Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL)

The best strategy for incorporating imatinib in front-line treatment of Ph+ acute lymphoblastic leukemia (ALL) has not been established. We enrolled 92 patients with newly diagnosed Ph+ ALL in a prospective, multicenter study to investigate sequentially 2 treatment schedules with imatinib administered concurrent to or alternating with a uniform induction and consolidation regimen. Coadministration of imatinib and induction cycle 2 (INDII) resulted in a complete remission (CR) rate of 95% and polymerase chain reaction (PCR) negativity for BCR-ABL in 52% of patients, compared with 19% in patients in the alternating treatment cohort (P = .01). Remarkably, patients with and without a CR after induction cycle 1 (INDI) had similar hematologic and molecular responses after concurrent imatinib and INDII. In the concurrent cohort, grades III and IV cytopenias and transient hepatotoxicity necessitated interruption of induction in 87% and 53% of patients, respectively; however, duration of induction was not prolonged when compared with patients receiving chemotherapy alone. No imatinib-related severe hematologic or nonhematologic toxicities were noted with the alternating schedule. In each cohort, 77% of patients underwent allogeneic stem cell transplantation (SCT) in first CR (CR1). Both schedules of imatinib have acceptable toxicity and facilitate SCT in CR1 in the majority of patients, but concurrent administration of imatinib and chemotherapy has greater antileukemic efficacy.     

Effect of Selenium and Vitamin E Supplementation on Plasma Protein Carbonyl Levels in Patients With Arsenic-Related Skin Lesions

An estimated 35 million people in Bangladesh have been chronically exposed to arsenic in drinking water and are at risk of an array of adverse health conditions. The mechanisms of arsenic toxicity have not been well established; however, oxidative stress has been one commonly proposed pathway. In this study, we evaluated the effect of antioxidant supplementation on plasma protein oxidation among patients with arsenical skin lesions participating in a randomized double-blinded placebo-controlled trial of vitamin E and selenium. Subjects were randomized to 1 of 4 treatments arms (vitamin E, selenium, combination, or placebo) and were treated for a 6-mo period. We observed a dose-dependent increase in adjusted protein carbonyl levels by arsenic exposure status in the pretreatment samples, although trends were not statistically significant. Following the 6-mo intervention, there was a decrease in protein carbonyl levels in each treatment group, although no resultant decrease was significantly different from that seen in the placebo group. Although we did not see a notable effect of selenium or vitamin E supplementation on changes in protein carbonyl levels, these preliminary data demonstrate a feasible methodological approach for the assessment of plasma protein carbonyls in relation to environmental toxicants in a human population and their potential use as endpoints in intervention trials.     

Allicin Purified From Fresh Garlic Cloves Induces Apoptosis in Colon Cancer Cells Via Nrf2

Allicin (diallyl thiosulfinate) is the best-known biologically active component in freshly crushed garlic extract. We developed a novel, simple method to isolate active allicin, which yielded a stable compound in aqueous solution amenable for use in in vitro and in vivo studies. We focused on the in vitro effects of allicin on cell proliferation of colon cancer cell lines HCT-116, LS174T, HT-29, and Caco-2 and assessed the underlying mechanisms. This allicin preparation exerted a time- and dose-dependent cytostatic effect on these cells at concentrations ranging from 6.2 to 310 μM. Treatment with allicin resulted in HCT-116 apoptotic cell death as demonstrated by enhanced hypodiploid DNA content, decreased levels of B-cell non-Hodgkin lymphoma-2 (Bcl-2), increased levels of bax and increased capability of releasing cytochrome c from mitochondria to the cytosol. Allicin also induced translocation of NF-E2-related factor-2 (Nrf2) to the nuclei of HCT-116 cells. Luciferase reporter gene assay showed that allicin induces Nrf2-mediated luciferase transactivation activity. SiRNA knock down of Nrf2 significantly affected the capacity of allicin to inhibit HCT-116 proliferation. These results suggest that Nrf2 mediates the allicin-induced apoptotic death of colon cancer cells.     

Factors Associated with Prenatal Care and Seeking Assistance in Public Hospitals in Vitória,Espírito Santo,Brazil

Adequate prenatal care provides an opportunity for counseling and reducing the complications associated with pregnancy and delivery. Our objective was to describe the demographic, behavioral, and clinical profile of the pregnant women hospitalized at public maternity hospitals and to identify factors associated with six or more prenatal consultations in Vitória, Brazil. A cross-sectional study of 1,380 women was conducted in public maternity hospitals in Vitória, Brazil. Sixty-seven percent of participants had ≥6 prenatal consultations. Reasons for hospitalization were vaginal delivery (55.7%), cesarean section (32.9%), clinical treatment (7.7%), and abortion/miscarriage (3.7%). Having ≥9 years of schooling (odds ratio, OR = 1.8; 95% confidence interval, CI: 1.1–3.1), being married (OR = 1.9; 95% CI: 1.2–2.9) and delivering at term (OR = 3.6; 95% CI: 1.6–8.2) were significantly independently associated with having ≥6 prenatal consultations. Although higher education, being married, and delivering at term were associated with ≥6 prenatal consultations in this population, the high rate of Cesarean sections demonstrates the need for ongoing educative strategies among health professionals.     

Nutritional risk among Brazilian children 2 to 6 years old: A multicenter study

ObjectiveTo estimate the nutritional risk in children 2 to 6 y old.MethodsThe sample consisted of 3058 children enrolled in public and private schools in nine Brazilian cities. The assessment of nutrient intake was based on 1-d data combining direct individual weighing of foods and a food diary. A second evaluation of food consumption was conducted in a subsample to estimate the usual intake.ResultsThere was low prevalence of inadequate intake of vitamin B6 (<0.001%), riboflavin (<0.001%), niacin (<0.001%), thiamin (<0.001%), folate (<0.001%), phosphorus (<0.1%), magnesium (<0.1%), iron (<0.5%), copper (<0.001%), zinc (<0.5%), and selenium (<0.001%). However, 22% of children younger than 4 y and 5% of children older than 4 y consumed fiber quantities larger than the adequate intake. Approximately 30% of the sample consumed more saturated fat than recommended. The prevalence of inadequate vitamin E intake ranged from 15% to 29%. More than 90% of the children had an inadequate vitamin D intake. In children older than 4 y, the prevalence of inadequate calcium intake was approximately 45%. Sodium intake was higher than the upper intake level in 90% of children younger than 4 y and 73% of children older than 4 y.ConclusionsThe prevalence of inadequate dietary intake was low for most nutrients. However, fiber, calcium, and vitamin D and E intakes were lower than recommended. Moreover, children consumed large amounts of sodium and saturated fat.     

Center of pressure and the projection of the time-course of sitting skill acquisition

A normal time-course for the acquisition of sitting is essential. A delay in sitting may affect other developmental milestones, resulting in deficiencies in overall skill. Therefore, our aim was to identify variables whose measures at the very beginning of sitting would allow for the projection of the evolution of the sitting skill. Center of pressure data were collected from the postural sway of twenty-six typically developing infants while sitting on a force platform with a beginning ability to sit upright. Spatial, temporal and frequency variables of postural sway were obtained from both the medial/lateral and anterior/posterior directions of sway. Discriminant function analysis was conducted to identify potential predictors of the duration between onset and fully independent sitting. Gender (p = 0.025), median frequency (p = 0.006), and correlation dimension (p = 0.002) were identified to be predictive of grouping with 73.1% correct classification of the participating infants into short, mid, and long delay groups. In conclusion, measures taken at the earliest stage of sitting may allow the projection of the time-course to achieve independent sitting for typical infants. This approach may be useful for monitoring typical development.     

Trends in bacterial resistance in a tertiary university hospital over one decade

The objective of this study was to investigate bacterial resistance trends, infection sites and the relationship between resistance and admittance to the intensive care unit (ICU). A total of 53,316 bacteria identified between 1999 and 2008 were evaluated. Multidrug resistance was characterized when gram-negative bacilli (GNB) presented resistance to two or more classes of antibiotics. Gram-positive cocci (CPC) were assessed for resistance to penicillin, oxacillin and vancomycin. GNB were the most common (66.1%) isolate. There was a 3.7-fold overall increase in multidrug resistant GNB over the study period; Acinetobacter baumanii and Staphylococcus aureus were the most prevalent. Highest increases were recorded for Klebsiella pneumoniae (14.6-fold) and enterococci (73-fold). The resistance rates for GNB and GPC were 36% and 51.7%, respectively. Most multidrug resistant GNB and GPC were recovered from ICU patients (p-value < 0.001). Vancomycin-resistant enterococci were isolated during this decade with an increase of 18.7% by 2008. These data confirm the worldwide trend in multidrug bacterial resistance.     

Ambulatory education in the internal medicine clerkship at Southern Illinois University school of medicine

The Internal Medicine Clerkship at Southern Illinois University has included an ambulatory experience in its curriculum for 3 years. Six students at a time rotate through the required 3‐week ambulatory block; this block is repeated three times during the 11‐week Internal Medicine Clerkship so that all 18 students each clerkship are accommodated. The schedule provides students with extensive clinical exposure in a variety of ambulatory settings and includes formal educational activities such as small‐group seminars on ambulatory topics and a workshop utilizing standardized patients in outpatient settings. In their evaluations of the ambulatory experience, more than half the students felt the ambulatory block made them more positive about the specialty of internal medicine. Despite many barriers to ambulatory education, including the burden imposed on faculty time and the strain on office productivity, the quality of education in the ambulatory setting has improved, and students have prospered. Future directions for the ambulatory experience include modifying the structure to include a longitudinal experience. It is hoped that, by implementing a longitudinal clinic experience, students will become comfortable in a particular office environment and will have a better opportunity to function as a productive member of a health care team.