• Concordance of outcomes of pairs of kidneys transplanted into different recipients.

      Traynor, Carol; O'Kelly, Patrick; Denton, Mark; Magee, Colm; Conlon, Peter J; Department of Nephrology, Beaumont Hospital, Dublin, Ireland. caroltraynor@physicians.ie (2012-09)
      Kidney transplant outcomes are influenced by donor characteristics, including age and gender. Additional donor factors, both genetic and environmental, also influence graft outcome. We aim to assess the strength of donor factors in determining kidney transplant outcomes by comparing paired kidneys from a single donor transplanted into different recipients. We conducted a retrospective cohort study of outcomes of pairs of deceased donor kidneys transplanted in our centre between 1992 and 2008. We examined the relationship within pairs for eGFR at 1 year and at 5 years post-transplant using Spearman's Correlation and the concordance of pairs of transplant kidneys with respect to the occurrence of acute rejection and delayed graft function (DGF). A total of 652 recipient pairs were analysed. Spearman's correlation for eGFR was 0.36 at 1 year and 0.36 at 5 years post-transplant. The incidence of DGF was 11%. The odds ratio of DGF occurring if the contralateral kidney had DGF was 5.99 (95% CI, 3.19-11.25). There is a significant degree of relationship within pairs of kidneys transplanted from the same donor for serum creatinine at 1 year and 5 years post-transplant and also for the occurrence of delayed graft function.
    • A concordance study between automated and manual HER2 FISH testing

      O'Grady, Anthony; Daly, Etáin; Kay, Elaine; Starczynski, Jane; RCSI Education & Research Centre, Beaumont Hospital, Dublin, Ireland. Birmingham Heartlands Hospital, Birmingham, England. (2011-08)
      This study comprised a randomized, blinded concordance assessment between the automated Leica HER2 FISH System and two manual assays, the Abbott Molecular PathVysion DNA Probe Kit and the Kreatech Poseidon ERBB2 probe. Testing was performed on 100 breast cancer cases pre-characterized for protein and/or gene amplification status.
    • Congenital absence of the posterior arch of the atlas: a benign anomaly?

      Waheed, M A; Gilligan, P; Department of Emergency Medicine, Beaumont Hospital, Beaumont Road, Dublin 9, Ireland. Mirwaheed28@yahoo.com (2010-10)
    • Contrast-induced nephrotoxicity: possible synergistic effect of stress hyperglycemia.

      O'Donnell, David H; Moloney, Michael A; Bouchier-Hayes, David J; Lee, Michael J; Department of Radiology and Vascular Surgery, Beaumont Hospital, The Royal College of Surgeons in Ireland, Dublin, Ireland. davidhodonnell@hotmail.com <davidhodonnell@hotmail.com> (2010-07)
      Oxidative stress on the renal tubules has been implicated as a mechanism of injury in both stress hyperglycemia and contrast-induced nephrotoxicity. The purpose of this study was to determine whether the combination of these effects has a synergistic effect on accentuating renal tubular apoptosis and therefore increasing the risk of contrast-induced nephrotoxicity.
    • Contrasting effects of maternal and paternal age on offspring intelligence: the clock ticks for men too.

      Cannon, Mary; Department of Psychiatry, Royal College of Surgeons in Ireland and Beaumont Hospital, RCSI Education and Research Centre, Beaumont Hospital, Dublin, Ireland. marycannon@rcsi.ie (2009-03-10)
    • The contribution of alcohol to fatal traumatic head injuries in the forensic setting.

      Cryan, J; Catháin, N O; Curtis, M; Cassidy, M; Brett, F M; Department of Neuropathology, Beaumont Hospital, Beaumont, Dublin 9. cryanjane@hotmail.com (2010-11)
      Excessive drinking increases the risk of dying unnaturally. In the Republic of Ireland such deaths are referred to the State Pathologist. Blood alcohol concentration (BAC) is routinely measured. We created a database of cases presenting to the State Pathologist over a nine year period (2000-2008 inclusive) to evaluate the relationship between alcohol and fatal traumatic brain injuries (FTBI). Of a total of 1778 cases, 332 (275 Male [M]; 57 Female [F]) died of head injuries. Fatalities were highest in males aged 36-50 (N = 97) and 26-35 (N = 73). Assaults (N = 147), falls (N = 95), road traffic accidents (RTA) (N = 50) and suicide (N = 15) were the commonest modes of presentation. A positive blood alcohol concentration (BAC) was found in 36% of assaults, 41% of falls and 40% of suicides. In the RTA group BAC was positive in 59% of pedestrians, 33% of drivers and 14% of passengers. Alcohol clearly plays a significant role in FTBI in the forensic setting.
    • The contribution of retrospective memory, attention and executive functions to the prospective and retrospective components of prospective memory following TBI.

