• Laparotomy and laparoscopy diversely affect macrophage-associated antimicrobial activity in a murine model

      Huang, Shun Gen; Li, Yi Ping; Zhang, Qi; Redmond, H Paul; Wang, Jiang Huai; Wang, Jian (2013-06-20)
      Abstract Background Surgical intervention-related trauma contributes largely to the development of postoperative immunosuppression, with reduced resistance to secondary bacterial infection. This study compared the impact of laparotomy versus laparoscopy on macrophage-associated bactericidal ability and examined whether laparotomy renders the host more susceptible to microbial infection. Results BALB/c mice were randomized into control, laparotomy, and laparoscopy groups. Laparotomy, but not laparoscopy, significantly downregulated CR3 expression on macrophages, diminished macrophage-induced uptake and phagocytosis of E. coli and S. aureus, and impaired macrophage-mediated intracellular bacterial killing. Consistent with this, mice that underwent laparotomy displayed substantially higher bacterial counts in the blood and visceral organs as well as a significantly enhanced mortality rate following bacterial infection, whereas mice subjected to laparoscopy did not show any defects in their bacterial clearance. Conclusion Laparotomy has an adverse effect on host innate immunity against microbial infection by impairing macrophage-mediated phagocytosis and killing of the invaded bacteria. By contrast, laparoscopy appears to preserve macrophage-associated bactericidal ability, thus alleviating the development of postoperative immunosuppression.
    • Lapse and relapse following inpatient treatment of opiate dependence.

      Smyth, B P; Barry, J; Keenan, E; Ducray, K; Addiction Service, Bridge House, Cherry Orchard Hospital, Ballyfermot, Dublin 10. bobby.smyth@hse.ie (2010-06)
      We conducted a prospective follow-up study of consecutive opiate dependent patients admitted to a residential addiction treatment service for detoxification. We measured the rate of relapse following discharge, and sought to identify factors that were associated with early relapse (i.e., a return to daily opiate use). Follow-up interviews were conducted with 109 patients, of whom, 99 (91%) reported a relapse. The initial relapse occurred within one week in 64 (59%) cases. Multivariate survival analysis revealed that earlier relapse was significantly predicted by younger age, greater heroin use prior to treatment, history of injecting, and a failure to enter aftercare. Unexpectedly, those who were in a relationship with an opiate user had significantly delayed relapse. Those who completed the entire six-week inpatient treatment programme also had a significantly delayed relapse. In order to reduce relapse and the associated increased risk of fatal overdose, services providing residential opiate detoxification should prepare people for admission, strive to retain them in treatment for the full admission period and actively support their entry into planned aftercare in order to improve outcome.
    • The last medical decade.

      Murphy, J F A (2010-04)
    • Latecomers to the electronic health record table

      O'Mahoney, B (Irish Medical Journal, 2011-06)
    • Leadership, fairness and gender: a practitioner's perspective [doctoral thesis]

      Flynn, Colette; University College Cork (University College Cork, 2014-10)
    • Learning from H1N1--hospital doctors and pandemic influenza.

      Kane, N B; Healy, G M; Connolly, M A (2010-05)
    • Learning from the past

      Harding, Mairead (Irish Dental Association, 2012-06)
    • Lentiviral vector mediated modification of mesenchymal stem cells & enhanced survival in an in vitro model of ischaemia

      McGinley, Lisa; McMahon, Jill; Strappe, Padraig; Barry, Frank; Murphy, Mary; O'Toole, Daniel; O'Brien, Timothy (2011-03-07)
      Abstract Introduction A combination of gene and cell therapies has the potential to significantly enhance the therapeutic value of mesenchymal stem cells (MSCs). The development of efficient gene delivery methods is essential if MSCs are to be of benefit using such an approach. Achieving high levels of transgene expression for the required period of time, without adversely affecting cell viability and differentiation capacity, is crucial. In the present study, we investigate lentiviral vector-mediated genetic modification of rat bone-marrow derived MSCs and examine any functional effect of such genetic modification in an in vitro model of ischaemia. Methods Transduction efficiency and transgene persistence of second and third generation rHIV-1 based lentiviral vectors were tested using reporter gene constructs. Use of the rHIV-pWPT-EF1-α-GFP-W vector was optimised in terms of dose, toxicity, cell species, and storage. The in vivo condition of ischaemia was modelled in vitro by separation into its associated constituent parts i.e. hypoxia, serum and glucose deprivation, in which the effect of therapeutic gene over-expression on MSC survival was investigated. Results The second generation lentiviral vector rHIV-pWPT-EF1-α-GFP-W, was the most efficient and provided the most durable transgene expression of the vectors tested. Transduction with this vector did not adversely affect MSC morphology, viability or differentiation potential, and transgene expression levels were unaffected by cryopreservation of transduced cells. Over-expression of HSP70 resulted in enhanced MSC survival and increased resistance to apoptosis in conditions of hypoxia and ischaemia. MSC differentiation capacity was significantly reduced after oxygen deprivation, but was preserved with HSP70 over-expression. Conclusions Collectively, these data validate the use of lentiviral vectors for efficient in vitro gene delivery to MSCs and suggest that lentiviral vector transduction can facilitate sustained therapeutic gene expression, providing an efficient tool for ex vivo MSC modification. Furthermore, lentiviral mediated over-expression of therapeutic genes in MSCs may provide protection in an ischaemic environment and enable MSCs to function in a regenerative manner, in part through maintaining the ability to differentiate. This finding may have considerable significance in improving the efficacy of MSC-based therapies.
    • Levels of S100B are raised in female patients with schizophrenia

