Dose-banding of carboplatin: rationale and proposed banding scheme.

BACKGROUND: In dose-banding (DB) prescribed doses of cancer chemotherapy are fitted to doseranges or 'bands' and standard doses for each band are provided using a selection of pre-filled infusions or syringes, either singly or in combination. DB is used for several drugs where dose is based on body surface area. No DB-scheme has been reported for carboplatin, which, in clinical practice, is routinely dosed according to renal function. STUDY OBJECTIVE: To assess the rationale for DB of carboplatin with regards to factors that influence dosing accuracy, develop a DB scheme, and discuss its potential use and limitations. METHODS: Prospective evaluations of carboplatin area under the plasma concentration -- time curve (AUC) following application of the Calvert-formula were identified by a literature search. A relevant carboplatin dose range for construction of a DB-scheme with Calvert-formula based doses was obtained from published glomerular filtration rate distributions for patients receiving carboplatin. RESULTS: A DB-scheme was developed for individually calculated carboplatin doses of 358-1232 mg, with 35 mg increments between each standard dose and a maximum deviation of 4.7% from prescribed dose. The proposed DB-scheme covers the GFR-ranges 47-221 mL/min and 26-151 mL/min for patients receiving doses based on the target AUCs of 5 and 7 mg/mL/min, respectively. CONCLUSION: There is a strong scientific rationale to support DB of carboplatin. The proposed banding scheme could introduce benefits to patients and healthcare staff but, as with other DB schemes, should be validated with prospective clinical and pharmacokinetic studies to confirm safety and efficacy.     

Postgerminative growth and lipid catabolism in oilseeds lacking the glyoxylate cycle

The glyoxylate cycle is regarded as essential for postgerminative growth and seedling establishment in oilseed plants. We have identified two allelic Arabidopsis mutants, icl-1 and icl-2, which lack the glyoxylate cycle because of the absence of the key enzyme isocitrate lyase. These mutants demonstrate that the glyoxylate cycle is not essential for germination. Furthermore, photosynthesis can compensate for the absence of the glyoxylate cycle during postgerminative growth, and only when light intensity or day length is decreased does seedling establishment become compromised. The provision of exogenous sugars can overcome this growth deficiency. The icl mutants also demonstrate that the glyoxylate cycle is important for seedling survival and recovery after prolonged dark conditions that approximate growth in nature. Surprisingly, despite their inability to catalyze the net conversion of acetate to carbohydrate, mutant seedlings are able to break down storage lipids. Results suggest that lipids can be used as a source of carbon for respiration in germinating oilseeds and that products of fatty acid catabolism can pass from the peroxisome to the mitochondrion independently of the glyoxylate cycle. However, an additional anaplerotic source of carbon is required for lipid breakdown and seedling establishment. This source can be provided by the glyoxylate cycle or, in its absence, by exogenous sucrose or photosynthesis.     

How to use the world's scarce selenium resources efficiently to increase the selenium concentration in food

The world's rare selenium resources need to be managed carefully. Selenium is extracted as a by-product of copper mining and there are no deposits that can be mined for selenium alone. Selenium has unique properties as a semi-conductor, making it of special value to industry, but it is also an essential nutrient for humans and animals and may promote plant growth and quality. Selenium deficiency is regarded as a major health problem for 0.5 to 1 billion people worldwide, while an even larger number may consume less selenium than required for optimal protection against cancer, cardiovascular diseases and severe infectious diseases including HIV disease. Efficient recycling of selenium is difficult. Selenium is added in some commercial fertilizers, but only a small proportion is taken up by plants and much of the remainder is lost for future utilization. Large biofortification programmes with selenium added to commercial fertilizers may therefore be a fortification method that is too wasteful to be applied to large areas of our planet. Direct addition of selenium compounds to food (process fortification) can be undertaken by the food industry. If selenomethionine is added directly to food, however, oxidation due to heat processing needs to be avoided. New ways to biofortify food products are needed, and it is generally observed that there is less wastage if selenium is added late in the production chain rather than early. On these bases we have proposed adding selenium-enriched, sprouted cereal grain during food processing as an efficient way to introduce this nutrient into deficient diets. Selenium is a non-renewable resource. There is now an enormous wastage of selenium associated with large-scale mining and industrial processing. We recommend that this must be changed and that much of the selenium that is extracted should be stockpiled for use as a nutrient by future generations.     

