• 051 Valproate and the risk for congenital malformations; is formulation and dosage regime important?

      Mawhinney, E.; Campbell, J.; Craig, J.; Russell, A.; Smithson, W.; Parsons, L.; Robertson, I.; Irwin, B.; Morrison, P.; Liggan, B.; et al. (2012)
    • A 12-year review of Staphylococcus aureus bloodstream infections in haemodialysis patients: more work to be done.

      Fitzgerald, S F; O'Gorman, J; Morris-Downes, M M; Crowley, R K; Donlon, S; Bajwa, R; Smyth, E G; Fitzpatrick, F; Conlon, P J; Humphreys, H; et al. (2012-02-01)
      Staphylococcus aureus bloodstream infections (BSI) are a significant cause of morbidity and mortality in haemodialysis patients. This study describes a 12-year retrospective review of S. aureus BSI in a large haemodialysis centre in a tertiary referral hospital. The overall rate of S. aureus BSI was 17.9 per 100 patient-years (range 9.7-36.8). The rate of meticillin-resistant S. aureus (MRSA) BSI was 5.6 per 100 patient-years (range 0.9-13.8). Infective complications occurred in 11% of episodes, the most common being infective endocarditis (7.6%). Ten percent of patients died within 30 days of S. aureus being isolated from blood. Most cases of S. aureus BSI (83%) were related to vascular catheters. The provision of lower-risk vascular access, such as arteriovenous fistulae, and reduced use of intravascular catheters should be priorities in all haemodialysis units. Where alternative vascular access cannot be established, interventions to reduce the risk of catheter-related infections should be implemented to reduce morbidity and mortality in this vulnerable patient group.
    • 14-3-3 σ expression effects G2/M response to oxygen and correlates with ovarian cancer metastasis.

      Ravi, Dashnamoorthy; Chen, Yidong; Karia, Bijal; Brown, Adam; Gu, Ting Ting; Li, Jie; Carey, Mark S; Hennessy, Bryan T; Bishop, Alexander J R; Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, Texas, United States of America. (2011)
      In vitro cell culture experiments with primary cells have reported that cell proliferation is retarded in the presence of ambient compared to physiological O₂ levels. Cancer is primarily a disease of aberrant cell proliferation, therefore, studying cancer cells grown under ambient O₂ may be undesirable. To understand better the impact of O₂ on the propagation of cancer cells in vitro, we compared the growth potential of a panel of ovarian cancer cell lines under ambient (21%) or physiological (3%) O₂.
    • 17beta-estradiol rapidly mobilizes intracellular calcium from ryanodine-receptor-gated stores via a PKC-PKA-Erk-dependent pathway in the human eccrine sweat gland cell line NCL-SG3.

      Muchekehu, Ruth W; Harvey, Brian J; Molecular Medicine Laboratories, Royal College of Surgeons in Ireland, RCSI Education and Research Centre, Smurfit Building, Beaumont Hospital, P.O. Box 9063, Dublin 9, Ireland. rmuchekehu@ucsd.edu (2008-09)
      We describe a novel rapid non-genomic effect of 17beta-estradiol (E2) on intracellular Ca2+ ([Ca2+]i) signalling in the eccrine sweat gland epithelial cell line NCL-SG3. E2 had no observable effect on basal [Ca2+]i, however exposure of cells to E2 in the presence of the microsomal Ca2+ ATPase pump inhibitor, thapsigargin, produced a secondary, sustained increase in [Ca2+]i compared to thapsigargin treatment alone, where cells responded with a transient single spike-like increase in [Ca2+]i. The E2-induced increase in [Ca2+]i was not dependent on the presence of extracellular calcium and was completely abolished by ryanodine (100 microM). The estrogen receptor antagonist ICI 182,780 (1 microM) prevented the E2-induced effects suggesting a role for the estrogen receptor in the release of [Ca2+]i from ryanodine-receptor-gated stores. The E2-induced effect on [Ca2+]i could also be prevented by the protein kinase C delta (PKCdelta)-specific inhibitor rottlerin (10 microM), the protein kinase A (PKA) inhibitor Rp-adenosine 3',5'-cyclic monophosphorothioate (200 microM) and the MEK inhibitor PD98059 (10 microM). We established E2 rapidly activates the novel PKC isoform PKCepsilon, PKA and Erk 1/2 MAPK in a PKCdelta and estrogen-receptor-dependent manner. The E2-induced effect was specific to 17beta-estradiol, as other steroids had no effect on [Ca2+]i. We have demonstrated a novel mechanism by which E2 rapidly modulates [Ca2+]i release from ryanodine-receptor-gated intracellular Ca2+ stores. The signal transduction pathway involves the estrogen receptor coupled to a PKC-PKA-Erk 1/2 signalling pathway.
    • 20 year old lady with a paraspinal mass.

