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Biomedical subjects

E Murphy

Publications and source records attributed to E Murphy.

At least 73 records · Page 4Linked to original sources
PubMed1999

Combining qualitative interviews with video-recorded consultations: gaining insight into GPs' decision-making.

BACKGROUND: Studies of GPs' decision-making are important for facilitating our understanding of GPs' consulting behaviours. We have used a novel combination of semi-structured interviews and video-recorded consultations to research the influences on decisions made by GPs during their consultations. OBJECTIVE: We describe the use of GPs' video-recorded consultations as a stimulus for focused, semi-structured interviews and to discuss how this research method compares with other approaches for studying GPs' decision-making during consultations. METHODS: GPs' surgery sessions were video-recorded and later they were shown video recordings of themselves consulting with smokers before participating in semi-structured interviews about these consultations. Interviews aimed to describe the factors which GPs perceived to influence their decisions to discuss or not discuss smoking with patients. DISCUSSION: This technique can be used to research decisions, which are made frequently by GPs. It is probably most appropriate for gaining insight into decision-making during mundane consultations, to which GPs would otherwise give little thought.

Decision Making↗
PubMed1999

The oncostatic action of melatonin in an ovarian carcinoma cell line.

Melatonin is reported to reduce proliferation in many cell types, but the effect is small and the results are inconsistent. Information on the mechanism by which melatonin exerts its antiproliferative effects might provide insight into the variability of the response. In an ovarian adenocarcinoma cell line (BG-1), we find that melatonin at concentrations of 10(-9)-10(-7) M caused a 20-25% reduction in cell number. Melatonin also resulted in a similar reduction in [3H]-thymidine incorporation with no significant increase in cell death as measured by trypan blue incorporation. The Kd for melatonin reduction in cell number was approximately 5 x 10(-10) M. Melatonin ML2 receptors have a Kd for melatonin binding in the low nM range and are linked to the production of the calcium mobilizing agent inositol-1,4,5-trisphosphate (IP3). To investigate whether melatonin signaling involves an increase in cytosolic-free calcium. BG-1 cells were loaded with the calcium sensitive indicator, fura-2. Acute addition of melatonin (10(-5)-10(-9) M) did not alter cytosolic calcium. Addition of the putative nuclear receptor agonist CGP52608 caused a dose-dependent inhibition of cell number with a Kd of approximately 2 x 10(-9) M. Addition of CGP52608 caused a similar reduction in [3H]-thymidine incorporation. Neither melatonin (10(-8) M-10(-5) M) nor CGP52608 at concentrations below 10(-7) M induced cell death associated with the inhibition of cell proliferation; however, addition of CGP52608 at a high dose (10(-7) M) caused an increase in cell death, consistent with apoptosis. Growth inhibition by melatonin or CGP52608 did not alter the percentage of cells in G1 versus S/G2/M.

Adenocarcinoma↗
PubMed1999

Lipoxygenase metabolism of arachidonic acid in ischemic preconditioning and PKC-induced protection in heart.

We tested the hypothesis that activation of the 12-lipoxygenase (12-LO) pathway of arachidonic acid metabolism contributes to the protective effect of protein kinase C (PKC) activation and ischemic preconditioning (PC), and we report, in perfused rat heart, that both PC and the PKC activator 1,2-dioctanoyl-sn-glycerol (DOG) confer a similar protective effect and stimulate a comparable accumulation of 12-LO metabolites. The 12-LO product, 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], was increased in DOG-treated (22.8 +/- 4.4 ng/g wet wt) and PC hearts (26.8 +/- 5.5 ng/g wet wt) compared with control (13.8 +/- 2.1 ng/g wet wt, P < 0. 05), and this increase was blocked by 12-LO or PKC inhibitors. Both DOG pretreatment and PC improved recovery of left ventricular developed pressure (LVDP) nearly twofold after 20 min of ischemia; this improvement was blocked by 12-LO inhibitors and was mimicked by infusion of 12-hydroperoxyeicosatetraenoic acid [12(S)-HpETE; 67 +/- 6% recovery of LVDP vs. 35 +/- 3% for untreated hearts]. Also, the protection afforded by 12(S)-HpETE, as well as by PC, was attenuated by the K+-channel blocker 5-hydroxydecanoate, suggesting that the downstream mechanisms of 12(S)-HpETE-mediated protection are similar to PC. Furthermore, PC stimulates 12-LO metabolism in perfused rabbit heart, and 12-LO inhibition blocks PC-induced cardioprotection. Thus the data suggest that 12-LO metabolism plays an important role in cardioprotection.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1999

Genetic and physiologic analysis of the role of uncoupling protein 3 in human energy homeostasis.

