摘要:

Multiple sclerosis is now a treatable disease and several immunomodulating therapies exist, but their clinical efficacy is moderate and treatment failure during the course of the disease is an increasing problem. As agents with different targets are available, the question was raised whether combination of these therapies would:be safe;result in reduction of adverse effects; andprovide synergistic benefit by additive or complementary modes of action.The areas under clinical investigation are general immunosuppression as well as more targeted approaches that interfere with antigen presentation, immune cell transmigration, release of myelinotoxic factors or even axonal damage. Combination of these immunomodulatory drugs seems to be rational and promising. Nevertheless, combination therapies need to be studied in carefully designed clinical trials in selected patient populations in order to demonstrate additive or synergistic effects. This article will summarise current drug combination strategies in relapsing-remitting multiple sclerosis and provide an overview of the initial clinical trials.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Cytomegalovirus (CMV) infection in solid organ transplantation is associated with significant morbidity and mortality. Primary infection, secondary infection or superinfection may occur in this setting. Progression to disease may ensue with development of symptoms, with or without organ involvement. The mainstay of treatment of CMV disease is intravenous ganciclovir. Aside from protective organ matching and use of CMV-seronegative blood products, methods of preventing CMV infection and disease include passive immunisation with immunoglobulins, vaccination, and prophylaxis with antiviral agents such as aciclovir, oral or intravenous ganciclovir, and oral valaciclovir. A promising subunit vaccine is currently being investigated. Pre-emptive therapy is a form of prevention that is based either on the early detection of CMV or targeting of transplant recipients with risk factors for CMV. New sensitive laboratory assays, including the pp65 antigenaemia assay, qualitative, quantitative and reverse-transcription polymerase chain reaction assays, hybridisation assays, and nucleic acid sequence-based assays, have the ability to detect early CMV replication before disease becomes evident. These assays are being used as prospective surveillance tests, with pre-emptive therapy initiated when they become positive or demonstrate an increasing titre.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Significant advances have been made in the field of liver-directed gene therapy. Many diseases are potential targets for gene therapy, including diseases that have exclusive liver involvement and those with systemic manifestations as a result of defective protein synthesis from the liver. Examples are Crigler-Najjar syndrome type 1, α1-antitrypsin deficiency and haemophilia A and B.Strategies for gene delivery include the use of viral and nonviral vectors. In addition to previously developed viral vectors, such as retroviruses, adenoviruses and adeno-associated viruses, new viral vectors such as lentiviruses are being investigated extensively. Nonviral vectors for gene delivery include liposomes and receptor−mediated gene therapy.A strategy to correct gene defects has been developed using chimaeric RNA/DNA oligonucleotides, and methods to inhibit aberrant or deleterious gene expression using ribozymes, antisense oligonucleotides and dominant-negative gene products are being developed. However, more research focusing on more efficient gene expression and safety will be required before gene therapy can be routinely applicable.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Hepatitis B virus (HBV) infection is still an important cause of cirrhosis, hepatocellular carcinoma and acute liver failure worldwide, and orthotopic liver transplantation (OLT) is the only effective treatment for many of these conditions. Until recently, however, OLT in patients with HBV infection was associated with a high rate of graft loss due to viral recurrence. The use of long term passive immunoprophylaxis with high dosage human polyclonal immunoglobulin against HBV (HBIg) has, for the first time, allowed favourable outcomes after OLT in a selected group of patients, but this treatment is associated with high cost and questionable efficacy in patients with high viral loads. In the last few years alternative approaches have arisen, namely the use of the reverse transcriptase inhibitor lamivudine and the induction of anti-HBV seroconversion by HBV vaccination as a means of discontinuing HBIg treatment. In this article we review the advantages and drawbacks of each of these prophylactic strategies, particularly emphasising the viability of administering HBV vaccination to these patients.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

The activation of dominant oncogenes and inactivation of tumour suppressor genes may result in cancer. These genetic events may represent novel targets for cancer therapy. Antisense nucleic acids can be used to modulate the expression of selected genes, and to suppress malignant behaviour in cancer cells. Nevertheless, in practice, the selection of suitable antisense targets still remains a trial-and-error procedure. Promising targets for antisense cancer therapy that have been extensively studied include proteases and protease receptors, telomerase, fusion genes, the Bcl family of proteins and various protein kinases. Combinations of antisense oligonucleotides with cytotoxic agents offer important advantages in cancer therapy. However, control oligonucleotides must be carefully chosen to separate the antisense effect from the many potential nonspecific effects. Several antisense drugs have been very effective inin vitroexperiments, and have entered clinical trials. Successive generations of antisense drugs, including molecules with novel backbones or other structural modifications, chimeric oligonucleotides and peptide nucleic acids, are currently in development.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

▴ Lanoteplase is a recombinant plasminogen activator, which when administered as a single bolus intravenous injection, displays thrombolytic activity.▴ In the phase II InTIME trial, lanoteplase dose-dependently increased reperfusion rates at 60 and 90 minutes in patients with acute myocardial infarction and at 90 (but not 60) minutes lanoteplase 120 kU/kg was significantly superior to alteplase in restoring TIMI grade 2 and 3 flow (in 83.0 and 71.4% of patients, respectively).▴ Preliminary results from the phase III InTIME-II study showed that lanoteplase was as effective as alteplase in decreasing 30-day mortality.▴ At 30 days, the combined incidence of death, reinfarction, major bleeding and heart failure was lower with lanoteplase 120 kU/kg than with alteplase 100mg.▴ From preliminary results of the large InTIME-II study, lanoteplase 120 kU/kg showed a greater incidence of intracranial haemorrhage and mild bleeding than alteplase ≤100mg, but a similar incidence of stroke. The smaller InTIME study showed a tendency for fewer adverse events with lanoteplase.Features and properties of lanoteplase (SUN9216, BMS200980, FEX1, nPA)

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