Mobilization of early hematopoietic progenitor cells with BB-10010: a genetically engineered variant of human macrophage inflammatory protein- 1 alpha

BB-10010 is a genetically engineered variant of human macrophage inflammatory protein-1 alpha with improved solution properties. We show here that it mobilizes stem cells into the peripheral blood. We investigated the mobilizing effects of BB-10010 on the numbers of circulating 8-day spleen colony-forming units (CFU-S8), CFU-S12, and progenitors with marrow repopulating ability (MRA). A single subcutaneous dose of BB-10010 caused a twofold increase in circulating numbers of CFU-S8, CFU-S12, and MRA 30 minutes after dosing. We also investigated the effects of granulocyte colony-stimulating factor (G- CSF) and the combination of G-CSF with BB-10010 on progenitor mobilization. Two days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA progenitors by 25.7-, 19.8-, and 27.7-fold. A single administration of BB-10010 after 2 days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA even further to 38-, 33-, and 100- fold. Splenectomy resulted in increased circulating progenitor numbers but did not change the pattern of mobilization. Two days of treatment with G-CSF then increased circulating CFU-S8, CFU-S12, and MRA by 64-, 69-, and 32-fold. A single BB-10010 administration after G-CSF treatment further increased them to 85-, 117-, and 140-fold, respectively, compared with control. We conclude that BB-10010 causes a rapid increase in the number of circulating hematopoietic progenitors and further enhances the numbers induced by pretreatment with G-CSF. BB- 10010 preferentially mobilized the more primitive progenitors with marrow repopulating activity, releasing four times the number achieved with G-CSF alone. Translated into a clinical setting, this improvement in progenitor cell mobilization may enhance the efficiency of harvest and the quality of grafts for peripheral blood stem cell transplantation.     

Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium

Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator- inhibitor. High concentrations of thrombin-but not of factor Xa or IXa-- had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor.     

Optimal management strategies for placenta accreta

Objective  To determine which interventions for managing placenta accreta were associated with reduced maternal morbidity.
Design  Retrospective cohort study.
Setting  Two tertiary care teaching hospitals in Utah.
Population  All identified cases of placenta accreta from 1996 to 2008.
Methods  Cases of placenta accreta were identified using standard ICD-9 codes for placenta accreta, placenta praevia, and caesarean hysterectomy. Medical records were then abstracted for maternal medical history, hospital course, and maternal and neonatal outcomes. Maternal and neonatal complications were compared according to antenatal suspicion of accreta, indications for delivery, preoperative preparation, attempts at placental removal before hysterectomy, and hypogastric artery ligation.
Main outcome measures  Early morbidity (prolonged maternal intensive care unit admission, large volume of blood transfusion, coagulopathy, ureteral injury, or early re-operation) and late morbidity (intra-abdominal infection, hospital re-admission, or need for delayed re-operation).
Results  Seventy-six cases of placenta accreta were identified. When accreta was suspected, scheduled caesarean hysterectomy without attempting placental removal was associated with a significantly reduced rate of early morbidity compared with cases in which placental removal was attempted (67 versus 36%, P = 0.038). Women with preoperative bilateral ureteric stents had a lower incidence of early morbidity compared with women without stents (18 versus 55%, P = 0.018). Hypogastric artery ligation did not reduce maternal morbidity.
Conclusions  Scheduled caesarean hysterectomy with preoperative ureteric stent placement and avoiding attempted placental removal are associated with reduced maternal morbidity in women with suspected placenta accreta.     

Nursing prioritization of the patient need for care: A tacit knowledge embedded in the clinical decision-making literature

Every day in clinical settings, nurses practise in complex and dynamic situations. Nurses work to achieve emergent order in these situations through nursing prioritization of the patient need for care. As direct research on nursing prioritization had not been reported, a study, using critical realism as method, was designed to discern the profession's embedded understanding from within the clinical decision-making literature. The research synthesizes a tacit knowledge on nursing prioritization of the patient need for care from key international literature (from 1966 to 2003). Nursing prioritization was discerned in both education and practice literatures; interrelationships between these and theoretical approaches were also identified. Nursing prioritization of the patient need for care was revealed both as a non-sequential decision-making process throughout unfolding patient situations and as an advanced skill of nursing practice. Increasing confidence with this skill is the hallmark of developing expertise.     

The acceptability of waiting times for elective general surgery and the appropriateness of prioritising patients

Background  

Problematic waiting lists in public health care threaten the equity and timeliness of care provision in several countries. This study assesses different stakeholders' views on the acceptability of waiting lists in health care, their preferences for priority care of patients, and their judgements on acceptable waiting times for surgical patients.     

26万女性队列人群中乳腺癌与人工流产关系的研究（上海）

目的：评估人工流产（指手术流产）对乳腺癌危险性的可能影响。方法：研究在上海267040例妇女的一项乳房自我检查随机试验的队列人群中进行，由队列研究和巢式病例对照研究两部分组成。结果：依据基线调查表采集的资料分析，人工流产不增加乳腺癌危险性。调整潜在的混淆因素后，OR=1．06（95％CI：0．91～1．25）。人工流产次数增加无危险性趋势增加。从更详细的652例乳腺癌病例和694例对照资料分析，得出相似的结果。人工流产发生在首次生育后不增加危险性；少数妇女在首次生育前人工流产以及妊娠13周后人工流产，虽然被观察到危险性有增加，但无显著性统计学意义。结论：在中国，人工流产不是乳腺癌发生的重要原因。