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1.  Human Breast Tumor Cells Are More Resistant to Cardiac Glycoside Toxicity Than Non-Tumorigenic Breast Cells 
PLoS ONE  2013;8(12):e84306.
Cardiotonic steroids (CTS), specific inhibitors of Na,K-ATPase activity, have been widely used for treating cardiac insufficiency. Recent studies suggest that low levels of endogenous CTS do not inhibit Na,K-ATPase activity but play a role in regulating blood pressure, inducing cellular kinase activity, and promoting cell viability. Higher CTS concentrations inhibit Na,K-ATPase activity and can induce reactive oxygen species, growth arrest, and cell death. CTS are being considered as potential novel therapies in cancer treatment, as they have been shown to limit tumor cell growth. However, there is a lack of information on the relative toxicity of tumor cells and comparable non-tumor cells. We have investigated the effects of CTS compounds, ouabain, digitoxin, and bufalin, on cell growth and survival in cell lines exhibiting the full spectrum of non-cancerous to malignant phenotypes. We show that CTS inhibit membrane Na,K-ATPase activity equally well in all cell lines tested regardless of metastatic potential. In contrast, the cellular responses to the drugs are different in non-tumor and tumor cells. Ouabain causes greater inhibition of proliferation and more extensive apoptosis in non-tumor breast cells compared to malignant or oncogene-transfected cells. In tumor cells, the effects of ouabain are accompanied by activation of anti-apoptotic ERK1/2. However, ERK1/2 or Src inhibition does not sensitize tumor cells to CTS cytotoxicity, suggesting that other mechanisms provide protection to the tumor cells. Reduced CTS-sensitivity in breast tumor cells compared to non-tumor cells indicates that CTS are not good candidates as cancer therapies.
doi:10.1371/journal.pone.0084306
PMCID: PMC3862803  PMID: 24349570
2.  What Do Patients Choose to Tell Their Doctors? Qualitative Analysis of Potential Barriers to Reattributing Medically Unexplained Symptoms 
BACKGROUND
Despite both parties often expressing dissatisfaction with consultations, patients with medically unexplained symptoms (MUS) prefer to consult their general practitioners (GPs) rather than any other health professional. Training GPs to explain how symptoms can relate to psychosocial problems (reattribution) improves the quality of doctor–patient communication, though not necessarily patient health.
OBJECTIVE
To examine patient experiences of GPs’ attempts to reattribute MUS in order to identify potential barriers to primary care management of MUS and improvement in outcome.
DESIGN
Qualitative study.
PARTICIPANTS
Patients consulting with MUS whose GPs had been trained in reattribution. A secondary sample of patients of control GPs was also interviewed to ascertain if barriers identified were specific to reattribution or common to consultations about MUS in general.
APPROACH
Thematic analysis of in-depth interviews.
RESULTS
Potential barriers include the complexity of patients’ problems and patients’ judgements about how to manage their presentation of this complexity. Many did not trust doctors with discussion of emotional aspects of their problems and chose not to present them. The same barriers were seen amongst patients whose GPs were not trained, suggesting the barriers are not particular to reattribution.
CONCLUSIONS
Improving GP explanation of unexplained symptoms is insufficient to reduce patients’ concerns. GPs need to (1) help patients to make sense of the complex nature of their presenting problems, (2) communicate that attention to psychosocial factors will not preclude vigilance to physical disease and (3) ensure a quality of doctor–patient relationship in which patients can perceive psychosocial enquiry as appropriate.
doi:10.1007/s11606-008-0872-x
PMCID: PMC2659146  PMID: 19089505
doctor–patient communication; medically unexplained symptoms; reattribution
3.  Why do General Practitioners Decline Training to Improve Management of Medically Unexplained Symptoms? 
Background
General practitioners’ (GPs) communication with patients presenting medically unexplained symptoms (MUS) has the potential to somatize patients’ problems and intensify dependence on medical care. Several reports indicate that GPs have negative attitudes about patients with MUS. If these attitudes deter participation in training or other methods to improve communication, practitioners who most need help will not receive it.
Objective
To identify how GPs’ attitudes to patients with MUS might inhibit their participation with training to improve management.
Design
Qualitative study.
Participants
GPs (N = 33) who had declined or accepted training in reattribution techniques in the context of a research trial.
Approach
GPs were interviewed and their accounts analysed qualitatively.
Results
Although attitudes that devalued patients with MUS were common in practitioners who had declined training, these coexisted, in the same practitioners, with evidence of intuitive and elaborate psychological work with these patients. However, these practitioners devalued their psychological skills. GPs who had accepted training also described working psychologically with MUS but devalued neither patients with MUS nor their own psychological skills.
Conclusions
GPs’ attitudes that suggested disengagement from patients with MUS belied their pursuit of psychological objectives. We therefore suggest that, whereas negative attitudes to patients have previously been regarded as the main barrier to involvement in measures to improve patient management, GPs devaluing of their own psychological skills with these patients may be more important.
doi:10.1007/s11606-006-0094-z
PMCID: PMC1855690  PMID: 17443362
medically unexplained symptoms; general practitioners; management; psychological skills; attitudes
4.  Why do General Practitioners Decline Training to Improve Management of Medically Unexplained Symptoms? 
Background
General practitioners’ (GPs) communication with patients presenting medically unexplained symptoms (MUS) has the potential to somatize patients’ problems and intensify dependence on medical care. Several reports indicate that GPs have negative attitudes about patients with MUS. If these attitudes deter participation in training or other methods to improve communication, practitioners who most need help will not receive it.
Objective
To identify how GPs’ attitudes to patients with MUS might inhibit their participation with training to improve management.
Design
Qualitative study.
Participants
GPs (N = 33) who had declined or accepted training in reattribution techniques in the context of a research trial.
Approach
GPs were interviewed and their accounts analysed qualitatively.
Results
Although attitudes that devalued patients with MUS were common in practitioners who had declined training, these coexisted, in the same practitioners, with evidence of intuitive and elaborate psychological work with these patients. However, these practitioners devalued their psychological skills. GPs who had accepted training also described working psychologically with MUS but devalued neither patients with MUS nor their own psychological skills.
Conclusions
GPs’ attitudes that suggested disengagement from patients with MUS belied their pursuit of psychological objectives. We therefore suggest that, whereas negative attitudes to patients have previously been regarded as the main barrier to involvement in measures to improve patient management, GPs devaluing of their own psychological skills with these patients may be more important.
doi:10.1007/s11606-006-0094-z
PMCID: PMC1855690  PMID: 17443362
medically unexplained symptoms; general practitioners; management; psychological skills; attitudes

Results 1-4 (4)