The effect of modern intensive monitoring in obstetrics on infant mortality and the incidence of hypoxia and acidosis

Peer Reviewe

Hospitalizations and Costs Incurred at the Facility Level After Scale-Up of Malaria Control: Pre-Post Comparisons From Two Hospitals in Zambia

There is little evidence on the impact of malaria control on the health system, particularly at the facility level. Using retrospective, longitudinal facility-level and patient record data from two hospitals in Zambia, we report a pre-post comparison of hospital admissions and outpatient visits for malaria and estimated costs incurred for malaria admissions before and after malaria control scale-up. The results show a substantial reduction in inpatient admissions and outpatient visits for malaria at both hospitals after the scale-up, and malaria cases accounted for a smaller proportion of total hospital visits over time. Hospital spending on malaria admissions also decreased. In one hospital, malaria accounted for 11% of total hospital spending before large-scale malaria control compared with \u3c 1% after malaria control. The findings demonstrate that facility-level resources are freed up as malaria is controlled, potentially making these resources available for other diseases and conditions

Hypoxia inducible factor 1α gene (HIF-1α) splice variants: potential prognostic biomarkers in breast cancer

<p>Abstract</p> <p>Background</p> <p>Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator of genes regulating oxygen homeostasis. The HIF-1 protein is composed of two HIF-1α and HIF-1β/aryl hydrocarbon receptor nuclear translocator (ARNT) subunits. The prognostic relevance of HIF-1α protein overexpression has been shown in breast cancer. The impact of HIF-1α alternative splice variant expression on breast cancer prognosis in terms of metastasis risk is not well known.</p> <p>Methods</p> <p>Using real-time quantitative reverse transcription PCR assays, we measured mRNA concentrations of total <it>HIF-1α </it>and 4 variants in breast tissue specimens in a series of 29 normal tissues or benign lesions (normal/benign) and 53 primary carcinomas. In breast cancers <it>HIF-1α </it>splice variant levels were compared to clinicopathological parameters including tumour microvessel density and metastasis-free survival.</p> <p>Results</p> <p><it>HIF-1α </it>isoforms containing a three base pairs TAG insertion between exon 1 and exon 2 (designated <it>HIF-1α</it>^<it>TAG</it>) and <it>HIF-1α</it>^{<it>736 </it>}mRNAs were found expressed at higher levels in oestrogen receptor (OR)-negative carcinomas compared to normal/benign tissues (<it>P </it>= 0.009 and <it>P </it>= 0.004 respectively). In breast carcinoma specimens, lymph node status was significantly associated with <it>HIF-1α</it>^{<it>TAG </it>}mRNA levels (<it>P </it>= 0.037). Significant statistical association was found between tumour grade and <it>HIF-1α</it>^{<it>TAG </it>}(<it>P </it>= 0.048), and total <it>HIF-1α </it>(<it>P </it>= 0.048) mRNA levels. <it>HIF-1α</it>^{<it>TAG </it>}mRNA levels were also inversely correlated with both oestrogen and progesterone receptor status (<it>P </it>= 0.005 and <it>P </it>= 0.033 respectively). Univariate analysis showed that high <it>HIF-1α</it>^{<it>TAG </it>}mRNA levels correlated with shortened metastasis free survival (<it>P </it>= 0.01).</p> <p>Conclusions</p> <p>Our results show for the first time that mRNA expression of a <it>HIF-1α</it>^{<it>TAG </it>}splice variant reflects a stage of breast cancer progression and is associated with a worse prognosis.</p> <p>See commentary: <url>http://www.biomedcentral.com/1741-7015/8/45</url></p

Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms: a joint European LeukemiaNet/MPN&amp;MPNr-EuroNet (COST action BM0902) study

Item does not contain fulltextReliable detection of JAK2-V617F is critical for accurate diagnosis of myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific assays can be applied to monitor disease response. However, there has been no consistent approach to JAK2-V617F detection, with assays varying markedly in performance, affecting clinical utility. Therefore, we established a network of 12 laboratories from seven countries to systematically evaluate nine different DNA-based quantitative PCR (qPCR) assays, including those in widespread clinical use. Seven quality control rounds involving over 21,500 qPCR reactions were undertaken using centrally distributed cell line dilutions and plasmid controls. The two best-performing assays were tested on normal blood samples (n=100) to evaluate assay specificity, followed by analysis of serial samples from 28 patients transplanted for JAK2-V617F-positive disease. The most sensitive assay, which performed consistently across a range of qPCR platforms, predicted outcome following transplant, with the mutant allele detected a median of 22 weeks (range 6-85 weeks) before relapse. Four of seven patients achieved molecular remission following donor lymphocyte infusion, indicative of a graft vs MPN effect. This study has established a robust, reliable assay for sensitive JAK2-V617F detection, suitable for assessing response in clinical trials, predicting outcome and guiding management of patients undergoing allogeneic transplant

Successful treatment of a chronic-phase T-315I-mutated chronic myelogenous leukemia patient with a combination of imatinib and interferon-alfa

The T315I BCR-ABL mutation in chronic myelogenous leukemia (CML) patients is responsible for up to 20% of all clinically observed resistance. This mutation confers resistance not only to imatinib, but also to second-generation BCR-ABL tyrosine kinases, such as nilotinib and dasatinib. A number of strategies have been implemented to overcome this resistance, but allogeneic stem cell transplantation remains the only established therapeutic option for a cure. A 61-year-old male was diagnosed with Philadelphia chromosome-positive chronic-phase CML in 2002. He was initially treated with imatinib and complete cytogenetic response (CCyR) was achieved 12 months later. However, after 18 months, a loss of CCyR was observed and a molecular study at 24 months revealed a T315I mutation of the BCR-ABL gene. At 30 months, imatinib/interferon-alfa (IFNα) combination therapy was initiated in an effort to overcome the resistance. Thirty months later, he re-achieved CCyR, and the T315I BCR-ABL mutation disappeared at 51 months. To our knowledge, this is the first case report showing the effectiveness of imatinib/IFNα combination therapy for CML patients bearing the T315I BCR-ABL mutation