Evaluation of paladai cup feeding in breast-fed preterm infants compared with bottle feeding

This pilot study developed an appropriate procedure to evaluate the paladai cup compared to bottle feeding in preterm infants, using weighed napkins and video analysis to assess amount of spillage, volume consumed, time taken and physiological stability. Paladai results demonstrated increased spillage, increased feed times with more stress cues.     

Spatial and quantitative mapping of glycolysis and hypoxia in glioblastoma as a predictor of radiotherapy response and sites of relapse

European Journal of Nuclear Medicine and Molecular Imaging - Tumor hypoxia is a centerpiece of disease progression mechanisms such as neoangiogenesis or aggressive hypoxia-resistant malignant cells...     

Implementing a nutritional assessment tool in the community: a report describing the process, audit and problems encountered

This short report outlines the implementation and audit of a nutritional assessment tool designed for use by community nurses working with adults and elderly people. Implementation included providing training and adapting the assessment tool for community use. The audit results, although inconclusive, do suggest that while nurses acknowledged the usefulness of the NAT, there was little change in nursing practice. The difficulties in auditing a change in working practice are demonstrated and the necessity of adapting the assessment tool to ensure it is suitable for local needs is highlighted.     

Decreased NADPH:cytochrome P-450 reductase activity and impaired drug activation in a mammalian cell line resistant to mitomycin C under aerobic but not hypoxic conditions

Mitomycin C (MMC) is regarded as the prototype bioreductive alkylating agent in clinical use. To elucidate the biochemical basis of MMC resistance, we isolated a drug resistant derivative (designated CHO-MMC) of a Chinese hamster ovary cell line (CHO-K1) by exposure to progressively higher concentrations of MMC. CHO-MMC cells exhibited a 17-fold increase in resistance to MMC and were 33-fold cross-resistant to the monofunctional derivative, decarbamoyl mitomycin C. In contrast, CHO-MMC cells showed only a 2-fold level of resistance to BMY 25282, a more easily activated analogue of MMC, and exhibited parental sensitivity to MMC under radiobiologically hypoxic conditions. CHO-MMC cells showed no increased resistance to a range of DNA damaging agents including several other alkylating agents (e.g., melphalan and methyl methanesulfonate). Cross-resistance to drugs associated with the multidrug resistant phenotype (e.g., Adriamycin and vincristine) was present only at very low levels. Using a specific high performance liquid chromatography technique, we examined the rates of reduction of MMC and BMY 25282 in cell extracts from CHO-K1 and CHO-MMC cells under both aerobic (air) and hypoxic (N2) conditions. Reduction rates for both drugs were at least 30-fold faster under nitrogen than in air. Metabolism of MMC was undetectable in air but was readily detectable under nitrogen and was 2- 3-fold slower in CHO-MMC cell extracts than in CHO-K1 cell extracts. Although BMY 25282 was more readily reduced under nitrogen, no difference was detected between extracts from CHO-K1 or CHO-MMC cells in the rate of reduction of BMY 25282 under either air or nitrogen. The activity of NADPH:cytochrome P-450 (cytochrome c) reductase, an enzyme implicated in the bioreductive activation of MMC, was 3-4-fold lower in CHO-MMC cells than in the parental line. These findings suggest that the resistance of CHO-MMC cells to MMC under aerobic conditions may be due to impaired metabolic activation of the drug as a result of a decrease in NADPH:cytochrome P-450 reductase activity. This supports the view that decreased bioreductive enzyme activity may be a significant mechanism for acquired resistance to MMC in tumor cells in vivo and that more readily activated analogues may be potentially useful in overcoming this specific form of resistance.     

Cross-sensitivity to topoisomerase II inhibitors in cytotoxic drug-hypersensitive Chinese hamster ovary cell lines

We have isolated a Chinese hamster ovary cell line, designated ADR-1, which exhibits hypersensitivity to a range of drugs which are thought to inhibit the action of the enzyme topoisomerase II. These include anthracyclines, other classes of intercalating agents, and the epipodophyllotoxin, etoposide. No significant sensitivity to radiation, or to mono- and bifunctional alkylating agents was seen, although mild cross-sensitivity to the radiomimetic agent bleomycin was observed. We have monitored the level of DNA strand breaks induced by topoisomerase II inhibitors in ADR-1 cells using alkaline elution. At equimolar Adriamycin (doxorubicin) doses, more protein-associated DNA strand breaks are induced in ADR-1 cells than in wild-type cells. This enhanced level of drug-induced strand breaks does not appear to be a function of increased drug uptake as both lines accumulate similar levels of radiolabeled daunomycin. Both the rate of repair of strand breaks and the final percentage of strand breaks rejoined was equivalent in the 2 cell lines. These results are consistent with an enhancement in the level of topoisomerase II-dependent DNA breakage in ADR-1 cells following exposure to topoisomerase II inhibitors. We have previously reported the isolation of 2 bleomycin-sensitive Chinese hamster ovary cell lines, BLM-1 and BLM-2 (C. N. Robson et al., Cancer Res. 45:5304-5309, 1985). While BLM-1 exhibited cross-sensitivity only to Adriamycin, BLM-2 was shown to be hypersensitive not only to Adriamycin out also to certain alkylating agents and to ionizing radiation. In this paper, we show that both BLM-1 and BLM-2 also exhibit mild cross-sensitivity to a range of topoisomerase II inhibitors. These results indicate that intercalating agents and epipodophyllotoxins exert their cytotoxicity via common mechanisms and suggest that the maintenance of normal levels of cellular resistance to these agents requires the products of several different genes.     

