摘要:

Rotavirus is the most important cause of severe gastroenteritis in infants and children worldwide. Efforts to develop a vaccine have concentrated on live oral vaccines, especially with attenuated animal viruses. Because studies with rhesus monkey rotavirus and bovine rotavirus RIT 4237 or WC3 were inconsistent, reassortant rhesus and bovine vaccines have been developed that include the gene encoding the neutralising protein, VP7, of several human strains. These efforts culminated in the licensure of a tetravalent rhesus rotavirus vaccine, in 1998. Subsequent reports linking vaccination to intussusception, however, led to withdrawal of this vaccine. Trials, nevertheless, continue with an oral bovine reassortant vaccine and an attenuated human strain, 89-12. Other strategies in preclinical development include the use of virus-like particles, DNA vaccines and subunit vaccines given by mucosal and nonmucosal routes.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Liver transplantation is now widely recognised as an effective treatment option for patients with advanced liver disease. Many units now achieve greater than 85% survival at 1 year, with the majority of patients having a high quality of life.The maintenance of a high quality of life requires careful clinical management to ensure that the continued maintenance of excellent liver graft function is not achieved at the expense of immunosuppressive drug complications or morbidity.Acute liver rejection will occur in between 30 to 45% of patients, although with modern immunosuppressive protocols, usually combining one of the calcineurin agents, either cyclosporin or tacrolimus, with both azathioprine and corticosteroids (prednisolone) ensures that relatively few grafts are lost from severe acute rejection.While the incidence and severity of acute rejection may be one factor in raising the risk of chronic rejection, it may not be the principal one in many patients. It is important to recognise that the frequency of rejection also varies with the primary underlying liver disease, with patients with hepatitis B or alcoholic liver disease having relatively low rejection rates, compared with patients with primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC), which range between 20 to 70%.Chronic rejection will account for some 5% of grafts lost in the first 3 to 5 years. Indeed, there is some evidence that the incidence of chronic rejection is actually declining over the past few years. While the reason for this apparent decline is uncertain, and it could relate to better immunosuppression management, or more likely to the growing recognition that chronic graft dysfunction may be due to recurrent liver disease, such as autoimmune hepatitis, PBC, PSC, or recurrent hepatitis C. The differentiation of recurrent primary liver disease from chronic rejection can prove to be very difficult in clinical practice. Thus, the clinician must carefully monitor liver and graft function, evaluate any biochemical changes, and try to reach a clear diagnosis before considering any modification of immunosuppressive schedules.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Recombinant interleukin-2 (rIL-2) produces remissions in several human tumours, including metastatic renal cell cancer (RCC) and malignant melanoma. High-dose intravenous bolus rIL-2 is approved in the US in these 2 indications, based on evidence of rIL-2−induced durable remissions in a significant minority of patients. Due to the toxicity associated with high-dose rIL-2, alternative regimens were investigated in RCC, including low-dose intravenous bolus, subcutaneous outpatient regimens and continuous intravenous infusion, yielding similar response rates. A prospective randomised trial comparing different doses and routes of administration is underway. Because response rates to single agent rIL-2 are inadequate, combination therapies were studied. In RCC patients, a combination of rIL-2 and IFNα resulted in better response rates than either cytokine alone, with no apparent survival advantage. Combination with chemotherapy increased toxicity and had no proven benefit. Results of adoptive immunotherapy studies combining rIL-2 with either lymphokine-activated killer cells or tumour infiltrating lymphocytes were comparable to those of rIL-2 alone. In malignant melanoma, combination therapy of rIL-2 with chemotherapy was explored. Results of single-institution phase II combination studies of variable chemotherapy and rIL-2 and IFNα regimens were promising and randomised trials are underway.rIL-2 is being is evaluated in haematological malignancies. The rationale is based on pre-clinical evidence that a variety of leukaemic blasts are sensitive to cytolysis or growth inhibition mediated by rIL-2−activated immune effector cells.New immunotherapeutic strategies may ultimately improve the anti-tumour efficacy of rIL-2−based therapy. Early trials using rIL-2 as adjuvant therapy to vaccines or dendritic cell-based therapy have yielded promising results.rIL-2 therapy initiates a cytokine-mediated pro-inflammatory process leading to an adverse effect profile that is quite different from traditional chemotherapeutic agents. Dose-limiting toxicities are primarily cardiovascular and pulmonary and are dose-dependent in frequency and severity. Patients receiving high-dose regimens may require intensive care unit support, limiting its use to those with excellent performance status and adequate organ function. Patients receiving less intensive dose regimens may require less rigorous screening and monitoring. It has been postulated that rIL-2 related toxicity is mediated through the release of secondary cytokines, including TNF, IFNγ, IL-6 and IL-1. With the increasing understanding of the pathophysiological mechanisms of the effects of rIL-2, it is possible that concurrent administration of selective cytokine antagonists may reduce the toxicity associated with rIL-2 without interfering with its anti-neoplastic activity.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

