摘要:

Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating neuropathy that is associated with long-lasting morbidity and a substantial risk of mortality. The 2 reference treatments, plasma exchange and intravenous immunoglobulins (IVIg), do not change the functional prognosis for the most severely ill patients.The pathogenesis of GBS involves humoral and cellular immune dysfunctions that have only recently been characterised. Antibodies to nerve antigens may participate in complement activation, antibody-dependent macrophage cytotoxicity and reversible conduction failure. The cellular immune reaction is associated with increases in pro-inflammatory cytokines [such as tumour necrosis factor-α (TNFα)] and matrix metalloproteinases (MMPs; e.g. MMP-9), and a decrease in anti-inflammatory cytokines [such as transforming growth factor-β1 (TGFβ1)]. All the changes favour adhesion to and transmigration across the endothelium of immune cells, a key phenomenon associated with GBS. Recovery from GBS is characterised by the normalisation of these changes. Experimental allergic neuritis (EAN), the experimental model of GBS, has strikingly similar immunological characteristics.The usual treatment options for patients with GBS (plasma exchange and IVIg) mainly target the humoral component of the immune response. Interferon-β (IFNβ) is a cellular immunomodulator that inhibits antigen presentation and TNFα production and binding, and modulates macrophage properties. IFNβ increases anti-inflammatory T cell functions and the production of anti-inflammatory cytokines, such as TGFβ1. IFNβ has important effects on leukodiapedesis, caused by modulating the expression of cell adhesion molecules and the MMP-9 proteinases. It has been used with success in EAN, in some patients with acute exacerbation of chronic inflammatory demyelinating polyneuropathy, and in 1 patient with GBS. The pathophysiology of patients with GBS, an understanding of IFNβ properties and results of experimental studies support the investigation of IFNβ in trials of patients with GBS.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Therapeutic angiogenesis is a rapidly evolving approach to the treatment of advanced coronary disease. The availability of growth factors such as basic fibroblast growth factor (bFGF or FGF2) has made possible the practical clinical application of this research. In this article, we summarise the basic biology of bFGF, a prototypical angiogenic growth factor, and the preclinical studies with this growth factor, and analyse recent clinical experience. While much remains to be learned, bFGF has been clearly shown to induce effective growth of new vasculature in a variety of animal models. The initial clinical data are promising, with patients demonstrating improvement in symptoms, quality of life and exercise tolerance. At the same time, the adverse effects profile has, to date, remained relatively benign.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Platelet-activating factor (PAF) is a potent lipid-derived mediator of inflammation that is considered to have a potential role in the pathogenesis of asthma. PAF is produced by many cells associated with asthmatic inflammation and has the ability to evoke some of the clinical hallmarks of asthma, such as bronchoconstriction, mucus production and airway hyperresponsiveness (AHR). In addition, PAF has profound chemoattractant properties for eosinophils and neutrophils and it promotes an increase in microvascular permeability and oedema formation within the airways. Nevertheless, the definitive role of PAF in asthma remains elusive. PAF is formed as a result of the action of phospholipase A2and acetyltransferase on membrane phospholipids and it is degraded by a PAF-specific acetylhydrolase. The biological effects of PAF are mediated by the activation of specific receptors expressed on effector cell surfaces, although intracellular signalling and paracrine actions have been described. In addition, at least part of the pulmonary effects of PAF could be related to the secondary release of leukotrienes. In the clinical setting, different ways of modifying the activity of PAF have been explored, in particular the inhibitory actions of PAF receptor antagonists. Both natural and synthetic PAF receptor antagonists have shown conflicting results. Although second generation PAF antagonists (apafant, UK-74505, SR-27417A) appear to have a good protective effect against the systemic and pulmonary actions of inhaled PAF, the protective effects of these compounds on allergen-induced responses and AHR are more modest. In the treatment of asthma, PAF receptor antagonists have failed to produce a significant impact in either acute asthma attacks or the maintenance therapy of chronic forms. Other pharmacological interventions of proven efficacy in asthma, such as salbutamol or 5-lipoxygenase antagonists, have shown some anti-PAF effects. Whether the overall negative results with PAF receptor antagonists indicate that extracellular PAF is not a relevant mediator of airway inflammation or that the compounds explored are not capable of blocking the paracrine actions of PAF remains speculative. A PAF synthase inhibitor could be valuable in the elucidation of the role of PAF and it might be a promising and useful complementary therapeutic tool in the future.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

