• Genomic priming of the antisecretory response to estrogen in rat distal colon throughout the estrous cycle.

      O'Mahony, Fiona; Alzamora, Rodrigo; Chung, Ho-Lam; Thomas, Warren; Harvey, Brian J; Department of Molecular Medicine, Royal College of Surgeons in Ireland, Education and Research Centre Smurfit Building, Beaumont Hospital, P.O. Box 9063, Dublin 9, Ireland. fomahony@rcsi.ie (2009-11)
      The secretion of Cl(-) across distal colonic crypt cells provides the driving force for the movement of fluid into the luminal space. 17beta-Estradiol (E2) produces a rapid and sustained reduction in secretion in females, which is dependent on the novel protein kinase C delta (PKC delta) isozyme and PKA isoform I targeting of KCNQ1 channels. This sexual dimorphism in the E2 response is associated with a higher expression level of PKC delta in female compared with the male tissue. The present study revealed the antisecretory response is regulated throughout the female reproductive (estrous) cycle and is primed by genomic regulation of the kinases. E2 (1-10 nm) decreased cAMP-dependent secretion in colonic epithelia during the estrus, metestrus, and diestrus stages. A weak inhibition of secretion was demonstrated in the proestrus stage. The expression levels of PKC delta and PKA fluctuated throughout the estrous cycle and correlated with the potency of the antisecretory effect of E2. The expression of PKC delta and PKA were up-regulated by estrogen at a transcriptional level via a PKC delta-MAPK-cAMP response element-binding protein-regulated pathway indicating a genomic priming of the antisecretory response. PK Cdelta was activated by the membrane-impermeant E2-BSA, and this response was inhibited by the estrogen receptor antagonist ICI 182,780. The 66-kDa estrogen receptor-alpha isoform was present at the plasma membrane of female colonic crypt cells with a lower abundance found in male colonic crypts. The study demonstrates estrogen regulation of intestinal secretion both at a rapid and transcriptional level, demonstrating an interdependent relationship between both nongenomic and genomic hormone responses.
    • Giant cell arteritis involving the mesenteric arteries.

      Azeez, Maha Abdul; Browne, Peter; O'Connell, Paul; Roysten, Derval; Department of Rheumatology, Beaumont Hospital, Beaumont Road, Dublin, D9, Republic of Ireland. mahaazeez@hotmail.com (2009-10)
    • GIST with a twist--upregulation of PDGF-B resulting in metachronous gastrointestinal stromal tumor and dermatofibrosarcoma protuberans.

      McCarthy, Colin J; O'Brien, Gavin C; Cummins, Robert J; Kay, Elaine W; Broe, Patrick J; Department of Surgery, The Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland. colin.mccarthy@iol.ie (2010-02)
      A 61-year-old male was referred following an incidental radiological discovery of an intra-abdominal mass. His medical history included excision of a lumbar dermatofibrosarcoma protuberans (DFSP) 5 years previously. A CT scan of the abdomen revealed a mass arising from the greater curvature of the stomach. Upper GI endoscopy was normal. He underwent successful laparoscopic resection of this mass.
    • GLUT-1 expression and response to chemoradiotherapy in rectal cancer.

      Brophy, Sarah; Sheehan, Katherine M; McNamara, Deborah A; Deasy, Joseph; Bouchier-Hayes, David J; Kay, Elaine W; Department of Surgery, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin, Ireland. sbrophy@rcsi.ie (2009-12-15)
      Preoperative chemoradiotherapy is used in locally advanced rectal cancer to reduce local recurrence and improve operability, however a proportion of tumors do not undergo significant regression. Identification of predictive markers of response to chemoradiotherapy would improve patient selection and may allow response modification by targeting of specific pathways. The aim of this study was to determine whether expression of glucose transporter-1 (GLUT-1) and p53 in pretreatment rectal cancer biopsies was predictive of tumor response to chemoradiotherapy. Immunohistochemical staining for GLUT-1 and p53 was performed on 69 pretreatment biopsies and compared to tumor response in the resected specimen as determined by the tumor regression grade (TRG) scoring system. GLUT-1 expression was significantly associated with reduced response to chemoradiotherapy and increasing GLUT expression correlated with poorer response (p=0.02). GLUT-1 negative tumors had a 70% probability of good response (TRG3/4) compared to a 31% probability of good response in GLUT-1 positive tumors. GLUT-1 may be a useful predictive marker of response to chemoradiotherapy in rectal cancer.
    • Granzyme B-dependent proteolysis acts as a switch to enhance the proinflammatory activity of IL-1α.