Reduced levels of drug-induced DNA cross-linking in nitrogen mustard-resistant Chinese hamster ovary cells expressing elevated glutathione S-transferase activity

We have reported previously (C. N. Robson et al., Cancer Res., 46: 6290-6294, 1986) the isolation of a Chinese hamster ovary cell line, designated CHO-Chlr, that exhibits resistance to bifunctional nitrogen mustards while maintaining the normal parental level of sensitivity to several other alkylating agents. We have compared the rate of formation and repair of DNA cross-links induced by mechlorethamine in CHO-Chlr and parental CHO-K1 cells, both in intact cells and in isolated nuclei. Equimolar doses of mechlorethamine induce significantly fewer DNA interstrand cross-links in CHO-Chlr cells than in CHO-K1 cells, but levels of DNA-protein adducts are approximately equivalent in the two lines. There is a correlation between the relative resistance of CHO-Chlr cells to mechlorethamine (34-fold) and the amount of drug required to induce approximately equal numbers of DNA interstrand cross-links in the two cell lines. This strongly implicates DNA-DNA adducts in the cytotoxic action of mechlorethamine. DNA cross-linking studies on isolated nuclei reveal only minor differences between the two lines even with identical drug treatments. The rate of cross-link repair is comparable in the two cell lines. These results, taken together with our earlier observation that the rate of drug accumulation is identical in these two lines, suggest that enhanced cytoplasmic drug detoxification is the underlying resistance mechanism in CHO-Chlr cells. We have measured cellular glutathione S-transferase activity, using both the general substrate 1-chloro-2,4-dinitrobenzene, and substrates with some specificity for the different classes of transferase isoenzymes. Total enzyme activity (as measured with 1-chloro-2,4-dinitrobenzene) is elevated 3-fold in the resistant cells. A 2- and 5-fold increase, respectively, in activity against ethacrynic acid and cumene hydroperoxide is detectable in CHO-Chlr cells. This elevation in catalytic activity in the resistant cells is reflected in higher levels of both the Yf- and Ya-type transferase subunits.     

The performance of older people on everyday visual asks

The participation rates and performance of 100 elderly subjects on everyday visual tasks were investigated. The Everyday Literacy and Numeracy Assessment (ELNA), which is based on the scenario of going to die doctor and includes 16 real-life tasks, was used to assess performance on reading and writing tasks. More than 50 per cent of the subjects, had some difficulty with 10 of the 16 items on die ELNA, and 20 per cent of subjects were rated as performing inadequately on the ELNA. Small but significant correlations were found between years of schooling and ELNA score, and examiner's ratings of vision, co-ordination and mental ability and ELNA score. Results suggest that a significant proportion of people over die age of 60 have difficulties using everyday printed material. The optometrist should play a larger role within community and wider gerontology teams in assessing everyday visual disability and handicap. In addition, optometrists have an important role in raising community awareness of the visual needs of the elderly.     

A medical ethics issues survey of residents in five pediatric training programs

Few pediatric training programs offer formal instruction or have ethics consultants to assist residents with ethical dilemmas. Moreover, even if such assistance were available, it is not clear that educators have an adequate understanding of (1) the range and frequency of possible ethical dilemmas residents may encounter, (2) residents' most troublesome concerns, (3) their use of resources to resolve issues, and (4) their own ethics belief systems. A sample of convenience (51 residents) at five midsouth residency programs was queried during 25-minute open-ended interviews to answer ethical questions; there were no refusals to participate. The "most troublesome" cases cited by the residents were related to life-and-death issues (withholding and withdrawing life support), child abuse and neglect cases, and disputes regarding patient care that arise between services. Two thirds of those surveyed indicated that they are still somewhat troubled by these difficult ethical problems. Surprisingly, residents stated that they relied on their peers more often than their attending physicians for effective assistance in resolving their most troublesome dilemmas. We support continuing education and research efforts to help residents and educators feel "more comfortable" in resolving ethical dilemmas.     

Early childhood mortality from community-acquired infections.

In this study, the authors identified maternal and child characteristics that were independent predictors of death from infectious diseases acquired in the community and determined if these factors could be used to identify groups of children with excess risk of mortality from infection. A historical cohort study was conducted of children less than 5 years of age between 1985 and 1994 (the study period), who were born in Tennessee, and had complete information on their birth certificates. The primary outcome was death from infection identified from death certificates and confirmed through medical record review. Among the 1,014,976 children less than 5 years of age, who contributed 3,351,568 child-years of follow-up, there were 247 deaths from infections (7.4 deaths from infections per 100,000 child-years). Respiratory infections accounted for approximately one half of the deaths. Children having three or more older siblings or birth weight of less than 1,500 g had a 3-fold and 10-fold increased risk of death from infection, respectively, while children with both characteristics had a nearly 20-fold increased risk that persisted beyond the first year of life. Interventions should be focused on prevention of these infections in vulnerable children. At-risk children should be targeted for careful follow-up and early hospitalization when signs of infection develop.