By virtue of its potential effects on rates of energy expenditure, uncoupling protein 3 (UCP3) is an obesity candidate gene. We identified nine sequence variants in UCP3, including Val9Met, Val102Ile, Arg282Cys, and a splice site mutation in the intron between exons 6 and 7. The splice mutation results in an inability to synthesize mRNA for the long isoform (UCP3L) of UCP3. Linkage (sib pair), association, and transmission disequilibrium testing studies on 942 African-Americans did not suggest a significant effect of UCP3 on body composition in this group. In vastus lateralis skeletal muscle of individuals homozygous for the splice mutation, no UCP3L mRNA was detectable; the short isoform (UCP3S) was present in an increased amount. In this muscle, we detected no alterations of in vitro mitochondrial coupling activity, mitochondrial respiratory enzyme activity, or systemic oxygen consumption or respiratory quotient at rest or during exercise. These genetic and physiologic data suggest the following possibilities: UCP3S has uncoupling capabilities equivalent to UCP3L; other UCPs may compensate for a deficiency of bioactive UCP3L; UCP3L does not function primarily as a mitochondrial uncoupling protein.

Alternative Splicing↗
PubMed1999

A triad of research roles: experiential learning in an undergraduate research course.

This article describes an innovative approach to teaching undergraduate research content directly involving students in a faculty research study, and a student research project undertaken in a nursing research course. Junior-level students participated as research subjects in a faculty study focusing on the health perceptions of baccalaureate nursing students, became data collectors in a related student project on the health perceptions of lay people, and became consumers of the research by analyzing the findings and clinical relevance of these studies. This strategy for teaching research assisted students to master undergraduate research content by participatory involvement in several distinct phases of the research process. The project generated considerable interest and served to foster positive attitudes toward nursing research while concurrently increasing students' comfort level with the total process.

Adolescent↗
PubMed1999

Ready to retire?

Only 24.5% of nurses are vested in their workplace retirement plan. Are you one of them?

Humans↗
PubMed1998

Regulation of the Ca2+ gradient across the sarcoplasmic reticulum in perfused rabbit heart. A 19F nuclear magnetic resonance study.

Myocardial contractility depends on Ca2+ release from and uptake into the sarcoplasmic reticulum (SR). The Ca2+ gradient between the SR matrix and the cytosol (SR Ca2+ gradient) is maintained by the SR Ca2+-ATPase using the free energy available from hydrolysis of ATP. The activity of the SR Ca2+-ATPase is not only dependent on the energy state of the cell but is also kinetically regulated by SR proteins such as phospholamban. To evaluate the importance of thermodynamic and kinetic regulation of the SR Ca2+ gradient, we examined the relationship between the energy available from ATP hydrolysis (DeltaGATP) and the energy required for maintenance of the SR Ca2+ gradient (DeltaGCa2+SR) during physiological and pathological manipulations that alter DeltaGATP and the phosphorylation state of phospholamban. We used our previously developed 19F nuclear magnetic resonance method to measure the ionized [Ca2+] in the SR of Langendorff-perfused rabbit hearts. We found that addition of either pyruvate or isoproterenol resulted in an increase in left ventricular developed pressure and an increase in [Ca2+]SR. Pyruvate increased DeltaGATP, and the increase in the SR Ca2+ gradient was matched to the increase in DeltaGATP; DeltaGATP increased from 58.3+/-0.5 to 60.4+/-1.0 kJ/mol (P<0.05), and DeltaGCa2+SR increased from 47.1+/-0.3 to 48.5+/-0.1 kJ/mol (P<0.05). In contrast, the increase in the SR Ca2+ gradient in the presence of isoproterenol occurred despite a decline in DeltaGATP from 58. 3+/-0.5 to 55.8+/-0.6 kJ/mol. Thus, the data indicate that the SR Ca2+ gradient can be increased by an increase in DeltaGATP, and that the positive inotropic effect of pyruvate can be explained by improved energy-linked SR Ca2+ handling, whereas the results with isoproterenol are consistent with removal of the kinetic limitation of phospholamban on the activity of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase, which allows the SR Ca2+ gradient to move closer to its thermodynamic limit. Ischemia decreases DeltaGATP, and this should also have an effect on SR Ca2+ handling. During 30 minutes of ischemia, DeltaGATP decreased by 12 kJ/mol, but the decrease in DeltaGCa2+SR was 16 kJ/mol, greater than would be predicted by the fall in DeltaGATP and consistent with increased SR Ca2+ release and increased SR Ca2+ cycling. Because ischemic preconditioning is reported to decrease SR Ca2+ cycling during a subsequent sustained period of ischemia, we examined whether ischemic preconditioning affects the relationship between the fall in DeltaGATP and the fall in DeltaGCa2+SR during ischemia. We found that preconditioning attenuated the fall in DeltaGCa2+SR during ischemia; the fall in DeltaGCa2+SR was of comparable magnitude to the fall in DeltaGATP, and this was associated with a significant improvement in functional recovery during reperfusion. The data suggest that there is both thermodynamic regulation of the SR Ca2+ gradient by DeltaGATP and kinetic regulation, which can alter the relationship between DeltaGATP and DeltaGCa2+SR.

Adenosine Triphosphate↗
PubMed1998

Characterization of a novel subset of CD8(+) T cells that expands in patients receiving interleukin-12.

IL-12 has significant antitumor activity in mice that may be mediated by CD8(+) T cells. We show in this report that repeated subcutaneous injections of IL-12 in patients with cancer resulted in the selective expansion of a subset of peripheral blood CD8(+) T cells. This T cell subset expressed high levels of CD18 and upregulated IL-12 receptor expression after IL-12 treatment in vivo. In normal subjects, these CD3(+)CD8(+)CD18(bright) T cells expressed IL-12 and IL-2 receptors and adhesion/costimulatory molecules to a greater degree than other CD8(+) and CD4(+) T cells. They appeared morphologically as large granular lymphocytes, although they did not express NK cell markers such as CD56. In addition, CD8(+)CD18(bright) T cells were almost exclusively T cell receptor (TCR) alphabeta+, and exhibited a TCR Vbeta repertoire that was strikingly oligoclonal, whereas the Vbeta repertoire of CD18(dim) T cells was polyclonal. Although CD8+CD18(bright) T cells demonstrated little functional responsiveness to IL-12 or IL-2 alone in vitro, they responded to the combination of IL-12+IL-2 with strong IFN-gamma production and proliferation and enhanced non-MHC-restricted cytolytic activity. In contrast, CD18(dim) T cells were not activated by IL-12 or IL-2, alone or in combination. These findings demonstrate that CD8+CD18(bright) T cells are a unique population of peripheral blood lymphocytes with features of both memory and effector cells that are capable of TCR-independent activation through combined stimulation with IL-12+IL-2. As this activation results in IFN-gamma production and enhanced cytolytic activity, these T cells may play a role in innate as well as acquired immunity to tumors and infectious pathogens. Additional studies will be necessary to determine whether CD8+CD18(bright) T cells mediate the antitumor effect of IL-12 or IL-2 administered to cancer patients, and if so, whether maximal activation of these T cells with the combination of IL-12+IL-2 in vivo can augment the clinical effectiveness of these cytokines.

CD8-Positive T-Lymphocytes↗
PubMed1998

Reducing the risk of sudden infant death syndrome: a review of the scientific literature.

In March 1997 a multidisciplinary forum was convened by the National SIDS Council of Australia to review recent evidence concerning risk factors of sudden infant death syndrome (SIDS) and to revise and refine the current guidelines for reducing the risk of SIDS. The forum provided an assessment of the evidence for recommendations to reduce the risk of SIDS using an evidence-based process. Strong evidence has now accumulated that the intervention campaigns to reduce prone sleeping during infancy have been followed by SIDS rate declines. Recent data indicate that the supine position is not associated with an increase in significant morbidity outcomes and provides greater protection for SIDS than the side position, which may be unstable. Covering of the baby's head by bedding is strongly related to SIDS. The infant's sleeping environment should be carefully set up to ensure that the baby's head, including the face, cannot be obstructed during sleep. Parental smoking is strongly associated with SIDS. Structural supportive interventions for parental smoking cessation are required. Bedsharing increases the risk of SIDS amongst smokers and the data are currently not sufficient to provide complete reassurance to nonsmoking parents that bedsharing is safe. Infants should be maintained in a comfortable temperature zone. The evidence for a protective effect of breast-feeding is conflicting, so breast-feeding cannot be promoted strongly as reducing the risk of SIDS. Immunisation has not been associated with SIDS. Parents and carers should be aware of the current guidelines. Health professionals should also be aware of the evidence on which the current recommendations are based. Effective health education programmes should lead to a further decline in SIDS mortality in Australia.

Australia↗
PubMed1998

The dose-effect relationships between torture and psychiatric symptoms in Vietnamese ex-political detainees and a comparison group.

The purpose of this study was to determine in Vietnamese ex-political detainees newly arrived into the United States a) the prevalence of torture and psychiatric symptoms and b) the dose-effect relationships between cumulative torture experience and the psychiatric symptoms of posttraumatic stress disorder (PTSD) and major depression. The study population included Vietnamese ex-political detainees (N = 51) and a comparison group (N = 22). All respondents received culturally validated instruments with known psychometric properties including Vietnamese versions of the Hopkins Symptom Checklist-25 and the Harvard Trauma Questionnaire. The ex-political detainees, in contrast to the comparison group, had experienced more torture events (12.2 SD = 4.2 vs. 2.6 SD = 3.1) and had higher rates of PTSD (90% vs. 79%) and depression (49% vs. 15%). Dose-effect relationships between cumulative torture experience and psychiatric symptoms were positive with the PTSD subcategory of "increased arousal" revealing the strongest association. These findings provide evidence that torture is associated with psychiatric morbidity in Vietnamese refugees. The demonstration of significant dose-effect responses supports the hypothesis that torture is a major risk factor in the etiology of major depression and PTSD. The generalizability of these results to other torture survivor groups is unknown. The interaction between torture and other pre- and post-migration risk factors over time in different cultural settings still needs to be examined.

Adult↗
PubMed1998

Catching goldfish: quality in qualitative research.

This paper reviews the contribution of qualitative methods to health services research (HSR) and discusses some of the issues involved in recognizing quality in such work. The place of qualitative work is first defined by reference to Archie Cochrane's agenda for HSR and the limitations of the recent focus on randomized trials as the standard method. Health care practice involves large elements of improvisation which cannot be captured by evidence-based approaches. Qualitative methods offer ways of understanding this improvisation and of identifying more efficient and effective practices, as well as considering the traditional topics of equity and humanity. The methodological procedures of qualitative work reflect a long-established inductive tradition in scientific practice. The logic of grounded theory provides a contemporary specification. In its application, it is quite different from the methodological anarchy of postmodernism. The use of qualitative research and the theoretically stated generalizations which arise from it inform reflective work by health service managers, planners and clinicians.

Evidence-Based Medicine↗
PubMed1997

The leptin receptor mediates apparent autocrine regulation of leptin gene expression.

The possibility that the leptin receptor (LEPR) mediates autocrine regulation of leptin expression in adipose tissue was examined in 10-day-old Zucker rat pups with different copy numbers of the leptin receptor mutation (Lepr(fa)). Plasma leptin concentrations and adipose tissue mRNA levels for leptin were related to copy number of the mutation (fa/fa > fa/+ > +/+). These relationships were independent of plasma insulin concentration. Reduced copy number for the functional leptin receptor apparently results in a diminished negative feedback signal to the leptin gene in adipose tissue. Thus, leptin appears to close a short regulatory loop controlling its own synthesis in adipose tissue.

Adipose Tissue↗
PubMed1997

K-ras is an essential gene in the mouse with partial functional overlap with N-ras.

Mammalian ras genes are thought to be critical in the regulation of cellular proliferation and differentiation and are mutated in approximately 30% of all human tumors. However, N-ras and H-ras are nonessential for mouse development. To characterize the normal role of K-ras in growth and development, we have mutated it by gene targeting in the mouse. On an inbred genetic background, embryos homozygous for this mutation die between 12 and 14 days of gestation, with fetal liver defects and evidence of anemia. Thus, K-ras is the only member of the ras gene family essential for mouse embryogenesis. We have also investigated the effect of multiple mutations within the ras gene family. Most animals lacking N-ras function and heterozygous for the K-ras mutation exhibit abnormal hematopoietic development and die between days 10 and 12 of embryogenesis. Thus, partial functional overlap appears to occur within the ras gene family, but K-ras provides a unique and essential function.

Anemia↗