      O'Toole, Orna; O'Hare, Alan; Grogan, Liam; Bolger, Ciaran; Brett, Francesca M; Department of Neuropathology, Beaumont Hospital, Dublin, UK. (2010-05)
      A 20 year old female presented with a 4 month history of right upper limb pain and paraesthesias. She had no systemic symptoms and no prior medical or family history of note. MRI revealed a right-sided intradural extramedullary mass extending from C7-T1 and displacing the spinal cord. While awaiting surgery her symptoms progressed to involve the right lower limb. She was re-imaged and the lesion now extended from C5 to T3 with spinal cord compression at C7-T1. The radiological features and recent rapid growth were felt to be in keeping with a large plexiform neurofibroma. The patient underwent emergency resection of the lesion and pathology revealed Hodgkin's Lymphoma (HL)-mixed cellularity type. A mediastinal mass was identified on further imaging and biopsy confirmed the diagnosis of HL-stage IV. The patient is currently undergoing treatment with ABVD chemotherapy. CNS-HL is extremely rare and may occur de novo or in association with systemic disease. Lesions may be parenchymal or dural based and are usually intracranial with an increased risk of CNS involvement in HL-mixed-cellularity type as in our patient. This is the first report in the literature of CNS-HL radiologically mimicking a paraspinal plexiform neurofibroma.
    • 6 The expression and role of thromboxane synthase in NSCLC: correlation with angiogenic factors and patient survival

      Cathcart, M.C.; Gately, K.; Cummins, R.; Kay, E.; Pidgeon, G.P.; O'Byrne, K.J. (2011-01)
    • 67 Can HDAC expression be used to stratify mesothelioma patients for appropriate treatment regimens?

      Baird, A.-M.; Flynn, L.; O'Donnell, E.; Jennings, C.J.; Thomas, W.; Barr, M.; O'Byrne, K.; Gray, S. (2012)
    • Aberrant DNA methylation associated with MTHFR C677T genetic polymorphism in cutaneous squamous cell carcinoma in renal transplant patients.

      Laing, M E; Cummins, R; O'Grady, A; O'Kelly, P; Kay, E W; Murphy, G M; Department of Dermatology, RCSI ERC Smurfit Building, Beaumont Hospital, Dublin 9, Ireland. mrylaing@yahoo.co.uk (2010-08)
      Global hypomethylation appears to be a feature of SCC. Aberrant methylation of DNA appears related to polymorphisms of MTHFR. Such findings suggest that intervention in the form of demethylating agents or folate supplementation might be beneficial in the treatment or prevention of SCC.
    • Absence of consensus in diagnostic criteria for familial neurodegenerative diseases.

      Byrne, Susan; Elamin, Marwa; Bede, Peter; Hardiman, Orla; Trinity College Institute of Neurosciences, Beaumont Hospital, Trinity College, Dublin, Ireland. suabyrne@gmail.com (2012-04)
      A small proportion of cases seen in neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), Parkinson's disease and Alzheimer disease are familial. These familial cases are usually clinically indistinguishable from sporadic cases. Identifying familial cases is important both in terms of clinical guidance for family members and for gene discovery.
    • Access to in-patient stroke services and multidisciplinary team (MDT) rehabilitation: current demands and capacity

      O’Sullivan, EJ; Williams, DJ; Shanahan-O’Connell, J; Kirrane, K; Armitage, D; Leahy, W; O’Flaherty, E; Horgan, NF (Irish Medical Journal, 2014-06)
      The objective of this project was to analyse the current access to in-patient stroke services and MDT rehabilitation in an acute stroke centre and to compare these services to the recommended â National Clinical Guidelines and Recommendations for the Care of People with Stroke and TIAâ (IHF 2010). A retrospective chart review was carried out, recording activity statistics of all patients admitted with acute stroke over a three-month period. 73 patients (male=40, 54.8%) were included. Patients were discharged from the stroke service after a mean stay of 20.2 days (SD.= 19.3). 76.7% (N=56) of patients were admitted to the acute stroke unit (ASU). The mean length of time from admission to first assessment 3.4 days (SD.=2.68), with an average of 138 minutes of treatment received per day across all disciplines. This is compared to the IHFâ s recommendation of patients being assessed within 24-48 hours of admission and receiving 180 minutes of treatment across all disciplines. As demands for stroke MDT services increase, it is important to recognise the benefits of increasing staff and resources to maintain and continue to improve standards of care
    • Accidental ecstasy ingestion in a two year old.

      Cassidy, N; Casey, P B; Tracey, J A (2009-02)
    • Accuracy of death certification

      Tormey, W. P. (2011-11)
    • The accuracy of death certification for ALS/MND in Ireland

      Yeo, L; Lynch, C; Hardiman, O; Beaumont Hospital, Beaumont Road, Dublin 9, Ireland. (2009)
    • Acromegaly associated with gangliocytoma.

      Crowley, R K; Al-Derazi, Y; Lynch, K; Rawluk, D; Thompson, C J; Farrell, M; Agha, A; Academic Department of Endocrinology, Beaumont Hospital, Dublin 9, Ireland, rachelcrowley@hotmail.com. (2009-09-30)
      BACKGROUND: Acromegaly secondary to growth hormone-releasing hormone (GHRH) excess is rare. AIMS/CASE DESCRIPTION: We report two patients with acromegaly who were diagnosed with sellar gangliocytomas that were immunopositive for GHRH. Tumour tissue persisted after debulking surgery and in the second case this was associated with persistent growth hormone hypersecretion, successfully suppressed by a somatostatin analogue. CONCLUSIONS: The development of functional pituitary adenomas in association with sellar gangliocytomas is poorly understood. We present a brief discussion of the possible aetiology of these unusual pituitary tumours.
    • Activation of stretch-activated channels and maxi-K+ channels by membrane stress of human lamina cribrosa cells.

      Irnaten, Mustapha; Barry, Richard C; Quill, Barry; Clark, Abbot F; Harvey, Brian J P; O'Brien, Colm J; Molecular Medicine Laboratories, RCSI Education and Research Centre, Beaumont Hospital, Dublin, Ireland. irnatenm@yahoo.fr (2009-01)
      The results show that hypotonic stress of human LC cells activates SAC and Ca(2+)-dependent maxi-K(+) channels and that the increase in [Ca(2+)](i) during cell swelling was predominantly from extracellular sources (or intracellular stores other than the endoplasmic reticulum). These findings improve the understanding of how LC cells respond to cell membrane stretch. Further experiments in this area may reveal future targets for novel therapeutic intervention in the management of glaucoma.
    • Activation of the epidermal growth factor receptor (EGFR) by a novel metalloprotease pathway.

      Bergin, David A; Greene, Catherine M; Sterchi, Erwin E; Kenna, Cliona; Geraghty, Patrick; Belaaouaj, Abderrazzaq; Taggart, Clifford C; O'Neill, Shane J; McElvaney, Noel G; Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland. (2008-11-14)
      Neutrophil Elastase (NE) is a pro-inflammatory protease present at higher than normal levels in the lung during inflammatory disease. NE regulates IL-8 production from airway epithelial cells and can activate both EGFR and TLR4. TACE/ADAM17 has been reported to trans-activate EGFR in response to NE. Here, using 16HBE14o-human bronchial epithelial cells we demonstrate a new mechanism by which NE regulates both of these events. A high molecular weight soluble metalloprotease activity detectable only in supernatants from NE-treated cells by gelatin and casein zymography was confirmed to be meprin alpha by Western immunoblotting. In vitro studies demonstrated the ability of NE to activate meprin alpha, which in turn could release soluble TGFalpha and induce IL-8 production from 16HBE14o- cells. These effects were abrogated by actinonin, a specific meprin inhibitor. NE-induced IL-8 expression was also inhibited by meprin alpha siRNA. Immunoprecipitation studies detected EGFR/TLR4 complexes in NE-stimulated cells overexpressing these receptors. Confocal studies confirmed colocalization of EGFR and TLR4 in 16HBE14o- cells stimulated with meprin alpha. NFkappaB was also activated via MyD88 in these cells by meprin alpha. In bronchoalveolar lavage fluid from NE knock-out mice infected intra-tracheally with Pseudomonas aeruginosa meprin alpha was significantly decreased compared with control mice, and was significantly increased and correlated with NE activity, in bronchoalveolar lavage fluid from individuals with cystic fibrosis but not healthy controls. The data describe a previously unidentified lung metalloprotease meprin alpha, and its role in NE-induced EGFR and TLR4 activation and IL-8 production.
    • Activation of the ubiquitin proteasome pathway (UPP) in colon cancer; The potential of proteasome inhibition as a novel treatment modality

      McCawley, N; Conlon, S; Cummins, R J; Hector, S; Kay, E W; Concannon, C G; Prehn, J H M; Deasy, J; McNamara, D A (2011-01)
    • Acupuncture as an adjunct to pulmonary rehabilitation.

      Deering, Brenda M; Fullen, Brona; Egan, Claire; McCormack, Niamh; Kelly, Emer; Pender, Mary; Costello, Richard W; Department of Respiratory Medicine, Beaumont Hospital and the associated, Education and Research Centre, University College of Dublin, Dublin, Ireland. (2012-02-01)
      PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and by both systemic and airway inflammation. In COPD, acupuncture has been shown to improve quality-of-life scores and decrease breathlessness; similar findings have also been reported after pulmonary rehabilitation (PR). The hypothesis of this study was that acupuncture in conjunction with pulmonary rehabilitation would improve COPD outcome measures compared to pulmonary rehabilitation alone. METHODS: The design was a randomized prospective study; all subjects had COPD. There were 19 controls, 25 who underwent PR, and 16 who had both acupuncture and PR. The primary outcome measure was a change in measures of systemic inflammation at the end of PR and at 3 month followup. Lung function, including maximum inspiratory pressure (PiMax), quality-of-life scores, functional capacity including steps taken, dyspnea scores, and exercise capacity, were secondary endpoints. RESULTS: After PR, both groups had significantly improved quality-of-life scores, reduced dyspnea scores, improved exercise capacity, and PiMax, but no change in measures of systemic inflammation compared with the controls. There were no differences in most of the outcome measures between the 2 treatment groups except that subjects who had both acupuncture and PR remained less breathless for a longer period. CONCLUSION: The addition of acupuncture to PR did not add significant benefit in most of the outcomes measured.
    • Acute ischaemic colitis in a young woman

      Levins, K; Kelly, O; Beausang, A; Gulmann, C; Harewood, G; Cahill, R (Irish Medical Journal (IMJ), 2012-10)
    • Acute limb ischemia in cancer patients: should we surgically intervene?

      Tsang, Julian S; Naughton, Peter A; O'Donnell, Jill; Wang, Tim T; Moneley, Daragh S; Kelly, Cathal J; Leahy, Austin L; Department of Vascular Surgery, Royal College of Surgeons Ireland, Beaumont, Hospital, Dublin, Ireland. julianst@yahoo.com (2012-02-01)
      BACKGROUND: Cancer patients have an increased risk of venous thromboembolic events. Certain chemotherapeutic agents have also been associated with the development of thrombosis. Reported cases of acute arterial ischemic episodes in cancer patients are rare. METHODS: Patients who underwent surgery for acute limb ischemia associated with malignancy in a university teaching hospital over a 10-year period were identified. Patient demographics, cancer type, chemotherapy use, site of thromboembolism, treatment and outcome were recorded. RESULTS: Four hundred nineteen patients underwent surgical intervention for acute arterial ischemia, 16 of these patients (3.8%) had associated cancer. Commonest cancer sites were the urogenital tract (n = 5) and the lungs (n = 5). Eight patients (50%) had been recently diagnosed with cancer, and four (25%) of these cancers were incidental findings after presentation with acute limb ischemia. Four patients (25%) developed acute ischemia during chemotherapy. The superficial femoral artery was the most frequent site of occlusion (50%), followed by the brachial (18%) and popliteal (12%) arteries. All patients underwent thromboembolectomy, but two (12%) patients subsequently required a bypass procedure. Six patients (37%) had limb loss, and in-patient mortality was 12%. Histology revealed that all occlusions were due to thromboembolism, with no tumor cells identified. At follow-up, 44% of patients were found to be alive after 1 year. CONCLUSION: Cancer and chemotherapy can predispose patients to acute arterial ischemia. Unlike other reports that view this finding as a preterminal event most appropriately treated by palliative measures, in this series, early diagnosis and surgical intervention enabled limb salvage and patient survival.