• Maintenance immunosuppression with intermittent intravenous IL-2 receptor antibody therapy in renal transplant recipients.

      Gabardi, Steven; Catella, Jennifer; Martin, Spencer T; Perrone, Ronald; Chandraker, Anil; Magee, Colm C; McDevitt-Potter, Lisa M; Abdominal Organ Transplant Clinical Specialist–Departments of Transplant Surgery and Pharmacy Services, and the Renal Division, Brigham and Women's Hospital, Boston, MA, USA. sgabardi@partners.org (2011-09)
      To report what we believe to be the first 2 cases of long-term (>24 months) intermittent intravenous interleukin-2 receptor antibody (IL-2RA) therapy for maintenance immunosuppression following renal transplantation.
    • Male fertility in cystic fibrosis.

      Chotirmall, S H; Mann, A K; Branagan, P; O'Donohoe, C; Lyons, A M; Flynn, M G; Gunaratnam, C; O'Neill, S J; McElvaney, N G; Respiratory Research Division, Education & Research Centre, Beaumont Hospital, Dublin. schotirmall@rcsi.ie (2011-04-05)
      Infertility rates among males with cystic fibrosis (CF) approximate 97%. No information is currently available within Ireland determining an understanding of fertility issues and the best methods of information provision to this specialized group. This study aimed to determine understanding and preferred approaches to information provision on fertility issues to Irish CF males. A Descriptive Study utilizing prospective coded questionnaires was mailed to a male CF cohort (n=50). Sections included demographics, fertility knowledge & investigation. Response rate was 16/50 (32%). All were aware that CF affected their fertility. More than two-thirds (n=11) were able to provide explanations whilst only one-third (n=5) provided the correct explanation. Significant numbers stated thoughts of marriage and a future family. Half have discussed fertility with a healthcare professional (HCP). Mean age of discussion was 21.9 years. One third preferred an earlier discussion. The commonest first source for information was written material which was also the preferred source. Three-quarters requested further information preferring again, written material. Significant gaps in sex education of Irish CF males exist. Discussion should be initiated by HCPs and centre-directed written material devised to address deficiencies.
    • Male lupus: a diagnosis often delayed--a case series and review of the literature.

      Ambrose, N L; Kearns, G; Mohammad, A; Rheumatology Department, Beaumont Hospital, Dublin, Ireland. nambrose2001@yahoo.co.uk (2011-03)
      Systemic lupus erythematosus (SLE) is an auto-immune disease that is characterised by autoantibody production. Male lupus is rare, apart from at either end of the age spectrum.
    • Male lupus: a diagnosis often delayed--a case series and review of the literature.

      Ambrose, N L; Kearns, G; Mohammad, A; Rheumatology Department, Beaumont Hospital, Dublin, Ireland., nambrose2001@yahoo.co.uk (2012-02-01)
      INTRODUCTION: Systemic lupus erythematosus (SLE) is an auto-immune disease that is characterised by autoantibody production. Male lupus is rare, apart from at either end of the age spectrum. AIM: In this series, we review the histories of six male lupus patients attending our service. RESULTS: Our patients presented in middle age and tended to develop haematological abnormalities, renal involvement and neurological manifestations which preceded the onset of their skin and joint complaints. Our patients accrued damage rapidly and overall did badly. They tended to respond sub-optimally to standard treatments. These cases highlight the need an increased awareness that male SLE patients present with a wide variety of symptoms, and that they accrue damage quickly. There is a need for timely diagnosis and appropriate initiation of treatment. This may help avoid preventable organ damage and increase the survival of men with SLE.
    • Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers.

      Campbell, E; Kennedy, F; Russell, A; Smithson, W H; Parsons, L; Morrison, P J; Liggan, B; Irwin, B; Delanty, N; Hunt, S J; et al. (2014-09)
      Antiepileptic drug (AED) exposure during pregnancy increases the risk of major congenital malformations (MCMs). The magnitude of this risk varies by AED exposure. Here we provide updated results from the UK Epilepsy and Pregnancy Register of the risk of MCMs after monotherapy exposure to valproate, carbamazepine and lamotrigine.
    • Malignant melanoma and breast carcinoma: a bidirectional correlation.

      Ho, W L; Comber, H; Hill, A D K; Murphy, G M; Department of Dermatology, Beaumont Hospital, Dublin 9, Ireland, drwlho@yahoo.com. (2009-03-05)
      BACKGROUND: Epidemiologic and genetic studies have suggested a bidirectional association between breast carcinoma (BC) and malignant melanoma (MM). OBSERVATION: We present a series of patients with MM and BC detected in our department within a span of 6 months, raising concerns for the high associations between the two malignancies. This led us to match the concordance of the two tumours in the National Irish Cancer Registry. CONCLUSION: The national figures provide evidence of a link between BC and MM. We recommend increased awareness among clinicians leading to more detailed surveillance of both second primary tumours. All MM patients with a family history of BC should be referred to a breast clinic. Women above the age of 40 with MM should undergo annual mammography and those less than 40 may be better evaluated with a breast MRI. All breast cancer patients should be made aware of the significance of changing moles and those with suspicious lesions referred to a dermatologist for evaluation.
    • Malignant melanoma and breast carcinoma: a bidirectional correlation.

      Ho, W L; Comber, H; Hill, A D K; Murphy, G M; Department of Dermatology, Beaumont Hospital, Dublin 9, Ireland. drwlho@yahoo.com (2012-02-01)
      BACKGROUND: Epidemiologic and genetic studies have suggested a bidirectional association between breast carcinoma (BC) and malignant melanoma (MM). OBSERVATION: We present a series of patients with MM and BC detected in our department within a span of 6 months, raising concerns for the high associations between the two malignancies. This led us to match the concordance of the two tumours in the National Irish Cancer Registry. CONCLUSION: The national figures provide evidence of a link between BC and MM. We recommend increased awareness among clinicians leading to more detailed surveillance of both second primary tumours. All MM patients with a family history of BC should be referred to a breast clinic. Women above the age of 40 with MM should undergo annual mammography and those less than 40 may be better evaluated with a breast MRI. All breast cancer patients should be made aware of the significance of changing moles and those with suspicious lesions referred to a dermatologist for evaluation.
    • Malignant otitis externa: An Australian case series.

      Royal College of Surgeons Ireland, Otolaryngology, Beaumont Hospital, Dublin,, Ireland. (2012-02-01)
      OBJECTIVES: To establish a clinicopathological profile of malignant otitis externa (MOE) in an Australian tertiary referral institution. STUDY DESIGN: Retrospective cohort outcomes study. METHODS: 24 patients were identified with MOE between January 1998 and July 2007. Patients were classified into Radiological Grades I-IV. Laboratory investigations Including C-reactive protein (CRP), white cell count (WCC), glycosylated haemoglobin (HBA1c) and average glucose level over admission were recorded. RESULTS: Radiological Grade was significantly associated with duration of therapy (rank correlation 0.57, p = 0.004). CRP was a useful indicator confirming disease resolution. Diabetics with MOE had elevated average blood sugar levels during their Hospital admission (p < 0.001) and had poor overall glycaemic control represented by Elevated HBA1c scores (p < 0.001). CONCLUSIONS: Malignant otitis externa is a rare disease, which is best managed in a multidisciplinary team setting. This practical grading system can be used to predict the duration of therapy at time of diagnosis, which enables the efficient utilisation of Hospital resources. Poorly controlled diabetics are more susceptible to developing. MOE than diabetics with satisfactory glycaemic control and may represent a subgroup of more brittle diabetics. CRP combined with appropriate clinical and radiological investigations is useful in assessing disease resolution.
    • The management of amyotrophic lateral sclerosis.

      Phukan, Julie; Hardiman, Orla; Dept. of Neurology, Beaumont Hospital, and Trinity College Institute of Neuroscience, Dublin 9, Ireland. (2009-02)
      The terms amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND) refer to a condition characterized by motor system degeneration with relative preservation of other pathways. Although there have been advances in symptomatic treatment, ALS remains an incurable condition. Advances in ALS management prolong survival but simultaneously raise challenging ethical dilemmas for physicians, patients and their families. Here, we review current practice in the management of ALS including pharmacological treatment, nutritional management, respiratory care, and evolving strategies in the management of cognitive impairment.
    • Management of parenteral nutrition associated hyperglycaemia: A comparison of subcutaneous and intravenous insulin regimen

      Neff, K; Donegan, D; MacMahon, J; O’Hanlon, C; Keane, N; Agha, A; Thompson, C; Smith, D (Irish Medical Jorunal, 2014-05)
      PN is associated with significant hyperglycaemia, which may be detrimental to clinical outcome. There are few data on the management of this phenomenon outside of intensive care units. In our unit, we studied the efficacy of protocol-based intravenous insulin delivery as compared to subcutaneous insulin prescribed individually outside of the critical care setting. In a retrospective review over a two-year period, we compared patients with PN-associated hyperglycaemia who had received both modes of insulin therapy. A total of 122 who developed PN-associated hyperglycaemia were identified. Those on the intravenous insulin regimen were within glycaemic target for more time than those on the subcutaneous regimen (62% Vs 43%, p=0.008). We therefore conclude that outside of the critical care setting, intravenous insulin delivers better glycaemic control and should therefore be considered optimum therapy for patients with PN-associated hyperglycaemia.
    • Management of respiratory symptoms in ALS.

