• Limiting cardiovascular risk in Irish rheumatoid arthritis patients.

      Ambrose, N L; O'Connell, P; Kearns, G; Rheumatology Department, Beaumont Hospital, Dublin, Ireland. nambrose2001@yahoo.co.uk (2009-03)
      Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease and premature death.
    • Linking audit and clinical effectiveness in the lung tumour service

      Gorman, Sharon; Kelly, Jacinta; Midland Regional Hospital, Mullingar (Midland Regional Hospital, Mullingar, 2009-05-28)
      Clinical Audit plays an important role in the evaluation of care and clinical outcomes for all patients. In conjunction with the respiratory nurse specialist a retrospective chart audit of the regional lung cancer service was undertaken at the Midlands Regional Hospital Mullingar (MRHM). The lung cancer service has been established for four years and has set its standards in line with NICE guidelines and Irish guidelines for the clinical management of lung cancer. An audit tool was developed by the audit facilitator in conjunction with the respiratory nurse specialist and key department personnel. The tool aimed to measure length of time taken for key steps in the patients care pathway. A pilot audit was carried out and the tool was evaluated. The audit tool provided accurate recording of information at key points in the patient’s care which allows for a thorough service evaluation. The data collected and analysed gives vital information on the quality of service, and showed where there are deficits in service provision that need to be addressed.
    • Linking audit and clinical effectiveness in the lung tumour service

      Gorman, S; Doyle, C; O’Brien, A; Midlands Regional Hospital Mullingar (MRHM). (International Society for Quality in Health Care, 2009)
      The aim of the audit is to capture the lung cancer patient’s care pathway, to improve clinical effectiveness, advance service quality and improve standards of care by reducing diagnosis and treatment time delays.
    • Lipid raft association restricts CD44-ezrin interaction and promotion of breast cancer cell migration.

      Donatello, Simona; Babina, Irina S; Hazelwood, Lee D; Hill, Arnold D K; Nabi, Ivan R; Hopkins, Ann M; Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland. (2012-12)
      Cancer cell migration is an early event in metastasis, the main cause of breast cancer-related deaths. Cholesterol-enriched membrane domains called lipid rafts influence the function of many molecules, including the raft-associated protein CD44. We describe a novel mechanism whereby rafts regulate interactions between CD44 and its binding partner ezrin in migrating breast cancer cells. Specifically, in nonmigrating cells, CD44 and ezrin localized to different membranous compartments: CD44 predominantly in rafts, and ezrin in nonraft compartments. After the induction of migration (either nonspecific or CD44-driven), CD44 affiliation with lipid rafts was decreased. This was accompanied by increased coprecipitation of CD44 and active (threonine-phosphorylated) ezrin-radixin-moesin (ERM) proteins in nonraft compartments and increased colocalization of CD44 with the nonraft protein, transferrin receptor. Pharmacological raft disruption using methyl-β-cyclodextrin also increased CD44-ezrin coprecipitation and colocalization, further suggesting that CD44 interacts with ezrin outside rafts during migration. Conversely, promoting CD44 retention inside lipid rafts by pharmacological inhibition of depalmitoylation virtually abolished CD44-ezrin interactions. However, transient single or double knockdown of flotillin-1 or caveolin-1 was not sufficient to increase cell migration over a short time course, suggesting complex crosstalk mechanisms. We propose a new model for CD44-dependent breast cancer cell migration, where CD44 must relocalize outside lipid rafts to drive cell migration. This could have implications for rafts as pharmacological targets to down-regulate cancer cell migration.
    • Lipoprotein subclass patterns in women with polycystic ovary syndrome (PCOS) compared with equally insulin-resistant women without PCOS.

