Cardioplegia flow dynamics in an in vitro model.

The flow of fluids in extracorporeal circuits does not conform to conventional Poiseuille mechanics which confounds calculating cardioplegia (CP) flow distribution. The purpose of this study was to quantify CP flow dynamics in a model simulating coronary atherosclerosis across varying sized restrictions. An in vitro preparation was designed to assess hydraulic fluid movement across paired restrictions of 51, 81 and 98% lumen reductions. Volume data were obtained at variable flow, temperature, viscosity and pressure conditions. CP delivered through 14- and 18-gauge (GA) conduits at 8 degrees C and 100 mmHg infusion pressure revealed that both four to one and crystalloid CP solutions had significantly less total percentage flow through the 14-GA conduit, p < 0.0001 and p < 0.001, respectively. Overall, 4:1 CP exhibited the most favorable fluid dynamics at 8 degrees C in that it delivered the highest percentages of total CP flow through the smaller lumen conduit. At both 8 degrees C and 37 degrees C delivery, blood CP resulted in the least homogeneous fluid distribution at all delivery parameters. The results in relation to blood viscosity indicate that, although the 8 degrees C blood CP had a significantly greater viscosity than 37 degrees C blood CP, it did not produce an effect in fluid distribution. These data show that increasing the cardioplegic solution hematocrit causes an inhomogeneous fluid distribution regardless of delivery temperature or infusion pressure.     

hMSC-mediated Concurrent Delivery of Endostatin and Carboxylesterase to Mouse Xenografts Suppresses Glioma Initiation and Recurrence

Glioma stem cells (GSCs) are known to be maintained within a “vascular niche” thereby, disruption of this microenvironment using antiangiogenesis agents is a promising therapeutic modality. However, this regimen leads to treatment failure and tumor recurrence in patients with glioblastoma multiforme (GBM). Therefore, more effective therapeutic approaches that can eradicate GSCs and the bulk tumors are needed. Toward this goal, we examined the antitumor effects of an antiangiogenesis approach combined with conventional chemotherapy on suppressing glioma xenograft growth. We established three genetically engineered mesenchymal stem cell (MSC) lines (GE-AF-MSCs) by stably transducing the gene encoding endostatin (an antiangiogenesis factor), the gene encoding secretable form of carboxylesterase 2 (sCE2, a prodrug-activating enzyme), or a mixture of both genes. Among the three GE-AF-MSC cell lines, injection of amniotic fluid (AF)-MSCs-endostatin-sCE2 cells into U87MG-EGFRvIII-driven orthotopic brain tumor and postsurgery tumor recurrence models, and subsequent CPT11 treatment yielded the strongest antitumor responses, including diminished angiogenesis, increased cell death, and a reduced Nestin-positive GSC population. Therefore, our antitumor strategy provides a novel basis for designing stem cell-mediated therapeutic approaches to target and eradicate GSCs and the bulk tumors.     

Laboratory managers' perceptions of the impact of teaching on the clinical laboratory.

OBJECTIVE: To determine managers' perceptions of the impact of teaching students on the clinical laboratory, including: productivity, costs, recruitment/new employee orientation, staff morale/attitude, and staff professionalism. Managers' views on responsibility for teaching and reasons for not having students were also determined. DESIGN: Written survey, randomized sampling. PARTICIPANTS: Five hundred laboratory managers certified by the National Credentialing Agency. MAIN OUTCOME MEASURES: Participants completed a forced-choice written survey consisting of demographic information and statements assessing the impact of teaching. RESULTS: Managers agreed with impact statements on professionalism, recruitment, and new employee orientation. They were also in agreement that clinical teaching is essential. Neutral responses were obtained for impact statements related to laboratory productivity, costs, and staff morale and attitude. Over 90% of respondents who presently had students or who had had students at one time indicated that they hired their graduates. CONCLUSIONS: Laboratory managers understand the importance of clinical education and the benefits to recruitment, new employee orientation, and staff professionalism. Managers are undecided about the effects of teaching on laboratory costs and staff productivity.     

A population-based case-control study of Selective Serotonin Reuptake Inhibitors (SSRIs) and breast cancer: The impact of duration of use, cumulative dose and latency

Background  

Selective serotonin reuptake inhibitors (SSRIs), a popular class of antidepressants, may increase breast cancer risk by stimulating the secretion of prolactin, a potential tumour promoter. We evaluated the effects of duration of SSRI use, cumulative dose, and latency on the risk of breast cancer by conducting a population-based case-control study utilizing Saskatchewan health databases.     

A novel modular device for 3-D bone cell culture and non-destructive cell analysis

Synthetic materials have emerged as bone substitutes for filling bone defects of critical sizes. Because bone healing requires a mechanically resistant matrix (scaffold) attractive to osteogenic cells and must allow revascularization for nutrient and oxygen supply, scaffold-based strategies focus on the further development of chemical and physical qualities of the material. Cellular ingrowth towards the scaffold center is critical; therefore selective information from inner regions, in particular from the central part, is essential.In this paper we introduce a novel modular in vitro system for three-dimensional (3-D) in vitro bone cell cultures. This 3-D system is developed exclusively for in vitro research purposes, with special emphasis on the geometrical scaffold design (pore size, pore design). The system is composed of a stack of titanium slices which are mounted on a clamp and which enable the separate monitoring of cell growth patterns on every single slice of the slide stack. In this way we are able to gain selective information about the regulation of the cell physiology in the inner part of the 3-D construct which can be used for the development of an optimized scaffold design for orthopedic implants.