An exploration of socio-economic and food characteristics of high trans fatty acid consumers in the Dutch and UK national surveys after voluntary product reformulation

Trans fatty acids (TFA) increase the risk of mortality and chronic diseases. TFA intakes have fallen since reformulation, but may still be high in certain, vulnerable, groups. This paper investigates socio-economic and food consumption characteristics of high TFA consumers after voluntary reformulation in the Netherlands and UK. Post-reformulation data of adults aged 19–64 was analysed in two national surveys: the Dutch National Food Consumption Survey (DNFCS) collected 2007–2010 using 2*24hr recalls (N = 1933) and the UK National Diet and Nutrition Survey (NDNS) years 3&4 collected 2010/11 and 2011/12 using 4-day food diaries (N = 848). The socio-economic and food consumption characteristics of the top 10% and remaining 90% TFA consumers were compared. Means of continuous data were compared using t-tests and categorical data means using chi-squared tests. Multivariate logistic regression models indicated which socio-demographic variables were associated with high TFA consumption. In the Dutch analyses, women and those born outside the Netherlands were more likely to be top 10% TFA consumers than men and Dutch-born. In the UK unadjusted analyses there was no significant trend in socio-economic characteristics between high and lower TFA consumers, but there were regional differences in the multivariate logistic regression analyses. In the Netherlands, high TFA consumers were more likely to be consumers of cakes, buns & pastries; cream; and fried potato than the remaining 90%. Whereas in the UK, high TFA consumers were more likely to be consumers of lamb; cheese; and dairy desserts and lower crisps and savoury snack consumers. Some socio-demographic differences between high and lower TFA consumers were evident post-reformulation. High TFA consumers in the Dutch 2007–10 survey appeared more likely to obtain TFA from artificial sources than those in the UK survey. Further analyses using more up-to-date food composition databases may be needed

Examining assumptions regarding valid electronic monitoring of medication therapy: development of a validation framework and its application on a European sample of kidney transplant patients

BACKGROUND: Electronic monitoring (EM) is used increasingly to measure medication non-adherence. Unbiased EM assessment requires fulfillment of assumptions. The purpose of this study was to determine assumptions needed for internal and external validity of EM measurement. To test internal validity, we examined if (1) EM equipment functioned correctly, (2) if all EM bottle openings corresponded to actual drug intake, and (3) if EM did not influence a patient's normal adherence behavior. To assess external validity, we examined if there were indications that using EM affected the sample representativeness. METHODS: We used data from the Supporting Medication Adherence in Renal Transplantation (SMART) study, which included 250 adult renal transplant patients whose adherence to immunosuppressive drugs was measured during 3 months with the Medication Event Monitoring System (MEMS). Internal validity was determined by assessing the prevalence of nonfunctioning EM systems, the prevalence of patient-reported discrepancies between cap openings and actual intakes (using contemporaneous notes and interview at the end of the study), and by exploring whether adherence was initially uncharacteristically high and decreased over time (an indication of a possible EM intervention effect). Sample representativeness was examined by screening for differences between participants and non-participants or drop outs on non-adherence. RESULTS: Our analysis revealed that some assumptions were not fulfilled: 1) one cap malfunctioned (0.4%), 2) self-reported mismatches between bottle openings and actual drug intake occurred in 62% of the patients (n = 155), and 3) adherence decreased over the first 5 weeks of the monitoring, indicating that EM had a waning intervention effect. CONCLUSION: The validity assumptions presented in this article should be checked in future studies using EM as a measure of medication non-adherence

Comparing the Epidermal Growth Factor Interaction with Four Different Cell Lines: Intriguing Effects Imply Strong Dependency of Cellular Context

The interaction of the epidermal growth factor (EGF) with its receptor (EGFR) is known to be complex, and the common over-expression of EGF receptor family members in a multitude of tumors makes it important to decipher this interaction and the following signaling pathways. We have investigated the affinity and kinetics of 125I-EGF binding to EGFR in four human tumor cell lines, each using four culturing conditions, in real time by use of LigandTracer®

The in vitro effect of gefitinib ('Iressa') alone and in combination with cytotoxic chemotherapy on human solid tumours

