Systemic treatment of colorectal cancer.

Palliative and adjuvant treatment for colorectal cancer has been, until recently, largely dependent on 5-fluorouracil (5-FU)-based chemotherapy. Oral fluoropyrimidines have been evaluated in the advanced disease setting and they appear to be as effective as 5-FU, but are safer and more convenient for most patients. Irinotecan and oxaliplatin are new cytotoxic agents, which are active in 5-FU-resistant disease, but which may also be combined with 5-FU as initial therapy in advanced disease. Initial combination therapy leads to improved response rates and more prolonged progression-free survival compared with 5-FU monotherapy. Standard regimens for adjuvant therapy usually involve 6 months of chemotherapy using 5-FU and folinic acid. Recent trials of capecitabine, oxaliplatin and irinotecan in the adjuvant setting are ongoing, or have recently completed accrual, and may lead to a change in future clinical practice. Biological therapies are playing an increasing role in the management of colorectal cancer. Farnesyl transferase inhibition, inhibition of the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF) are undergoing evaluation in advanced disease. In the adjuvant setting, both passive and active immunotherapeutic approaches have been studied. In addition, a large trial will evaluate the role of cyclo-oxygenase(COX)-2 inhibitors as adjuvant therapy. Further research is required in order to define the optimal sequence and combination of these different cytotoxic and biological therapies, in order to secure the best possible outcome for various subgroups of patients with both early and advanced stage colorectal cancer.

Limiting dilution analysis: quantification of IL-2 producing allospecific lymphocytes after renal and cardiac transplantation.

A rapid and robust limiting dilution assay was developed to measure the frequency of donor-reactive, IL-2 (interleukin 2) producing, helper T lymphocytes in the peripheral T cell population of organ allograft recipients. The IL-2 bioassay was performed using two methodologies to assess the response of CTLL-2 indicator cells. The first depended on spectrophotometric detection of bioreduced XTT whilst the second involved measurement of [3H]thymidine incorporation. The radioisotopic method was slightly more sensitive but both assays could be used for analysis of limiting dilution culture supernatants after primary incubation of recipient lymphocytes with donor splenic cells for 48 hours. All the assays produced results which conformed to single hit kinetics, indicating that IL-2 was production was dependent on a single limiting cell type. The frequency of allospecific helper lymphocytes in the peripheral T cell population of normal volunteers did not vary significantly during a 28-day period. It was found that immunosuppressed allograft recipients had a significantly reduced proportion of T cells in their peripheral blood mononuclear cell population. However, it was possible to measure the frequency of donor-reactive helper cells in the T cell population of transplant patients. These frequency values were very low in two renal allograft recipients who were HLA-DR matched to their donor organs. Three of four HLA-DR mismatched cardiac recipients showed a significant decrease in the frequency of their donor-reactive helper lymphocytes during the period of monitoring. The fourth patient, who received antilymphocyte antibodies for the first three days after transplantation, showed significant fluctuations in the frequency of these cells. The four cardiac recipients showed little histopathological evidence of acute graft rejection with only one patient experiencing a brief episode of moderate rejection; this patient showed a high frequency of donor-reactive helper cells when assayed immediately after this episode but the frequency subsequently declined.

Nurse practitioners' role in complementary and alternative medicine: active or passive?

Complementary and alternative medical (CAM) therapies are emerging as a significant force that is shaping the delivery of health care in the United States. The physician-scientists of conventional medicine are slowly easing into the process of evaluating and integrating CAM therapies. After all factors are considered, should the role of NPs in this process be active or passive? This article explores reasons why NPs should or should not take an active role in evaluating and integrating CAM therapies. It proposes a role that NPs could have in determining the influence of complementary and alternative medicine on their clinical practice.