Predictors of survival and toxicity in patients on adjuvant therapy with 5-fluorouracil for colorectal cancer.

The present study aimed at investigating whether the simultaneous evaluation of pharmacokinetic, pharmacogenetic and demographic factors could improve prediction on toxicity and survival in colorectal cancer patients treated with adjuvant 5-fluorouracil (5FU)/leucovorin therapy. One hundred and thirty consecutive, B2 and C Duke's stage colorectal cancer patients were prospectively enrolled. 5FU pharmacokinetics was evaluated at the first cycle. Thymidylate synthase (TYMS) 5'UTR and 3'UTR polymorphisms and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms were assessed in peripheral leukocytes. Univariate and multivariate analyses were applied to evaluate which variables could predict chemotherapy-induced toxicity, disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed that: (a) low 5FU clearance was an independent predictive factor for severe toxicity (OR=7.32; P<0.0001); (b) high-5FU clearance predicted poorer DFS (HR=1.96; P=0.041) and OS (HR=3.37; P=0.011); (c) advanced age was associated with shorter DFS (HR=3.34; P=0.0008) and OS (HR=2.66; P=0.024); (d) the C/C genotype of the MTHFR C677T polymorphism was protective against grade 3-4 toxicity (P=0.040); (e) none of the TYMS polymorphisms could explain 5FU toxicity or clinical outcome.

A novel G/C single-nucleotide polymorphism in the double 28-bp repeat thymidylate synthase allele.

Thymidylate synthase (TYMS) is the main molecular target for fluoropyrimidine anticancer drugs, and its expression has been correlated with the number of repeats of a 28-bp sequence in the 5'-untranslated region of the TYMS gene and with the presence of a G --> C single-nucleotide polymorphism in the second repeat of 3R alleles. Based on this double polymorphism, three main TYMS alleles have so far been identified: TYMS 2R, TYMS 3RC and TYMS 3RG. During genetic analysis of TYMS polymorphisms in 100 colorectal cancer patients, three patients revealed an unexpected 113-bp band after electrophoresis of the restriction fragment length polymorphism analysis. Subsequent sequencing revealed two 28-bp repeats in the 5'-untranslated region and the presence in both repeats of cytosine instead of guanine at the 12th nucleotide. This allele variant (TYMS 2RC) has not been previously described in man. All three patients were heterozygotes for TYMS 2RC and experienced grade 2-3 chemotherapy-related toxicity.

Evaluation of microcomputer nutritional teaching games in 1,876 children at school.

OBJECTIVE: We evaluated in a prospective study microcomputer nutritional teaching games and their contribution to the children's acquisition of nutritional knowledge and improvement of eating habits. MATERIAL AND METHODS: One thousand eight hundred seventy-six children aged 7-12 years took part in this study at school. All 16 schools of the same school district were randomized into two groups: games group and control group, both receiving conventional nutritional teaching by their teachers. The children in the games group played computer games during the conventional nutritional teaching period (2 hours a week for 5 weeks). At completion of the study, dietetic knowledge and dietary records were evaluated in both groups. RESULTS: Dietary knowledge tests results were better in the games group (p<0.001). The children in the games group had a significantly better balanced diet for an energy intake of about 1900 kilocalories: more carbohydrate (46.4 +/- 0.2% vs 45.7 +/- 0.2%, p<0.05), less fat (37.1 +/- 0.1% vs 37.6 +/- 0.2%, p<0.05), less protein (16.5 +/- 0.1% vs 16.7 +/- 0.1%, p<0.05), less saccharose (11.5 +/- 0.1% vs 12.2 +/- 0.2%, p<0.001), more calcium (p<0.001) and more fiber (p<0.05). The games group had a better snack at 10 a.m., a less copious lunch and less nibbling (p<0.001). CONCLUSION: The children in the games group had slightly but significantly better nutritional knowledge and dietary intake compared to children in the control group. Using our micro computer nutritional teaching games at school provides an additional and modern support to conventional teaching.

Multicenter randomized evaluation of a nutritional education software in obese patients.

OBJECTIVE: To study the efficacy of the nutritional education software, Nutri-Expert, in the management of obese adult patients. MATERIAL AND METHODS: Two groups of obese patients were followed up over one year in a randomized study: the first group received close traditional management (seven nutritional visits over the year, with physicians and dietitians conjointly) and the second one also used at home by Minitel the Nutri-Expert system. 557 patients were enrolled in the study by 16 French centers of diabetology and nutrition. Body mass index (BMI), tests of dietetic knowledge, dietary records and centralized biological measurements were assessed at inclusion, 6 and 12 months. 341 patients were evaluable at the end of the year. RESULTS: The group using Nutri-Expert scored significantly better in the tests of dietetic knowledge than the control group. For all patients, nutritional education led to a significant improvement in BMI, dietary records and biological measurements, without significant difference between the two groups. Five years after the end of the study, the weight of 148 patients was recorded; mean BMI was significantly lower than the initial value but there was no significant difference between the two groups. CONCLUSION: In the management of obese patients, Nutri-Expert system has a role to play in reinforcing nutritional knowledge; if regular follow-up is not possible, or if a large series of obese patients is to be treated, Nutri-Expert could partly replace traditional management, for example between visits.

Quantitative analysis of ribonucleoside triphosphates in human lymphoid cells by micellar electrokinetic capillary chromatography.

Micellar electrokinetic capillary chromatography (MECC) was applied to develop an analytical method for quantitation of ribonucleoside triphosphates (rNTPs) in human lymphoid cells obtained from patients with B-chronic lymphocytic leukaemia (B-CLL) and cutaneous lymphomas. The results of this analysis showed a significant depression of intracellular rNTPs in patients with B-CLL, compared with rNTPs of healthy controls. These data are in agreement with other studies in which rNTP separations were performed with traditional high-performance liquid chromatography. MECC has proved to be a useful tool for intracellular rNTPs determination, revealing possible new applications in the study of the metabolic state of human cells. In addition, this method can be useful in monitoring the effect of many drugs (antiviral, antineoplastic) which interfere with nucleotide metabolism.