Biomedical subjects

Ann Gallagher

Publications and source records attributed to Ann Gallagher.

12 recordsLinked to original sources

PubMed2006

Estrogen receptor alpha positive breast tumors and breast cancer cell lines share similarities in their transcriptome data structures.

Established human breast cancer cell lines are widely used as experimental models in breast cancer research. While these cell lines and their variants share many phenotypic characteristics with human breast tumors, the extent to which they reflect the underlying molecular biology of breast cancer remains controversial. We explored this issue using a probabilistic rather than heuristic approach. Data from gene expression microarrays were used to compare the global structures of the transcriptomes of three estrogen receptor alpha positive (ER+) human breast cancer cell lines (MCF-7, T47D, ZR-75-1) and 13 human breast tumors (11 ER+; 2 ER-). Linear representations of the respective data structures were obtained by deriving those top principal components (PCs) required to capture > or =80% of the cumulative variance for each data set (M PCs). We then identified those genes most highly correlated with the M PCs (Pearson's correlation coefficient r > or =0.800) and identified a group of 36 genes commonly correlated with both the cell line (M = 5 PCs) and tumor (M = 6 PCs) data structures. All 36 common genes were correlated with PC1 from the breast tumor data: 21/36 genes were correlated with PC1, 14/36 genes correlated with PC2, and 1/36 genes correlated with PC3 from the cell line data. Genes important in defining the data structures include NFkappaB p65, IGFBP-6, ornithine decarboxylase-1, and paxillin. When data from MDA-MB-435 xenografts (ER-) were included in the analysis, we were unable to find any common genes between these xenografts and the breast tumors. These data clearly imply that MCF-7, T47D, and ZR-75-1 cells and ER+ breast tumors share substantial global similarities in the structures of their respective transcriptomes, and that these cell lines are good models in which to identify molecular events that are likely to be important in some ER+ human breast cancers.

Animals↗

PubMed2005

Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial.

PURPOSE: In an open-label trial we have previously demonstrated that paroxetine reduces hot flashes. We initiated a stratified, randomized, double-blind, cross-over, placebo-controlled trial to investigate the efficacy of paroxetine 10 mg and 20 mg compared to placebo in reducing hot flash frequency and composite score. A secondary objective was to evaluate quality of life (QOL) parameters. PATIENTS AND METHODS: Women who suffered at least two hot flashes a day for 1 month or longer were eligible. Women were randomly assigned to 4 weeks of paroxetine 10 mg or 20 mg followed by placebo for 4 weeks, or placebo for 4 weeks followed by paroxetine 10 mg or 20 mg for 4 weeks. Participants completed baseline daily hot flash diaries for one week prior to the start of the study and throughout the study, and QOL questionnaires at baseline, week 5 and week 9. RESULTS: 279 women were screened, and 151 were randomly assigned. Paroxetine 10 mg reduced hot flash frequency and composite score by 40.6% and 45.6%, respectively, compared to 13.7% and 13.7% for placebo (P = .0006 and P = .0008, respectively). Paroxetine 20 mg reduced hot flash frequency and composite score by 51.7% and 56.1%, respectively, compared with 26.6% and 28.8% for placebo (P = .002 and P = .004, respectively). Efficacy was similar between the two doses, but women were less likely to discontinue low-dose paroxetine. Paroxetine 10 mg was associated with a significant improvement in sleep compared with placebo (P = .01). CONCLUSION: Paroxetine is an effective treatment for hot flashes in women with or without a prior breast cancer.

Adult↗

PubMed2004

A pilot study to establish a clinical model to perform phase II studies of breast cancer chemopreventive agents in women at high risk with biomarkers as surrogate endpoints for activity.

PURPOSE: Use of surrogate end point biomarkers in phase II trials may help select agents that appear to have activity and might be evaluated in future phase III definitive trials of breast cancer prevention. We performed a pilot clinical trial to establish the logistics for a clinical model to perform phase II studies of breast cancer chemopreventive agents in women at high risk with novel imaging techniques and candidate surrogate end point biomarkers for activity. We chose tamoxifen to establish proof of principal with a known effective agent. EXPERIMENTAL DESIGN: Women at a high risk of developing a new breast cancer and for whom tamoxifen was recommended were eligible. The women underwent baseline and 3 and 6 months mammogram and magnetic resonance imaging (MRI) of one breast to identify areas of water-like intensity (epithelial) and to determine the changes over time and MRI-directed core breast biopsies of these areas for surrogate end point biomarkers analysis. RESULTS: From August 1999 to March 2001, 26 women underwent baseline imaging and core biopsies. Sixteen women took tamoxifen and 10 chose not to. Overall, 79% of the samples contained glandular tissue evaluable for histology, but only 66% of the samples were evaluable for marker analysis. Only 12 patients had specimens with glandular tissue sufficient for marker analysis both at baseline and in at least one follow-up. Because of the small number of women with matched samples, marker analysis was not informative. CONCLUSIONS: This study shows the feasibility of obtaining serial core breast biopsies from women at a high risk of developing a new breast cancer. Patient participation in this model is satisfactory, and such a model may provide indication of drug activity. MRI-directed biopsy did not provide a high yield of evaluable samples, and additional work on adequate collection of epithelial tissue for surrogate end point biomarker analysis is thus necessary.

Adult↗

PubMed2004

A pilot surrogate end point biomarker trial of perillyl alcohol in breast neoplasia.

PURPOSE: Efficient strategies to screen promising agents in early phase development are essential for rapid progress in breast cancer chemoprevention. We report our experience with the natural compound perillyl alcohol (POH) administered in a short-term surrogate end point biomarker (SEB) protocol, using the "window" between diagnostic and definitive surgery. EXPERIMENTAL DESIGN: Eligible patients included those with a diagnosis of atypical ductal hyperplasia, ductal carcinoma in situ, lobular carcinoma in situ, or invasive carcinoma (<3 cm in size) that required further surgery. Thirty-seven of 267 women screened were enrolled in the study (14%). Five women received single-dose POH (1.5 g/m2) 2 days before surgery, 16 received escalating doses of POH (1.2 g/m2 to 4.8 g/m2/day) for 2 days before surgery, and 16 served as untreated controls. Exploratory SEB analysis [estrogen receptor, progesterone receptor, proliferation, apoptosis, M6P/insulin-like growth factor (IGF)-2R, IGF1, IGF2 and transforming growth factor beta] was conducted before and after POH. RESULTS: Only a small portion of the population screened entered the study. Reasons for nonparticipation included protocol ineligibility, conflict of timing of surgery, miscellaneous logistical reasons, or patient's choice. POH administration was well tolerated and did not interfere with surgical management. The power to observe changes in candidate SEB was diminished by a 44% incidence of cases in which the index lesion was not present in the definitive surgical specimen. CONCLUSIONS: Preoperative POH exposure was safe and suitable for a more definitive phase II SEB study. Further investigations must overcome logistical obstacles to accrual, and they must focus on approaches to maximize tissue collection and to incorporate genomic analysis of target lesions.

Aged↗

PubMed2004

Detection of LOH and mitochondrial DNA alterations in ductal lavage and nipple aspirate fluids from hngh-risk patients.

We describe a method for the isolation of free DNA from ductal lavage (DL) and nipple aspirate fluid (NAF), and its evaluation for the presence of LOH at the BRCA1 and FHIT genes and for mitochondrial DNA (mtDNA) mutations at the D310 marker, to improve early detection of breast cancer. We evaluated 26 DL and six NAF samples from 14 women of known BRCA1 status, who have no clinical evidence of breast tumors: nine mutation carriers and five non-carriers. LOH studies at the BRCA1 locus were possible in 19/26 DL samples, and at the FHIT locus in 16/26 samples. In 4/9 mutation carriers we found LOH at the BRCA1 allele, and in two of these we also found LOH at the FHIT allele. In one of the mutation carriers with BRCA1 LOH, invasive breast cancer was subsequently detected, and the tumor showed the same LOH as the DL. In one of the true negatives, BRCA1 and FHIT LOH were detected. The mitochondrial studies were possible in all 26 DL samples and a somatic mutation was found in 3/9 carriers, two of whom also had LOH at the BRCA1 locus, and in none of the non-carriers. mtDNA mutation evaluation was possible in 4/6 NAF samples. The NAF and DL results were concordant. One NAF sample from a BRCA1 patient showed a mtDNA mutation. Our data demonstrates the feasibility of performing molecular studies using the free DNA present in the ductal fluid, while the intact cells can be used for cytologic studies.

Acid Anhydride Hydrolases↗

PubMed2004

Dignity and respect for dignity--two key health professional values: implications for nursing practice.

It is argued that dignity can be considered both subjectively, taking into account individual differences and idiosyncrasies, and objectively, as the foundation of human rights. Dignity can and should also be explored as both an other-regarding and a self-regarding value: respect for the dignity of others and respect for one's own personal and professional dignity. These two values appear to be inextricably linked. Aristotle's doctrine of the mean enables nurses to reflect on the appropriate degree of respect for the dignity of others and of respect for themselves. To develop an understanding of the rationale for and the significance and implications of dignity in health care practice, a view of human nature is proposed that implies vulnerability and fallibility, and that urges that an ethic of aspiration is embraced. Anonymized vignettes are included to illustrate points about the everyday nature of dignity.

Ethical Relativism↗

PubMed2003

Breaking bad news revisited: the push for negotiated disclosure and changing practice implications.

This article revisits the ethical, legal, professional and emotional issues involved with disclosing bad news. The authors examine the push for disclosure that has come from a number of quarters in the UK, including ethical and legal challenges, in particular the Bristol Royal Inquiry Report, professional codes of conduct, health policy and the expectations of the public. The contribution of nurses to breaking bad news is not widely discussed in the literature. With the development of new nursing roles and evidence-based practice it is timely to consider the role of nurses in this process. The article highlights some limitations with current guidelines for breaking bad news, in particular, that these guidelines tend to be constructed from a professional standpoint and lack patient-centred evidence. The issue of emotional labour and how it relates to giving bad news is discussed with respect to professional staff and patients. The article concludes by raising some practice implications, including: the importance of context and continuity; the significance of information and support; the desirable qualities of the professional; and issues to consider in determining patient preferences.

Emotions↗

PubMed2002

Development and validation of a method for using breast core needle biopsies for gene expression microarray analyses.

PURPOSE: Gene expression microarray technologies have the potential to define molecular profiles that may identify specific phenotypes(diagnosis), establish a patient's expected clinical outcome (prognosis), and indicate the likelihood of a beneficial effect of a specific therapy (prediction). We wished to develop optimal tissue acquisition, processing, and analysis procedures for exploring the gene expression profiles of breast core needle biopsies representing cancer and noncancer tissues. EXPERIMENTAL DESIGN: Human breast cancer xenografts were used to evaluate several processing methods for prospectively collecting adequate amounts of high-quality RNA for gene expression microarray studies. Samples were assessed for the preservation of tissue architecture and the quality and quantity of RNA recovered. An optimized protocol was applied to a small study of core needle breast biopsies from patients, in which we compared the molecular profiles from cancer with those from noncancer biopsies. Gene expression data were obtained using Research Genetics, Inc. Named Genes cDNA microarrays. Data were visualized using simple hierarchical clustering and a novel principal component analysis-based multidimensional scaling. Data dimensionality was reduced by simple statistical approaches. Predictive neural networks were built using a multilayer perceptron and evaluated in an independent data set from snap-frozen mastectomy specimens. RESULTS: Processing tissue through RNALater preserves tissue architecture when biopsies are washed for 5 min on ice with ice-cold PBS before histopathological analysis. Cell margins are clear, tissue folding and fragmentation are not observed, and integrity of the cores is maintained, allowing optimal pathological interpretation and preservation of important diagnostic information. Adequate concentrations of high-quality RNA are recovered; 51 of 55 biopsies produced a median of 1.34 microg of total RNA (range, 100 ng to 12.60 microg). Snap-freezing or the use of RNALater does not affect RNA recovery or the molecular profiles obtained from biopsies. The neural network predictors accurately discriminate between predominantly cancer and noncancer breast biopsies. CONCLUSIONS: The approaches generated in these studies provide a simple, safe, and effective method for prospectively acquiring and processing breast core needle biopsies for gene expression studies. Gene expression data from these studies can be used to build accurate predictive models that separate different molecular profiles. The data establish the use and effectiveness of these approaches for future prospective studies.

Animals↗

PubMedDate not supplied

Too clever to care?

Explore the source record for details and available documents.

Altruism↗

PubMedDate not supplied

The ethical divide.

Ethics is an area of growing interest in nursing and is a compulsory part of nurse education. Yet record numbers of nurses care being removed from the register and media stories of poor practice are rife. This article explores the issues. Ethics is about how we ought to behave towards one another. Ethics can be seen as elitist and too theoretical, failing to bridge the theory-practice gap. Discussion of ethics in health care tends to concentrate on issues with a 'gee-whizz' factor. Health care is a moral enterprise and, therefore, nursing has moral ends.

Education, Nursing↗

PubMedDate not supplied

Work-based learning: challenges and opportunities.

This article discusses some of the challenges and opportunities arising from the development and implementation of an innovative work-based open and distance learning programme available exclusively to healthcare assistants working in general health and mental health practice. The programme is based on a partnership between the sponsoring organisation and the Open University. The focus is on the development of standards of proficiency, service user involvement, partnership working, skills development and the pedagogic implications of a work-based learning format.

Adult↗

PubMedDate not supplied

Dignity in care: the views of patients and relatives.

There have been concerns about a lack of dignity in health care over recent years, particularly in relation to the care of older people. Efforts to ensure that dignity has a central place in health care discourse and practice continue, but what appears to be lacking in the literature is the perspective of older people and their relatives on what this means and how dignity is maintained or diminished during health care provision. This article reports on a small pilot study that explores dignity in health care and the circumstances that may influence it.

Aged↗