• Accuracy of sonographic determination of placental cord insertion site in twin pregnancies

      Kent, E; McAuliffe, F; Geary, M; Daly, S; Higgins, JR; Dornan, J; Morrison, J J; Burke, G; Higgins, S; Carroll, S; et al. (2010)
    • Accuracy of whole-body low-dose multidetector CT (WBLDCT) versus skeletal survey in the detection of myelomatous lesions, and correlation of disease distribution with whole-body MRI (WBMRI).

      Gleeson, T G; Moriarty, J; Shortt, C P; Gleeson, J P; Fitzpatrick, P; Byrne, B; McHugh, J; O'Connell, M; O'Gorman, P; Eustace, S J; et al. (Skeletal radiology, 2009-03)
      The aim of the study is to assess the feasibility of whole-body low-dose computed tomography (WBLDCT) in the diagnosis and staging of multiple myeloma and compare to skeletal survey (SS), using bone marrow biopsy and whole-body magnetic resonance imaging (WBMRI; where available) as gold standard.
    • Accurate intra-articular knee joint injection in the obese? 'Fat Chance!'-A clinical lesson and recommendations for secondary referral.

      McGarry, James G; Livingston, Kerr; Daruwalla, Zubin J; Department of Orthopaedic Surgery, Tallaght Hospital, Dublin, Ireland. (2011-04-12)
      Abstract Corticosteroid joint injections are perceived as being an effective treatment for symptomatic knee osteoarthritis, with a very low risk of complications. While the procedure is often performed in secondary care by orthopaedic surgeons and rheumatologists (and trainees in either specialty), the role of general practitioners (GPs) in chronic disease management has long existed with joint injections also frequently performed in primary care. The perception that serious complications from corticosteroid knee joint injections are rare and that their benefits in treating symptomatic knee osteoarthritis significantly outweigh the risks has not been well addressed. We present a case of a 71-year-old obese female who presented to her general practitioner (GP) with worsening left knee pain and radiographic changes consistent with osteoarthritis. She was administered a corticosteroid joint injection, which gave minimal relief, and over the next few days resulted in worsening severe pain, erythema and swelling. She returned to the GP who commenced oral antibiotics and referred her to casualty. A large knee abscess was diagnosed and intravenous antibiotics were commenced. The patient was admitted under the orthopaedic surgeons with her treatment consisting of multiple surgical procedures over a prolonged duration. Although lengthy, her postoperative recovery was unremarkable. Based on this case report and our review of the literature, we highlight the potential complications associated with corticosteroid knee joint injections and suggest certain patients for whom we would recommend secondary referral before any intervention in primary care.
    • Acetabular fractures following rugby tackles: a case series.

      Good, Daniel W; Leonard, Michael; Lui, Darren; Morris, Seamus; McElwain, John P; Department of Trauma Orthopaedics and Reconstructive Pelvic and Acetabular Surgery, Adelaide and Meath Incorporating the National Childrens Hospital, Tallaght, Dublin 24, Ireland. goodd@tcd.ie. (Journal of medical case reports, 2011)
      Rugby is the third most popular team contact sport in the world and is increasing in popularity. In 1995, rugby in Europe turned professional, and with this has come an increased rate of injury.
    • Achieving diagnosis by consensus

      Kane, Bridget; Luz, Saturnino (2009-08)
      This paper provides an analysis of the collaborative work conducted at a multidisciplinary medical team meeting, where a patient’s definitive diagnosis is agreed, by consensus. The features that distinguish this process of diagnostic work by consensus are examined in depth. The current use of technology to support this collaborative activity is described, and experienced deficiencies are identified. Emphasis is placed on the visual and perceptual difficulty for individual specialities in making interpretations, and on how, through collaboration in discussion, definitive diagnosis is actually achieved. The challenge for providing adequate support for the multidisciplinary team at their meeting is outlined, given the multifaceted nature of the setting, i.e. patient management, educational, organizational and social functions, that need to be satisfied.
    • Acid suppression increases rates of Barrett's esophagus and esophageal injury in the presence of duodenal reflux.