      Clune-Ryberg, Melanie; Blanco-Campal, Alberto; Carton, Simone; Pender, Niall; O'Brien, Donncha; Phillips, Jack; Delargy, Mark; Burke, Teresa; School of Psychology, University College Dublin, Belfield, Dublin 4, Ireland. (2011)
      Despite the prevalence of prospective memory (PM) problems, relatively little is known about the processes underlying impairment following TBI. This study sought to examine PM performance, using a multiple-task, multiple-response video-based paradigm in which initial encoding of the cue-action associations was ensured (Video-Assessment of Prospective Memory; VAPM).
    • A cross-sectional MRI study of brain regional atrophy and clinical characteristics of temporal lobe epilepsy with hippocampal sclerosis.

      Department of Molecular and Cellular Therapeutics, The Royal College of Surgeons , in Ireland, Dublin 2, Ireland; Department of Neurophysics, Beaumont Hospital,, Dublin 9, Ireland. (2012-02-01)
      PURPOSE: Applying a cross-sectional design, we set out to further characterize the significance of extrahippocampal brain atrophy in a large sample of 'sporadic' mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS). By evaluating the influence of epilepsy chronicity on structural atrophy, this work represents an important step towards the characterization of MRI-based volumetric measurements as genetic endophenotypes for this condition. METHODS: Using an automated brain segmentation technique, MRI-based volume measurements of several brain regions were compared between 75 patients with 'sporadic' MTLE+HS and 50 healthy controls. Applying linear regression models, we examined the relationship between structural atrophy and important clinical features of MTLE+HS, including disease duration, lifetime number of partial and generalized seizures, and history of initial precipitating insults (IPIs). RESULTS: Significant volume loss was detected in ipsilateral hippocampus, amygdala, thalamus, and cerebral white matter (WM). In addition, contralateral hippocampal and bilateral cerebellar grey matter (GM) volume loss was observed in left MTLE+HS patients. Hippocampal, amygdalar, and cerebral WM volume loss correlated with duration of epilepsy. This correlation was stronger in patients with prior IPIs history. Further, cerebral WM, cerebellar GM, and contralateral hippocampal volume loss correlated with lifetime number of generalized seizures. CONCLUSION: Our findings confirm that multiple brain regions beyond the hippocampus are involved in the pathogenesis of MTLE+HS. IPIs are an important factor influencing the rate of regional atrophy but our results also support a role for processes related to epilepsy chronicity. The consequence of epilepsy chronicity on candidate brain regions has important implications on their application as genetic endophenotypes.
    • Cryptogenic cirrhosis: or is it? An unusual case of portal hypertension.

      Leyden, Jan E; Looby, Seamus; Gulmann, Christian; Patchett, Stephen E; Department of Gastroenterology & Hepatology, Beaumont Hospital/Royal College of Surgeons in Ireland, Dublin, Ireland. janleyden@eircom.net (2010-09)
    • Current and future treatment options in osteoporosis.

      Brewer, Linda; Williams, David; Moore, Alan; General and Geriatric Medicine, Beaumont Hospital, Dublin, Ireland., lindabrewer@physicians.ie (2012-02-01)
      PURPOSE: The incidence of osteoporosis-related fractures will increase substantially over the coming decades as the population ages globally. This has important economic and public health implications, contributing substantially to morbidity and excess mortality in this population. METHODS: When prescribing for older patients the effectiveness profile of drugs needs to be balanced against their tolerability in individual patients. RESULTS: Currently we have good anti-fracture data to support the use of many available anti-resorptive and anabolic drugs including bisphosphonates, strontium ranelate and recombinant human parathyroid hormone. We also have evidence to demonstrate the importance of calcium and vitamin D repletion in these patients. However, in recent years our understanding of normal bone physiology and the mechanisms underlying the development of osteoporosis has significantly advanced and this has led to the development of new therapies. Novel agents, particularly denosumab, but also inhibitors of cathepsin K and anabolic agents that act on Wnt signalling, will increase the therapeutic options for clinicians in the coming years. CONCLUSION: This review discusses the evidence supporting the use of currently available treatment options for osteoporosis and potential future advances in drug therapy. Particular consideration should be given when prescribing for certain older patients who have issues with compliance or tolerance and also in those with co-morbidities or levels of frailty that may restrict the choice of therapy. Understanding the evidence for the benefit and possible harm of osteoporosis treatments is critical to appropriate management of this patient population.
    • Current and future treatment options in osteoporosis.

      Brewer, Linda; Williams, David; Moore, Alan; General and Geriatric Medicine, Beaumont Hospital, Dublin, Ireland, lindabrewer@physicians.ie. (2011-04)
      The incidence of osteoporosis-related fractures will increase substantially over the coming decades as the population ages globally. This has important economic and public health implications, contributing substantially to morbidity and excess mortality in this population.
    • Current status of MR colonography.

