摘要:

Tremendous progress with liver transplantation for hepatitis B−related liver disease has occurred over the past decade, primarily through advances in antiviral therapy. In the most recent clinical trials, reinfection of the transplanted allograft with host hepatitis B virus has been shown to be rare, even in patients with evidence of viral replication at the time of liver transplantation. The elimination of recurrent infection has allowed centres to investigate more cost-effective protocols. However, additional research, both clinical and basic, is needed to prevent the emergence of drug-resistant infections.This article compares the current protocols for the prevention of recurrent infection with reference to the worldwide experience of liver transplantation for hepatitis B over the last 30 years. Nonviraemic patients (positive for hepatitis B surface antigen only) can receive a liver transplant with a low risk of recurrent infection using lamivudine alone, hepatitis B immunoglobulin (HBIG) alone or HBIG and lamivudine in combination. Viraemic patients (positive for either hepatitis B e antigen or viral DNA) should receive treatment exclusively with HBIG plus lamivudine. A pretransplant course of lamivudine may not be necessary in either group of patients, and it poses the additional risk of the emergence of a YMDD mutant infection prior to transplantation.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Interferon-alpha (IFNα) can induce major cytogenetic responses in 30 to 40% of patients with chronic myelogenous leukaemia (CML) and up to 50% when combined with cytarabine (ara-C). These responses translate into a survival advantage. However, the management of patients treated with IFNα requires experience to optimise the therapy. The optimal dose should be used and the addition of ara-C should be considered. It is advisable to lower the white blood cell count (WBC) before the start of therapy and increase the dose to the ideal dose gradually over 1 to 2 weeks. Some myelosuppression should be tolerated to keep a WBC in the range of 2 to 4 · 109/L. Dosages should be adjusted as needed when grade 3 or persistent grade 2 toxicity occurs, and adverse effects should be managed promptly and aggressively to improve tolerance. Patients should be monitored closely with cytogenetic and possibly other analyses such as fluorescentin situhybridisation (FISH) and polymerase chain reaction (PCR) to determine response. The duration of therapy is controversial, but it should be kept in mind that whenever the decision is made to use IFNα for therapy in CML, the patient should be given the best opportunity to achieve a cytogenetic response as this will probably translate into a survival advantage.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Breast cancer treatment has now entered a new era in which biological therapies, based on a rapidly expanding cellular and molecular understanding of breast cancer pathogenesis, have joined the standard armamentarium of surgery, radiation, chemotherapy, and hormone therapy. In 1998, the anti-HER2 humanised monoclonal antibody trastuzumab became the first biological therapy to receive US Food and Drug Administration (FDA) approval for the treatment of breast cancer, thus marking a milestone that almost certainly will be repeated with other new agents. HER2 (ErbB2) has been the focus of many therapeutic strategies because of its frequent gene amplification and overexpression in breast cancer, its role in tumourigenesis and cancer progression, and its prognostic and predictive significance in clinical studies.In preclinical studies, trastuzumab showed antiproliferative activity againstHER2-overexpressing breast cancersin vitroand in tumour xenograft models. In a phase II clinical trial of 222 stage IV patients, trastuzumab was associated with an objective response rate of 15%. A randomised phase III clinical trial demonstrated that first-line chemotherapy for stage IV patients in combination with trastuzumab was significantly superior to chemotherapy alone. Chemotherapy plus trastuzumab was associated with a median time to progression of 7.2 months, versus 4.5 months for chemotherapy alone (p < 0.001), and a response rate of 45% versus 29% for chemotherapy alone (p = 0.001).Other novel therapies involving antibody targeting of HER2 are under development, including bispecific antibodies, immunotoxins, and immunoliposomes. Vaccine approaches are also under active investigation, including those directed against HER2 and mucin antigens. Gene therapy strategies under development include gene transfer of immunomodulatory genes and of anti-oncogene constructs. Other biological therapies include agents designed to induce differentiation or inhibit invasion, angiogenesis and metastasis.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

