Efficacy and safety profile of amifostine in the preoperative combined therapy of esophageal cancer patients.

The aim of this study was to assess the protective effect and the safety profile of amifostine in 16 esophageal cancer patients undergoing neoadjuvant chemo-radiation therapy (group A) compared to 21 matched patients (group B), treated with the same schedule without receiving amifostine, and considered as controls. Haematological and extra-haematological toxicity were evaluated according to WHO criteria and considered as result of amifostine activity. The bone marrow toxicity was globally lower in group A than in group B. We recorded 4 cases of mucosities in group B compared to 1 case in group A. amifostine-related side effects were few (2 cases of hypotension and 1 of vomiting), mild, and well controlled. In conclusion, amifostine seems to be effective and safe when used as protective agent also in esophageal cancer.

Desferioxamine increases iron depletion and apoptosis induced by ara-C of human myeloid leukaemic cells.

We investigated whether changes in iron metabolism and the transferrin receptor (TRF-R) expression were involved in the antileukaemic effects of arabinoside cytosine (ara-C). Treatment with 100 nM ara-C for 48h reduced thymidine uptake and increased the surface expression of the TRF-R on leukaemic blasts derived from 13/16 (81%) patients and on the HL-60 and U-937 cell lines. Whereas intracellular non-haem iron was strongly depleted 24 h after ara-C addition, TRF-R up-regulation and recovery of intracellular non-haem iron concentration occurred together after a longer exposure of the cultured cells to the drug. Since iron is an essential regulator of cell proliferation we have evaluated the effects of the combination between ara-C and the iron chelator desferioxamine (DSF) on the growth of HL-60 and U-937 cells. We found that desferioxamine strongly potentiated the effects of ara-C on leukaemic cell growth inhibition and apoptosis. This is the first report of a positive interaction between ara-C and an iron chelator in terms of antileukaemic effects.

Biliary sludge and gallstones in pregnancy: incidence, risk factors, and natural history.

OBJECTIVE: To evaluate the incidence and symptoms of and risk factors for biliary sludge and gallstones during pregnancy and to assess the natural history of these conditions in the first year after delivery. DESIGN: Cohort study. PATIENTS: A total of 272 pregnant women recruited in the first trimester. MEASUREMENTS: Biliary sludge and gallstones were diagnosed using ultrasonography, both during pregnancy and after delivery. Predictors of the presence or disappearance of sludge and stones were examined. MAIN RESULTS: Overall, from the first trimester of pregnancy until the immediate postpartum period, 67 women were newly diagnosed with biliary sludge, and 6 women were newly diagnosed with gallstones. The respective incidence rates were 31% (95% Cl, 25% to 37%) and 2% (95% Cl, 0.2% to 4%). During pregnancy, 28% of women experienced biliary pain, which was associated only with presence of stones. After delivery, 92 women had sludge and 23 had stones. Sludge disappeared in 61% of these women (Cl, 50% to 73%) after a mean follow-up of 5 months, and stones disappeared in 28% of women (Cl, 10% to 46%) after 9.7 months of follow-up. CONCLUSIONS: Biliary sludge occurred frequently during pregnancy but was generally asymptomatic and often disappeared spontaneously after delivery. Gallstones were much less frequent and were more likely to be associated with biliary pain.

Prenatal diagnosis of haemoglobin disorders by cordocentesis at 12 weeks' gestation.

Prenatal diagnosis of haemoglobin disorders is accepted to be a useful procedure to avoid births of infants with homozygous diseases. Advances in sampling and molecular techniques, such as polymerase chain reaction (PCR) and chorionic villus sampling (CVS), have made earlier and safer first-trimester prenatal diagnosis possible. However, these procedures need previous studies of at-risk couples, which can be very time-consuming when a number of different beta-thalassaemia mutations occur in the region. We describe the possibility of making a first-trimester prenatal diagnosis by cordocentesis and fetal blood analysis at the 12th week of gestation. We found no statistically significant difference (p greater than 0.05) between beta/gamma values in fetuses at the 12th and 18th weeks of gestation. In seven affected fetuses aborted at the 12th week of gestation, the diagnosis was confirmed in all cases by PCR analysis. These findings suggest that early cordocentesis could be an alternative procedure to CVS and PCR analysis.