Notizen: Research information in nurses’ clinical decision-making: what is useful? Aim. To examine those sources of information which nurses find useful for reducing the uncertainty associated with their clinical decisions. Background. Nursing research has concentrated almost exclusively on the concept of research implementation. Few, if any, papers examine the use of research knowledge in the context of clinical decision-making. There is a need to establish how useful nurses perceive information sources are, for reducing the uncertainties they face when making clinical decisions. Design. Cross-case analysis involving qualitative interviews, observation, documentary audit and Q methodological modelling of shared subjectivities amongst nurses. The case sites were three large acute hospitals in the north of England, United Kingdom. One hundred and eight nurses were interviewed, 61 of whom were also observed for a total of 180 hours and 122 nurses were involved in the Q modelling exercise. Results. Text-based and electronic sources of research-based information yielded only small amounts of utility for practising clinicians. Despite isolating four significantly different perspectives on what sources were useful for clinical decision-making, it was human sources of information for practice that were overwhelmingly perceived as the most useful in reducing the clinical uncertainties of nurse decision-makers. Conclusions. It is not research knowledge per se that carries little weight in the clinical decisions of nurses, but rather the medium through which it is delivered. Specifically, text-based and electronic resources are not viewed as useful by nurses engaged in making decisions in real time, in real practice, but those individuals who represent a trusted and clinically credible source are. More research needs to be carried out on the qualities of people regarded as clinically important information agents (specifically, those in clinical nurse specialist and associated roles) whose messages for practice appear so useful for clinicians.

Notizen: Aim.  To examine the barriers that nurses feel prevent them from using research in the decisions they make. Background.  A sizeable research literature focusing on research utilization in nursing has developed over the past 20 years. However, this literature is characterized by a number of weaknesses: self-reported utilization behaviour; poor response rates and small, nonrandom sampling strategies. Design.  Cross-case analysis involving anonymised qualitative interviews, observation, documentary audit and Q methodological modelling of shared subjectivities amongst nurses. The case sites were three large acute hospitals in the north of England. One hundred and eight nurses were interviewed, 61 of whom were also observed for a total of 180 h, and 122 nurses were involved in the Q modelling exercise (response rate of 64%). Results.  Four perspectives were isolated that encompassed the characteristics associated with barriers to research use. These related to the individual, organization, nature of research information itself and environment. Nurses clustered around four main perspectives on the barriers to research use: (1) Problems in interpreting and using research products, which were seen as too complex, ‘academic’ and overly statistical; (2) Nurses who felt confident with research-based information perceived a lack of organizational support as a significant block; (3) Many nurses felt that researchers and research products lack clinical credibility and that they fail to offer the desired level of clinical direction; (4) Some nurses lacked the skills and, to a lesser degree, the motivation to use research themselves. These individuals liked research messages passed on to them by a third party and sought to foster others' involvement in research-based practice, rather than becoming directly involved themselves. Conclusions.  Rejection of research knowledge is not a barrier to its application. Rather, the presentation and management of research knowledge in the workplace represent significant challenges for clinicians, policy-makers and the research community.

Notizen: The accessibility of research-based knowledge for nurses in United Kingdom acute care settings Background. The successful dissemination of the results of the National Health Service (NHS) research and development strategy and the development of evidence based approaches to health care rely on clinicians having access to the best available evidence; evidence fit for the purpose of reducing the uncertainties associated with clinical decisions. Aim. To reveal the accessibility of those sources of information actually used by nurses, as well as those which they say they use. Design. Mixed method case site, using interview, observational, Q sort and documentary audit data in medical, surgical and coronary care units (CCUs) in three acute hospitals. Results. Three perspectives on accessibility were identified: (a) the humanist – in which human sources of information were the most accessible; (b) local information for local needs – in which locally produced resources were seen as the most accessible and (c) moving towards technology – in which information technology begins to be seen as accessible. Nurses’ experience in a clinical specialty is positively associated with a perception that human sources such as clinical nurse specialists, link nurses, doctors and experienced clinical colleagues are more accessible than text based sources. Clinical specialization is associated with different approaches to accessing research knowledge. Coronary care unit nurses were more likely to perceive local guidelines, protocols and on-line databases as more accessible than their counterparts in general medical and surgical wards. Only a third of text-based resources available to nurses on the wards had any explicit research base. These, and the remainder were out of date (mean age of textbooks 11 years), and authorship hard to ascertain. Conclusion. A strategy to increase the use of research evidence by nurses should harness the influence of clinical nurse specialists, link nurses and those engaged in practice development. These roles could act as ‘conduits’ through which research-based messages for practice, and information for clinical decision making, could flow. This role should be explored and enhanced.

Notizen: Abstract: In the current study we examined the effects of coadministration of a serotonin 5-HT1A antagonist, (±)-1-(1H-indol-4-yloxy)-3-(cyclohexylamino)-2-propanol maleate (LY 206130), and a dual 5-HT and norepinephrine (NE) uptake inhibitor, duloxetine, on extracellular levels of NE, 5-HT, dopamine (DA), 5-hydroxyindoleacetic acid, and 3,4-dihydroxyphenylacetic acid in rat hypothalamus microdialysates. LY 206130 (3.0 mg/kg, s.c.) alone significantly increased NE and DA levels by 60 and 34%, respectively, without affecting 5-HT levels. Duloxetine administration at 4.0 mg/kg, i.p. alone produced no significant changes in levels of 5-HT, NE, or DA. In contrast, when LY 206130 and duloxetine were coadministered at 3.0 mg/kg, s.c. and 4.0 mg/kg, i.p., respectively, 5-HT, NE, and DA levels increased to 5.7-, 4.8-, and threefold over their respective basal levels. These data demonstrate that antagonism of somatodendritic 5-HT1A autoreceptors and concomitant inhibition of 5-HT and NE uptake with duloxetine may promote synergistic increases in levels of extracellular 5-HT, NE, and DA in hypothalamus of conscious, freely moving rats.

Notizen: Abstract: Slices of hippocampal area CA1 were used to test inhibitors of arachidonic acid metabolism for their effects on glutamate/aspartate release from the CA3-derived Schaffer collateral, commissural, and ipsilateral associational terminals. Test compounds [3 µM nordihydroguaiaretic acid (NDGA) and 1 µM 3-[3-(4-chlorobenzyl)-3-tert-butylthio-5-isopropylindol-2-yl]-2,2-dimethyl-propanoic acid (MK-886)] that reduced the production and release of 5-lipoxygenase metabolites also selectively reduced the K+-evoked release of aspartate. In contrast, the cyclooxygenase inhibitor indomethacin (100 µM) selectively enhanced the release of glutamate. At a concentration (100 µM) that nonselectively depressed the release of arachidonic acid and its metabolites, NDGA markedly depressed the release of aspartate, glutamate, and GABA. An inhibitor of the 12-lipoxygenase and an inhibitor of nitric oxide synthase did not affect the K+-evoked release of any transmitter amino acid. These results suggest that a 5-lipoxygenase product selectively enhances aspartate release and a cyclooxygenase product selectively depresses glutamate release. They are also consistent with previous evidence that arachidonic acid and/or platelet-activating factor enhances the release and depresses the uptake of glutamate and aspartate. The K+-evoked release of excitatory amino acids is much more sensitive to modulation by lipid mediators than is GABA release. Activation of NMDA receptors may enhance the K+-evoked release of glutamate and aspartate from CA1 slices by stimulating the production and release of lipid modulators.

Notizen: Abstract: Autoradiographic studies have shown that σ receptors are enriched in the locus coeruleus, the origin of noradrenergic projections to the cerebellum, as well as in the Purkinje, molecular, and granular layers and the interpositus cerebellar nucleus of the cerebellum itself. In contrast, the cerebellum is relatively poor in phencyclidine (PCP) binding sites, which have been historically confused with σ sites. The high ratio of σ to PCP receptors in cerebellum is advantageous for discriminating σ-mediated physiological effects. σ agonists and antagonists have been shown to regulate N-methyl-d-aspartate (NMDA)-stimulated norepinephrine release in hippocampus, which is innervated by locus coeruleus projections. We now report that σ drugs also regulate norepinephrine release from cerebellum. In contrast to findings in the hippocampus, where regulation is via σ1 and σ2 receptors, σ-mediated regulation in cerebellum seems to be primarily via σ1 receptors. In radioligand binding studies, we find that σ receptors primarily of the σ1 type are present in the cerebellum. We further report that binding to σ receptors in cerebellum is not affected by the addition of NMDA or glycine or by the presence of NMDA antagonists, suggesting that σ receptors are not located within the NMDA-operated cation channel in this brain region.

Notizen: Abstract: Peroxynitrite is a powerful oxidant formed by the near-diffusion-limited reaction of nitric oxide with superoxide. Large doses of peroxynitrite (〉2 mM) resulted in rapid cell swelling and necrosis of undifferentiated PC12 cells. However, brief exposure to lower concentrations of peroxynitrite (EC50 = 850 µM) initially (3–4 h) caused minimal damage to low-density cultures. By 8 h, cytoplasmic shrinkage with nuclear condensation and fragmentation became increasingly evident. After 24 h, 36% of peroxynitrite-treated cells demonstrated these features associated with apoptosis. In addition, 46% of peroxynitrite-treated cells demonstrated DNA fragmentation (by terminal-deoxynucleotide transferase-mediated dUTP-digoxigenin nick end-labeling) after 7 h, which was inhibited by posttreatment with the endonuclease inhibitor aurintricarboxylic acid. Serum starvation also resulted in apoptosis in control cells (23%), the percentage of which was not altered significantly by peroxynitrite treatment. Although peroxynitrite is known to be toxic to cells, the present study provides a first indication that peroxynitrite induces apoptosis. Furthermore, pretreatment of cells with nerve growth factor or insulin, but not epidermal growth factor, was protective against peroxynitrite-induced apoptosis. However, both acidic and basic fibroblast growth factors greatly increased peroxynitrite-initiated apoptosis, to 63 and 70%, respectively. Thus, specific trophic factors demonstrate differential regulation of peroxynitrite-induced apoptosis in vitro.

Notizen: Abstract: Carcinoid tumors are a group of neuroendocrine neoplasms distributed widely throughout the body but most commonly occurring in the gut. These tumors retain many characteristics of their neural crest origin, including secretion of neuroactive peptides and responsiveness to neurotrophic substances. Nerve growth factor (NGF), a neurotrophic protein involved in maintenance and differentiation of peripheral sympathetic and sensory neurons, regulates growth of several neural tumor cells by inducing a differentiated phenotype and subsequent inhibition of cell growth rate. We examined the actions of NGF in a functioning human pancreatic carcinoid cell line (termed BON). NGF has no effect on the cytoarchitecture or constitutive secretion of bioamines in this carcinoid cell line. NGF, however, stimulates the in vitro cellular proliferation of BON cells. BON cells possess mRNA for the NGF receptors (p75LNGFR and p140trkA) and membrane-associated tyrosine kinase activity is increased in response to NGF. Both the mitogenic activity of NGF, as well as the receptor-linked tyrosine kinase activity, can be abrogated in BON cells by the trkA inhibitor K-252a and specific anti-NGF antibody. Our studies demonstrate that NGF is a mitogen for this carcinoid cell line without effect on cellular phenotype or cytoarchitecture. NGF may play a role in the development and progression of human carcinoid tumors.

Notizen: Abstract: Forskolin treatment of cerebellar granule cells in culture resulted in bidirectional regulation of the expression of GABAA receptor α1 and α6 subunits. Thus, forskolin applied at 2 days in vitro (DIV) increased expression of the α1 subunit but decreased the expression of the α6 subunit. Values with respect to control cultures, both assayed at 9 DIV by immunoblotting, were 310 ± 48% for α1 and 25 ± 16% for the α6 subunit. Similar effects were evoked following chronic treatment with both dibutyryl cyclic AMP and 3-isobutyl-1-methylxanthine. Dideoxyforskolin had no effect on the level of expression of either the α1 or the α6 GABAA receptor subunits. The changes in subunit expression were accompanied by a 1.7-fold increase in number of total specific [3H]Ro 15-4513 binding sites expressed by intact cerebellar granule cells. This increase in total binding sites was accommodated by a 2.7-fold increase in number of diazepam-sensitive Ro 15-4513 binding sites in accordance with the observed increase in α1 subunit expression. The number of diazepam-insensitive subtype of binding sites were not significantly changed. These results suggest that GABAA receptor subtype expression can be differentially regulated by intracellular cyclic AMP concentration.