      Afonina, Inna S; Tynan, Graham A; Logue, Susan E; Cullen, Sean P; Bots, Michael; Lüthi, Alexander U; Reeves, Emer P; McElvaney, Noel G; Medema, Jan P; Lavelle, Ed C; et al. (2011-10-21)
      Granzyme B is a cytotoxic lymphocyte-derived protease that plays a central role in promoting apoptosis of virus-infected target cells, through direct proteolysis and activation of constituents of the cell death machinery. However, previous studies have also implicated granzymes A and B in the production of proinflammatory cytokines, via a mechanism that remains undefined. Here we show that IL-1α is a substrate for granzyme B and that proteolysis potently enhanced the biological activity of this cytokine in vitro as well as in vivo. Consistent with this, compared with full-length IL-1α, granzyme B-processed IL-1α exhibited more potent activity as an immunoadjuvant in vivo. Furthermore, proteolysis of IL-1α within the same region, by proteases such as calpain and elastase, was also found to enhance its biological potency. Thus, IL-1α processing by multiple immune-related proteases, including granzyme B, acts as a switch to enhance the proinflammatory properties of this cytokine.
    • Group follow-up compared to individual clinic follow-up after structured education for type 1 diabetes: The Irish DAFNE Study

      Dinneen, S F; O'Hara, M; Newell, J; Coffey, N; O'Shea, D; Smith, D; Courtney, H; McGurk, C; O'Scannail, M; Breen, C (Springer, 2011-09)
    • Guidelines on the facilities required for minor surgical procedures and minimal access interventions.

      Humphreys, H; Coia, J E; Stacey, A; Thomas, M; Belli, A-M; Hoffman, P; Jenks, P; Mackintosh, C A; Department of Clinical Microbiology, Royal College of Surgeons in Ireland,, Dublin, Ireland; Department of Microbiology, Beaumont Hospital, Dublin, Ireland. (2012-02-01)
      There have been many changes in healthcare provision in recent years, including the delivery of some surgical services in primary care or in day surgery centres, which were previously provided by acute hospitals. Developments in the fields of interventional radiology and cardiology have further expanded the range and complexity of procedures undertaken in these settings. In the face of these changes there is a need to define from an infection prevention and control perspective the basic physical requirements for facilities in which such surgical procedures may be carried out. Under the auspices of the Healthcare Infection Society, we have developed the following recommendations for those designing new facilities or upgrading existing facilities. These draw upon best practice, available evidence, other guidelines where appropriate, and expert consensus to provide sensible and feasible advice. An attempt is also made to define minimal access interventions and minor surgical procedures. For minimal access interventions, including interventional radiology, new facilities should be mechanically ventilated to achieve 15 air changes per hour but natural ventilation is satisfactory for minor procedures. All procedures should involve a checklist and operators should be appropriately trained. There is also a need for prospective surveillance to accurately determine the post-procedure infection rate. Finally, there is a requirement for appropriate applied research to develop the evidence base required to support subsequent iterations of this guidance.
    • Has the ThinPrep method of cervical screening maintained its improvement over conventional smears in terms of specimen adequacy?

      Treacy, A; Reynolds, J; Kay, E W; Leader, M; Grace, A; Department of Pathology, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. anntreacy@mac.com (2009-04)
      Liquid-based cytology (LBC) has replaced conventional smear assessment in many centers over recent years. In our laboratory this transfer took place in 1999. At that time we performed a split sample study comparing the conventional method of cervical smear evaluation with the ThinPrep system. This split sample study identified a dramatic improvement in specimen adequacy with LBC. While 11% of conventional preparations were reported as unsatisfactory and almost 9% were reported as suboptimal, evaluation of the same cases using LBC saw this combined figure reduced to 2.3%. AIM: To evaluate whether this dramatic fall in unsatisfactory smears has been maintained with the use of LBC. The database for all smears reported for 2005 (100% LBC) was interrogated. The number of unsatisfactory reports was calculated. The reason for an unsatisfactory report was recorded for each case. The overall unsatisfactory rate was compared with that reported in the 1999 split sample study. A total of 41,312 smear tests were reported in 2005. 1,342 (3.25%) were reported as unsatisfactory. Our findings support the ongoing value of LBC in a routine cervical screening laboratory in terms of continuing to maintain a low rate of unsatisfactory smears.
    • The health care journeys experienced by people with epilepsy in Ireland: what are the implications for future service reform and development?

      Varley, J; Delanty, N; Normand, C; Fitzsimons, M; Epilepsy Research Department, Beaumont Hospital, Dublin, Ireland. trimvarleys@gmail.com (2011-02)
      Opportunities exist to significantly improve the quality and efficiency of epilepsy care in Ireland. Historically, epilepsy research has focused on quantitative methodologies that often fail to capture the invaluable insight of patient experiences as they negotiate their health care needs. Using a phenomenological approach, we conducted one-to-one interviews with people with epilepsy, reporting on their understanding of their health care journey from onset of symptoms through to their first interaction with specialist epilepsy services. Following analysis of the data, five major themes emerged: delayed access to specialist epilepsy review; uncertainty regarding the competency and function of primary care services; significant unmet needs for female patients with epilepsy; disorganization of existing epilepsy services; and unmet patient information needs. The findings reveal important insights into the challenges experienced by people with epilepsy in Ireland and identify the opportunities for future service reorganization to improve the quality and efficiency of care provided.
    • The health care journeys experienced by people with epilepsy in Ireland: what are the implications for future service reform and development?

      Varley, J; Delanty, N; Normand, C; Fitzsimons, M; Epilepsy Research Department, Beaumont Hospital, Dublin, Ireland., trimvarleys@gmail.com (2012-02-01)
      Opportunities exist to significantly improve the quality and efficiency of epilepsy care in Ireland. Historically, epilepsy research has focused on quantitative methodologies that often fail to capture the invaluable insight of patient experiences as they negotiate their health care needs. Using a phenomenological approach, we conducted one-to-one interviews with people with epilepsy, reporting on their understanding of their health care journey from onset of symptoms through to their first interaction with specialist epilepsy services. Following analysis of the data, five major themes emerged: delayed access to specialist epilepsy review; uncertainty regarding the competency and function of primary care services; significant unmet needs for female patients with epilepsy; disorganization of existing epilepsy services; and unmet patient information needs. The findings reveal important insights into the challenges experienced by people with epilepsy in Ireland and identify the opportunities for future service reorganization to improve the quality and efficiency of care provided.
    • Healthcare-associated infection in Irish long-term care facilities: results from the First National Prevalence Study.

      Cotter, M; Donlon, S; Roche, F; Byrne, H; Fitzpatrick, F; Department of Clinical Microbiology, Beaumont Hospital, Dublin, Ireland. mcotter@mater.ie (2012-03)
      Prevalence of healthcare-associated infection (HCAI) and antimicrobial use in Irish long-term care facilities (LTCFs) has never been studied.
    • HER-2 positive and p53 negative breast cancers are associated with poor prognosis.

      Al-azawi, Dhafir; Leong, Sum; Wong, Limy; Kay, Elaine; Hill, Arnold D K; Young, Leonie; Department of Surgery, Beaumont Hospital, Dublin, Ireland. dalazawi@rcsi.ie (2011-06)
      p53 and HER-2 coexpression in breast cancer has been controversial. These markers were tested using immunohistochemistry and HercepTest. HER-2 expression is related to reduced breast cancer survival (p = .02) . p53 expression relates to HER-2 expression (p = .029). Coexpression between p53 and HER-2 has no relation to prognosis. On univariate and multivariate analysis, combination of HER-2 positive and p53 negative expression was associated with a poor prognosis (p = .018 and p = .027, respectively), while the combination of HER-2 negative and p53 positive expression was associated with a favorable prognosis (p = .022 and p = .010, respectively). Therefore the expression of these markers should be considered collectively.
    • HER-2 positive and p53 negative breast cancers are associated with poor prognosis.

      Al-azawi, Dhafir; Leong, Sum; Wong, Limy; Kay, Elaine; Hill, Arnold D K; Young, Leonie; Department of Surgery, Beaumont Hospital, Dublin, Ireland. dalazawi@rcsi.ie (2012-02-01)
      p53 and HER-2 coexpression in breast cancer has been controversial. These markers were tested using immunohistochemistry and HercepTest. HER-2 expression is related to reduced breast cancer survival (p = .02) . p53 expression relates to HER-2 expression (p = .029). Coexpression between p53 and HER-2 has no relation to prognosis. On univariate and multivariate analysis, combination of HER-2 positive and p53 negative expression was associated with a poor prognosis (p = .018 and p = .027, respectively), while the combination of HER-2 negative and p53 positive expression was associated with a favorable prognosis (p = .022 and p = .010, respectively). Therefore the expression of these markers should be considered collectively.
    • HER2 testing in the UK: recommendations for breast and gastric in-situ hybridisation methods

      Bartlett, J. M. S.; Starczynski, J.; Atkey, N.; Kay, E.; O'Grady, A.; Gandy, M.; Ibrahim, M.; Jasani, B.; Ellis, I. O.; Pinder, S. E.; et al. (2011)
      These guidelines supplement existing guidelines on HER2 testing by immunohistochemistry and in-situ hybridisation(ISH) methods in the UK. They provide a specific focus on aspects of guidance relevant to HER2 ISH testing methods, both fluorescent and chromogenic. They are formulated to give advice on methodology, interpretation and quality control for ISH-based testing of HER2 status in common tumour types, including both breast and gastric tumours. The aim is to ensure that all ISH-based testing is accurate, reliable and timely.
    • Hereditary cerebral haemorrhage with amyloidosis

      Chalissery, A J; O'Rourke, D; Cryan, J; Rawluk, D; Brett, F; Farrell, M; Moroney, J T (2010-09)
    • Hidden extras: the projected impact of colorectal cancer screening and the burden of procedures on screening centers.

      Dunne, Cara; Harewood, Gavin C; Department of Gastroenterology, Beaumont Hospital, Dublin, Ireland. (2011-08)
    • High concentrations of pepsin in bronchoalveolar lavage fluid from children with cystic fibrosis are associated with high interleukin-8 concentrations.

      McNally, P; Ervine, E; Shields, M D; Dimitrov, B D; El Nazir, B; Taggart, C C; Greene, C M; McElvaney, N G; Greally, P; Respiratory Research Division, Royal College of Surgeons in Ireland, Beaumont, Hospital, Dublin, Ireland. paul.mcnally@olchc.ie (2012-02-01)
      BACKGROUND: Gastro-oesophageal reflux is common in children with cystic fibrosis (CF) and is thought to be associated with pulmonary aspiration of gastric contents. The measurement of pepsin in bronchoalveolar lavage (BAL) fluid has recently been suggested to be a reliable indicator of aspiration. The prevalence of pulmonary aspiration in a group of children with CF was assessed and its association with lung inflammation investigated. METHODS: This was a cross-sectional case-control study. BAL fluid was collected from individuals with CF (n=31) and healthy controls (n=7). Interleukin-8 (IL-8), pepsin, neutrophil numbers and neutrophil elastase activity levels were measured in all samples. Clinical, microbiological and lung function data were collected from medical notes. RESULTS: The pepsin concentration in BAL fluid was higher in the CF group than in controls (mean (SD) 24.4 (27.4) ng/ml vs 4.3 (4.0) ng/ml, p=0.03). Those with CF who had raised pepsin concentrations had higher levels of IL-8 in the BAL fluid than those with a concentration comparable to controls (3.7 (2.7) ng/ml vs 1.4 (0.9) ng/ml, p=0.004). Within the CF group there was a moderate positive correlation between pepsin concentration and IL-8 in BAL fluid (r=0.48, p=0.04). There was no association between BAL fluid pepsin concentrations and age, sex, body mass index z score, forced expiratory volume in 1 s or Pseudomonas aeruginosa colonisation status. CONCLUSIONS: Many children with CF have increased levels of pepsin in the BAL fluid compared with normal controls. Increased pepsin levels were associated with higher IL-8 concentrations in BAL fluid. These data suggest that aspiration of gastric contents occurs in a subset of patients with CF and is associated with more pronounced lung inflammation.
    • High concentrations of pepsin in bronchoalveolar lavage fluid from children with cystic fibrosis are associated with high interleukin-8 concentrations.

      McNally, P; Ervine, E; Shields, M D; Dimitrov, B D; El Nazir, B; Taggart, C C; Greene, C M; McElvaney, N G; Greally, P; Respiratory Research Division, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland. paul.mcnally@olchc.ie (2011-02)
      Gastro-oesophageal reflux is common in children with cystic fibrosis (CF) and is thought to be associated with pulmonary aspiration of gastric contents. The measurement of pepsin in bronchoalveolar lavage (BAL) fluid has recently been suggested to be a reliable indicator of aspiration. The prevalence of pulmonary aspiration in a group of children with CF was assessed and its association with lung inflammation investigated.
    • High fetal plasma adenosine concentration: a role for the fetus in preeclampsia?

      Espinoza, Jimmy; Espinoza, Andres F; Power, Gordon G; Department of Obstetrics and Gynecology, William Beaumont Hospital, Royal Oak, Michigan and Oakland University, Rochester, MI, USA. jimmy.espinoza@beaumont (2012-02-01)
      OBJECTIVE: Clinical observations suggest a role for the fetus in the maternal manifestations of preeclampsia, but the possible signaling mechanisms remain unclear. This study compares the fetal plasma concentrations of adenosine from normal pregnancies with those from preeclampsia. STUDY DESIGN: This secondary data analysis included normal pregnancies (n = 27) and patients with preeclampsia (n = 39). Patients with preeclampsia were subclassified into patients with (n = 25) and without (n = 14) abnormal uterine artery Doppler velocimetry (UADV). RESULTS: Fetal plasma concentrations of adenosine were significantly higher in patients with preeclampsia (1.35 +/- 0.09 mumol/L) than in normal pregnancies (0.52 +/- 0.06 mumol/L; P < .0001). Fetal plasma concentrations of adenosine in patients with preeclampsia with abnormal UADV (1.78 +/- 0.15 mumol/L), but not with normal UADV (0.58 +/- 0.14 mumol/L), were significantly higher than in normal pregnancies (P < .0001). CONCLUSION: Patients with preeclampsia with sonographic evidence of chronic uteroplacental ischemia have high fetal plasma concentrations of adenosine.
    • High incidence of osteoporosis and fractures in an aging post-polio population.

      Mohammad, Ausaf F; Khan, Khalid Ali; Galvin, Leo; Hardiman, Orla; O'Connell, Paul G; Department of Rheumatology, Beaumont Hospital, Dublin, Ireland. ausafmohammad@gmail.com (2009)
      Since the polio epidemic in Ireland in the 1950s, most polio survivors are approaching into the 6th and 7th decade of their lives. There is little data about bone density and risk of fractures in these patients. In 2006, we undertook an audit of post-polio patients attending rheumatology and neurology outpatient clinics in a university teaching hospital. Our aim was to determine the prevalence of osteoporosis (OP), falls and fractures and to evaluate the association of bone density with other potential contributing factors to OP.