      Thornton, Eavan; Morrin, Martina M; Yee, Judy; Department of Radiology, Beaumont Hospital, Beaumont, Dublin 9, Ireland. eavanthornton@gmail.com (2010-01)
      The search for an acceptable colorectal cancer screening examination has led to the development of virtual colonoscopy, which includes both computed tomographic (CT) colonography and magnetic resonance (MR) colonography. As indicated by the much larger number of published studies on CT colonography than on MR colonography, multidetector CT appears to be more suitable for colorectal screening than does MR colonography, in part reflecting the ease and speed of performing CT, as well as the increased spatial resolution, decreased cost, and wider availability of CT colonography. The main advantage of MR colonography over CT colonography is that it does not use ionizing radiation, which has important implications for colorectal cancer screening. The use of dark-lumen MR colonography to screen patients for colorectal cancer as well as other abdominopelvic disease could make it more attractive than CT. With the integration of 3.0-T MR colonography, fecal tagging, and parallel imaging into research and clinical settings, new MR colonography protocols must be optimized. Future MR colonography research should address issues such as image characteristics, presence of artifacts, management of specific absorption rate, and hardware-related modifications.
    • Cutaneous metastases from gastric carcinoma: an unusual presentation.

      Dzever, A; Daruwalla, Z J; Arumugasamy, M; Grogan, L; Broe, P; Beaumont Hospital, Beaumont, Dublin 9. (2012-05)
      We report the case of a 71-year-old gentleman who intially developed cutaneous metastases from gastric carcinoma on his chin and cheek resembling sebaceous cysts.
    • Cyclooxygenase as a target for chemoprevention in colorectal cancer: lost cause or a concept coming of age?

      Doherty, Glen A; Murray, Frank E; Beaumont Hospital, Department of Gastroenterology, Beaumont Road, Dublin, D8, Ireland. glen_doherty@hotmail.com (2009-02)
      COX-2 is upregulated at an early stage in colorectal carcinogenesis and generates prostaglandins, which promote cancer cell proliferation, impair apoptosis and enhance angiogenesis, promoting tumour growth and metastasis. There are ample data from animal models and human studies to demonstrate enhanced tumour progression associated with COX-2 activity in cancer cells. Conversely, NSAIDs including aspirin inhibit COX-2 and, therefore, have anti-neoplastic properties. There has been sustained interest in COX-2 as a chemopreventive target in colorectal cancer (CRC) and although both aspirin and COX-2 selective NSAIDs have demonstrated efficacy, adverse effects have limited their widespread adoption. In particular, evidence of the cardiovascular effects of COX-2 selective inhibitors has led to questioning of the suitability of COX-2 as a target for chemoprevention. This review examines the basis for targeting COX-2 in CRC chemoprevention, evaluates the efficacy and safety of the approach and examines future strategies in this area.
    • Cystic Fibrosis liver disease: A ten year follow-up study

      Gallagher, C L; Gallagher, C G; O'Laoide, R; Canny, G; Hayes, R; Slattery, D; Greally, P; Daly, L; Durie, P; Broderick, A; et al. (2011-01)
    • The cystic fibrosis neutrophil: a specialized yet potentially defective cell.

      Hayes, Elaine; Pohl, Kerstin; McElvaney, Noel G; Reeves, Emer P; Respiratory Research Division, Department of Medicine, Education and Research Centre, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland. (2011-04)
      Cystic fibrosis (CF) is one of the commonest genetically inherited diseases in the world. It is characterized by recurrent respiratory tract infections eventually leading to respiratory failure. One of the hallmarks of this disease is a persistent and predominantly neutrophil driven inflammation. Neutrophils provide the first line of defence by killing and digesting phagocytosed bacteria and fungi, yet despite advances in our understanding of the molecular and cellular basis of CF, there remains a paradox of why recruited CF neutrophils fail to eradicate bacterial infections in the lung. This review describes mechanisms involved in neutrophil migration, microbial killing and apoptosis leading to inflammatory resolution. We discuss dysregulated neutrophil activity and consider genetic versus inflammatory neutrophil reprogramming in CF and ultimately pharmacological modulation of the CF neutrophil for therapeutic intervention.
    • The cystic fibrosis neutrophil: a specialized yet potentially defective cell.

