The severe combined immunodeficient-human peripheral blood stem cell (SCID-huPBSC) mouse: a xenotransplant model for huPBSC-initiated hematopoiesis

Mononuclear cells (MNCs) containing peripheral blood stem cells (PBSCs) were obtained from solid-tumor patients undergoing mobilizing chemotherapy followed by granulocyte colony-stimulating factor for PBSC transplantation-supported dose-intensified anticancer chemotherapy and were transplanted into unconditioned "nonleaky" young severe combined immunodeficient mice. Multilineage engraftment was shown by flow cytometry and immunocytochemistry using monoclonal antibodies to various human cell surface antigens as well as identification of human immunoglobulin in murine sera. Within a dose range of MNCs suitable for transplantation (10 to 36 x 10(6) cells/graft) the number of CD34+ cells injected (optimal at > 0.7 x 10(6)/graft) determined the yield of human cells produced in recipient animals. Engraftment of hu PBSC preparations resulted in prolonged generation of physiologic levels of human cytokines including interleukin-3 (IL-3), IL-6, and granulocyte- macrophage colony-stimulating factor, which were detectable in the murine blood over a period of at least 4 months. In vivo survival of immature human progenitor cells was preserved even 9 months after transplantation. Because human IL-3 is known to stimulate early hematopoiesis, a rat fibroblast cell line was stably transfected with a retroviral vector carrying the human IL-3 gene and cotransplanted subcutaneously as additional source of growth factor. Cotransplants of this cell line producing sustained in vivo levels of circulating human IL-3 for at least 12 weeks significantly accelerated the process of engraftment of huPBSC and spurred the spread of mature human cells to the murine spleen, liver, thymus, and peripheral blood. Cotransplants of allogeneic human bone marrow stromal cells derived from long-term cultures resulted in a comparable--though less prominent--support of engraftment.     

Bedbug Complaints among Public Housing Residents—New York City, 2010–2011

Few studies have evaluated population-level risk factors for having a bedbug infestation. We describe characteristics associated with bedbug complaints among New York City Housing Authority (NYCHA) residents. Unique households receiving bedbug extermination services in response to a complaint during January 1, 2010 to December 31, 2011 were identified from NYCHA’s central facilities work order database. We examined associations between household characteristics and having a bedbug complaint using a generalized estimating equation Poisson regression model, accounting for clustering by housing development. Of the 176,327 NYCHA households, 11,660 (6.6 %) registered a bedbug complaint during 2010–2011. Bedbug complaints were independently associated with households having five or more children versus no children (prevalence ratio [PR] = 2.0), five or more adults versus one adult (PR = 1.6), a head of household (HOH) with impaired mobility (PR = 1.3), a household member receiving public assistance (PR = 1.2), a household income below poverty level (PR = 1.1), and a female HOH (PR = 1.1). Infestations were less likely to be reported by households with employed members (PR = 0.9), and an HOH aged 30–44 years (PR = 0.9) or 45–61 years (PR = 0.9), compared with an HOH aged 18–29 years. These results indicate that bedbug control efforts in public housing should be targeted toward households with low income and high occupancy.     

Breast Cancer Diagnosis from Screening in Trinidad and Tobago: Opportunities for Cancer Prevention

Trinidad and Tobago (TT) experiences the highest breast cancer mortality in the Caribbean; the distribution of traditional breast cancer risk factors in this population has not been analyzed. Data on women who underwent breast cancer screening at the TT Cancer Society between January 2009–December 2011(N = 2,689) were retrospectively collected. The screening detected 131 incident breast cancers; variables significantly associated with breast cancer diagnosis were, a positive family history of breast cancer (adjusted odds ratio [OR_adj]: 1.55; 95 % CI 1.00–2.41), presence of symptoms (OR_adj: 1.91; 95 % CI 1.25–2.92), and previous breast surgery (OR_adj: 1.67; 95 % CI 0.97–2.88). Breast cancer was significantly associated with increased breast density. Among healthy women, breast density was positively associated with nulliparity (OR_adj: 1.46, 1.37, 2.52 respectively for density level 2, 3 and 4 vs. 1) and previous breast surgeries (OR_adj: 2.27, 3.09 and 4.13 respectively for density level 2, 3 and 4 vs. 1). This analysis confirms that breast density is an important predictor of newly diagnosed breast cancer in this Caribbean population. Screening is still a diagnostic tool rather than a preventive measure in TT.     