      O’Connell, Kara; Thakore, Jogin; Dev, Kumlesh K (2013-05-24)
      Abstract Background The neurotrophic factor, S100B, is released primarily from astrocytes, with serum and CSF levels of S100B reported as altered in schizophrenia. However, many of these reports are contradictory. Here, serum levels of S100B in schizophrenia and influence of age, gender, medication and illness severity were examined. Methods Serum S100B levels were measured in patients with schizophrenia treated with clozapine. Lifestyle, metabolic and illness severity parameters were correlated with S100B concentrations. Results Data showed raised serum levels of S100B in schizophrenia female patients, but not male patients, compared to controls. Correlation analysis demonstrated a positive association between S100B serum concentrations and BMI. Conclusions This study supports previous findings that adipocytes may contribute to S100B serum concentrations in females, in addition to astrocytes. This study also supports the hypothesis that metabolic effects of medication, lifestyle choices and the illness itself, may be contributing factors to altered levels of S100B.
    • Lifestyle practices and the health promoting environment of hospital nurses.

      Hope, A; Kelleher, C C; O'Connor, M; Centre for Health Promotion Studies, National University of Ireland, Galway, Republic of Ireland. (1998-08)
      Lifestyle practices and the health promoting environment of hospital nurses This paper examined the lifestyle practices of hospital nurses and the impact of specific interventions in the hospital environment. The perception of nurse as health promoter and as carer of AIDS patients was also examined. A self-administered questionnaire was used to collect data at two different time periods. The sample represented 729 nurses (at pre- and post-time periods), both qualified and student nurses. Qualified nurses reported the highest stress levels while student nurses reported more negative lifestyle practices such as smoking, alcohol consumption and drug use. A greater number of current smokers (29%) consumed alcohol and used drugs than non-smokers. The impact of intervention strategies around compliance with smoking policy and work-site walk routes reduced exposure to passive smoking at work for qualified nurses and increased exercise participation for both groups of nurses. Workplace was identified as the main source of stress which included relationships at work and demands of the job. Hospital nurses experiencing high work stress were more likely to use professional support and personal coping (discuss problems with friends/family, have a good cry and eat more) than others. Nurses believed in the importance of health promotion as part of their work; however, qualified nurses felt more confident and gave more health related information than student nurses. Student nurses perceived a lower risk of contacting AIDS through work and a higher concern/worry in caring for AIDS patients than qualified nurses.
    • Limited cross-border infections in patients newly diagnosed with HIV in Europe

      Frentz, Dineke; Wensing, Annemarie M J; Albert, Jan; Paraskevis, Dimitrios; Abecasis, Ana B; Hamouda, Osamah; Jørgensen, Louise B; Kücherer, Claudia; Struck, Daniel; Schmit, Jean-Claude; et al. (2013-04-03)
      Abstract Background International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patients were determined across Europe. Results Data came from the SPREAD programme which collects samples of newly diagnosed patients that are representative for national HIV epidemics. 4260 pol sequences from 25 European countries and Israel collected in 2002–2007 were included.We identified 457 clusters including 1330 persons (31.2% of all patients). The cluster size ranged between 2 and 28. A number of 987 patients (74.2%) were part of a cluster that consisted only of patients originating from the same country. In addition, 135 patients (10.2%) were in a cluster including only individuals from neighboring countries. Finally, 208 patients (15.6%) clustered with individuals from countries without a common border. Clustering with patients from the same country was less prevalent in patients being infected with B subtype (P-value <0.0001), in men who have sex with men (P-value <0.0001), and in recently infected patients (P-value =0.045). Conclusions Our findings indicate that the transmission of HIV-1 in Europe is predominantly occurring between patients from the same country. This could have implications for HIV-1 transmission prevention programmes. Because infections through travelling between countries is not frequently observed it is important to have good surveillance of the national HIV-1 epidemics.
    • Linguistic and psychometric validation of the Diabetes-Specific Quality-of-Life Scale in U.K. English for adults with type 1 diabetes.