      Hardiman, Orla; HRB Clinician Scientist, Trinity College and Beaumont Hospital, Dublin, Ireland, orla@hardiman.net. (2011-03)
      Respiratory insufficiency is a frequent feature of ALS and is present in almost all cases at some stage of the illness. It is the commonest cause of death in ALS. FVC is used as important endpoint in many clinical trials, and in decision-making events for patients with ALS, although there are limitations to its predictive utility. There are multiple causes of respiratory muscle failure, all of which act to produce a progressive decline in pulmonary function. Diaphragmatic fatigue and weakness, coupled with respiratory muscle weakness, lead to reduced lung compliance and atelectasis. Increased secretions increase the risk of aspiration pneumonia, which further compromises respiratory function. Bulbar dysfunction can lead to nutritional deficiency, which in turn increases the fatigue of respiratory muscles. Early recognition of respiratory decline and symptomatic intervention, including non-invasive ventilation can significantly enhance both quality of life and life expectancy in ALS. Patients with respiratory failure should be advised to consider an advance directive to avoid emergency mechanical ventilation.
    • Management of respiratory symptoms in ALS.

      Hardiman, Orla; HRB Clinician Scientist, Trinity College and Beaumont Hospital, Dublin, Ireland. , orla@hardiman.net (2012-02-01)
      Respiratory insufficiency is a frequent feature of ALS and is present in almost all cases at some stage of the illness. It is the commonest cause of death in ALS. FVC is used as important endpoint in many clinical trials, and in decision-making events for patients with ALS, although there are limitations to its predictive utility. There are multiple causes of respiratory muscle failure, all of which act to produce a progressive decline in pulmonary function. Diaphragmatic fatigue and weakness, coupled with respiratory muscle weakness, lead to reduced lung compliance and atelectasis. Increased secretions increase the risk of aspiration pneumonia, which further compromises respiratory function. Bulbar dysfunction can lead to nutritional deficiency, which in turn increases the fatigue of respiratory muscles. Early recognition of respiratory decline and symptomatic intervention, including non-invasive ventilation can significantly enhance both quality of life and life expectancy in ALS. Patients with respiratory failure should be advised to consider an advance directive to avoid emergency mechanical ventilation.
    • Manifesto for the current understanding and management of traumatic brain injury-induced hypopituitarism.

      Tanriverdi, F; Agha, A; Aimaretti, G; Casanueva, F F; Kelestimur, F; Klose, M; Masel, B E; Pereira, A M; Popovic, V; Schneider, H J; et al. (2011)
      Traumatic brain injury (TBI)-induced hypopituitarism remains a relevant medical problem, because it may affect a significant proportion of the population. In the last decade important studies have been published investigating pituitary dysfunction after TBI. Recently, a group of experts gathered and revisited the topic of TBI-induced hypopituitarism. During the 2-day meeting, the main issues of this topic were presented and discussed, and current understanding and management of TBI-induced hypopituitarism are summarized here.
    • Massive hepatic cyst presenting as right-sided heart failure.

      O'Connor, A; Lee, M; McEntee, G; McNamara, D A; Department of Surgery, Beaumont Hospital, Dublin 9, Ireland, aoconnor@rcsi.ie. (2010-01-30)
      A 70-year-old woman presented with clinical features of right heart failure. Cardiopulmonary investigations included an echocardiogram, which showed a hepatic cyst compromising venous return and affecting right atrial filling and a CT abdomen showed a 15.5 x 11.5 cm-cystic mass involving the right hepatic lobe and compressing the right atrium. Percutaneous drainage of the cyst was performed. This led to complete resolution of symptoms but these recurred as the fluid re-accumulated. Subsequent definitive treatment with excision of the cyst was undertaken with symptomatic cure. This case is the first report of a hepatic cyst presenting as right heart due to compression of the right atrium.
    • Maternal anemia as a risk factor for schizophrenia: A population-based, record-linkage study and meta-analysis

      Cannon, M; Cotter, D R; Tanskanen, A; Jones, P B; Murray, R; Huttunen, M O (Oxford Journals, 2011-03)
    • Measurement of the unfolded protein response (UPR) in monocytes.

