Medicine & Health

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Now showing 1 - 10 of 59
  • (2008) Lomax, A; Bertrand, P. P; Barajas, A; Bertrand, R
    Conference Paper
    Serotonin (5-HT) containing enterochromaffin (EC) cells of the intestine detect chemical and mechanical stimuli in the lumen and respond by releasing 5-HT on to afferent nerve terminals. Recent electrochemical studies in healthy mucosa have shown that the real-time release of 5-HT is a dynamic and highly regulated process, but how this might change in disease is unknown. Our aim was to characterize real-time uptake and release of 5-HT in a mouse model of colitis and compare it with ELISA measurements of 5-HT. Real-time electrochemical methods were coupled with an ELISA assay to determine the effect on 5-HT availability of a mouse model of inflammation (5% w/v dextran sodium sulphate (DSS) induced colitis). Peak and steady state (SS) 5-HT concentrations (calculated from the oxidation current at +400 mV; amperometry mode) were measured with our without the serotonin reuptake transporter blocker fluoxetine (1 lM) in control and DSS-treated mice. Paired and unpaired data were compared with a one way ANOVA (P < 0.05). In mouse colon, SS release of 5-HT was 1.9 ± 0.6 lM (n = 9) and compression-evoked release was 7.1 ± 2.5 lM (n = 9). In DSS treated mice, the release of 5-HT was significantly increased (SS: 3.4 ± 0.6 lM; peak: 14.7 ± 3.0 lM; n = 11). In control mice, fluoxetine significantly increased peak (9.9 ± lM) but not SS release (2.6 ± 0.4 lM), while in DSS mice both were significantly increased (SS: 7.3 ± 1.2 lM; peak: 23.4 ± 4.1 lM). The effects of fluoxetine in DSS mice were greater than in control. ELISA assays supported these data, showing an increase in 5-HT release detected from inflamed colon (n = 5) compared to control (n = 5) in unstimulated or mechanically stimulated preparations and with or without fluoxetine. The release and uptake of 5-HT from the EC cells of the mouse colon are increased during DSS colitis. Our electrochemical data show that both peak and steady state levels are increased and these changes are mirrored by the ELISA data. In addition, the localised 5-HT concentrations at the site of release, measured using amperometry, are significantly higher than those reported using ELISA techniques. Overall, these data show that during colitis, 5-HT availability will be increased. These raised concentrations may substantially alter the activation or desensitisation of serotonin receptors on afferent nerve terminals.

  • (2007) Bertrand, P. P
    Conference Paper
    Background/Aims: Enterochromaffin (EC) cells are sensors in the intestinal lumen that detect chemical or mechanical stimuli and respond with the release of serotonin (5-HT). 5-HT can activate local reflexes but whether local activation of enteric neural circuits also evoke 5-HT release is unclear. Methods: Recordings were made from full-thickness preparations of guinea pig ileum using electrochemical techniques with carbon fibre electrodes placed in the mucosa to measure local concentrations of 5-HT. The tension in the circular muscle (CM) was recorded with a force transducer. Amplitude and time course of local 5-HT release events and muscle contractions were measured and compared using paired Student’s t-test with Bonferroni’s correction for multiple comparisons. Results: Stretch of the CM caused 5-HT release and reflex contraction of the CM. Focal electrical stimulation of the intestine near to the carbon fibre electrode evoked 5-HT release and caused a local contraction in the ring of CM where the recording site was located. Paralysis of the smooth muscle with papaverine (100 mm; n55), sodium nitroprusside (100 mm; n55) or isoproterenol (1 mm; n55) significantly reduced (o25% of control) the stretch-evoked release of 5-HT. Similarly, isoproterenol (1 mm; n54) or sodium nitroprusside (100 mm; n53), abolished (o10% of control) the electrically evoked release of 5-HT. Atropine (1 mm; n53), which would be expected to block muscarinic input to the EC cell, did not reduce stretch-evoked 5-HT release. Conclusion: The present study provides direct evidence that activated enteric nerves are not responsible for the 5-HT release seen during local reflexes. There was little residual 5-HT release in response to stretch or electrical stimulation of the nerves in paralysed preparations and atropine did not reduce reflex-evoked 5-HT release. Together, these data suggest that mechnical, and not neural, stimuli provide an important excitatory input to the EC cells.