      Cooke, Debbie; O'Hara, Mary Clare; Beinart, Naomi; Heller, Simon; La Marca, Roberto; Byrne, Molly; Mansell, Peter; Dinneen, Sean F; Clark, Marie; Bond, Rod; et al. (Diabetic Care, 2013-05)
      To develop a linguistically and psychometrically validated U.K. English (U.K./Ireland) version of the Diabetes-Specific Quality-of-Life Scale (DSQOLS) for adults with type 1 diabetes.
    • Lipofuscin accumulation and autophagy in glaucomatous human lamina cribrosa cells

      McElnea, Elizabeth M; Hughes, Emily; McGoldrick, Aloysius; McCann, Amanda; Quill, Barry; Docherty, Neil; Irnaten, Mustapha; Farrell, Michael; Clark, Abbot F; O’Brien, Colm J; et al. (2014-12-02)
      Abstract Background Disease associated alterations in the phenotype of lamina cribrosa (LC) cells are implicated in changes occurring at the optic nerve head (ONH) in glaucoma. Lipofuscin, the formation of which is driven by reactive oxygen species (ROS), is an intralysosomal, non-degradable, auto-fluorescent macromolecule which accumulates with age and can affect autophagy - the lysosomal degradation of a cell’s constituents. We aimed to compare the content of lipofuscin-like material and markers of autophagy in LC cells from normal and glaucoma donor eyes. Methods The number and size of peri-nuclear lysosomes were examined by transmission electron microscopy (TEM). Cellular auto-fluorescence was quantified by flow cytometry. Cathepsin K mRNA levels were assessed by PCR. Autophagy protein 5 (Atg5) mRNA and protein levels were analysed by PCR and Western blot. Protein levels of subunits of the microtubule associated proteins (MAP) 1A and 1B, light chain 3 (LC3) I and II were analysed by Western blot. Immunohistochemical staining of LC3-II in ONH sections from normal and glaucomatous donor eyes was performed. Results A significant increase in the number of peri-nuclear lysosomes [4.1 × 10,000 per high power field (h.p.f.) ± 1.9 vs. 2.0 × 10,000 per h.p.f. ± 1.3, p = 0.002, n = 3] and whole cell auto-fluorescence (83.62 ± 45.1 v 41.01 ± 3.9, p = 0.02, n = 3) was found in glaucomatous LC cells relative to normal LC cells. Glaucomatous LC cells possessed significantly higher levels of Cathepsin K mRNA and Atg5 mRNA and protein. Enhanced levels of LC3-II were found in both LC cells and optic nerve head sections from glaucoma donors. Conclusions Increased lipofuscin formation is characteristic of LC cells from donors with glaucoma. This finding confirms the importance of oxidative stress in glaucoma pathogenesis. Intracellular lipofuscin accumulation may have important effects on autophagy the modification of which could form the basis for future novel glaucoma treatments.
    • Lipoprotein particle distribution and skeletal muscle lipoprotein lipase activity after acute exercise

      Harrison, Michael; Moyna, Niall M; Zderic, Theodore W; O’Gorman, Donal J; McCaffrey, Noel; Carson, Brian P; Hamilton, Marc T (2012-06-06)
      AbstractBackgroundMany of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS), it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects.MethodsUsing a randomized cross-over design, very low density lipoprotein (VLDL) responses were evaluated in eight men on the morning after i) an inactive control trial (CON), ii) exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF), and iii) after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL).ResultsThe intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG) determined biochemically, and mean VLDL size were lower in EX-DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70–120 nm (large) particle range. In contrast, VLDL-TG was lower in both EX-DEF and EX-BAL compared to CON in the 43–55 nm (medium) particle range. VLDL-TG in smaller particles (29–43 nm) was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL) activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state.ConclusionsThese findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in LPL activity.
    • Listening to carers

      The Carers Association (The Carers Association, 2008-01)
    • Litigation in paediatrics

      Murphy, JFA (Irish Medical Journal, 2011-03)