摘要:

There is a body of evidence indicating that melanoma is an antigenic tumour. Since the efficacy of standard therapy in advanced stages of melanoma is rather poor, experimental immunotherapy aims to target this aggressive neoplasm. After the identification of several melanoma antigens, vaccination trials have been initiated in patients with metastatic disease using peptides, dendritic cells and gene therapy approaches including viral vectors or naked DNA. If the problems in inducing a constant and potent T cell response are solved, the stability of melanoma antigens and their presentation will decide whether these treatment approaches will reach significant relevance in daily clinical practice.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Multiple sclerosis is an inflammatory demyelinating disorder of the central nervous system. Immunological evidence from patients with multiple sclerosis and experimental models suggests that the cytokine interleukin-12 (IL-12) plays an important role in the pathogenesis of inflammatory demyelination. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, antibodies that block IL-12 can prevent relapses of the disease. Anti−IL-12 antibodies present a novel approach for preventing relapses in multiple sclerosis.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Common variable immunodeficiency (CVID) is not a homogeneous disease, as has become clear from recent scientific studies. This makes the interpretation of studies of clinical therapeutics difficult to assess and raises questions about historical case reports.The evidence for the optimum use of replacement immunoglobulin in CVID is reviewed. This therapy represents the current gold standard, despite attempts to use other immunostimulatory compounds. Questions of product properties, product selection, adverse events and infectious risks are addressed. Products are not interchangeable and have different physicochemical characteristics. Despite intravenous immunoglobulin being in use for 20 years, there are still unanswered questions over dose and target trough IgG levels, particularly with respect to patients with established lung disease.The management of organ-based complications of CVID is discussed. This includes the treatment of unusual infections such as mycoplasmas and enteroviruses, which are specific to antibody deficiency. The diagnosis and treatment of the granulomatous disease of CVID is discussed. The role of surgery, including lung transplantation, in the management of CVID complications is reviewed. There are few available data on optimum strategies for antibiotic usage for bacterial infective complications and it is clear that present regimens, at least in severe recurrent sinus disease, are not consistently effective. Better clinical trials are required to identify appropriate regimens and validate or disprove widely held assumptions about therapy in CVID.Despite advances in diagnosis and management, there is abundant evidence in the UK that patients do not yet receive rapid diagnosis and optimum therapy, even within the limited published data currently available. This leads to considerable avoidable morbidity and mortality.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

The resurgence of interest in thalidomide in the last decade has been remarkable. Thalidomide has established its own niche market particularly for the dermatological manifestations associated with HIV, Behçet's disease, graft-versus-host disease and systemic lupus erythematosus. To a large extent this has resulted from initial empirical uncontrolled studies in conditions resistant to other drug therapies. Appropriate trials are now being published for most of the prevalent indications. Thalidomide produces partial inhibition of tumour necrosis factor-α productionin vivobut recent data reveals that it can also act as a co-stimulatory molecule for T cell activationin vitro, resulting in increased production of interleukin-2 and interferon-γ. Hence in addition to monocyte inhibitory activity, thalidomide can exert a co-stimulatory or adjuvant-like effect on T cell responses. The unraveling of the molecular basis of thalidomide's therapeutic effects would suggest that an expansion of the use of thalidomide and its analogues in other conditions is highly likely. It remains imperative, however, that physicians using this fascinating drug are familiar with its risks and adverse effects.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Corticosteroids are widely used for the treatment of inflammatory skin disorders. However, systemic and local adverse drug reactions, especially skin atrophy, are potential complications that limit their use. Several attempts have been made to increase the safety of topical corticosteroid treatment, including new application schedules, special vehicles and new agents.In particular, the group of hydrocortisone and prednisolone double esters, with prednicarbate as the first and most often prescribed representative, seem to be equipotent alternatives to the gold standard betamethasone 17-valerate with respect to anti-inflammatory activity. At the same time, these new agents induce less skin atrophy, which may result from a unique skin metabolism and a specific influence on the cytokine network in the epidermis and dermis.On the basis of these effects, a new approach toin vitroquantification of the benefit−risk ratio has been developed. As already suggested by investigations in human volunteers, the benefit−risk ratio of the new compounds appears to be increased. Therefore, recent research has focused on drugs that selectively modulate cytokine release.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

The level of exhaled nitric oxide (NO) has been demonstrated to reflect the degree of airway inflammation in patients with asthma and to be related to the severity of asthma, as well as to the efficacy of treatment. In contrast, lung function tests provide information about airway volumes and flows reflecting the level of airway obstruction, but do not allow any direct information about the degree of airway inflammation.Several studies have evaluated the relationships between the level of airway inflammation assessed by exhaled NO and the levels of airway obstruction and/or bronchial hyperresponsiveness in asthmatic adults and children.These studies highlight the complex pathophysiology of asthma and suggest that exhaled NO may have a promising role in addition to lung function measurement in the evaluation of asthma severity in children.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

In the short time span since the cloning of the human genes for factors VIII, IX and VII, recombinant factor (rF)VIII, rFIX and rFVIIa concentrates have been produced and standardised, have entered clinical trials, and have been licensed for clinical use in the US, Europe and elsewhere. Even more recently, a new generation of recombinant clotting factor concentrates has emerged, including rFVIII concentrates formulated with sucrose rather than human serum albumin and a B-domain−deleted rFVIII preparation. Additionally, rFVIII concentrates which contain no human or animal proteins in their manufacture are in development, as is a combination rFVIII plus recombinant von Willebrand factor concentrate.The clinical experience in previously treated patients with each of the existing recombinant products has documented that inhibitor development is not increased with any of them. As expected, there has been no reported instance of disease transmission with any of the recombinant clotting factor concentrates. Since their introduction, usage of each of the recombinant clotting factor concentrates has dramatically increased in countries where these products are licensed, available and affordable.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

ObjectiveTo study the effects of monotherapy with leucocyte interferon-α (IFNα) versus IFNα + ribavirin in patients with chronic hepatitis C who were nonresponders to previous courses of recombinant or lymphoblastoid IFNα.Design and settingThis was a nonblind randomised study of outpatients at 3 centres in Palermo, Sicily, Italy.Patients and participantsWe recruited 72 patients (48 males, 24 females), mean age 48.8 ± 6.6 years (range 31 to 63 years), with biopsy-proven chronic hepatitis C, predominantly genotype 1b.Interventions24 patients (group A) received IFNα 6MU 3 times weekly for 6 months, and 48 patients (group B) received IFNα 6MU 3 times weekly + ribavirin 1200 mg/day for 6 months. ALT levels and adverse effects were monitored monthly, and hepatitis C virus (HCV) RNA levels were measured at study entry, at the end of treatment and after a 6-month follow-up.ResultsAt baseline all patients were HCV-RNA positive and had ALT levels greater than twice normal. Mean post-treatment serum HCV-RNA levels were below baseline in group A, but the virus was eradicated in only 1 patient; 6 patients had normalised serum ALT levels. In group B at end of treatment, 12 patients were negative for HCV-RNA and serum ALT levels were normal in 18. At follow-up, all group A patients had elevated ALT levels and positive HCV-RNA. In group B, 3 patients were still negative for HCV-RNA and 4 had normal ALT. In 4 patients in group B, therapy was suspended because of anaemia, depression and decrease in neutrophil count; a flu-like syndrome was recorded with no frequency difference between groups.ConclusionsThese results suggest that patients with chronic hepatitis C unresponsive to IFNα monotherapy could benefit from combination therapy with IFNα + ribavirin.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS