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: When standard triple therapy fails to eradicate Helicobacter pylori, quadruple ‘rescue’ therapy is often used which, in Europe, generally comprises colloidal bismuth subcitrate (CBS) based triple therapy and a proton pump inhibitor. Since hypochlorhydria could greatly increase absorption of the toxic bismuth ion from CBS, we investigated the bismuth status of patients receiving anti-H. pylori quadruple therapy.〈section xml:id="abs1-3"〉〈title type="main"〉Materials and Methods.In a prospective open label study 34 patients with nonulcer dyspepsia or peptic ulcer disease, who had failed to eradicate H. pylori with standard triple therapy, were subsequently treated with CBS, omeprazole, amoxycillin and metronidazole (BOAM). A further 35 patients received triple therapy for the eradication of H. pylori: CBS, amoxycillin and metronidazole (BAM) (n = 18); placebo bismuth, amoxycillin and metronidazole (AM) (n = 9); or omeprazole, amoxycillin and metronidazole (OAM) (n = 8). Whole blood bismuth levels were determined before and within 24 hours of completing treatment. Analysis of bismuth was by inductively coupled plasma mass spectrometry, and concentrations were compared between groups and with the Hillemand ‘alarm level’ for blood bismuth (50–100 µg/l).〈section xml:id="abs1-4"〉〈title type="main"〉Results.BOAM gave higher blood bismuth levels than BAM (difference in means 13.1, CI 6.0–20.2, p 〈 .001); three (8.8%) patients taking BOAM had concentrations within the Hillemand alarm level at 54.2, 64.7 and 91.8 µg/l. OAM and AM did not alter baseline blood bismuth levels.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions.Caution should be observed in prescribing CBS with gastric acid suppression, and alternative bismuth preparations should be considered.

Notizen: Objectives. The aim of this study was to compare the dissolution, bioavailability, and anti–Helicobacter pylori activity of bismuth subnitrate and colloidal bismuth subcitrate. This could, first, provide insights into the mechanism of action of bismuth and, second, help to develop optimal therapeutic strategies.Methods. Solubility and aquated size of bismuth species were determined in human gastric juice, while absorption into blood and urinary excretion of bismuth was determined in volunteers. Activity against H. pylori was determined in vitro in the presence and absence of antibiotics, while H. pylori eradication was compared in vivo.Results. Bismuth from colloidal bismuth subcitrate was at least 10% soluble and ultrafilterable and was absorbed in volunteers (〉0.5%), whereas that from bismuth subnitrate was insoluble and not absorbed (〈0.01%). Colloidal bismuth subcitrate was active against H. pylori (mean inhibitory concentration, ≤12.5 μg/ml), while bismuth subnitrate was inactive (〉400 μg/ml); neither was synergistic with antibiotics. With in vivo triple therapy, bismuth subnitrate was as effective as colloidal bismuth subcitrate in eradicating H. pylori (74% and 70% eradicated, respectively).Conclusions. Colloidal bismuth subcitrate, unlike bismuth subnitrate, is partially soluble, absorbed in humans, and directly toxic to H. pylori in vitro. Surprisingly, however, these preparations had similar efficacy in vivo against H. pylori within triple therapy, suggesting that bismuth compounds may also exhibit indirect antimicrobial effects. We propose that this is an effect on the gastric mucus layer. Nonabsorbable bismuth compounds should be preferentially considered in bismuth-based therapies against H. pylori, as they would minimize toxicity while maintaining efficacy.

Notizen: Proteolytic fragments of huntingtin (htt) in human lymphoblast cell lines from HD and control cases were compared to those in human HD striatal and cortical brain regions, by western blots with epitope-specific antibodies. HD lymphoblast cell lines were heterozygous and homozygous for the expanded CAG triplet repeat mutations, which represented adult onset and juvenile HD. Lymphoblasts contained NH2- and COOH-terminal htt fragments of 20–100 kDa, with many similar htt fragments in HD compared to control lymphoblast cell lines. Detection of htt fragments in a homozygous HD lymphoblast cell line demonstrated proteolysis of mutant htt. It was of interest that adult HD lymphoblasts showed a 63–64 kDa htt fragment detected by the NH2-domain antibody, which was not found in controls. In addition, control and HD heterozygous cells showed a common 60–61 kDa band (detected by the NH2-domain antibody), which was absent in homozygous HD lymphoblast cells. These results suggest that the 63–64 kDa and 60–61 kDa NH2-domain htt fragments may be associated with mutant and normal htt, respectively. In juvenile HD lymphoblasts, the presence of a 66-kDa, instead of the 63–64 kDa N-domain htt fragment, may be consistent with the larger polyglutamine expansion of mutant htt in the juvenile case of HD. Lymphoblasts and striatal or cortical regions from HD brains showed similarities and differences in NH2- and COOH-terminal htt fragments. HD striatum showed elevated levels of 50 and 45 kDa NH2-terminal htt fragments [detected with anti(1–17) serum] compared to controls. Cortex from HD and control brains showed similar NH2-terminal htt fragments of 50, 43, 40, and 20 kDa; lymphoblasts also showed NH2-terminal htt fragments of 50, 43, 40, and 20 kDa. In addition, a 48-kDa COOH-terminal htt band was elevated in HD striatum, which was also detected in lymphoblasts. Overall, results demonstrate that mutant and normal htt undergo extensive proteolysis in lymphoblast cell lines, with similarities and differences compared to htt fragments observed in HD striatal and cortical brain regions. These data for in vivo proteolysis of htt are consistent with the observed neurotoxicity of recombinant NH2-terminal mutant htt fragments expressed in transgenic mice and in transfected cell lines that may be related to the pathogenesis of HD.

Notizen: Background.  Although the anti-Helicobacter pylori activity of bismuth is well established, the therapeutic potential of other metal ions against the organism is not known.Materials and Methods.  We measured the minimum inhibitory concentrations of a series of metal ions, including several cobalt (II) compounds against four type strains and seven clinical isolates of H. pylori using three standard broth culture media and a defined medium. Other intestinal bacteria were also investigated for specificity of action.Results.  Cobalt chloride had marked activity against H. pylori (minimum inhibitory concentration range was 0.03–1.0 mg/l). The effect was specific because other transition metals had no effect and other intestinal bacteria were not affected by cobalt chloride. Activity was attributable to free cobalt ions as ligands inhibited activity in proportion to their affinity for the ions. Inhibition of cobalt activity was also observed in the presence of nickel, in a dose dependent fashion. However, cobalt activity was not directed towards the nickel-dependent urease enzyme because its effect was similar in wild-type and urease negative mutant strains of H. pylori. Finally, the viability of H. pylori was reduced at the same rate with 2 mg/l cobalt as with 1 mg/l amoxicillin.Conclusions.  Cobalt competes for nickel in its acquisition by H. pylori, but mediates toxicity in a nonurease dependent fashion. As cobalt MIC is similar to some antibiotics and 10 to a hundred times lower than for bismuth, cobalt may represent an effective form of therapy for H. pylori infection.

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: Opioids have been found to modulate the immune system by regulating the function of immunocompetent cells. Several studies suggest that the interaction between immune and opioid systems is not unidirectional, but rather reciprocal, in nature. In the CNS, one cellular target of immune system activation is the astrocytes. These glial cells have been shown to produce the opioid peptide, proenkephalin, to express the μ-, δ-, and κ-opioid receptors, and to respond to the immune factor interleukin-1β (IL1β) with an increased proenkephalin synthesis. To characterize more completely the astrocytic opioid response to immune factor stimulation, we examined the effect of IL1β (1 ng/ml) on the μ-receptor mRNA expression in primary astrocyte-enriched cultures derived from rat (postnatal day 1–2) cortex, striatum, cerebellum, hippocampus, and hypothalamus. A 24-h treatment with IL1β produced a 70–80% increase in the μ-receptor mRNA expression in the striatal, cerebellar, and hippocampal cultures but had no effect on this expression in the cortical and hypothalamic cultures. This observation represents one of the few demonstrated increases in levels of the μ-receptor mRNA in vitro or in vivo, since the cloning of the receptor. The enhanced μ-receptor mRNA expression, together with the previous observation that IL1β stimulates proenkephalin synthesis in astrocytes, supports the IL1β-mediated regulation of an astroglial opioid peptide and receptor in vitro, a phenomenon that may be significant in the modulation of the gliotic response to neuronal damage. Therefore, the astroglial opioid “system” may be important in the IL1β-initiated, coordinated response to CNS infection, trauma, or injury.

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.