BACKGROUND: Activation of the epidermal growth factor receptor (EGFR) triggers downstream signaling pathways that regulate many cellular processes involved in tumour survival and growth. Gefitinib ('Iressa') is an orally active tyrosine kinase inhibitor (TKI) targeted to the ATP-binding domain of EGFR (HER1; erbB1). METHODS: In this study we have used a standardised ATP-based tumour chemosensitivity assay (ATP-TCA) to measure the activity of gefitinib alone or in combination with different cytotoxic drugs (cisplatin, gemcitabine, oxaliplatin and treosulfan) against a variety of solid tumours (n = 86), including breast, colorectal, oesophageal and ovarian cancer, carcinoma of unknown primary site, cutaneous and uveal melanoma, non-small cell lung cancer (NSCLC) and sarcoma. The IC50 and IC90 were calculated for each single agent or combination. To allow comparison between samples the Index(SUM )was calculated based on the percentage tumour growth inhibition (TGI) at each test drug concentration (TDC). Gefitinib was tested at concentrations ranging from 0.0625–2 microM (TDC = 0.446 microg/ml). This study represents the first use of a TKI in the assay. RESULTS: There was heterogeneity in the degree of TGI observed when tumours were tested against single agent gefitinib. 7% (6/86) of tumours exhibited considerable inhibition, but most showed a more modest response resulting in a low TGI. The median IC50 value for single agent gefitinib in all tumours tested was 3.98 microM. Interestingly, gefitinib had both positive and negative effects when used in combination with different cytotoxics. In 59% (45/76) of tumours tested, the addition of gefitinib appeared to potentiate the effect of the cytotoxic agent or combination (of these, 11% (5/45) had a >50% decrease in their Index(SUM)). In 38% of tumours (29/76), the TGI was decreased when the combination of gefitinib + cytotoxic was used in comparison to the cytotoxic alone. In the remaining 3% (2/76) there was no change observed. CONCLUSION: The in vitro model suggests that gefitinib may have differential effects in response to concomitant cytotoxic chemotherapy with the agents tested during this study. The mechanism involved may relate to the effect of TKIs on growth rate versus their effect on the ability of the cell to survive the stimulus to apoptosis produced by chemotherapy

Relative fat oxidation is higher in children than adults

Background: Prepubescent children may oxidize fatty acids more readily than adults. Therefore, dietary fat needs would be higher for children compared with adults. The dietary fat recommendations are higher for children 4 to 18 yrs (i.e., 25 to 35% of energy) compared with adults (i.e., 20 to 35% of energy). Despite this, many parents and children restrict dietary fat for health reasons. Methods: This study assessed whether rates of fat oxidation are similar between prepubescent children and adults. Ten children (8.7 ± 1.4 yr, 33 ± 13 kg mean ± SD) in Tanner stage 1 and 10 adults (41.6 ± 8 yr, 74 ± 13 kg) were fed a weight maintenance diet for three days to maintain body weight and to establish a consistent background for metabolic rate measurements (all foods provided). Metabolic rate was measured on three separate occasions before and immediately after breakfast and for 9 hrs using a hood system (twice) or a room calorimeter (once) where continuous metabolic measurements were taken. Results: During all three sessions whole body fat oxidation was higher in children (lower RQ) compared to adults (mean RQ= 0.84 ± .016 for children and 0.87 ± .02, for adults, p < 0.02). Although, total grams of fat oxidized was similar in children (62.7 ± 20 g/24 hrs) compared to adults (51.4 ± 19 g/24 hrs), the grams of fat oxidized relative to calorie expenditure was higher in children (0.047 ± .01 g/kcal, compared to adults (0.032 ± .01 p < 0.02). Females oxidized more fat relative to calorie expenditure than males of a similar age. A two way ANOVA showed no interaction between gender and age in terms of fax oxidation. Conclusion: These data suggest that fat oxidation relative to total calorie expenditure is higher in prepubescent children than in adults. Consistent with current dietary guidelines, a moderate fat diet is appropriate for children within the context of a diet that meets their energy and nutrient needs. Originally published Nutrition Journal, Vol. 6, No. 19, Aug 200

EGFR-specific T cell frequencies correlate with EGFR expression in head and neck squamous cell carcinoma

Background\ud In head and neck squamous cell carcinoma (HNSCC), expression levels of the epidermal growth factor receptor (EGFR) correlate with poor prognosis and decreased survival rates. As the mechanisms responsible for cellular immune response to EGFR in vivo remain unclear, the frequency and function of EGFR-specific cytotoxic T cells (CTL) was determined in HNSCC patients.\ud \ud Methods\ud The frequency of CTL specific for the HLA-A2.1-restricted EGFR-derived YLN peptide (YLNTVQPTCV) and KLF peptide (KLFGTSGQKT) was determined in 16 HLA-A2.1+ HNSCC patients and 16 healthy HLA-A2.1+ individuals (NC) by multicolor flow cytometry. Patients' results were correlated to EGFR expression obtained by immunohistochemistry in corresponding tumor sections. Proliferation and anti-tumor activity of peptide-specific CTL was demonstrated by in vitro stimulation with dendritic cells pulsed with the peptides.\ud \ud Results\ud Frequency of EGFR-specific CTL correlated significantly with EGFR expression in tumor sections (p = 0.02, r2 = 0.6). Patients with elevated EGFR scores (> 7) had a significantly higher frequency of EGFR-specific CTL than NC and patients with low EGFR scores (< 7). EGFR-specific CTL from cancer patients were expanded ex vivo and produced IFN-γ upon recognition of EGFR+ target cells.\ud \ud Conclusion\ud EGFR expressed on HNSCC cells induces a specific immune response in vivo. Strategies for expansion of EGFR-specific CTL may be important for future immunotherapy of HNSCC patients