      Phelan, N; O'Connor, A; Kyaw-Tun, T; Correia, N; Boran, G; Roche, H M; Gibney, J; Department of Endocrinology and Diabetes, Adelaide and Meath Hospital, and School, of Public Health and Population Science, University College Dublin, Dublin 24,, Ireland. (2012-02-01)
      OBJECTIVES: Women with polycystic ovary syndrome (PCOS) are more insulin resistant and display an atherogenic lipid profile compared with normal women of similar body mass index (BMI). Insulin resistance (IR) at least partially underlies the dyslipidemia of PCOS, but it is unclear whether PCOS status per se confers additional risk. RESEARCH DESIGN AND METHODS: Using a case-control design, we compared plasma lipids and lipoprotein subclasses (using polyacrylamide gel tube electrophoresis) in 70 women with PCOS (National Institutes of Health criteria) and 70 normal women pair matched for age, BMI, and IR (homeostasis model assessment-IR, quantitative insulin sensitivity check index, and the Avignon Index). Subjects were identified as having a (less atherogenic) type A pattern consisting predominantly of large low-density lipoprotein (LDL) subfractions or a (more atherogenic) non-A pattern consisting predominantly of small-dense LDL subfractions. RESULTS: Total, high-density lipoprotein, or LDL cholesterol, or triacylglycerol did not differ between the groups, but very low-density lipoprotein levels (P<0.05) were greater in women with PCOS, whereas a non-A LDL profile was seen in 12.9% compared with 2.9% of controls (P<0.05, chi2). Multiple regression analysis revealed homeostasis model assessment-IR and waist circumference to be independent predictors of very low-density lipoprotein together explaining 40.2% of the overall variance. Logistic regression revealed PCOS status to be the only independent determinant of a non-A LDL pattern (odds ratio 5.48 (95% confidence interval 1.082-27.77; P<0.05). CONCLUSIONS: Compared with women matched for BMI and IR, women with PCOS have potentially important differences in lipid profile with greater very low-density lipoprotein levels and increased rates of a more atherogenic non-A LDL pattern.
    • Lipoxin A4 stimulates calcium-activated chloride currents and increases airway surface liquid height in normal and cystic fibrosis airway epithelia.

      Verrière, Valia; Higgins, Gerard; Al-Alawi, Mazen; Costello, Richard W; McNally, Paul; Chiron, Raphaël; Harvey, Brian J; Urbach, Valérie; Department of Molecular Medicine, RCSI Education and Research Centre, Beaumont Hospital, Dublin, Ireland. (2012)
      Cystic Fibrosis (CF) is a genetic disease characterised by a deficit in epithelial Cl(-) secretion which in the lung leads to airway dehydration and a reduced Airway Surface Liquid (ASL) height. The endogenous lipoxin LXA(4) is a member of the newly identified eicosanoids playing a key role in ending the inflammatory process. Levels of LXA(4) are reported to be decreased in the airways of patients with CF. We have previously shown that in normal human bronchial epithelial cells, LXA(4) produced a rapid and transient increase in intracellular Ca(2+). We have investigated, the effect of LXA(4) on Cl(-) secretion and the functional consequences on ASL generation in bronchial epithelial cells obtained from CF and non-CF patient biopsies and in bronchial epithelial cell lines. We found that LXA(4) stimulated a rapid intracellular Ca(2+) increase in all of the different CF bronchial epithelial cells tested. In non-CF and CF bronchial epithelia, LXA(4) stimulated whole-cell Cl(-) currents which were inhibited by NPPB (calcium-activated Cl(-) channel inhibitor), BAPTA-AM (chelator of intracellular Ca(2+)) but not by CFTRinh-172 (CFTR inhibitor). We found, using confocal imaging, that LXA(4) increased the ASL height in non-CF and in CF airway bronchial epithelia. The LXA(4) effect on ASL height was sensitive to bumetanide, an inhibitor of transepithelial Cl(-) secretion. The LXA(4) stimulation of intracellular Ca(2+), whole-cell Cl(-) currents, conductances and ASL height were inhibited by Boc-2, a specific antagonist of the ALX/FPR2 receptor. Our results provide, for the first time, evidence for a novel role of LXA(4) in the stimulation of intracellular Ca(2+) signalling leading to Ca(2+)-activated Cl(-) secretion and enhanced ASL height in non-CF and CF bronchial epithelia.
    • Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study.