BackgroundShort courses of oral prednisolone are used as rescue therapy for severe asthma exacerbations. This study compares nebulised budesonide or oral prednisolone, both followed by budesonide Turbohaler®, as a treatment for severe asthma exacerbations, in the absence of life-threatening features.Patients and MethodsThirteen adults admitted to hospital were randomised to receive either nebulised budesonide (4mg 8-hourly) for 48 to 72 hours followed by budesonide Turbohaler®(1600µg twice daily for 7 days, then 800µg twice daily for 21 days) for 28 days or prednisolone (40mg daily) for 9 to 11 days followed by budesonide Turbohaler®(800µg twice daily) for 21 days. The primary efficacy variable was the change from baseline at 48 hours in forced expiratory volume in 1 second (FEV1). Secondary efficacy variables included an assessment of symptom severity (0 = none, 1 = mild, 2 = moderate, 3 = severe).ResultsDifficulties were experienced with patient recruitment in the emergency setting. The results presented are from an incomplete study. Change in FEV1from baseline to 48 hours was not statistically significantly different between the groups (the study was underpowered to detect a difference in change in FEV1, as the power to detect a prespecified difference between groups was 18%). Nebulised budesonide significantly reduced the severity of wheeze after 24 hours compared with prednisolone [estimate of treatment effect = −0.95; 95% confidence intervals (CI) = −1.76 to −0.15; p = 0.0336 between groups] and 48 hours (estimate of treatment effect = −0.79; 95% CI = −1.42 to −0.15; p = 0.0326 between groups).ConclusionWhile oral prednisolone or intravenous hydrocortisone, oxygen and bronchodilators are the mainstay of acute management in severe asthma, the results of this study suggest that nebulised budesonide may assist in regaining control of symptoms during exacerbations of asthma.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

The role of Thymoglobulin®(TMG), a polyclonal rabbit-derived antithymocyte globulin, in the prevention and treatment of acute renal allograft rejection is the focus of this review.TMG and the polyclonal horse-derived antithymocyte globulin Atgam®(ATG) have been compared in a multicentre double-blind, randomised study in 163 renal allograft recipients who were experiencing acute rejection. TMG 1.5 mg/kg/day was significantly more effective than ATG 15 mg/kg/day for the primary end-point (88vs76%; return of serum creatinine to baseline at the end of therapy or within 14 days of initiation of treatment). The greatest differences in favour of TMG were seen in patients with moderately severe rejection episodes. Recurrent episodes of rejection occurred significantly less often in patients who achieved the primary end-point and thus were less frequent in recipients of TMG than ATG. For a composite end-point, return of serum creatinine to baseline and a functioning allograft at 30 days, TMG tended to be more effective than ATG, but the difference was not statistically significant. A pharmacoeconomic analysis of this trial suggests that treatment with TMG is a cost saving strategy compared with ATG.In a small randomised trial TMG and muromonab-CD3 demonstrated similar efficacy in patients with acute allograft rejection.TMG was more effective than ATG as induction immunosuppressive therapy in 72 adult renal allograft recipients in a comparative single centre study. During 12 months of follow-up post-transplantation, the overall incidence of acute rejection episodes, a primary end-point, was significantly lower in patients treated for ≥7 days with TMG 1.5 mg/kg/day than ATG 15 mg/kg/day (4vs25%). TMG is also used for induction therapy in corticosteroid-free immunosuppressive regimens.Leucopenia occurred in significantly more TMG than ATG recipients who received the drugs for induction therapy or as treatment of acute rejection. Importantly, there was no significant difference in the frequency of infection in the 2 groups. Indeed, the incidence of CMV disease was significantly lower among TMG- than ATG-treated patients (12.5%vs33.3%) during 1 year of follow-up after induction therapy with either agent.ConclusionsTMG is at least equivalent to ATG for the reversal of acute renal allograft rejection and appears to be superior to ATG when used as induction immunosuppressive therapy in renal transplantation. A pharmacoeconomic analysis of the pivotal US study also suggests that there are cost benefits for TMG compared with ATG. Therefore, TMG is an effective alternative to ATG (and perhaps the currently available monoclonal preparation) and extends the choice of treatments for the management of acute renal allograft rejection.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS