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  • 1
    ISSN: 1471-0528
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In the fetal lamb model of hypoxic–ischaemic injury, the insult is followed by EEG depression, after which seizures emerge at 7–13 hours. We explored the relationship between the emergence of electrographic seizures and our estimate of the time of the cerebral injury in nine babies who underwent continuous video-EEG monitoring from soon after birth. Babies with prelabour insults had their first seizures before 12 hours of age, whereas those whose insult was peripartum had seizure onset at 18–20 hours of age. EEG seizure onset time could have important clinical and medico-legal applications, and be related to the time or severity of the insult, or both.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Anaesthesia 58 (2003), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Anaesthesia 57 (2002), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary In a randomised, double-blinded, two-centre trial we evaluated the effect of a microbiological filter (Supor®, Pall Life Sciences) on propofol injection pain. We studied 336 unpremedicated adult patients, who graded pain experienced during induction of anaesthesia with propofol on a 4-point verbal rating scale. Use of the microfilter reduced both the incidence and severity of propofol injection pain (p 〈 0.001). Incidence of severe pain in the filter group was 2.4% compared with 16.6% in the control group. Overall, 33.7% in the filter group experienced pain compared with 62.1% in the control group. A microbiological filter may provide a non-pharmacological alternative to a lidocaine/propofol mixture for reducing injection pain. It would also reduce the risk of any glass and bacterial contamination.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 20 (2004), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In the central nervous system, regeneration of injured axons and sprouting of intact axons are suppressed by myelin-derived molecules that bind to the Nogo receptor (NgR). We used a soluble form of the NgR (sNgR), constructed as an IgG of the human NgR extracellular domain, to manipulate plasticity of uninjured primary afferent and descending monoaminergic projections to the rat spinal cord following dorsal rhizotomy. Rats with quadruple dorsal rhizotomies were treated with intrathecal sNgR or saline, or were left untreated for 2 weeks. Rhizotomy alone resulted in sprouting of serotonergic axons and to a lesser extent, tyrosine-hydroxylase (TH)-expressing axons, while axons expressing dopamine-β-hydroxylase (DβH) were unaffected. Human IgG immunohistochemistry revealed that sNgR infused into the intrathecal space penetrated approximately 300 µm into spinal white and grey matter. Separate axonal populations differed in their responses to intrathecal sNgR: TH-expressing and DβH-expressing axons responded most and least vigorously, respectively. Serotonergic axons were identified by serotonin (5-HT) or serotonin transporter (SERT) immunohistochemistry. Interestingly, a large increase in 5-HT compared to SERT-positive axons density in both saline and sNgR-treated rats indicated that serotonergic axons both sprouted and increased their transmitter content in response to rhizotomy and sNgR treatment. Calcitonin gene-related peptide-positive axons were largely depleted ipsilaterally by rhizotomy, and sNgR increased axon density only in deeper contralateral laminae (III–V). GAP-43 immunohistochemistry revealed a small increase in axon density following dorsal rhizotomy that was further augmented by sNgR treatment. These results reveal a differential effect of myelin antagonism on distinct populations of spinally projecting axons.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Drotrecogin alfa (activated) is licensed in Europe for the treatment of severe sepsis in patients with multiple organ failure. We constructed a model to assess the cost effectiveness of drotrecogin alfa (activated) from the perspective of the UK National Health Service when used in adult intensive care units. Patient outcomes from a 28-day international clinical trial (PROWESS) and a subsequent follow-up study (EVBI) were supplemented with UK data. Cost effectiveness was assessed as incremental cost per life year and per quality adjusted life year saved compared to placebo alongside best usual care. Applying the 28-day mortality outcomes of the PROWESS study, the model produced a cost per life year saved of £4608 and cost per quality adjusted life year saved of £6679. Equivalent results using actual hospital outcomes were £7625 per life year and £11 051 per quality adjusted life year. Drotrecogin alfa (activated) appears cost effective in treating severe sepsis in UK intensive care units.