Impact on and use of an inner-city London Infectious Diseases Department by international migrants: a questionnaire survey

Background  

The UK has witnessed a considerable increase in immigration in the past decade. Migrant may face barriers to accessing appropriate health care on arrival and the current focus on screening certain migrants for tuberculosis on arrival is considered inadequate. We assessed the implications for an inner-City London Infectious Diseases Department in a high migrant area.     

Raising research awareness among midwives and nurses: does it work?

OBJECTIVE: The primary aim of the study was to evaluate the effectiveness of two approaches to increase research awareness among midwives and nurses. DESIGN: Quasi-experimental with the attitudes of staff in the two groups being measured at two points (January and October 1997). SAMPLE: All midwives and nurses working in four clinical areas in an acute NHS Trust. The intervention arm of the study involved all midwives and nurses in the Clinical Directorate of Obstetrics and Gynaecology, while the control arm involved all nurses working in a specialist oncology and haematology unit and in the children's directorate. ETHICS: The Joint Ethics Committee considered approval unnecessary because the study involved staff and not patients. DATA COLLECTION: Data were collected by self-complete questionnaires. INTERVENTIONS: A programme of education with policy and practice interventions targeted at ward sisters. OUTCOME MEASURES: Staff attitudes to, knowledge of, and level of involvement in, research. RESULTS: The study demonstrated a significant increase in both knowledge and use of research resources. Following the programme of education, staff in the intervention group were significantly more likely to use resources associated with research utilization and to report that they had read a research paper within the last month. STUDY LIMITATIONS: The time scale of the intervention was restricted by the funding available; a significant Hawthorne effect was evident with both groups showing an increase in knowledge; the pragmatic nature of the study meant that it was not possible to randomize the study groups; the scale of the study did not permit an economic evaluation. CONCLUSIONS: The introduction of clinical governance challenges healthcare providers to improve the care they deliver. There are huge opportunities for Trusts to invest in developing staff knowledge and use of research. However, staff will only seize these opportunities if there is an appropriate, enabling environment--an environment that delivers intensive interventions and is sensitive to the wider structural factors in the NHS affecting staff morale and commitment. In the absence of this environment, what may be seen as opportunities to managers may be regarded as just another burden by staff.     

Topographic patterns of intestinal metaplasia and gastric cancer

OBJECTIVE: The role of intestinal metaplasia in gastric oncogenesis has been demonstrated by both cross-sectional and longitudinal studies. This study was designed to determine whether, in a population at high risk for gastric cancer, different topographical patterns and phenotypes of intestinal metaplasia were associated with different degrees of cancer risk. METHODS: A total of 68 Colombian patients with gastric cancer and 67 controls with nonulcer dyspepsia were studied by an extensive biopsy protocol. Intestinal metaplasia was assessed semiquantitatively by histology and was characterized histochemically. In both patients and controls, the Spearman's correlation test was applied to the test if the gastric distribution of metaplastic lesions resulted in specific topographical patterns associated with different risks for cancer. RESULTS: Four topographical patterns of intestinalization emerged: 1) "Focal," in 14 cancer patients and 16 controls; 2) "Antrum-predominant," in seven cancer patients and six controls; 3) "Magenstrasse" (involving the lesser curvature from cardia to pylorus) in 25 cancer patients and four controls. This pattern was associated with higher cancer risk (OR = 5.7; 95% CI: 1.3-26) than were the two less extensive patterns; and 4) "Diffuse," involving essentially the entire gastric mucosa with the exception of the fundus, was unique to 13 cancer patients. The OR for cancer was 12.2; 95% CI: 2.0-72.9. Incomplete-type metaplasia significantly correlated with the extent of total metaplasia and was also associated with greater cancer risk. CONCLUSIONS: In a population with high risk for gastric cancer, the extension of intestinal metaplasia correlates with the extent of its "incomplete" phenotype and is significantly associated with increased cancer risk. Both the extent and location of intestinal metaplasia along the lesser curvature (from the cardia to the prepyloric zones) identify patients with the highest cancer risk.