Research by staff affiliated to St. James's Hospital

Recent Submissions

  • Transcriptome level analysis in Rett syndrome using human samples from different tissues.

    Shovlin, Stephen; Tropea, Daniela (Orphanet Journal of Rare Diseases, 2018-07-11)
    The mechanisms of neuro-genetic disorders have been mostly investigated in the brain, however, for some pathologies, transcriptomic analysis in multiple tissues represent an opportunity and a challenge to understand the consequences of the genetic mutation. This is the case for Rett Syndrome (RTT): a neurodevelopmental disorder predominantly affecting females that is characterised by a loss of purposeful movements and language accompanied by gait abnormalities and hand stereotypies. Although the genetic aetiology is largely associated to Methyl CpG binding protein 2 (MECP2) mutations, linking the pathophysiology of RTT and its clinical symptoms to direct molecular mechanisms has been difficult. One approach used to study the consequences of MECP2 dysfunction in patients, is to perform transcriptomic analysis in tissues derived from RTT patients or Induced Pluripotent Stem cells. The growing affordability and efficiency of this approach has led to a far greater understanding of the complexities of RTT syndrome but is also raised questions about previously held convictions such as the regulatory role of MECP2, the effects of different molecular mechanisms in different tissues and role of X Chromosome Inactivation in RTT. In this review we consider the results of a number of different transcriptomic analyses in different patients-derived preparations to unveil specific trends in differential gene expression across the studies. Although the analyses present limitations- such as the limited sample size- overlaps exist across these studies, and they report dysregulations in three main categories: dendritic connectivity and synapse maturation, mitochondrial dysfunction, and glial cell activity. These observations have a direct application to the disorder and give insights on the altered mechanisms in RTT, with implications on potential diagnostic criteria and treatments.
  • Current advances in the treatment of giant cell arteritis: the role of biologics.

    Low, Candice; Conway, Richard (Therapeutic Advances in Musculoskeletal Disease, 2019-01-01)
    Giant cell arteritis (GCA) is the most common form of systemic vasculitis. It is a potentially severe disease with 25% of patients suffering vision loss or stroke. Our treatment paradigm is based on glucocorticoids. Glucocorticoids are required in high doses for prolonged periods and subsequently are associated with a significant amount of treatment-related morbidity. Alternative treatment options are urgently needed to minimize these glucocorticoid adverse events. Many other agents, such as methotrexate and tumour necrosis factor alpha inhibitors have been used in GCA, with limited or no evidence of benefit. Our emerging understanding of the pathogenic processes involved in GCA has led to an increased interest in the use of biologic agents to treat the disease. Two randomized controlled trials have recently reported dramatic effects of the use of the interleukin-6 targeted biologic tocilizumab in GCA, with significant increases in remission rates and decreases in glucocorticoid burden. While encouraging, longer-term and additional outcomes are awaited to clarify the exact positioning of tocilizumab in the treatment approach. Emerging data for other biologic agents, particularly abatacept and ustekinumab, are also encouraging but less well advanced. We are at the dawn of a new era in GCA treatment, but uncertainties and opportunities abound.
  • Factors Associated with Maternal Wellbeing at Four Months Post-Partum in Ireland.

    Bennett, Annemarie E; Kearney, John M; 1 Department of Clinical Medicine, Trinity Centre for Health Sciences, St. James' Hospital Campus, Dublin 8, Ireland. 2 School of Biological Sciences, Dublin Institute of Technology, Kevin Street, Dublin 8, Ireland. (MDPI, 2018-05-14)
    This study aimed to examine factors associated with maternal wellbeing at four months post-partum in the Irish context. Socio-demographic, health behaviour and infant feeding data were collected in pregnancy, at birth and at 17 weeks post-partum. Maternal distress, body image and resilience were measured at 17 weeks post-partum. Binary logistic regression predicted maternal distress and statistical significance was taken at p < 0.05. One hundred and seventy-two women were followed-up in pregnancy, at birth and at 17 weeks post-partum. Three in five (61.6%, n106) initiated breastfeeding. At 17 weeks post-partum, 23.8% (n41) were exclusively or partially breastfeeding and over a third (36.0%, n62) of all mothers were at risk of distress. In multivariate analyses, independent predictors of distress included: low maternal resilience (p < 0.01, odds ratio (OR): 7.22 (95% confidence interval [CI]: 2.49–20.95)); unsatisfactory partner support (p = 0.02, OR: 3.89 (95% CI: 1.20–12.65)); older age (p = 0.02, OR: 1.11 (95% CI: 1.02–1.21)); and breastfeeding (p = 0.01, OR: 2.89 (95% CI: 1.29–6.47)). Routine assessment of emotional wellbeing and targeted interventions are needed to promote a more healthful transition to motherhood among women in Ireland.
  • Bio-collections in autism research.

    Reilly, Jamie; Gallagher, Louise; Chen, June L; Leader, Geraldine; Shen, Sanbing; 1 Regenerative Medicine Institute, School of Medicine, BioMedical Sciences Building, National University of Ireland (NUI), Galway, Ireland. 2 Trinity Translational Medicine Institute and Department of Psychiatry, Trinity Centre for Health Sciences, St. James Hospital Street, Dublin 8, Ireland. 3 Department of Special Education, Faculty of Education, East China Normal University, Shanghai, 200062 China. 4 Irish Centre for Autism and Neurodevelopmental Research (ICAN), Department of Psychology, National University of Ireland Galway, University Road, Galway, Ireland. (Biomed Central, 2017-01-01)
    Autism spectrum disorder (ASD) is a group of complex neurodevelopmental disorders with diverse clinical manifestations and symptoms. In the last 10 years, there have been significant advances in understanding the genetic basis for ASD, critically supported through the establishment of ASD bio-collections and application in research. Here, we summarise a selection of major ASD bio-collections and their associated findings. Collectively, these include mapping ASD candidate genes, assessing the nature and frequency of gene mutations and their association with ASD clinical subgroups, insights into related molecular pathways such as the synapses, chromatin remodelling, transcription and ASD-related brain regions. We also briefly review emerging studies on the use of induced pluripotent stem cells (iPSCs) to potentially model ASD in culture. These provide deeper insight into ASD progression during development and could generate human cell models for drug screening. Finally, we provide perspectives concerning the utilities of ASD bio-collections and limitations, and highlight considerations in setting up a new bio-collection for ASD research.
  • Improving the quality of radiation oncology: 10years' experience of QUATRO audits in the IAEA Europe Region.

    Izewska, Joanna; Coffey, Mary; Scalliet, Pierre; Zubizarreta, Eduardo; Santos, Tania; Vouldis, Ioannis; Dunscombe, Peter; 1 International Atomic Energy Agency, Vienna International Centre, Vienna, Austria. Electronic address: j.izewska@iaea.org. 2 Discipline of Radiation Therapy, School of Medicine, Trinity Centre for Health Sciences, St. James' Hospital, Dublin, Ireland. 3 Department of Radiotherapy, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Brussels, Belgium. 4 International Atomic Energy Agency, Vienna International Centre, Vienna, Austria. 5 University of Calgary, Canada. (Elsevier, 2018-01-01)
    The IAEA has developed a methodology for comprehensive quality audits of radiotherapy practices called Quality Assurance Team for Radiation Oncology (QUATRO). This study explores the factors that impacted quality of care among QUATRO audited centres in the IAEA Europe Region. The 31 QUATRO reports collected over 10years include extensive data describing the quality of radiotherapy at the audited centres. A coding key was developed to aggregate and review these data in terms of recommendations for improvement and positive findings (commendations). Overall 759 recommendations and 600 commendations were given. Eight centres recognized as centres of competence differed from other centres mostly because they operated complete quality management systems and were adequately staffed. Other centres had excessive staff workloads and many gaps in the process of care. Insufficient equipment levels were prevalent. Patient centredness, communication, dosimetry, quality control and radiation protection were frequently commended by QUATRO. This analysis points to barriers to quality care such as insufficient staffing, education/training, equipment and lack of quality management. It highlights the correlation between the human resources availability and quality of care. It has also identified common action items for enhancing quality of radiotherapy programmes in the Region.
  • Fatigue and Activity Management Education for Individuals with Systemic Lupus Erythematosus.

    O'Riordan, Ruth; Doran, Michele; Connolly, Deirdre; 1 Occupational Therapy Department, St. James' Hospital, James' Street, Dublin 8, Ireland. 2 Rheumatology Department, St. James' Hospital, James' Street, Dublin 8, Ireland. 3 Trinity Centre for Health Sciences, Discipline of Occupational Therapy, St. James' Hospital, James' Street, Dublin 8, Ireland. (Wiley, 2017-01-01)
    Fatigue and Activity Management Education (FAME) is a six-week occupational therapy-led programme focusing on fatigue and stress management, exercise, nutrition, and joint protection. Each session consists of education and goal setting. To assess the impact of FAME on occupational participation and fatigue management. Three programmes were facilitated with twenty-one women with SLE. A mixed methods design was used. Quantitative data were collected using self-reported questionnaires administered before, immediately after, and eight weeks after intervention. Data were analysed using descriptive and nonparametric inferential statistics. Qualitative data were collected through focus groups and interviews. Thematic analysis was carried out on the qualitative data. There was a statistically significant improvement in depression as measured by the Hospital Anxiety and Depression Scale and categories of "burden to others" and "fatigue" in the LupusQoL. There were nonsignificant improvements in fatigue, occupational participation, self-efficacy, and anxiety. Participants reported an improved understanding of fatigue and the impact of stress on fatigue. They also identified self-management strategies they were using on a daily basis.
  • CD10/ALDH cells are the sole cisplatin-resistant component of a novel ovarian cancer stem cell hierarchy.

    Ffrench, Brendan; Gasch, Claudia; Hokamp, Karsten; Spillane, Cathy; Blackshields, Gordon; Mahgoub, Thamir Mahmoud; Bates, Mark; Kehoe, Louise; Mooney, Aoibhinn; Doyle, Ronan; Doyle, Brendan; O'Donnell, Dearbhaile; Gleeson, Noreen; Hennessy, Bryan T; Stordal, Britta; O'Riain, Ciaran; Lambkin, Helen; O'Toole, Sharon; O'Leary, John J; Gallagher, Michael F; 1 Department of Histopathology, Trinity College Dublin, Central Pathology Laboratory, St. James's Hospital, Dublin 8, Ireland. 2 Pathology Research Laboratory, Coombe Women and Infant's University Hospital, Dublin 8, Ireland. 3 Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland. 4 Department of Obstetrics and Gynaecology, Trinity College Dublin, Trinity Centre for Health Sciences, St. James's Hospital, Dublin 8, Ireland. 5 School of Biological Sciences, Dublin Institute of Technology, Kevin Street, Dublin, Ireland. 6 Department of Clinical Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland. 7 Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland. 8 Department of Natural Sciences, Middlesex University, Hendon, London, UK. (Springer Nature, 2017-10-19)
    It is long established that tumour-initiating cancer stem cells (CSCs) possess chemoresistant properties. However, little is known of the mechanisms involved, particularly with respect to the organisation of CSCs as stem-progenitor-differentiated cell hierarchies. Here we aimed to elucidate the relationship between CSC hierarchies and chemoresistance in an ovarian cancer model. Using a single cell-based approach to CSC discovery and validation, we report a novel, four-component CSC hierarchy based around the markers cluster of differentiation 10 (CD10) and aldehyde dehydrogenase (ALDH). In a change to our understanding of CSC biology, resistance to chemotherapy drug cisplatin was found to be the sole property of CD10
  • The characterization of an intestine-like genomic signature maintained during Barrett's-associated adenocarcinogenesis reveals an NR5A2-mediated promotion of cancer cell survival.

    Duggan, Shane P; Behan, Fiona M; Kirca, Murat; Zaheer, Abdul; McGarrigle, Sarah A; Reynolds, John V; Vaz, Gisela M F; Senge, Mathias O; Kelleher, Dermot; 1 Department of Medicine, Division of Gastroenterology, University of British Columbia, 2775 Laurel Street, Vancouver, British Columbia, Canada. 2 Life Science Institute, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada. 3 Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, St James' Hospital, Dublin, Ireland. 4 Department of Gastroenterology, St James' Hospital, Dublin, Ireland. 5 Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St James' Hospital, Dublin 8, Ireland. 6 Medicinal Chemistry, Trinity Translational Medicine Institute, Trinity College Dublin, the University of Dublin, St James' Hospital, Dublin 8, Ireland. (Nature Publishing Group, 2016-09-02)
    Barrett's oesophagus (BO), an intestinal-type metaplasia (IM), typically arising in conjunction with gastro-oesophageal reflux disease, is a prominent risk factor for the development of oesophageal adenocarcinoma (OAC). The molecular similarities between IM and normal intestinal tissues are ill-defined. Consequently, the contribution of intestine-enriched factors expressed within BO to oncogenesis is unclear. Herein, using transcriptomics we define the intestine-enriched genes expressed in meta-profiles of BO and OAC. Interestingly, 77% of the genes differentially expressed in a meta-profile of BO were similarly expressed in intestinal tissues. Furthermore, 85% of this intestine-like signature was maintained upon transition to OAC. Gene networking analysis of transcription factors within this signature revealed a network centred upon NR5A2, GATA6 and FOXA2, whose over-expression was determined in a cohort of BO and OAC patients. Simulated acid reflux was observed to induce the expression of both NR5A2 and GATA6. Using siRNA-mediated silencing and an NR5A2 antagonist we demonstrate that NR5A2-mediated cancer cell survival is facilitated through augmentation of GATA6 and anti-apoptotic factor BCL-XL levels. Abrogation of NR5A2-GATA6 expression in conjunction with BCL-XL co-silencing resulted in synergistically increased sensitivity to chemotherapeutics and photo-dynamic therapeutics. These findings characterize the intestine-like signature associated with IM which may have important consequences to adenocarcinogenesis.
  • National Medicines Information Centre VOLUME 24 NUMBER 3 2018

    National Medicines Information Centre (National Medicines Information Centre St James Hospital, 2018-08)
    Newsletter of the National Medicines Information Centre
  • National Medicines Information Centre VOLUME 24 NUMBER 4 2018

    National Medicines Information Centre (National Medicines Information Centre St James Hospital, 2018-08)
    Newsletter of the National Medicines Information Centre
  • 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.
  • Therapeutics Today May 2018 Number 5

    National Medicines Information Centre, St. James’s Hospital (SJH) Dublin 8 (National Medicines Information Centre, St. James’s Hospital (SJH) Dublin 8, 2018-05)
  • Therapeutics Today April 2018 Number 4

    National Medicines Information Centre, St. James’s Hospital; Dept of Therapeutics Trinity College, Trinity Centre, SJH (National Medicines Information Centre, St. James’s Hospital, 2018-04)
    Newsletter of the National Medicines Information Centre, St. James’s Hospital.
  • The ‘Medication Safety Minute’− Microlearning in Medicine

    Relihan, Eileen (2018-04-06)
    Summary of an initiative of St. James’s Hospital (SJH) medication safety programme to highlighting prescribing safety issues. The project the ‘Medication Safety Minute' was based on the concept of ‘bite-sized learning’. The aim was to deliver a message which could be which could be read and understood in one minute or less. The project was selected for the HSE excellence awards showcase.
  • Methaemoglobinaemia: A Blue Light Emergency

    Uí Bhroin, S; McNamara, R; Kidney, E (Irish Medical Journal, 2018-03)
    Methaemoglobinaemia is a rare but potentially fatal condition. It occurs when the haem molecule of haemoglobin is oxidized from ferrous to ferric form1,2. Methaemoglobin has decreased oxygen carrying capacity. It also causes leftward shift of the oxygen dissociation curve, thus impairing tissue oxygenation1,2. Methaemoglobinaemia can be congenital or, more commonly, acquired3. Many toxins have been implicated in acquired methaemoglobinaemia including local anaesthetics, metoclopramide, cocaine and volatile nitrites4,5.
  • Portal Hypertensive Colopathy with Pelvic Varices presenting as Severe Lower GI Bleed treated with TIPSS

    Murphy, SF; Durand, M; McMorrow, JP; Meaney, JF; Guiney, M (Irish Medical Journal, 2018-02)
    We present the case of a 71-year-old lady with a background of significant alcohol intake who presented with frank lower gastrointestinal (GI) bleeding, lower abdominal pain and haemoglobin 6.3g/dL. CT abdominal angiogram showed right-sided colonic thickening, atrophic liver and enlarged superior mesenteric vein (SMV) and right-sided pelvic varix. This lead to a diagnosis of portal hypertensive colopathy secondary to alcoholic liver cirrhosis. The patient failed conservative management and underwent a Transjugular Intrahepatic Portosystemic Shunt (TIPSS) procedure. This lead to an immediate resolution of her lower-GI bleeding. Repeat CT at three weeks showed a decompressed SMV and resolution of the right-sided pelvic varix. The patient was discharged after three months following optimization of medical condition and social circumstances.
  • Outcomes of a Community-Based Paediatric Weight Management Programme in an Irish Midlands Setting

    Bennett, AE, N Canning, K Younger 2, MAT Flynn 1; Johnston Molloy, C; Glennon-Slattery, C; Loane, D (Irish Medical Journal, 2018-02)
    Ongoing investigation is needed into feasible approaches which reduce excess weight in childhood. This study aimed to assess the effectiveness of an adapted version of the Scottish Childhood Overweight Treatment Trial (SCOTT) in an Irish primary care setting. Families were offered monthly dietitian-led sessions for six months. These sessions targeted dietary habits, family meals, screen time and exercise. Of the 95 children (mean age 7.6 years) referred, 90.5% (n86) were obese and 9.5% (n9) were overweight. Fifty-one (53.7%) families opted into the programme from referral, and 18 completed the programme (64.7% attrition). Statistically significant reductions in body mass index (BMI) were observed between sessions one and six (25.7±4.2kg/m2 and 25.3±4.8kg/m2, respectively, p<0.01). BMI z-score modestly decreased by 0.2 (p=0.01). Despite these reductions, issues with programme referral, attrition and long-term effectiveness were evident. Further investigation into strategies which reduce paediatric overweight is warranted.
  • Laryngeal Chondrosarcoma: A rare cause of critical upper airway obstruction.

    Tuite, K; Oosthuizen, J.C; Subramaniam, T; Kinsella, J.B (Irish Medical Journal, 2018-01)
    Laryngeal cancers are rare, encompassing around one percent of all cancers. Suspicion should be raised if a patient presents with classical signs and symptoms; i.e. dysphonia, inspiratory stridor, dysphagia, odynophagia, neck mass, or persistent cough. Laryngeal chondrosarcoma is a rare form of laryngeal cancer, the diagnosis of which can be difficult. The case in question describes an unusual presentation of one such case, and its subsequent investigation, management and outcome.
  • Incorporating Oral Health as Part of Routine Diabetes Care in Ireland

    Ahern, J; Hamnvik, OP; Barrow, J; Nunn, J (Irish Medical Journal, 2017-11)
    Diabetes mellitus is a common disorder of glucose metabolism that is increasingly prevalent in the Irish population. It is associated with a range of complications leading to substantial morbidity and mortality. A less well-recognized complication of diabetes is periodontal disease. This is a chronic inflammatory disease affecting the periodontium, the specialized group of tissues that surround and support the teeth, including the gingiva (gums) and alveolar bone. Periodontal disease affects patients with diabetes with a greater prevalence and incidence than non-diabetic patients, and can itself exert negative effects on glucose control in people with diabetes. The National Clinical Programme for Diabetes in Ireland aims to reduce the morbidity and mortality associated with diabetes, which includes the development and dissemination of guidelines supporting integrated care. Based on the bidirectional relationship between diabetes mellitus and periodontal disease, we recommend that an oral health evaluation, as well as any necessary onward referral, be incorporated into the Irish recommendations for routine diabetes care, as part of the National Clinical Programme.
  • Interventions to Improve the Treatment of Malaria in an Acute Teaching Hospital in Ireland

    O’Connor, R; Morley, D; Relihan, E; Broderick, A; Merry, C; Bergin, C (Irish Medical Journal, 2017-11)
    Malaria is the most serious parasitic infection. At our institution over a two year period there were treatment errors in 18% (n=3) of cases. The aim of this multidisciplinary study was to ensure appropriate and timely treatment of malaria by implementation of a cluster of interventions: reconfiguration of existing guidelines, provision of prescribing information; delivery of education sessions to front-line staff and enabling rapid access to medication. Staff feedback was assessed through a questionnaire. Perceived benefits gained included awareness of guidelines (91%, n= 39), how to diagnose (81%, n =35), how to treat (86%, n=37), that treatment must be prompt (77%, n=33) and where to find treatment out of hours (84%, n=36). ‘Others’ perceived benefits (5% n= 2) noted referred to treatment in pregnancy. Going forward, a programme of on-going staff education, repeated audits of guideline compliance and promotion of reporting of medication errors should help ensure that these benefits are sustained

View more