    Type of Medium: Electronic Resource
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  • 6
    Publication Date: 2013-05-01
    Description: Laura Howard, Sean Wyatt, Guhan Nagappan, and Alun M. Davies The somatosensory and sympathetic innervation of the vertebrate head is derived principally from the neurons of trigeminal and superior cervical ganglia (SCG), respectively. During development, the survival of both populations of neurons and the terminal growth and branching of their axons in the tissues they innervate is regulated by the supply of nerve growth factor (NGF) produced by these tissues. NGF is derived by proteolytic cleavage of a large precursor protein, proNGF, which is recognised to possess distinctive biological functions. Here, we show that proNGF promotes profuse neurite growth and branching from cultured postnatal mouse SCG neurons. In marked contrast, proNGF does not promote the growth of trigeminal neurites. Studies using compartment cultures demonstrated that proNGF acts locally on SCG neurites to promote growth. The neurite growth-promoting effect of proNGF is not observed in SCG neurons cultured from p75 NTR -deficient mice, and proNGF does not phosphorylate the NGF receptor tyrosine kinase TrkA. These findings suggest that proNGF selectively promotes the growth of neurites from a subset of NGF-responsive neurons by a p75 NTR -dependent mechanism during postnatal development when the axons of these neurons are ramifying within their targets in vivo .
    Print ISSN: 0950-1991
    Electronic ISSN: 1477-9129
    Topics: Biology
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  • 7
    Publication Date: 2018-11-25
    Description: Laura Howard, Erin Wosnitzka, Darian Okakpu, Matthew A. White, Sean Wyatt, and Alun M. Davies TWE-PRIL is a naturally occurring fusion protein of components of two TNF superfamily members: the extracellular domain of APRIL; and the intracellular and transmembrane domains of TWEAK with no known function. Here, we show that April –/– mice (which lack APRIL and TWE-PRIL) exhibited overgrowth of sympathetic fibres in vivo , and sympathetic neurons cultured from these mice had significantly longer axons than neurons cultured from wild-type littermates. Enhanced axon growth from sympathetic neurons cultured from April –/– mice was prevented by expressing full-length TWE-PRIL in these neurons but not by treating them with soluble APRIL. Soluble APRIL, however, enhanced axon growth from the sympathetic neurons of wild-type mice. siRNA knockdown of TWE-PRIL but not siRNA knockdown of APRIL alone also enhanced axon growth from wild-type sympathetic neurons. Our work reveals the first and physiologically relevant role for TWE-PRIL and suggests that it mediates reverse signalling.
    Keywords: Neural development
    Print ISSN: 0950-1991
    Electronic ISSN: 1477-9129
    Topics: Biology
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  • 8
    Publication Date: 2013-11-20
    Description: Catarina Osorio, Pedro J. Chacon, Lilian Kisiswa, Matthew White, Sean Wyatt, Alfredo Rodriguez-Tebar, and Alun M. Davies Dendrite size and morphology are key determinants of the functional properties of neurons. Here, we show that growth differentiation factor 5 (GDF5), a member of the bone morphogenetic protein (BMP) subclass of the transforming growth factor β superfamily with a well-characterised role in limb morphogenesis, is a key regulator of the growth and elaboration of pyramidal cell dendrites in the developing hippocampus. Pyramidal cells co-express GDF5 and its preferred receptors, BMP receptor 1B and BMP receptor 2, during development. In culture, GDF5 substantially increased dendrite, but not axon, elongation from these neurons by a mechanism that depends on activation of SMADs 1/5/8 and upregulation of the transcription factor HES5. In vivo , the apical and basal dendritic arbours of pyramidal cells throughout the hippocampus were markedly stunted in both homozygous and heterozygous Gdf5 null mutants, indicating that dendrite size and complexity are exquisitely sensitive to the level of endogenous GDF5 synthesis.
    Print ISSN: 0950-1991
    Electronic ISSN: 1477-9129
    Topics: Biology
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