Translocation breakpoints are clustered on both chromosome 8 and chromosome 21 in the t(8;21) of acute myeloid leukemia

The t(8;21)(q22;q22) is consistently associated with acute myeloid leukemia (AML) M2. Recent data have suggested that breakpoints on chromosome 21 are clustered within a single intron of a novel gene, AML1, just downstream of a region of homology to the runt gene of D melanogaster. In this report, we confirm rearrangement at the same location in at least 12 of 18 patients with t(8;21). Furthermore, we have isolated recombinant clones spanning the breakpoint regions on both the der(8) and the der(21) from one patient. By using a chromosome 8 probe derived from these clones, we show that t(8;21) breakpoints are also clustered on chromosome 8.     

Working memory training and brain structure and function in extremely preterm or extremely low birth weight children

This study in children born extremely preterm (EP; <28 weeks’ gestational age) or extremely low birth weight (ELBW; <1,000 g) investigated whether adaptive working memory training using Cogmed® is associated with structural and/or functional brain changes compared with a placebo program. Ninety‐one EP/ELBW children were recruited at a mean (standard deviation) age of 7.8 (0.4) years. Children were randomly allocated to Cogmed or placebo (45‐min sessions, 5 days a week over 5–7 weeks). A subset had usable magnetic resonance imaging (MRI) data pretraining and 2 weeks posttraining (structural, n = 48; diffusion, n = 43; task‐based functional, n = 18). Statistical analyses examined whether cortical morphometry, white matter microstructure and blood oxygenation level‐dependent (BOLD) signal during an n‐back working memory task changed from pretraining to posttraining in the Cogmed and placebo groups separately. Interaction analyses between time point and group were then performed. There was a significant increase in neurite density in several white matter regions from pretraining to posttraining in both the Cogmed and placebo groups. BOLD signal in the posterior cingulate and precuneus cortices during the n‐back task increased from pretraining to posttraining in the Cogmed but not placebo group. Evidence for group‐by‐time interactions for the MRI measures was weak, suggesting that brain changes generally did not differ between Cogmed and placebo groups. Overall, while some structural and functional MRI changes between the pretraining and posttraining period in EP/ELBW children were observed, there was little evidence of training‐induced neuroplasticity, with changes generally identified in both groups. Trial registration Australian New Zealand Clinical Trials Registry, anzctr.org.au ; ACTRN12612000124831.     

The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection

Aim: To describe gut colonization in preterm infants using standard culture and 16S gene rRNA profiling, exploring differences in healthy infants and those who developed NEC/late onset sepsis (LOS). Methods: Ninety‐nine stools from 38 infants of median 27‐week gestation were cultured; 44 stools from 27 infants had their microbial profiles determined by 16S. Ordination analyses explored effects of patient variables on gut communities. Results: Standard microbiological culture identified a mean of two organisms (range 0–7), DGGE 12 (range 3–18) per patient. Enterococcus faecalis and coagulase negative staphylococci (CONS) were most common by culture (40% and 39% of specimens). Meconium was not sterile. No fungi were cultured. Bacterial community structures in infants with NEC and LOS differed from healthy infants. Infants who developed NEC carried more CONS (45% vs 30%) and less Enterococcus faecalis (31% vs 57%). 16S identified Enterobacter and Staphylococcus presence associated with NEC/LOS, respectively. Conclusions: Important differences were found in the gut microbiota of preterm infants who develop NEC/LOS. The relationship of these changes to current practices in neonatal intensive care requires further exploration.     

The hematopoietic stem cells of alpha-thalassemic mice

The alpha-thalassemic mouse has a hereditary microcytic anemia, almost certainly has a shortened RBC life span, and is a potential candidate for cell replacement therapy. In a routine study of bone marrow repopulating capacity using hemoglobin as a cell marker, normal donor marrow cells, but not alpha-thalassemic donor marrow cells, completely replaced the host cells. Further analysis showed that at least 30 times more alpha-thalassemic cells were required to outcompete normal donor cells injected simultaneously. The results were more extreme then expected and suggested a defect in a stem cell population as well as in the RBCs. Evidence that the multipotent and erythroid-committed stem cells in alpha-thalassemic mice are not decreased was shown by CFU-S and CFU-E assays. The combined results indicate that the deletion expresses itself most conspicuously in the RBC population. Tests were also performed to analyze repopulation kinetics in the Hbath-J/+ mice. In unirradiated alpha-thalassemic hosts, the hemoglobin from a normal donor persisted but did not replace the host hemoglobin. Sublethally irradiated alpha-thalassemic hosts, on the other hand, were easily repopulated with normal cells. We conclude that the alpha-thalassemic mouse is a good model for cell replacement therapy.     

Evaluation design of a reactivation care program to prevent functional loss in hospitalised elderly: A cohort study including a randomised controlled trial

Background

Elderly persons admitted to the hospital are at risk for hospital related functional loss. This evaluation aims to compare the effects of different levels of (integrated) health intervention care programs on preventing hospital related functional loss among elderly patients by comparing a new intervention program to two usual care programs.

Methods/Design

This study will include an effect, process and cost evaluation using a mixed methods design of quantitative and qualitative methods. Three hospitals in the Netherlands with different levels of integrated geriatric health care will be evaluated using a quasi-experimental study design. Data collection on outcomes will take place through a prospective cohort study, which will incorporate a nested randomised controlled trial to evaluate the effects of a stay at the centre for prevention and reactivation for patients with complex problems. The study population will consist of elderly persons (65 years or older) at risk for functional loss who are admitted to one of the three hospitals. Data is prospectively collected at time of hospital admission (T0), three months (T1), and twelve months (T2) after hospital admission. Patient and informal caregiver outcomes (e.g. health related quality of life, activities of daily living, burden of care, (re-) admission in hospital or nursing homes, mortality) as well as process measures (e.g. the cooperation and collaboration of multidisciplinary teams, patient and informal caregiver satisfaction with care) will be measured. A qualitative analysis will determine the fidelity of intervention implementation as well as provide further context and explanation for quantitative outcomes. Finally, costs will be determined from a societal viewpoint to allow for cost effectiveness calculations.

Discussion

It is anticipated that higher levels of integrated hospital health care for at risk elderly will result in prevention of loss of functioning and loss of quality of life after hospital discharge as well as in lower burden of care and higher quality of life for informal caregivers. Ultimately, the results of this study may contribute to the implementation of a national integrated health care program to prevent hospital related functional loss among elderly patients.

Trial registration

The Netherlands National Trial Register: NTR2317     

Marrow harvesting from normal donors

The experience at a single institution in harvesting marrow for allogeneic transplantation on 1,270 occasions from 1,160 normal donors is presented in detail, together with an analysis of all the donor complications. Four donors were less than 2 years old, and the youngest was 6 1/2 months. No special difficulties were encountered with these young donors. Hospitalization time was three days or less for 99% of the procedures. Six donors had life-threatening complications; three of a cardiopulmonary and two of an infectious nature, and one cerebrovascular embolic episode. Significant operative site morbidity, usually transient neuropathies, occurred in ten procedures. Ten percent of the donations were associated with transient postoperative fever of unknown origin. Increasing donor age was associated with a reduction of the cellularity of the marrow harvest. The use of stored autologous blood permitted the avoidance of blood bank transfusion in 81% of males, 69% of females, and 50% of children. It was concluded that the procedure was associated with a very low risk of complication, but that the involvement of normal donors in such an operation justifies stringent monitoring.     

Hair Mercury and Fish Consumption in Residents of O‘ahu,Hawai‘i

Recent studies have established that men are susceptible to cardiotoxicity from methylmercury exposure, which also poses risks to the pregnant woman. Hair samples were obtained and questionnaires for methylmercury exposure assessment were administered to 110 adults (57 men, 53 women) throughout O‘ahu, Hawai‘i during December 2010 to January 2011. Hair samples were analyzed for total mercury with a direct mercury analyzer. Men ≥ 46 years had a median of 2.0 µg/g, which was above the reference dose of 1 µg/g, as compared to younger men with a median 1.0 µg/g (P < 0.05). Hair concentrations from older women had a median of 1.2 µg/g of mercury compared to 0.6 µg/g for younger women. Additionally, 38% of women of childbearing age had a Hazard Index > 1.0. This indicates that both men and women were at risk for excessive methylmercury exposure. In the final regression model, male gender, age > 45 years, length of residency > 10 years in Hawai‘i, and fish consumption frequency > 1 meal per week were significant factors in increased hair mercury levels. Following safe fish consumption practices allows residents to reap health benefits of fish consumption without excessive toxicant exposure.     

Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony- stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte- CSF

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)