Prevalence of blood donation eligibility in Australia: A population survey

Background

Reliable estimates of the population proportion eligible to donate blood are needed by blood collection agencies to model the likely impact of changes in eligibility criteria and inform targeted population-level education, recruitment, and retention strategies. In Australia, the sole estimate was calculated 10+ years ago. With several subsequent changes to the eligibility criteria, an updated estimate is required.

Study Design and Methods

We conducted a cross-sectional national population survey to estimate eligibility for blood donation. Respondents were aged 18+ and resident in Australia. Results were weighted to obtain a representative sample of the population.

Results

Estimated population prevalence of blood donation eligibility for those aged 18–74 was 57.3% (95% CI 55.3–59.3). The remaining 42.7% (95% CI 40.7–44.7) were either temporarily (25.3%, 95% CI 23.5–27.2) or permanently ineligible (17.4%, 95% CI 16.1–18.9). Of those eligible at the time of the survey, that is, with the UK geographic deferral for variant Creutzfeldt-Jakob disease included, (52.9%, 95% CI 50.8–54.9), 14.2% (95% CI 12.3–16.3) reported donating blood within the previous 2 years. Eligibility was higher among men (62.6%, 95% CI 59.6–65.6) than women (52.8%, 95% CI 50.1–55.6). The most common exclusion factor was iron deficiency/anemia within the last 6 months; 3.8% (95% CI 3.2–4.6) of the sample were ineligible due to this factor alone.

Discussion

We estimate that approximately 10.5 million people (57.3% of 18–74-year-olds) are eligible to donate blood in Australia. Only 14.2% of those eligible at the time of survey reported donating blood within the previous 2 years, indicating a large untapped pool of potentially eligible blood donors.     

Consequences of meconium stained amniotic fluid: What does the evidence tell us?

Background

Meconium stained amniotic fluid (MSAF) is common and associated with meconium aspiration syndrome (MAS). Other consequences of meconium passage before birth are less well understood.

Methods

We reviewed the literature for original papers reporting on outcomes associated with MSAF.

Findings

Among preterm infants MSAF is more prevalent than previously believed and is associated with higher neonatal morbidity. Intrauterine exposure to meconium is associated with inflammation of tissues of the lung, chorionic plate and umbilical vessels and through various mechanisms may contribute to neonatal morbidity, independent of MAS. No compelling evidence supported an association between MSAF and increased neurological impairment, including early seizure activity.     

The GLP-2 analogue elsiglutide reduces diarrhoea caused by the tyrosine kinase inhibitor lapatinib in rats

Lapatinib is a small molecule tyrosine kinase inhibitor used to treat breast cancer, often in combination with chemotherapy. Diarrhoea commonly occurs in up to 78% of patients undertaking lapatinib treatment. The mechanism of this diarrhoea is currently unknown. Elsiglutide is a GLP-2 analogue known to increase cell proliferation and reduce apoptosis in the intestine. We used a previously developed rat model of lapatinib-induced diarrhoea to determine if co-treatment with elsiglutide was able to reduce diarrhoea caused by lapatinib. Additionally, we analysed the caecal microbiome of these rats to assess changes in the microbiome due to lapatinib. Rats treated with lapatinib and elsiglutide had less severe diarrhoea than rats treated with lapatinib alone. Serum lapatinib levels, blood biochemistry, myeloperoxidase levels and serum limulus amebocyte lysate levels were not significantly different between groups. Rats treated with lapatinib alone had significantly higher histopathological damage in the ileum than vehicle controls. This increase was not seen in rats also receiving elsiglutide. Rats receiving lapatinib alone had lower microbial diversity than rats who also received elsiglutide. Elsiglutide was able to reduce diarrhoea from lapatinib treatment. This does not appear to be via reduction in inflammation or barrier permeability, and may be due to thickening of mucosa, leading to increased surface area for fluid absorption in the distal small intestine. Microbial changes seen in this study require further research to fully elucidate their role in the development of diarrhoea.