CD34+ cells from acute myeloid leukemia, myelodysplastic syndromes, and normal bone marrow display different apoptosis and drug resistance-associated phenotypes.

Myelodysplastic syndromes and acute myeloid leukemia (AML) are heterogeneous disorders in which conflicting results in apoptosis and multidrug resistance (MDR) have been reported. We have evaluated by multiparameter flow cytometry the expression of apoptosis- (APO2.7, bcl-2, and bax) and MDR-related proteins [P-glycoprotein (P-gp), multidrug resistance protein (MRP), and lung resistance protein (LRP)] specifically on bone marrow (BM) CD34+ cells, and their major CD32-/dim and CD32+ subsets, in de novo AML (n=90), high-risk myelodysplastic syndrome (n=9), and low-risk myelodysplastic syndrome (n=21) patients at diagnosis, and compared with normal BM CD34+ cells (n=6). CD34+ myeloid cells from AML and high-risk myelodysplastic syndrome patients displayed higher expression of bcl-2 (P <0.0001) and lower reactivity for APO2.7 (P=0.002) compared with low-risk myelodysplastic syndrome and normal controls. Similar results applied to the two predefined CD34+ myeloid cell subsets. No significant differences were found in the expression of P-gp, MRP, and LRP between low-risk myelodysplastic syndrome patients and normal BM, but decreased expression of MRP (P <0.03) in AML and high-risk myelodysplastic syndromes and P-gp (P=0.008) in high-risk myelodysplastic syndromes were detected. Hierarchical clustering analysis showed that low-risk myelodysplastic syndrome patients were clustered next to normal BM samples, whereas high-risk myelodysplastic syndromes were clustered together and mixed with the de novo AML patients. In summary, increased resistance to chemotherapy of CD34+ cells from both AML and high-risk myelodysplastic syndromes would be explained more appropriately in terms of an increased antiapoptotic phenotype rather than a MDR phenotype. In low-risk myelodysplastic syndromes abnormally high apoptotic rates would be restricted to the CD34- cell compartments.     

Correlates of mammography screening among Hispanic women living in lower Rio Grande Valley farmworker communities.

Factors contributing to the underuse of mammography screening by female Hispanic farmworkers aged 50 years and older in the Lower Rio Grande Valley were determined through home-based, Spanish-language personal interviews (N = 200). Questions covered adherence to screening mammography guidelines (mammogram within 2 years), healthcare access, sociodemographic characteristics, and theoretical constructs related to breast cancer screening in the literature. Multivariate findings indicated that adherent women were 3.6 times more likely to have health insurance. Self-efficacy for obtaining a mammogram and decisional balance were also significantly related to adherence; age, income, and education variables were not associated, perhaps because of restricted variation. Results indicate continuing efforts are needed to ensure that medically underserved migrant farmworker women have access to health care services. In addition, efforts to increase their self-efficacy in obtaining a mammogram and to counter negative attitudes and opinions by stressing the positive prognosis associated with early detection are warranted.     

Smoking, exposure to secondhand smoke, and smoking restrictions in Tijuana, Mexico.

OBJECTIVE: To estimate the prevalence of tobacco use, exposure to secondhand smoke, and smoking restrictions in the home and workplace among residents of Tijuana, one of Mexico's largest cities. METHODS: This cross-sectional household survey was conducted in Tijuana, Baja California, Mexico, during 2003 and 2004. A population-based sample of 400 Tijuana adult residents responded to a tobacco survey, and 397 of the surveys were analyzed. RESULTS: About 22.9% (95% confidence interval (CI): 18.7%-27.1%) of Tijuana adults reported current smoking, and 53.9% (95% CI: 48.8%-58.9%) reported chronic exposure to secondhand smoke. Approximately 44.4% (95% CI: 37.9%-50.9%) of Tijuana adults had a nonsmoking policy in their workplace, while 65.8% (95% CI: 61.0%-70.6%) of Tijuana households were smoke-free. CONCLUSIONS: The results underline the need for increased tobacco control efforts, particularly stricter enforcement of existing passive smoking regulations, in order to expand protection from secondhand smoke from private settings to public ones and to curb the tobacco epidemic in Tijuana and elsewhere in Mexico.     

Phase II study of low-dose decitabine in patients with chronic myelogenous leukemia resistant to imatinib mesylate.

PURPOSE: To determine the activity of decitabine, a DNA methylation inhibitor, in imatinib-refractory or intolerant chronic myelogenous leukemia. MATERIALS AND METHODS: Thirty-five patients were enrolled in this phase II study (12 in chronic phase, 17 in accelerated phase, and six in blastic phase). Decitabine was administered at 15 mg/m2 intravenously over 1 hour daily, 5 days a week for 2 weeks. DNA methylation was measured using a LINE1 bisulfite/pyrosequencing assay. RESULTS: Complete hematologic responses were seen in 12 patients (34%) and partial hematologic responses in seven patients (20%), for an overall hematologic response rate of 54% (83% in chronic phase, 41% in accelerated phase, and 34% in blastic phase). Major cytogenetic responses were observed in six patients (17%), and minor cytogenetic responses were seen in 10 patients (29%) for an overall cytogenetic response rate of 46%. Median response duration was 3.5 months (range, 2 to 13+ months). Myelosuppression was the major adverse effect, with neutropenic fever in 28 (23%) of 124 courses of therapy. LINE1 methylation decreased from 71.3% +/- 1.4% (mean +/- standard error of the mean) to 60.7% +/- 1.4% after 1 week, 50.9% +/- 2.4% after 2 weeks, and returned to 66.5% +/- 2.7% at recovery of counts (median, 46 days). LINE1 methylation at the end of week 1 did not correlate with subsequent responses. However, at day 12, the absolute decrease in methylation was 14.5% +/- 3.0% versus 26.8% +/- 2.7% in responders versus nonresponders (P = .007). CONCLUSION: Decitabine induces hypomethylation and has clinical activity in imatinib refractory chronic myelogenous leukemia. We hypothesize that the inverse correlation between hypomethylation 2 weeks after therapy and response is due to a cell death mechanism of response, whereby resistant cells can withstand more hypomethylation.     

Allogeneic transplant with reduced intensity conditioning regimens may overcome the poor prognosis of B-cell chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene and chromosomal abnormalities (11q- and 17p-).

PURPOSE: To evaluate the efficacy of reduced intensity conditioning (RIC) allogeneic transplant in 30 patients with poor-prognosis chronic lymphocytic leukemia (CLL) and/or high-risk molecular/cytogenetic characteristics. EXPERIMENTAL DESIGN: Eighty-three percent of patients had active disease at the moment of transplant. That is, 14 of the 23 patients analyzed (60%) had unmutated immunoglobulin variable heavy-chain gene (IgV(H)) status; 8 of 25 patients (32%) had 11q-, with four of them also displaying unmutated IgV(H); and six (24%) had 17p- (five were also unmutated). RESULTS: After a median follow-up of 47.3 months, all 22 patients alive are disease free; overall survival and event-free survival (EFS) at 6 years were 70% and 72%, respectively. According to molecular/cytogenetic characteristics, overall survival and EFS for unmutated CLL and/or with 11q- aberration (n = 13) were 90% and 92%, respectively, not significantly different to those with normal in situ hybridization, 13q- and +12, or mutated CLL (n = 7). All six patients with 17p deletion were transplanted with active disease, including three with refractory disease; all except one reached complete remission after the transplant and two are alive and disease free. Nonrelapse mortality (NRM) was 20%; more than two lines before transplant is an independent prognostic factor for NRM (P = 0,02), EFS (P = 0.02), and overall survival (P = 0.01). Patients older than 55 years have a higher risk of NRM (hazard ratio, 12.8; 95% confidence interval, 1.5-111). Minimal residual disease was monitored by multiparametric flow cytometry in 21 patients. Clearance of CD79/CD5/CD19/CD23 cells in bone marrow was achieved in 68% and 94% of the patients at days 100 and 360, respectively. CONCLUSION: According to these results, RIC allogeneic transplant could overcome the adverse prognosis of patients with unmutated CLL as well as those with 11q- or 17p-.     

Oral iron absorption in infantile protein-energy malnutrition.

The ability of infants with protein-energy malnutrition to absorb iron was assessed using the serum iron response to a dose of ferrous sulfate providing 3 mg elemental iron per kg body weight. Responses were grouped as flat (delta serum Fe less than 30 microgram/dl), intermediate (30 to 100 microgram/dl), and normal (greater the 100 microgram/dl). Of 25 consecutively admitted children studied, seven had a flat, five an intermediate, and 13 a normal curve (mean delta serum Fe: 10 microgram/dl, 66 microgram/dl, and 175 microgram/dl, respectively). There were no differences among the three groups in hematocrit, fasting serum iron or transferrin saturation, severity of malnutrition, or evidence of other malabsorption sufficient to explain these differences. Although hematocrits, fasting serum iron, and transferrin saturations did not change appreciably during nutritional rehabilitation, all children with initially abnormal responses subsequently had normal tests.     

Epidemiology of postpartum haemorrhage: a systematic review

Postpartum haemorrhage (PPH) is an important cause of maternal mortality. We conducted a systematic review of the prevalence of PPH with the objective of evaluating its magnitude both globally and in different regions and settings: global figures, as well as regional, country and provincial variations, are likely to exist but are currently unknown. We used prespecified criteria to select databases, recorded the database characteristics and assessed their methodological quality. After establishing PPH (>or=500 mL blood loss) and severe PPH (SSPH) (>or=1000 mL blood loss) as main outcomes, we found 120 datasets (involving a total of 3,815,034 women) that reported PPH and 70 datasets (505,379 women) that reported SPPH in the primary analysis. The prevalence of PPH and SPPH is approximately 6% and 1.86% of all deliveries, respectively, with a wide variation across regions of the world. The figures we obtained give a rough estimate of the prevalence of PPH and suggest the existence of some variations. For a reliable picture of PPH worldwide - its magnitude, distribution and consequences - a global survey tackling this condition is necessary.     

The contribution of birth defects to spontaneous preterm birth

The purpose of this study was to determine if and which birth defects (BDs) are risk factors for spontaneous preterm delivery, and to quantify that risk. A case-control study of spontaneously delivered term (n = 21,093) and preterm (n = 2937; 12.2%) liveborn neonates, between 1996 and 2000, at Ramón Sardá Maternity Hospital of Buenos Aires, was performed. Selected risk factors were compared between term and preterm neonates, and risks of preterm birth in the presence of BDs were evaluated, using stratified and logistic regression analyses. Preterm versus term neonates showed higher rates of most of the selected maternal and neonatal risk factors. The prevalence of BDs among preterm and term neonates was 4.1 and 2.0%, respectively (p < 0.001). Newborns with BDs showed a higher adjusted risk for preterm birth than those without BDs (odds ratio, 2.16; 95% confidence interval, 1.92 to 2.40), with the highest risks for skeletal dysplasias, abdominal wall defects, chromosome, multiple, and minor anomalies. That neonates with BDs are at risk for spontaneous preterm birth, regardless of other factors, should lead to a readjustment of health policies aimed at the reduction of preterm delivery.