growth.Induction with polyclonal or monoclonal [muromonab-CD3 (OKT3)] anti-lymphocyte antibody therapy has been associated with improved survival and decreased rejection in many paediatric studies, especially in renal transplant recipients. Individualised dosages of antilymphocyte antibody are required in many instances for children in order to overcome increased numbers of lymphocytes. In addition, particular attention to xenosensitisation, infection and malignancy is required in paediatric transplant recipients receiving antilymphocyte therapy.The introduction of cyclosporin has improved patient and graft survival in children receiving transplants. However, because of pharmacokinetic differences, increased dosages and more frequent administration have been advocated, especially in young children. It has been suggested that a new microemulsion form of cyclosporin may have more consistent oral absorption and pharmacokinetic predictability associated with its use. This would be particularly beneficial in paediatric transplant recipients. Tacrolimus is similar to cyclosporin in its mechanism of action, and is very appealing for use in children due to its potential steroid-sparing effects. Considerations for tacrolimus administration parallel those for cyclosporin, in that children frequently require increased dosages compared with adults.Finally, new agents in development need to be studied in detail in children to ascertain appropriate dosage strategies and to identify possible unique adverse effects.

Miles, Jon; Fitzharris, Penny; Beasley, Richard

doi: 10.1007/bf03259306pmid: 32226273

SummaryThis review briefly outlines an approach to the management of high risk asthmatic patients. This approach involves: (i) identification of such high risk patients; (ii) investigation of precipitating factors contributing to severe attacks; and (iii) the introduction of a management strategy based on a simple system of self-assessment and self-treatment.

Kater, Louis; Gmelig-Meyling, Frits H. J.; Derksen, Ron H. W. M.; de la Faille, Harold Baart

doi: 10.1007/bf03259309pmid: N/A

SummaryThe aetiopathogenesis of systemic lupus erythematosus (SLE) is thought to comprise the combined action of hormonal influences and other factors, partly of exogenous and partly of endogenous nature, which leads to the production of autoantibodies and/or lymphoid cells, resulting in inflammatory processes. The fundamental characteristic is the occurrence in blood of autoantibodies against intranuclear cell components, usually designated as antinuclear antibodies. In addition, autoantibodies against cytoplasmically located antigens occur.Antibodies to DNA are the most prominent examples of autoantibodies, the most typical of which in SLE are antibodies to double-stranded DNA. Antibodies directed against different components of ribonucleoprotein particles include the anti-Sm, anti-SS-A (Ro) and anti-SS-B (La) antibodies. Antihistone antibodies directed against DNA-binding proteins, in particular against various histones, occur frequently in patients with drug-induced lupus. Antiphospholipid antibodies, notably lupus anticoagulant and anticardiolipin antibodies, are strongly associated with the antiphospholipid syndrome, but these antibodies can also occur in patients without features of lupus.This wide spectrum of autoantibodies implies a marked degree of chronic B lymphocyte activity. The question is whether these findings point to an intrinsic B cell aberration. There is also considerable evidence for a role of T cells in the pathogenesis of SLE. In addition, unbalanced cytokine production seems to occur. The disease also has genetic and gender aspects, and its activity may be modulated by sex hormones.Unfortunately, as the aetiology of SLE is still obscure and the pathogenetic mechanisms leading to organ disease not well understood, therapy is still limited to the use of agents with rather nonspecific anti-inflammatory properties, such as antimalarials, corticosteroids, cytotoxic drugs and apheresis. Most of these therapeutic modalities may not only benefit but also cause serious adverse effects. The eventual aim is to design immune intervention strategies, such as specific blocking peptides, by which harmful immune reactions will be eliminated leaving host defence immune reactivity intact. However, the most logical approach for immune intervention in the treatment of SLE has still to be defined.