The aim of this review is to summarise the available literature regarding the epidemiology and proposed mechanisms of skin cancer development in organ transplant recipients who are receiving lifelong treatment with immunosuppressive therapy and to review the different strategies for managing complications in this group of patients.Organ transplantation is complicated by an increased incidence of certain cancers, of which non-Hodgkin’s lymphoma, Kaposi’s sarcoma and squamous cell carcinoma are the most common. The most important risk factor for these cancers is immunosuppressive therapy. The relative importance of different immunosuppressive therapy regimens in relation to the development of skin cancer is still unclear. Immunosuppressionper semay play the most important role, but other mechanisms, which are independent of host immunity and which may be different for the various agents used, may also be of importance for the increased risk of cancer.Apart from immunosuppressive therapy, exposure to sunlight and infection with human papillomaviruses are believed to be the most important risk factors for the development of cutaneous squamous cell carcinoma in organ transplant recipients. Human papillomaviruses, no doubt, benefit considerably from immunosuppression, as is indicated by the large number of warts found in these patients, but many questions remain unanswered about their significance in cutaneous oncogenesis. The E6 protein from a range of cutaneous human papillomavirus types effectively inhibits apoptosis in response to ultraviolet light damage. It is, therefore, conceivable that the development of skin cancer in organ transplant recipients is the result of a complex interplay between exposure to ultraviolet radiation, human papillomavirus infection and genetic predisposition.Measures for protection from the sun are important for reducing the risk of skin cancer in organ transplant recipients. Regular surveillance of patients with skin problems and easy access to a dermatologist for these patients is advised. Changing the immunosuppressive regimen from azathioprine to cyclosporin orvice versadoes not seem to relieve the skin problems. Tapering the immunosuppressive therapy to the lowest possible dose may be of some advantage. Oral retinoids, e.g. acitretin, have some effect in reducing the number of keratotic skin lesions and in the prevention of skin cancer in organ transplant recipients. Resurfacing the back of the hand can be a successful treatment for patients with multiple skin cancers on the back of the hand and can be used prophylactically in patients with severely actinically damaged skin.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

New biological medical therapies and innovative surgical approaches have revolutionised the care of patients with Crohn's disease. Until these innovations began to be utilised over the past decade, studies of the economics of Crohn's disease care were relatively scarce. Questions from both clinical and economic standpoints now arise over potential choices between medical and surgical approaches to patients with Crohn's disease.Initial economic studies suggested that the vast majority of costs in Crohn's disease were due to inpatient services and surgery. The large variance in cost data between patients resulted in a very small percentage of patients accounting for a disproportionately large percentage of the overall costs, with the bulk of costs, charges and reimbursements accrued by surgical cases. Studies suggest that surgery would need to result in a decreased utilisation of outpatient services in order to be ‘cost-effective’.Evaluation of the clinical course of Crohn's disease suggests that the surgically-induced remission state is the longest remission state generally experienced by the patients, although sophisticated cost analysis fails to show enough of a remission benefit to offset the high costs associated with surgical procedures and post-operative convalescence. Bowel-sparing intestinal strictureplasty and minimally invasive laparoscopic surgeries have the potential to substantially decrease the costs associated with disease. These techniques need to be applied to a larger percentage of surgical Crohn's patients before the overall economic benefits can be fully assessed.Indirect costs and disability may account for most of the overall costs associated with Crohn's disease. Quality-of-life analyses have revealed that patients ill with Crohn's disease perform poorly, and the detrimental effects of medications or surgery may further increase disability in these patients. Future cost-utility studies may reveal the extent to which overall costs are affected by these issues.This review of the currently available literature on the economics of Crohn's disease suggests that medical therapy which can substantially reduce the utilisation of hospitalisations and surgery might be cost effective, even if the acquisition cost of the drug is high. However, broader application of specialised surgical techniques, together with the long post-operative remission state enjoyed by most Crohn's patients, may also offer a cost-effective long term approach to the disease. It is likely that both surgical and medical approaches will continue to be used in the treatment of Crohn's disease, with options for each patient being carefully considered on an individual basis.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS