• 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)
    • 116. Identification of pharmacological chaperones for feline and human GM1 gangliosidosis

      Rigat, Brigitte; Michael, Tropak; Crushell, Ellen; Daphne, Benedict; Martin, Douglas; Stuetz, Arnold; Callahan, John; Mahuran, Don (2009)
      WORLD (Research in Lysosomal Disease)meeting 2009
    • 11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle.

      Morgan, Stuart A; Sherlock, Mark; Gathercole, Laura L; Lavery, Gareth G; Lenaghan, Carol; Bujalska, Iwona J; Laber, David; Yu, Alice; Convey, Gemma; Mayers, Rachel; et al. (Diabetes, 2009-11)
      Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11beta-HSD1 inhibitors improve insulin sensitivity.
    • 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.
    • The 12q14 microdeletion syndrome: six new cases confirming the role of HMGA2 in growth.

      Lynch, Sally Ann; Foulds, Nicola; Thuresson, Ann-Charlotte; Collins, Amanda L; Annerén, Göran; Hedberg, Bernt-Oves; Delaney, Carol A; Iremonger, James; Murray, Caroline M; Crolla, John A; et al. (2011-05)
      We report six patients with array deletions encompassing 12q14. Out of a total of 2538 array investigations carried out on children with developmental delay and dysmorphism in three diagnostic testing centres, six positive cases yielded a frequency of 1 in 423 for this deletion syndrome. The deleted region in each of the six cases overlaps significantly with previously reported cases with microdeletions of this region. The chromosomal range of the deletions extends from 12q13.3q15. In the current study, we report overlapping deletions of variable extent and size but primarily comprising chromosomal bands 12q13.3q14.1. Four of the six deletions were confirmed as de novo events. Two cases had deletions that included HMGA2, and both children had significant short stature. Neither case had osteopoikilosis despite both being deleted for LEMD3. Four cases had deletions that ended proximal to HMGA2 and all of these had much better growth. Five cases had congenital heart defects, including two with atrial septal defects, one each with pulmonary stenosis, sub-aortic stenosis and a patent ductus. Four cases had moderate delay, two had severe developmental delay and a further two had a diagnosis of autism. All six cases had significant speech delay with subtle facial dysmorphism.
    • 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.
    • An 18FDG-PET/CT finding of a mediastinal abscess.

      Purcell, Yvonne Marie; Hegarty, Chris; Sharaf, Osama; Fabre, Aurélie; Skehan, Stephen J; St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. yvonne.purcell@gmail.com (2013-02)
      A 66-year-old man with left pyriform fossa squamous cell carcinoma (T2N0) was treated with chemoradiation. Nine months later, an emergency tracheostomy was performed for respiratory distress. Contrast-enhanced neck and thorax CT demonstrated a right pyriform mass. FDG-PET/CT showed linear increased uptake extending superiorly from the tracheostomy to the right Eustachian tube and inferiorly to the posterior mediastinum. Postmortem examination confirmed a 7 × 2.2 cm abscess extending from the right parapharyngeal, peritracheal, and prevertebral structures to the mediastinum.
    • 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.
    • A 25 analysis of perinatal mortality following placental abruption

      Ogunlewe, O; Moore, R; Walsh, J; Foley, M; Mahony, R (American Journal of Obstetrics and Gynecology, 2011-01)
      Society for Maternal-Fetal Medicine. The Pregnancy Meeting Feb 2011
    • 28th annual report of the National Rehabilitation Hospital 2008

      National Rehabilitation Hospital (National Rehabilitation Hospital, 2009)
    • 29th annual report of the National Rehabilitation Hospital 2009

      National Rehabilitation Hospital (National Rehabilitation Hospital, 2010)
    • A 5-year prospective observational study of the outcomes of international treatment guidelines for Crohn's disease.

      Cullen, Garret; Keegan, Denise; Mulcahy, Hugh E; O'Donoghue, Diarmuid P; Centre for Colorectal Disease, St. Vincent's University Hospital, Dublin,, Ireland. garret.cullen@ucd.ie (2012-02-01)
      BACKGROUND & AIMS: Therapeutic strategies for patients with Crohn's disease are based on American and European guidelines. High rates of corticosteroid dependency and low remission rates are identified as weaknesses of this therapy and as justification for early introduction of biologic agents (top-down treatment) in moderate/severe Crohn's disease. We reviewed outcomes and corticosteroid-dependency rates of patients with moderate-to-severe disease who were treated according to the international guidelines. METHODS: Consecutive patients (102) newly diagnosed with Crohn's disease in 2000-2002 were identified from a prospectively maintained database. Severity of disease was scored using the Harvey-Bradshaw Index (HBI). Disease was classified by Montreal classification. Five-year follow-up data were recorded. RESULTS: Seventy-two patients had moderate/severe disease at diagnosis (HBI >8). Fifty-four (75%) had nonstricturing, nonpenetrating disease (B1). Sixty-four (89%) received corticosteroids, and 44 (61%) received immunomodulators. Twenty-one patients (29%) received infliximab. Thirty-nine patients (54%) required resection surgery. At a median of 5 years, 66 of 72 (92%) patients with moderate/severe disease were in remission (median HBI, 1). Twenty-five patients (35%) required neither surgery nor biologic therapy. CONCLUSIONS: When international treatment guidelines are strictly followed, Crohn's disease patients can achieve high rates of remission and low rates of morbidity at 5 years. Indiscriminate use of biologic agents therefore is not appropriate for all patients with moderate-to-severe disease.
    • 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)
    • Abdominal CT findings in small bowel perforation.

      Ward, E; Killeen, R; Campbell, N; Torreggiani, W C (The British journal of radiology, 2009-06)