Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following myelodysplastic syndrome.

PURPOSE: Promoter hypermethylation of, for example, tumor-suppressor genes, is considered to be an important step in cancerogenesis and a negative risk factor for survival in patients with myelodysplastic syndromes (MDS); however, its role for response to therapy has not been determined. This study was designed to assess the effect of methylation status on the outcome of conventional induction chemotherapy. EXPERIMENTAL DESIGN: Sixty patients with high-risk MDS or acute myeloid leukemia following MDS were treated with standard doses of daunorubicin and 1-beta-d-arabinofuranosylcytosine. Standard prognostic variables and methylation status of the P15(ink4b) (P15), E-cadherin (CDH), and hypermethylated in cancer 1 (HIC) genes were analyzed before treatment. RESULTS: Forty percent of the patients achieved complete remission (CR). CR rate was lower in patients with high WBC counts (P = 0.03) and high CD34 expression on bone marrow cells (P = 0.02). Whereas P15 status alone was not significantly associated with CR rate (P = 0.25), no patient with hypermethylation of all three genes achieved CR (P = 0.03). Moreover, patients with CDH methylation showed a significantly lower CR rate (P = 0.008), and CDH methylation retained its prognostic value also in the multivariate analysis. Hypermethylation was associated with increased CD34 expression, but not with other known predictive factors for response, such as cytogenetic profile. CONCLUSIONS: We show for the first time a significant effect of methylation status on the outcome of conventional chemotherapy in high-risk MDS and acute myelogenous leukemia following MDS. Provided confirmed in an independent study, our results should be used as a basis for therapeutic decision-making in this patient group.     

The impact of maternal experience of violence and common mental disorders on neonatal outcomes: a survey of adolescent mothers in Sao Paulo,Brazil

Background  

Both violence and depression during pregnancy have been linked to adverse neonatal outcomes, particularly low birth weight. The aim of this study was to investigate the independent and interactive effects of these maternal exposures upon neonatal outcomes among pregnant adolescents in a disadvantaged population from Sao Paulo, Brazil.     

Must Macrosomic Fetuses be Delivered by a Caesarean Section? A Review of Outcome for 786 Babies ≥ 4,500 g

Because difficult vaginal delivery is more frequent with macrosomic fetuses, some writers recommend routine Caesarean section for the delivery of fetuses greater than or equal to 4,500 g. The purpose of this study was to evaluate the appropriateness of this recommendation. A retrospective review was undertaken to determine how many fetuses born in our hospital weighing greater than or equal to 4,500 g died or were permanently damaged as a consequence of mechanical difficulties at delivery. During a 10-year period, 590 (75%) of 786 cephalic babies weighing greater than or equal to 4,500 g and alive at the start of labour were born vaginally. No baby died or was permanently damaged as a consequence of mechanical difficulties at delivery. Routine Caesarean section for macrosomic fetuses to prevent death or damage from difficult delivery is not warranted by our results.     

Comparison of an elemental with a hydrolysed whey formula in intolerance to cows' milk

In a double blind study, 40 infants with cows' milk intolerance of various causes were randomised to receive a nutritionally complete formula in which nitrogen was supplied either as whey hydrolysate or amino acids. The median age of infants was 10 weeks (range 36 weeks' gestation to 108 weeks' postnatal age). After a median follow up period of 25 weeks there was no significant difference in dietary intake between the formulas. Twenty four weeks after entry, weight and weight for length improved equally on both formulas. Plasma albumin improved significantly on the hydrolysed whey formula but not in the amino acid group. Both milks were palatable and normal intakes of formula were maintained. Biochemical and haematological indices remained within normal limits. There was no difference in stool frequency and vomiting between the two formulas. Two infants developed a probable allergic colitis while receiving hydrolysed whey. Amino acid formula may have a role in the management of atopic infants with severe cows' milk intolerance who have already reacted to whey or casein hydrolysate formula.