      Department of Surgery, Royal College of Surgeons, Connolly Hospital,, Blanchardstown, Dublin, Ireland. (2012-01-31)
      BACKGROUND: The contribution of gastric acid to the toxicity of alkaline duodenal refluxate on the esophageal mucosa is unclear. This study compared the effect of duodenal refluxate when acid was present, decreased by proton pump inhibitors (PPI), or absent. METHODS: We randomized 136 Sprague-Dawley rats into 4 groups: group 1 (n = 33) were controls; group 2 (n = 34) underwent esophagoduodenostomy promoting "combined reflux"; group 3 (n = 34) underwent esophagoduodenostomy and PPI treatment to decrease acid reflux; and group 4, the 'gastrectomy' group (n = 35) underwent esophagoduodenostomy and total gastrectomy to eliminate acid in the refluxate. Esophaguses were examined for inflammatory, Barrett's, and other histologic changes, and expression of proliferative markers Ki-67, proliferating cell nuclear antigen (PCNA), and epidermal growth factor receptor (EGFR). RESULTS: In all reflux groups, the incidence of Barrett's mucosa was greater when acid was suppressed (group C, 62%; group D, 71%) than when not suppressed (group B, 27%; P = 0.004 and P < .001). Erosions were more frequent in the PPI and gastrectomy groups than in the combined reflux group. Edema (wet weight) and ulceration was more frequent in the gastrectomy than in the combined reflux group. Acute inflammatory changes were infrequent in the PPI group (8%) compared with the combined reflux (94%) or gastrectomy (100%) groups, but chronic inflammation persisted in 100% of the PPI group. EGFR levels were greater in the PPI compared with the combined reflux group (P = .04). Ki-67, PCNA, and combined marker scores were greater in the gastrectomy compared with the combined reflux group (P = .006, P = .14, and P < .001). CONCLUSION: Gastric acid suppression in the presence of duodenal refluxate caused increased rates of inflammatory changes, intestinal metaplasia, and molecular proliferative activity. PPIs suppressed acute inflammatory changes only, whereas chronic inflammatory changes persisted.
    • Acoustic and temporal analysis of speech: A potential biomarker for schizophrenia.

      Rapcan, Viliam; D'Arcy, Shona; Yeap, Sherlyn; Afzal, Natasha; Thakore, Jogin; Reilly, Richard B; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland. rapcanv@tcd.ie (2010-11)
      Currently, there are no established objective biomarkers for the diagnosis or monitoring of schizophrenia. It has been previously reported that there are notable qualitative differences in the speech of schizophrenics. The objective of this study was to determine whether a quantitative acoustic and temporal analysis of speech may be a potential biomarker for schizophrenia. In this study, 39 schizophrenic patients and 18 controls were digitally recorded reading aloud an emotionally neutral text passage from a children's story. Temporal, energy and vocal pitch features were automatically extracted from the recordings. A classifier based on linear discriminant analysis was employed to differentiate between controls and schizophrenic subjects. Processing the recordings with the algorithm developed demonstrated that it is possible to differentiate schizophrenic patients and controls with a classification accuracy of 79.4% (specificity=83.6%, sensitivity=75.2%) based on speech pause related parameters extracted from recordings carried out in standard office (non-studio) environments. Acoustic and temporal analysis of speech may represent a potential tool for the objective analysis in schizophrenia.
    • Acquired Anterior Laryngeal Web in a Shotgun Injury

      Lennon, P; Lang, E; O Dwyer, T (Irish Medical Journal, 2015-06)
      We report the first case of an anterior laryngeal web post gunshot wound in the modern literature. A 27 year-old man suffered a close range shotgun injury to his neck. He presented with stridor and a large open neck wound. Emergency tracheostomy was required. A postoperative fibreoptic laryngoscopy revealed anterior glottic web formation. This case report highlights the difficulties in managing acquired anterior laryngeal webs and reviews the only other case in the in the literature from 1915.
    • Acquired Factor Xiii Deficiency: An Uncommon But Easily Missed Cause Of Severe Bleeding

      Fogarty, H; Byrne, M; O’Connell, NM; Ryan, K; White, B; O’Donnell, JS; Lavin, M (Irish Medical Journal, 2018-05)
      Factor XIII (FXIII) is a plasma clotting protein involved in clot stabilization. Severe FXIII deficiency may present with severe, even fatal bleeding. Critically however, routine coagulation assays may be normal and only specific FXIII assays will detect the abnormality. Herein we discuss a case report of a patient with acquired FXIII deficiency in order to highlight the clinical challenges associated with establishing the diagnosis and discuss the treatment approach. A 70-year-old man presented with a gluteal haematoma despite no preceding personal history of bleeding. Extensive initial haemostatic investigations were normal until a specific FXIII assay showed a marked reduction in FXIII levels. With directed treatment, bleeding episodes ceased and remission was achieved. Clinical awareness of FXIII deficiency is important, so appropriate testing can be implemented in patients with unexplained bleeding diatheses, particularly those in whom bleeding responds poorly to standard replacement therapy.
    • 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.
    • ACTH deficiency, higher doses of hydrocortisone replacement, and radiotherapy are independent predictors of mortality in patients with acromegaly.

      Sherlock, M; Reulen, R C; Alonso, A Aragon; Ayuk, J; Clayton, R N; Sheppard, M C; Hawkins, M M; Bates, A S; Stewart, P M; Centre for Endocrinology, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TH, United Kingdom. (The Journal of clinical endocrinology and metabolism, 2009-11)
      A number of retrospective studies report that patients with acromegaly have increased morbidity and premature mortality, with standardized mortality ratios (SMR) of 1.3-3. Many patients with acromegaly develop hypopituitarism as a result of the pituitary adenoma itself or therapies such as surgery and radiotherapy. Pituitary radiotherapy and hypopituitarism have also been associated with an increased SMR.
    • ACTH-secreting bronchial carcinoid: a diagnostic and therapeutic challenge.

      McDermott, J H; Thabit, H; Hickey, N; Thompson, C; Gaffney, E; Young, V; Sreenan, S; Department of Endocrinology, Royal College of Surgeons, Connolly Hospital Blanchardstown, Dublin 15, Ireland. John.McDermott1@mailc.hse.ie (2008-09)
      We describe a case of Cushing's syndrome due to ectopic ACTH secretion, where the only potential source on conventional imaging was a tiny benign-appearing lung nodule, which failed to take up radiolabelled octreotide.
    • Activated factor X signaling via protease-activated receptor 2 suppresses pro-inflammatory cytokine production from LPS-stimulated myeloid cells.

      Gleeson, Eimear M; O'Donnell, James S; Hams, Emily; Ni Ainle, Fionnuala; Kenny, Bridget-Ann; Fallon, Padraic G; Preston, Roger J S; Ireland. (2013-07-19)
      Vitamin K-dependent proteases generated in response to vascular injury and infection enable fibrin clot formation, but also trigger distinct immuno-regulatory signaling pathways on myeloid cells. Factor Xa, a protease crucial for blood coagulation, also induces protease-activated receptor-dependent cell signaling. Factor Xa can bind both monocytes and macrophages, but whether factor Xa-dependent signaling stimulates or suppresses myeloid cell cytokine production in response to Toll-like receptor activation is not known. In this study, exposure to factor Xa significantly impaired pro-inflammatory cytokine production from lipopolysaccharide-treated peripheral blood mononuclear cells, THP-1 monocytic cells and murine macrophages. Furthermore, factor Xa inhibited nuclear factor-kappa B activation in THP-1 reporter cells, requiring phosphatidylinositide 3-kinase activity for its anti-inflammatory effect. Active-site blockade, γ-carboxyglutamic acid domain truncation and a peptide mimic of the factor Xa inter-epidermal growth factor-like region prevented factor Xa inhibition of lipopolysaccharide-induced tumour necrosis factor-α release. In addition, factor Xa anti-inflammatory activity was markedly attenuated by the presence of an antagonist of protease-activated receptor 2, but not protease-activated receptor 1. The key role of protease-activated receptor 2 in eliciting factor Xa-dependent anti-inflammatory signaling on macrophages was further underscored by the inability of factor Xa to mediate inhibition of tumour necrosis factor-α and interleukin-6 release from murine bone marrow-derived protease-activated receptor 2-deficient macrophages. We also show for the first time that, in addition to protease-activated receptor 2, factor Xa requires a receptor-associated protein-sensitive low-density lipoprotein receptor to inhibit lipopolysaccharide-induced cytokine production. Collectively, this study supports a novel function for factor Xa as an endogenous, receptor-associated protein-sensitive, protease-activated receptor 2-dependent regulator of myeloid cell pro-inflammatory cytokine production.
    • Activated human neonatal CD8+ T cells are subject to immunomodulation by direct TLR2 or TLR5 stimulation.

      McCarron, Mark; Reen, Denis J; Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin,, Ireland. mark.mccarron@ucd.ie (2012-02-01)
      In conditions of optimal priming, the neonate possesses competency to mount quantitatively adult-like responses. Vaccine formulations containing sufficiently potent adjuvants may overcome the neonate's natural tendency for immunosuppression and provoke a similarly robust immune response. TLR expression on T cells represents the possibility of directly enhancing T cell immunity. We examined the ex vivo responsiveness of highly purified human cord blood-derived CD8(+) T cells to direct TLR ligation by a repertoire of TLR agonists. In concert with TCR stimulation, only Pam(3)Cys (palmitoyl-3-Cys-Ser-(Lys)(4)) and flagellin monomers significantly enhanced proliferation, CD25(+) expression, IL-2, IFN-gamma, TNF-alpha, and intracellular granzyme B expression. TLR2 and TLR5 mRNA was detected in the CD8(+) T cells. Blocking studies confirmed that the increase in IFN-gamma production was by the direct triggering of surface TLR2 or TLR5. The simultaneous exposure of CD8(+) T cells to both TLR agonists had an additive effect on IFN-gamma production. These data suggest that a combination of the two TLR ligands would be a potent T cell adjuvant. This may represent a new approach to TLR agonist-based adjuvant design for future human neonatal vaccination strategies requiring a CD8(+) component.
    • Activated protein C alters neutrophil reactive oxygen intermediates in preterm neonates

      Eliwan, HO; Watson, W; O'Neill, A; O'Hare, F; Molloy, EJ (Archives of Disease in Childhood, 2012-10)
    • 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 lamina cribrosa (LC) region of the optic nerve head is considered the primary site of damage in glaucomatous optic neuropathy. Resident LC cells have a profibrotic potential when exposed to cyclical stretch. However, the mechanosensitive mechanisms of these cells remain unknown. Here the authors investigated the effects of membrane stretch on cell volume change and ion channel activity and examined the associated changes in intracellular calcium ([Ca(2+)](i)).
    • 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)
    • Active protein C decrease endotoxin induced inflammatory responses in infants with neonatal encephalopathy

      Eliwan, HO; O'Hare, FO; Sweetman, D; Watson, W; O'Neill, A; Molloy, EJ (Archives of Disease in Childhood, 2012-10)
    • Active surveillance for low-risk prostate cancer: diversity of practice across Europe.

      Azmi, A; Dillon, R A; Borghesi, S; Dunne, M; Power, R E; Marignol, L; O'Neill, B D P; St. Luke's Radiation Oncology Centre, Beaumont Hospital, Dublin, Ireland, aini.azmi@slh.ie. (2014-03-21)
      Active surveillance (AS) is a recognised treatment option for low-risk prostate cancer (PCa).