The current management of hepatic allograft rejection after liver transplantation in children requires effective baseline immunosuppression to prevent rejection and rapid diagnosis and treatment to manage acute rejection episodes. The subsequent impact on chronic rejection is dependent on the combination of adequate prevention and the treatment of acute rejection.Tacrolimus is a macrolide lactone that inhibits the signal transduction of interleukin-2 (IL-2) via calcineurin inhibition. Introduced in 1989, tacrolimus was first used in the salvage of refractory acute or chronic rejection under cyclosporin or to rescue patients with significant cyclosporin-related complications. The majority of paediatric transplant centres use a combination of steroids with tacrolimus as a basic immunosuppressant regimen following paediatric liver transplantation. This combination has allowed the acute cellular rejection-free rate to increase to between 30 and 60%, while lowering the rate of refractory rejection to less than 5%. Corticosteroid-resistant rejection is commonly treated with monoclonal (muromonab CD3) or polyclonal preparations. Although most episodes of acute cellular rejection occur during the first 6 weeks after liver transplant, the appearance of late acute liver allograft rejection must raise the question of noncompliance, especially in the adolescent population. Chronic rejection is becoming increasingly rare under tacrolimus-based immunosuppression. Tacrolimus is effective in reversing refractory acute cellular rejection or early chronic rejection in patients initially treated with cyclosporin-based regimens. Patients with a history of noncompliance as well as children with autoimmune liver disease are at risk of chronic rejection. Retransplantation therapy for chronic rejection has, fortunately, become more rare in the tacrolimus era with only 3% of retransplants being performed for this indication.Newer immunosuppressive agents are further modifying the long term management of liver allograft rejection. These include mycophenolate mofetil, rapamycin and IL-2 antibodies such as daclizumab. The development of these agents is allowing patient-specific immunosuppressive management to minimise rejection as well as the complications related to immunosuppression.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Varicella vaccines have been developed, studied, tested and used since the early 1970s, first in Japan and subsequently in Europe, the US, Asia and South and Central America. Varicella vaccination was first used to immunise Japanese children in cancer remission, as wild-type varicella disease is often fatal in immunocompromised individuals. Since then, it has been licensed for use in healthy children as well. There are 3 manufacturers of the vaccine: Biken (Japan), Merck and Co. (US) and SmithKline Beecham (Belgium). The Biken vaccine has been approved for use in Japan since 1986 (although it was developed and used for research purposes from 1974). The Merck and Co. vaccine was approved in the US in March 1995 and the SmithKline Beecham vaccine was first licensed for use in immunocompromised children in 1984 and for healthy children in Sweden in October 1994. All 3 vaccines are derived from the Oka (Japanese) strain obtained from an immunologically normal 3-year-old Japanese boy named Oka with wild-type disease. Aventis-Pasteur has also purchased the rights to the Oka strain but no published literature is available for review.Use of the varicella vaccine has been controversial because many argue that: (i) the disease is mild and not worth preventing; (ii) the long term immunity provided by the vaccine is unknown; and (iii) the average age of those with the disease will increase if the vaccine is used and hence there will be more complications in older patients and, therefore, more costs.Because of some outbreaks of secondary bacterial infections after varicella in children in US day care centres, vaccination of healthy children is required in some states. It will be interesting to see whether other countries adopt a similar recommendation as more families have 2 working parents. The financial benefit of the vaccine (keeping parents at work) may encourage more use of the vaccine and a subsequent recommendation for immunisation schedules.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

▴ Adjuvanted influenza vaccine is composed of 2 type A and 1 type B inactivated influenza subunits combined with an oil-and-water emulsion (MF59). Each dose contains 15µg haemagglutinin per strain.▴ Adjuvanted influenza vaccine was immunogenic in elderly vaccinees and in younger adults after 1 to 3 consecutive annual injections.▴ According to studies available to date, the adjuvanted vaccine was more immunogenic than the nonadjuvanted subunit or split virus vaccines and the virosomal vaccine for 1 to 3 of the 3 strains tested per injection.▴ The immunogenic effect generally persisted for longer after the adjuvanted vaccine than the nonadjuvanted subunit vaccine in elderly recipients.▴ The adjuvanted vaccine also appeared to be more effective than the nonadjuvanted subunit vaccine against antigenically different heterovariant strains in elderly vaccinees.▴ The 28-day seroprotection rate in 4 studies was significantly greater after the adjuvanted vaccine for 1 or 2 of the 3 strains tested compared with the nonadjuvanted subunit vaccine and the virosomal vaccine and for 1 of 3 strains compared with the split virus vaccine.▴ The incidence of systemic adverse events was generally low. Local reactions such as pain, erythema and induration occurred more frequently with the adjuvanted than the 2 nonadjuvanted or the virosomal vaccines; however, these were mild and transient.Table.Features and properties of adjuvanted influenza vaccine

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS