Parents' decision to use vaccination services is complex and multi-factorial. Of particular interest are "vaccine-hesitant" parents who are in the middle of the continuum between vaccine acceptance and refusal. The objective of this qualitative longitudinal study was to better understand why mothers choose to vaccinate-or not-their newborns. Fifty-six pregnant mothers living in different areas of Quebec (Canada) were interviewed. These interviews gathered information on mothers' views about health and vaccination. Almost half of the mothers were categorized as vaccine-hesitant. A second interview was conducted with these mothers 3 to 11 months after birth to look at their actual decision and behavior concerning vaccination. Our results show the heterogeneity of factors influencing vaccine decision making. Although the majority of vaccine-hesitant mothers finally chose to follow the recommended vaccine schedule for their child, they were still ambivalent and they continued to question their decision.
A mouse model of renal failure, which is induced by the sequential electrocoagulation of the right renal cortex and left nephrectomy, was examined for the capacity to reproduce the characteristics of chronic uremia. Assessment was conducted six weeks after the second surgical procedure in 13 week old female C57BL/6 inbred mice with renal failure and in normal and sham-operated controls. The surgery, which was well tolerated, was free of local and systemic signs of inflammation or infection. Growth was significantly delayed in all animals post surgery however renal failure mice presented the most severe growth retardation. Biochemical analysis of plasma revealed multiple abnormalities with commensurate elevations of urea and creatinine. In addition to the expected hyperphosphatemia, hyperkalemia and acidosis, a significant increase in cholesterol was present. Furthermore, in contrast to controls, renal failure mice produced large volumes of urine which contained significant levels of protein. Renal failure mice presented profound hematological changes in the red cell series in which anemia was evident. Changes in plasma biochemistry and in bone histology revealed the presence of severe secondary hyperparathyroidism. It was therefore concluded that the described mouse model of chronic renal failure presented characteristics consistent with those observed clinically in end-stage renal disease.
The goal of this research was to develop a strategy to couple stem cell and gene therapy for in vivo delivery of erythropoietin (Epo) for treatment of anemia of ESRD. It was shown previously that autologous bone marrow stromal cells (MSCs) can be genetically engineered to secrete pharmacologic amounts of Epo in normal mice. Therefore, whether anemia in mice with mild to moderate chronic renal failure (CRF) can be improved with Epo gene-modified MSCs (Epo ؉ MSCs) within a subcutaneous implant was examined. A cohort of C57BL/6 mice were rendered anemic by right kidney electrocoagulation and left nephrectomy. In these CRF mice, the hematocrit (Hct) dropped from a prenephrectomy baseline of approximately 55% to 40% after induction of renal failure. MSCs from C57BL/6 donor mice were genetically engineered to secrete murine Epo at a rate of 3 to 4 units of Epo/10 6 cells per 24 h, embedded in a collagen-based matrix, and implanted subcutaneously in anemic CRF mice. It was observed that Hct increased after administration of Epo ؉ MSCs, according to cell dose. Implants of 3 million Epo ؉ MSCs per mouse had no effect on Hct, whereas 10 million led to a supraphysiologic effect. The Hct of CRF mice that received 4.5 or 7.5 million Epo ؉ MSCs rose to a peak 54 ؎ 4.0 or 63 ؎ 5.5%, respectively, at 3 wk after implantation and remained above 48 or 54% for >19 wk. Moreover, mice that had CRF and received Epo ؉ MSCs showed significantly greater swimming exercise capacity. In conclusion, these results demonstrate that subcutaneous implantation of Epo-secreting genetically engineered MSCs can correct anemia that occurs in a murine model of CRF.
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