摘要:

Recent studies strongly suggest that cerebral ischaemia initiates a focal inflammatory response that results in significant secondary injury to brain tissue, thereby extending the ultimate size of a stroke. Factors involved in this cascade include the release of cytokines that cause a pro-inflammatory and prothrombotic state on cerebral vessel endothelium, the expression of leucocyte adhesion molecules, and the release of chemotactic factors allowing the migration of leucocytes into the area of injured brain tissue causing further damage. Animal studies have clearly demonstrated the detrimental effects of these inflammatory mediators in stroke models and additionally have shown dramatic reduction in infarct size using leucocyte adhesion modification and cytokine receptor blockade. The approach of modifying the effects of inflammatory cytokines and/or limiting leucocyte adhesion and migration into the region of injury holds great promise for identifying agents that will give significant neuronal protection following a stroke.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Immune-mediated uveitis is a collective term referring to a group of potentially blinding intraocular inflammations which may coexist with systemic inflammatory diseases. T lymphocytes appear to play an important pathogenic role in uveitis, and these cells are therefore the logical target of drug therapy. Corticosteroids act nonspecifically, but are highly effective in controlling the inflammation rapidly. They are administered locally when disease is confined to the anterior portion of the eye. However, posterior eye involvement often requires systemic corticosteroid therapy, carrying a high risk of serious adverse effects when used for extended periods. In this situation, steroid-sparing agents are used.Few relevant randomised, controlled clinical trials have been performed, and the choice of systemic immunosuppressive regimen is usually guided by individual patient characteristics, cost, drug availability and physician preference. Patients should actively participate in therapeutic decision-making.Our first choice for steroid-sparing medication is often methotrexate, an antimetabolite which carries a low risk of adverse reactions when appropriately prescribed and monitored, is relatively inexpensive, and has once-weekly ease of use. For more severe uveitis, we may combine the immunomodulating agent cyclosporin with methotrexate and a corticosteroid. Azathioprine and cyclophosphamide are other treatment options. Steroid-sparing drugs also have significant potential for causing adverse effects, albeit less frequently than corticosteroids. Future therapies aim to reduce this problem by increasing the specificity of the therapeutic action.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Reactive arthritis follows infections of the urogenital or enteric tract with bacteria such asChlamydia,Yersinia,Shigella,SalmonellaorCampylobacter. Typically, one knee or ankle are affected for weeks to several months, with up to 20% of patients experiencing a chronic course of more than 1 year.The acute arthritis is treated nonspecifically with nonsteroidal anti-inflammatory drugs (NSAIDs), local measures such as arthrocentesis, cold pads and rest of the affected joint. If the triggering bacterium can be isolated inChlamydia-induced urogenital reactive arthritis, the infection should be treated specifically with antibacterials. Doxycycline 100mg twice daily, or erythromycin 500mg 4 times daily, for 10 to 14 days are effective forChlamydia, as is a single dose of azithromycin 1g. To prevent reinfections, the sexual partner should be treated concurrently.Although remnants of bacteria and even bacterial RNA, suggesting live bacteria, can be demonstrated in the joint, treatment with antibacterials, even for long periods, does not show any benefit over placebo in enteric forms of reactive arthritis. ForChlamydia-induced reactive arthritis, antibacterials given for 3 months in the absence of positive cultures from the urogenital tract may provide some benefit; however, further studies are needed before such treatment is recommended.For reactive arthritis lasting longer than 6 months, patients may benefit from sulfasalazine 2 g/day in addition to continued use of NSAIDs. In several placebo-controlled studies, sulfasalazine was well tolerated and moderately superior to placebo. Other disease-modifying antirheumatic drugs (DMARDs) can be tried in individual patients who do not respond to sulfasalazine. However, since no controlled studies are available to date for DMARDs other than sulfasalazine, the risk-benefit ratio of such treatment should be carefully discussed with the patient.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Aspirin (ASA)-sensitive asthma is characterised by a typical sequence of symptoms, including intense eosinophilic inflammation of nasal and bronchial tissues. It is more commonly found in non-atopic, middle-aged female asthmatic patients with chronic rhino-sinusitis and/or nasal polyps. The lysine-aspirin bronchoprovocation test has become a widely used diagnostic test. When ASA-sensitive asthma is confirmed, complete avoidance of ASA/non-steroidal anti-inflammatory agents (NSAIDs) is crucial in preventing life-threatening adverse reactions. The basic principle of pharmacotherapy is step-wise treatment based upon anti-inflammatory therapy. Corticosteroids are the mainstay of therapy and anti-leukotriene agents may be indicated for treatment of the underlying disease. ASA desensitisation may reduce inflammatory mucosal disease symptoms, particularly in the nasal passage.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

This review article focuses on intranasal immunisation against influenza, although it also encompasses antigen uptake and processing in the nasopharyngeal passages, host defence from influenza and current influenza vaccination practices. Improvement of current vaccination strategies is clearly required; current procedures involve repeated annual injections that sometimes fail to protect the recipient. It is envisaged that nonpercutaneous immunisation would be more attractive to potential vaccinees, thus improving uptake and coverage. As well as satisfying noninvasive criteria, intranasal influenza immunisation has a number of perceived immunological advantages over current procedures. Perhaps one of the greatest attributes of this approach is its potential to evoke the secretion of haemagglutinin-specific IgA antibodies in the upper respiratory tract, the main site of viral infection.Inactivated influenza vaccines have the advantage that they have a long history of good tolerability as injected immunogens, and in this respect are possibly more likely to be licensed than attenuated viruses. Inert influenza vaccines are poor mucosal immunogens, requiring several administrations, or prior immunological priming, in order to engender significant antibody responses. The use of vaccine delivery systems or mucosal adjuvants serves to appreciably improve the immunogenicity of mucosally applied inactivated influenza vaccines. As is the case when they are introduced parenterally, inactivated influenza vaccines are relatively poor stimulators of virus-specific cytotoxic T lymphocyte activity following nasal inoculation. Live attenuated intranasal influenza vaccines are at a far more advanced stage of clinical readiness (phase III versus phase I). With the use of live attenuated vaccines, it is possible to stimulate mucosal and cell-mediated immunological responses of a similar kind to those elicited by natural influenza infection. In children, recombinant live attenuated cold-adapted influenza viruses are well tolerated. Moreover, cold-adapted influenza viruses usually stimulate protective immunity following only a single nasal inoculation. Safety of recombinant live attenuated cold-adapted influenza viruses has also been demonstrated in high risk individuals with cystic fibrosis, asthma, cardiovascular disease and diabetes mellitus. They are not suitable for immunising immunocompromised patients, however, and are poorly efficacious in individuals with pre-existing immunity to strains closely antigenically matched with the recombinant virus. According to the reviewed literature, it is apparent that intranasal administration of vaccine as an aerosol is superior to administration as nose drops. The information reviewed in this paper suggests that nasally administered influenza vaccines could make a substantial impact on the human and economic cost of influenza.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

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 TH2 cytokine network and antisense oligodeoxynucleotide therapy.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS