Incomplete holism in pre-registration nurse education: the position of the biological sciences

There is an ongoing debate in nurse education concerning the role and delivery of the biological sciences in the nursing curriculum. One of the fundamental questions raised by this debate asks how best can teachers impart biological knowledge in a manner that can be readily applied by students and qualified nurses to inform their clinical practice. This paper will include a discussion of some of the features of pre-registration education that may have influenced the manner in which biological sciences are perceived, taught and used by nurses. It will be argued that nursing may have developed a form of incomplete holism and that this may be in part responsible for the challenges that remain to be met within this area of the nursing curriculum. As a response to incomplete holism an innovative approach within pre-registration education will be introduced. This development involves the use of linked teaching sessions which aim to develop the analytical skills necessary to apply physiological knowledge to nursing practice.     

Lack of correlation between thymidylate synthase levels in primary colorectal tumours and subsequent response to chemotherapy.

The increasing interest in 5-fluorouracil (5-FU) modulation and the development of new antifolates has focused attention in recent studies on the expression of the target enzyme thymidylate synthase (TS) as a determinant of drug sensitivity and resistance. Resistance to TS-directed drugs has been shown to occur in vitro and in vivo with increased expression of the enzyme (determined by enzymatic assays as well as protein and gene expression assays). Several studies have evaluated the role of TS as a prognostic indicator of clinical response to chemotherapy containing TS-directed drugs. We have used a polyclonal antibody to recombinant human TS to establish a silver-enhanced immunogold staining method to localize TS in human tumours. Human tumour cell lines with acquired resistance to TS inhibitors owing to increased levels of TS were used to confirm the specificity of immunostaining. Stained sections were evaluated by image analysis. Immunostaining in tumour sections was greatly reduced (>80%) by preabsorption of the antiserum with recombinant TS. The method was used to determine the extent of TS immunostaining in 134 primary human colorectal tumours. The results were then compared with the clinical outcome and response to chemotherapy for the treatment of subsequent metastatic disease. A wide range (approximately 100-fold) of TS immunostaining was observed in these primary tumour sections. Normal mucosal tissue levels were 5-10 times lower than those observed in the adjacent tumour tissue. The values for TS immunostaining did not correlate with clinical endpoints, such as time from diagnosis to relapse, response to chemotherapy for disseminated disease, nor with Dukes'' staging. This lack of correlation may be because this group of patients was selected on the basis of their need for palliative chemotherapy and did not include patients who were cured of their disease. Also, primary tumour TS expression may not give a good indication of the TS expression in metastatic lesions. The prognostic significance of TS protein expression in primary and metastatic lesions requires further evaluation.     

A method to reduce glutathione peroxidase levels in primary endothelial cell cultures

The purpose of this study was to develop culture conditions that would reduce glutathione peroxidase activity in bovine mammary endothelial cells. Conditions of reduce glutathione peroxidase activity were produced in vitro by culturing cells in selenium-deficient media. Low selenium levels were achieved by reducing serum concentrations; however, levels of essential growth factors also were reduced by this method. Therefore, cell proliferation was promoted by supplementation with combinations of defined serum components including insulin, transferrin, linoleic acid, bovine brain extract, and human epidermal growth factor. Out of seven different formulas tested, F12K medium containing 2% fetal bovine serum, insulin, transferrin, and linoleic acid was found to be conducive for cell proliferation. Upon confluence, endothelial cells cultured under these conditions consistently displayed short passage rates, consistent cell numbers, and classic cobblestone morphology when grown in the presence or absence of supplemental selenium. Additionally, these cells retained typical endothelial cell characteristics such as uptake of 1,1-dioctadecyl-3,3,3,3-tetramethylindo-carb ocyanine perchlorate acetylated low-density lipoprotein and the expression of cell adhesion molecules and von Willebrand Factor.     

Changes in transglutaminase activity in an experimental model of pulmonary fibrosis induced by paraquat.

An experimental model of pulmonary fibrosis has been developed by dosing rats with one-fifth the LD50 dose of the herbicide paraquat on 5 consecutive days. Approximately 50% of the rats died within 4 days of the completion of dosing, showing macroscopic changes and wet weight increases in the lung consistent with severe oedema. Those animals which died between Days 4 and 10 had markedly increased levels of hydroxyproline in the lung, maximum at Day 6, and increased prolyl hydroxylase activity, maximum at Day 4. These changes, together with an increase in thymidine incorporation into DNA, and increased lung DNA content, were consistent with the development of fibrosis. Measurement of transglutaminase activity in the lung showed marked increases at Days 4 and 10 after completion of dosing. This activity paralleled closely the changes in prolyl hydroxylase activity and became increasingly associated with particulate protein present in the "nuclear pellet" fraction. The presence of zymogen plasma transglutaminase trapped in lung homogenates could not be demonstrated but the contribution by the active plasma transglutaminase (Factor XIIIa) to increases shown at Day 4 cannot be ruled out.