      Hampel, Harald; Ewers, Michael; Burger, Katharina; Annas, Peter; Mortberg, Anette; Bogstedt, Anna; Frolich, Lutz; Schroder, Johannes; Schonknecht, Peter; Riepe, Matthias W; et al. (2012-02-01)
      OBJECTIVE: Lithium, a first-line drug for the treatment of bipolar depression, has recently been shown to regulate glycogen synthase kinase-3 (GSK-3), a kinase that is involved in the phosphorylation of the tau protein. Since hyperphosphorylation of tau is a core pathological feature in Alzheimer's disease, lithium-induced inhibition of GSK-3 activity may have therapeutic effects in Alzheimer's disease. In the current study, we tested the effect of short-term lithium treatment in patients with Alzheimer's disease. METHOD: A total of 71 patients with mild Alzheimer's disease (Mini-Mental State Examination score > or = 21 and < or = 26) were successfully randomly assigned to placebo (N = 38) or lithium treatment (N = 33) at 6 academic expert memory clinics. The 10-week treatment included a 6-week titration phase to reach the target serum level of lithium (0.5-0.8 mmol/L). The primary outcome measures were cerebrospinal fluid (CSF) levels of phosphorylated tau (p-tau) and GSK-3 activity in lymphocytes. Secondary outcome measures were CSF concentration of total tau and beta-amyloid(1-42) (Abeta(1-42)), plasma levels of Abeta(1-42), Alzheimer's Disease Assessment Scale (ADAS)-Cognitive summary scores, MMSE, and Neuropsychiatric Inventory (NPI). Patients were enrolled in the study from November 2004 to July 2005. RESULTS: No treatment effect on GSK-3 activity or CSF-based biomarker concentrations (P > .05) was observed. Lithium treatment did not lead to change in global cognitive performance as measured by the ADAS-Cog subscale (P = .11) or in depressive symptoms. CONCLUSIONS: The current results do not support the notion that lithium treatment may lead to reduced hyperphosphorylation of tau protein after a short 10-week treatment in the Alzheimer's disease target population. TRIAL REGISTRATION: (Controlled-Trials.com) Identifier: ISRCTN72046462.
    • Litigation in paediatrics

      Murphu, JFA (Irish Medical Journal, 2011-03)
      on the issue. This is understandable. Most individuals are healthy during their childhood and have less need of and less interaction with medical services when compared with adults. However, Paediatric litigation does happen and furthermore it is likely to increase in parallel with other specialties. Carroll and Buddenbaum1 have described the pattern of Paediatric litigation in the US. The annual incidence of malpractice claims has been quoted to be as high as 6.6 claims per 100 Paediatricians per year. Almost 30% of Paediatricians have been sued with many being sued on more than one occasion. Of these cases 36% were settled out of court, 33% were dropped by the plaintiff with the remainder going before the judiciary. The authors point out that in the US medical malpractice is a hotly debated issue. Litigation has a questionable impact on health care quality, cost, and access to services. The AMA believes that rising premiums are resulting in the curtailment of medical care particularly in states with high medico-legal rates. The Physician Insurers Association of America (PIAA) is a trade organisation which insures 60% of all private practicing physicians and surgeons has been a useful source of data. In the 20 year period 1985-2005 among a total of 214,226 claims there were 6363 (2.9%) Paediatric claims which ranked it 10th among the 28 specialties covered. The claims arose in equal numbers from the hospital and Paediatrician’s office settings. Common reasons for Paediatric litigation were errors in diagnosis (32%), incorrect performance of a medical or surgical procedure (13%), failure to monitor or manage a case effectively (10%) and medication error (5%). The top five medico-legal conditions were meningitis, routine infant or child checks, newborn respiratory problems, appendicitis and brain-damaged infants as a co-defendant with Obstetrics. Good quality information about litigation is important because the discussion among doctors is frequently confused by anecdotes and inaccuracies.
    • A little less conversation, more action please!

      Scully, Patricia; Midland Regional Hospital, Tullamore (Midland Regional Hospital, Tullamore, 2012-09-20)
      Interruptions and distractions are significant factors in medication errors in the pharmacy environment. “Although only a small percentage of these errors cause harm, medication errors need to be minimised in an effort to improve patient safety1.” Due to the volume of telephone calls within the Regional Oncology Haematology Pharmacy (ROHP), we decided to analyse all phone calls over a secound three week period , the phonecalls were analysed in the same way using the same time frame and parameters. The recommendations from the previous study were applied . The staff in ROHDU were told which extensions were to be used when directing queries into ROHP. All go ahead confirmations were to be emailed to ROHP as apposed to ring through on the phone.
    • Living alone does not account for the association between loneliness and sleep in older adults: Response to Hawkley, Preacher, and Cacioppo, 2010.

      McHugh, Joanna; Lawlor, Brian; Trinity College, TRIL Office, Hospital 4, St. James Hospital,Dublin, Ireland. mchughje@tcd.ie (2011-03)
    • Living with a diagnosis of non-small cell lung cancer: patients' lived experiences.

      McCarthy, Ita; Dowling, Maura; Tullamore General Hospital, Co.Offaly, Ireland. (2012-01-31)
      The aim of this study was to explore patients' experience of living with non-small cell lung cancer (NSCLC). Patients diagnosed with NSCLC know that their treatment is not with curative intent and can expect distressing symptoms. In this phenomenological study, six adults with a diagnosis of NSCLC were interviewed. Data was analysed guided by van Manen's six-step process. Four main themes were interpreted: 'Maintaining my life'; 'The enemy within'; 'Staying on the train', and 'I'm still me'. The study findings contribute to nurses' understanding of patients living with this distressing diagnosis, where treatment is palliative. Understanding these patients' experiences can help nurses to interact in a different way, and to maximize opportunities to care holistically for this group of patients and best meet their needs.
    • Living with an unfixable heart: a qualitative study exploring the experience of living with advanced heart failure.

      Ryan, Marie; Farrelly, Mary; Clinical Nurse Specialist, Heart Failure, CResT Department, St. James Hospital,, Dublin 8, Ireland. meryan@stjames.ie (2012-02-01)
      BACKGROUND: Nurses working with patients with advanced heart failure need knowledge that will help us to help patients cope with their situations of chronic illness. However, our knowledge bank is deficient due to the scarcity of inquiry that takes the affected person's point of view as its central focus. AIM: The aim of this study was to describe patients' experiences of living with advanced heart failure. METHODS: The study sample (N=9) consisted of male (N=6) and female (N=3) patients with advanced (NYHA classes III-IV) heart failure. The design was qualitative and open unstructured interviews were audio-taped and transcribed verbatim during 2006. RESULTS: Four main themes emerged: Living in the Shadow of Fear; Running on Empty; Living a Restricted life; and Battling the System. The experience of living with advanced heart failure was described as a fearful and tired sort of living characterised by escalating impotence and dependence. CONCLUSIONS: The findings suggest that there may be an illogical but enduring ethos of 'cure' pervading health care worker's attitudes to advanced heart failure care. This mindset might be working to hinder the application of additional or alternative therapies, which might better palliate the physical and psychosocial distress of patients.
    • LL-37 complexation with glycosaminoglycans in cystic fibrosis lungs inhibits antimicrobial activity, which can be restored by hypertonic saline.

      Bergsson, Gudmundur; Reeves, Emer P; McNally, Paul; Chotirmall, Sanjay H; Greene, Catherine M; Greally, Peter; Murphy, Philip; O'Neill, Shane J; McElvaney, Noel G; Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland. bergsson@here.is (2009-07-01)
      There is an abundance of antimicrobial peptides in cystic fibrosis (CF) lungs. Despite this, individuals with CF are susceptible to microbial colonization and infection. In this study, we investigated the antimicrobial response within the CF lung, focusing on the human cathelicidin LL-37. We demonstrate the presence of the LL-37 precursor, human cathelicidin precursor protein designated 18-kDa cationic antimicrobial protein, in the CF lung along with evidence that it is processed to active LL-37 by proteinase-3. We demonstrate that despite supranormal levels of LL-37, the lung fluid from CF patients exhibits no demonstrable antimicrobial activity. Furthermore Pseudomonas killing by physiological concentrations of exogenous LL-37 is inhibited by CF bronchoalveolar lavage (BAL) fluid due to proteolytic degradation of LL-37 by neutrophil elastase and cathepsin D. The endogenous LL-37 in CF BAL fluid is protected from this proteolysis by interactions with glycosaminoglycans, but while this protects LL-37 from proteolysis it results in inactivation of LL-37 antimicrobial activity. By digesting glycosaminoglycans in CF BAL fluid, endogenous LL-37 is liberated and the antimicrobial properties of CF BAL fluid restored. High sodium concentrations also liberate LL-37 in CF BAL fluid in vitro. This is also seen in vivo in CF sputum where LL-37 is complexed to glycosaminoglycans but is liberated following nebulized hypertonic saline resulting in increased antimicrobial effect. These data suggest glycosaminoglycan-LL-37 complexes to be potential therapeutic targets. Factors that disrupt glycosaminoglycan-LL-37 aggregates promote the antimicrobial effects of LL-37 with the caveat that concomitant administration of antiproteases may be needed to protect the now liberated LL-37 from proteolytic cleavage.
    • Local anaesthetic failure in endodontics

      Foot, N; Duncan, HF (Oxford, Wiley-Blackwell, 2011)
    • Local anaesthetic failure in endodontics.

      Foot, N ; Duncan, H F; Dublin Dental University Hospital (Wiley-Blackwell, 2011-07)
    • Local anaesthetics and chondrotoxicty: What is the evidence?

      Baker, Joseph F; Mulhall, Kevin J; Department of Orthopaedic Surgery, Cappagh National Orthopaedic Hospital, Dublin, Ireland. joseph.f.baker@gmail.com (Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA, 2012-11)
      Recent reports have suggested that local anaesthetic agents have a toxic effect on articular chondrocytes. This is despite the widespread intra-articular use of local anaesthetic agents following arthroscopic procedures for a number of years.
    • Localization of nuclear cathepsin L and its association with disease progression and poor outcome in colorectal cancer.

      Sullivan, Shane; Tosetto, Miriam; Kevans, David; Coss, Alan; Wang, Laimun; O'Donoghue, Diarmuid; Hyland, John; Sheahan, Kieran; Mulcahy, Hugh; O'Sullivan, Jacintha; et al. (2012-02-01)
      Previous in vitro studies have identified a nuclear isoform of Cathepsin L. The aim of this study was to examine if nuclear Cathepsin L exists in vivo and examine its association with clinical, pathological and patient outcome data. Cellular localization (nuclear and cytoplasmic) and expression levels v of Cathespin L in 186 colorectal cancer cases using immunohistochemistry. The molecular weight and activity of nuclear and cytoplasmic Cathepsin L in vivo and in vitro were assessed by Western blotting and ELISA, respectively. Epithelial nuclear staining percentage (p = 0.04) and intensity (p = 0.006) increased with advancing tumor stage, whereas stromal cytoplasmic staining decreased (p = 0.02). Using multivariate statistical analysis, survival was inversely associated with staining intensity in the epithelial cytoplasm (p = 0.01) and stromal nuclei (p = 0.007). In different colorectal cell lines and in vivo tumors, pro- and active Cathepsin L isoforms were present in both the cytoplasm and nuclear samples, with pro-Cathepsin L at 50 kDa and active Cathepsin L at 25 kDa. Purified nuclear and cytoplasmic fractions from cell lines and tumors showed active Cathepsin L activity. The identification of nuclear Cathepsin L may play an important prognostic role in colorectal disease progression and patient outcome. Moreover, these findings suggest that altering active nuclear Cathepsin L may significantly influence disease progression.
    • Localized osteoporosis and its consequences.

      Murphy, Claire-Louise; McCarthy, Eoghan M; Loong, Tan Boon; Doran, Michele; Cunnane, Gaye; Department of Rheumatology, St James' Hospital, Dublin, Ireland. (2012-02-01)
    • Localized plaques on the sacral area of a child.

      Fallon, J; Jones, B; Egan, C A; Department of Dermatology, Our Lady of Lourdes Hospital, Drogheda, Ireland., eur@health.ie (2012-02-01)