Progenitor Cell Therapy (United States)

Introducing papers from a symposium on Ethics, Politics, and Health hosted by the Department of Philosophy at MIC in November 2014 forming part of the Irish President's Initiative on Bioethics and others on autonomy from a conference held at St Mary's University, Twickenham in November 2015

Assessment of competence is a way of measuring if staff are fit for purpose. Clinical competences, against which performance is measured, have been developed in a wide range of clinical settings in recent years (Department of Health (DH), 2008). Several trusts also operate an assessment centre in the recruitment and selection of staff, and these frequently involve competency testing in order to be certain that their new recruits are fit for their post. Agenda for Change (DH, 2004a) firmly links pay to the competences expressed in the Knowledge and Skills Framework (DH, 2004b; c) yet the KSF has not been implemented in all trusts. In part 1 of this article (Bentley and Dandy-Hughes, 2010), the process of Southwark PCT's competency project was described. This involved the process of writing measurable, manageable competences from the KSF, in order to develop staff to be fit for purpose. Part 2 evaluates the use of the appraisal tool that was developed from the KSF, and examines the role of the nurse consultant in education who led the competency project.

The delivery of an effective community nursing workforce relies on competent staff. Commissioners will need to be assured that their providers employ competent, efficient staff who give value for money. The Knowledge and Skills Framework (KSF) was introduced as part of Agenda for Change to identify the competences required, but competency testing using the KSF has not been fully implemented across the UK, and measuring competency, using the KSF indicators, still leaves much room for variation and a non-standardized approach. In the first of this two-part article, the authors discuss the process through which the provider services of one London PCT developed standardized competences using the KSF which were linked to staff performance and which provided clear areas for individual development.

We assessed the effect standard-dose induction chemotherapy and tandem cycles of high-dose chemotherapy (HDC) have on outcomes in metastatic breast cancer. One hundred and one women with metastatic breast cancer were enrolled in two non-randomized phase II studies. The first group of 64 patients (induction group) received four cycles of docetaxel 75 mg/m2 and doxorubicin 50 mg/m2. The next 37 patients did not receive induction (no induction group). Both groups received two (tandem) cycles of HDC. Blood-derived stem cells were collected after the first HDC cycle, processed using CD34+ cell selection and then reinfused after the second HDC cycle. Outcomes were compared between the two groups and also to patients participating in the Philadelphia (inter-group) randomized metastatic breast cancer transplant trial (PBT-01). Intent-to-treat analysis revealed no significant differences in complete response rates (37.5% vs 27%; P = 0.20), overall response (75% vs 71%), median progression free survival (PFS) (11.9 vs 8 months; P = 0.24) and overall survival (OS) (>36 vs 25 months; P = 0.16), in the induction vs no induction groups, respectively. Adjusting for differences in known baseline characteristics, induction group patients were found to have significantly longer PFS (P = 0.002), OS (P = 0.01) and more frequent conversion from a partial to complete response (58% vs < or = 13%, P < or = 0.0002) when compared with PBT-01 patients. Induction chemotherapy administered prior to tandem cycles of HDC does not appear to adversely affect outcomes in metastatic breast cancer patients. Outcomes in our induction group also compare favorably with those observed in PBT-01 and warrant further clinical investigation.

IgG deposition at tissue sites characteristically leads to macrophage accumulation and organ injury. Although the mechanism by which deposited IgG induces tissue injury is not known, we have recently demonstrated that deposited IgG stimulates the release of IL-8 and monocyte chemoattractant protein-1 from normal human monocytes, which may drive inflammation. Since IgG also induces macrophage accumulation in these diseases, we hypothesized that deposited IgG protects monocytes from apoptosis. As an in vitro model of the effect of deposited IgG on monocyte survival, monocyte apoptosis was studied after FcgammaR cross-linking. Monocytes cultured on immobilized IgG, which induces FcgammaR cross-linking, were protected from apoptosis, whereas monocytes cultured with equivalent concentrations of F(ab')2 IgG or 50 times higher concentrations of soluble IgG, neither of which induces FcgammaR cross-linking, were not protected. Moreover, this protection was transferable, as supernatants from immobilized IgG-stimulated monocytes protected freshly isolated monocytes from apoptosis and contained functional M-CSF, a known monocyte survival factor. M-CSF mediated the monocyte survival induced by FcgammaR cross-linking, as neutralizing anti-human M-CSF Abs blocked the monocyte protection provided by either immobilized IgG or IgG-stimulated monocyte supernatants. These findings demonstrate a novel mechanism by which deposited IgG targets tissue macrophage accumulation through FcgammaR-mediated M-CSF release. This pathway may play an important role in promoting and potentiating IgG-mediated tissue injury.

The gene therapy strategy using the hsv1-thymidine kinase gene (TK) and ganciclovir (GCV) injections that has been used for treating human glioblastomas has not been as effective as expected after the first animal experiments. A better understanding of the different steps involved in this treatment, like gene transfer, gene expression, and sensitivity of the recipient cells is needed. Therefore, we studied 7 human glioblastoma cell lines (U87, U118, U251, SNB19, SNB75, SF295, SF539) for their sensitivity to the TK/GCV system. We also studied their in vitro bystander effect and their in vitro transfectability using LipofectAMINE as a transfection enhancer. According to this in vitro analysis, most of the glioblastoma cell lines should be sensitive to the TK/GCV system, but there is a significant need for agents to increase transfection efficiency.

While the antiarrhythmic effects of amiodarone are well-documented, its hemodynamic effects are not. We injected 5 mg/kg amiodarone i.v. in 16 patients undergoing coronary arteriography. Heart rate did not change. Aortic (systolic, diastolic and mean) and left ventricular (systolic and end-diastolic) pressures decreased significantly (p less than 0.01) at 5 and 15 minutes; systemic vascular resistance also fell significantly (p less than 0.05), while cardiac index increased slightly but significantly (p less than 0.05). Coronary vascular resistance decreased significantly (p less than 0.01) and coronary sinus blood flow rose in most patients, from a mean of 138 ml/min to 153 ml/min at 5 minutes (p less than 0.02); it then returned toward the control value at 15 minutes (mean 145 ml/min). Myocardial metabolism of O2 was normal and unchanged. Metabolism of lactate improved in five patients, remained unchanged in seven and deteriorated transiently in four. No undesirable hemodynamic and clinical side effects occurred when the drug was administered slowly. We conclude that amiodarone is a powerful systemic and coronary vasodilator. In addition to its present indications in the treatment of angina pectoris and arrhythmias, the drug might be very useful as an afterload-reducing agent.