      Hayes, Elaine; Pohl, Kerstin; McElvaney, Noel G; Reeves, Emer P; Respiratory Research Division, Department of Medicine, Education and Research, Centre, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9,, Ireland. (2012-02-01)
      Cystic fibrosis (CF) is one of the commonest genetically inherited diseases in the world. It is characterized by recurrent respiratory tract infections eventually leading to respiratory failure. One of the hallmarks of this disease is a persistent and predominantly neutrophil driven inflammation. Neutrophils provide the first line of defence by killing and digesting phagocytosed bacteria and fungi, yet despite advances in our understanding of the molecular and cellular basis of CF, there remains a paradox of why recruited CF neutrophils fail to eradicate bacterial infections in the lung. This review describes mechanisms involved in neutrophil migration, microbial killing and apoptosis leading to inflammatory resolution. We discuss dysregulated neutrophil activity and consider genetic versus inflammatory neutrophil reprogramming in CF and ultimately pharmacological modulation of the CF neutrophil for therapeutic intervention.
    • Cystic fibrosis, common variable immunodeficiency and Aspergers syndrome: an immunological and behavioural challenge.

      Chotirmall, S H; Low, T B; Hassan, T; Branagan, P; Kernekamp, C; Flynn, M G; Gunaratnam, C; McElvaney, N G; Respiratory Research Division, Department of Medicine, Education and Research Centre, Royal College of Surgeons in Ireland, Beaumont Hospital, Beaumont Road, Dublin 9, Republic of Ireland, schotirmall@rcsi.ie. (2009-08-07)
      INTRODUCTION: Cystic fibrosis (CF) is of particular importance in Ireland as the Irish population has both the highest incidence (2.98/10,000) and the highest carrier rate (1 in 19) in the world. Primary immunodeficiency has not been previously reported as co-existing with CF. CASE REPORT: We report a unique case of CF associated with a primary immunodeficiency syndrome-common variable immunodeficiency (CVID). DISCUSSION: Our patient has CF, CVID and the additional comorbidity of Aspergers syndrome. The challenges inherent in diagnosing and treating such a case are outlined herein and the successful management of this case is evidenced by the well-preserved lung function of our patient.
    • Cystic fibrosis, common variable immunodeficiency and Aspergers syndrome: an immunological and behavioural challenge.

      Chotirmall, S H; Low, T B; Hassan, T; Branagan, P; Kernekamp, C; Flynn, M G; Gunaratnam, C; McElvaney, N G; Respiratory Research Division, Department of Medicine, Education and Research, Centre, Royal College of Surgeons in Ireland, Beaumont Hospital, Beaumont Road,, Dublin 9, Republic of Ireland. schotirmall@rcsi.ie (2012-02-01)
      INTRODUCTION: Cystic fibrosis (CF) is of particular importance in Ireland as the Irish population has both the highest incidence (2.98/10,000) and the highest carrier rate (1 in 19) in the world. Primary immunodeficiency has not been previously reported as co-existing with CF. CASE REPORT: We report a unique case of CF associated with a primary immunodeficiency syndrome--common variable immunodeficiency (CVID). DISCUSSION: Our patient has CF, CVID and the additional comorbidity of Aspergers syndrome. The challenges inherent in diagnosing and treating such a case are outlined herein and the successful management of this case is evidenced by the well-preserved lung function of our patient.
    • Cytosolic phospholipase A2 activation correlates with HER2 overexpression and mediates estrogen-dependent breast cancer cell growth.

      Caiazza, Francesco; Harvey, Brian J; Thomas, Warren; Department of Molecular Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. (2010-05)
      Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) catalyzes the hydrolysis of membrane glycerol-phospholipids to release arachidonic acid as the first step of the eicosanoid signaling pathway. This pathway contributes to proliferation in breast cancer, and numerous studies have demonstrated a crucial role of cyclooxygenase 2 and prostaglandin E(2) release in breast cancer progression. The role of cPLA(2)alpha activation is less clear, and we recently showed that 17beta-estradiol (E2) can rapidly activate cPLA(2)alpha in MCF-7 breast cancer cells. Overexpression or gene amplification of HER2 is found in approximately 30% of breast cancer patients and correlates with a poor clinical outcome and resistance to endocrine therapy. This study reports the first evidence for a correlation between cPLA(2)alpha enzymatic activity and overexpression of the HER2 receptor. The activation of cPLA(2)alpha in response to E2 treatment was biphasic with the first phase dependent on trans-activation through the matrix metalloproteinase-dependent release of heparin-bound epidermal growth factor. EGFR/HER2 heterodimerization resulted in downstream signaling through the ERK1/2 cascade to promote cPLA(2)alpha phosphorylation at Ser505. There was a correlation between HER2 and cPLA(2)alpha expression in six breast cancer cell lines examined, and inhibition of HER2 activation or expression in the SKBR3 cell line using herceptin or HER2-specific small interfering RNA, respectively, resulted in decreased activation and expression of cPLA(2)alpha. Pharmacological blockade of cPLA(2)alpha using a specific antagonist suppressed the growth of both MCF-7 and SKBR3 cells by reducing E2-induced proliferation and by stimulating cellular apoptosis and necrosis. This study highlights cPLAalpha(2) as a potential target for therapeutic intervention in endocrine-dependent and endocrine-independent breast cancer.