  • (2006) Gattellari, Melina; Worthington, John; Zwar, N; Leung, Dominic; Gelder, James; Ukoumunne, O; Anderson, Craig
    Conference Paper
    Background: Warfarin reduces stroke risk associated with non-valvular atrial fibrillation (NVAF) yet is underutilised. Wider use of warfarin is advocated to reduce the risk of mortality and disability. Aims: We have funding to: 1) develop an innovative intervention (Stop-Stroke) to optimise General Practitioners' (GPs) management of NVAF; 2) evaluate Stop-Stroke using a rigorous, clustered RCT; 3) determine the incremental cost per life year saved due to Stop-Stroke. Methods: Random allocation of 110 GPs from across Australia to control or the Stop-Stroke intervention. Stop-Stroke will comprise patient identification and recall, management plans, peer coaching, specialist support and decision tools. Data will be collected from over 2500 patients. Primary Outcome: The proportion of patients with NVAF over 65 who are on 'appropriate' antithrombotic treatment (judged against standardised criteria) will be compared. 'Appropriate treatment' will be determined using standardised medical record audits and blinded expert review. Results and Analysis: Outcomes will be compared, adjusting for clustered randomisation. Analysis will be by intention to treat. Implications: There is no proven implementation strategy for enhancing the prevention of stroke in patients with NVAF. If effective, Stop-Stroke will bridge evidence-practice gaps in managing NVAF and reduce the risk of stroke and disability in the Australian community.

  • (2007) Gattellari, Melina; Worthington, John; Zwar, N; Middleton, S
    Conference Paper
    Background: Optimising the management of NVAF is proving difficult and the potential to reduce stroke risk is yet to be fully realised. Barriers to using anticoagulants need to be addressed. Aims: To describe GP management of NVAF and barriers to the use of warfarin. Methods: Representative survey of Australian GPs. b: Of the 593 GP participants (response = 64.3%), 46.2% reported the experience of an ischaemic stroke in their NVAF patients without anticoagulation. When asked to select treatment for a hypothetical NVAF patient at 'high' risk of stroke, 71.0% appropriately selected warfarin. In the presence of a minor falls risk, 45.4% of GPs selected warfarin. Only 28.8% would anticoagulate the patient at high risk of stroke with a history of recurrent nosebleeds and 16.9% would anti-coagulate such a patient with a treated peptic ulcer bleed. 37.9% agreed that 'it is hard to decide whether the benefits of warfarin outweigh the risks', while only 54.3% agreed they fully understood their patients' views on both the benefits and risks of warfarin. Conclusion: Any strategy to improve the evidence based management of NVAF must address the excessive concerns clinicians have about anticoagulation. We need to reduce anxiety about 'acts of commission' in the management of NVAF.

  • (1995) Bandyopadhyay, Srikanta; Mukherjee, S; Perera, D; Mori, K; Swain, M; Bell, Toby
    Conference Paper

  • (1998) Wool, R; Kusefoglu, S; Khot, S; Zhao, R; Palmese, Gaetano; Boyd, Andrew; Fisher, Keith; Bandyopadhyay, Srikanta; Williams, J; Wang, Chaoyuan
    Conference Paper

  • (2006) Gaff, C; Cowan, Ruth; Meiser, Bettina; Lindeman, G
    Conference Paper

  • (2003) Thewes, Belinda; Gunn, H; Meiser, Bettina
    Conference Paper

  • (2003) Kasparian, N; Meiser, Bettina; Hughes, T; Job, R; Mann, G
    Conference Paper

  • (2003) Tiller, K; Meiser, Bettina; Tucker, Katherine; Andrews, L; Gaff, C; Kirk, J; Phillips, K; Duding, T; Friedlander, Michael
    Conference Paper