      Carroll, Tomas P; Greene, Catherine M; McElvaney, Noel G; Department of Medicine, Royal College of Surgeons in Ireland, Education and, Research Centre, Beaumont Hospital, Dublin, Ireland. (2012-02-01)
      In mammalian cells, the primary function of the endoplasmic reticulum (ER) is to synthesize and assemble membrane and secreted proteins. As the main site of protein folding and posttranslational modification in the cell, the ER operates a highly conserved quality control system to ensure only correctly assembled proteins exit the ER and misfolded and unfolded proteins are retained for disposal. Any disruption in the equilibrium of the ER engages a multifaceted intracellular signaling pathway termed the unfolded protein response (UPR) to restore normal conditions in the cell. A variety of pathological conditions can induce activation of the UPR, including neurodegenerative disorders such as Parkinson's disease, metabolic disorders such as atherosclerosis, and conformational disorders such as cystic fibrosis. Conformational disorders are characterized by mutations that modify the final structure of a protein and any cells that express abnormal protein risk functional impairment. The monocyte is an important and long-lived immune cell and acts as a key immunological orchestrator, dictating the intensity and duration of the host immune response. Monocytes expressing misfolded or unfolded protein may exhibit UPR activation and this can compromise the host immune system. Here, we describe in detail methods and protocols for the examination of UPR activation in peripheral blood monocytes. This guide should provide new investigators to the field with a broad understanding of the tools required to investigate the UPR in the monocyte.
    • Measurement of the unfolded protein response (UPR) in monocytes.

      Carroll, Tomás P; Greene, Catherine M; McElvaney, Noel G; Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland. (2011)
      In mammalian cells, the primary function of the endoplasmic reticulum (ER) is to synthesize and assemble membrane and secreted proteins. As the main site of protein folding and posttranslational modification in the cell, the ER operates a highly conserved quality control system to ensure only correctly assembled proteins exit the ER and misfolded and unfolded proteins are retained for disposal. Any disruption in the equilibrium of the ER engages a multifaceted intracellular signaling pathway termed the unfolded protein response (UPR) to restore normal conditions in the cell. A variety of pathological conditions can induce activation of the UPR, including neurodegenerative disorders such as Parkinson's disease, metabolic disorders such as atherosclerosis, and conformational disorders such as cystic fibrosis. Conformational disorders are characterized by mutations that modify the final structure of a protein and any cells that express abnormal protein risk functional impairment. The monocyte is an important and long-lived immune cell and acts as a key immunological orchestrator, dictating the intensity and duration of the host immune response. Monocytes expressing misfolded or unfolded protein may exhibit UPR activation and this can compromise the host immune system. Here, we describe in detail methods and protocols for the examination of UPR activation in peripheral blood monocytes. This guide should provide new investigators to the field with a broad understanding of the tools required to investigate the UPR in the monocyte.
    • Mechanism of sphingosine 1-phosphate- and lysophosphatidic Acid-induced up-regulation of adhesion molecules and eosinophil chemoattractant in nerve cells.

      Costello, Richard W; Maloney, Michael; Atiyeh, Mazin; Gleich, Gerald; Walsh, Marie-Therese; Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, , Dublin 9, Ireland; E-Mails: rcostello@rcsi.ie (R.W.C.); micmaloney@rcsi.ie, (M.M.); matiyeh@rcsi.ie (M.A.). (2012-02-01)
      The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via G-protein coupled receptors S1P(1-5) and LPA(1-3) respectively, and are implicated in allergy. Eosinophils accumulate at innervating cholinergic nerves in asthma and adhere to nerve cells via intercellular adhesion molecule-1 (ICAM-1). IMR-32 neuroblastoma cells were used as an in vitro cholinergic nerve cell model. The G(i) coupled receptors S1P(1), S1P(3), LPA(1), LPA(2) and LPA(3) were expressed on IMR-32 cells. Both S1P and LPA induced ERK phosphorylation and ERK- and G(i)-dependent up-regulation of ICAM-1 expression, with differing time courses. LPA also induced ERK- and G(i)-dependent up-regulation of the eosinophil chemoattractant, CCL-26. The eosinophil granule protein eosinophil peroxidase (EPO) induced ERK-dependent up-regulation of transcription of S1P(1), LPA(1), LPA(2) and LPA(3), providing the situation whereby eosinophil granule proteins may enhance S1P- and/or LPA- induced eosinophil accumulation at nerve cells in allergic conditions.
    • Mechanism of sphingosine 1-phosphate- and lysophosphatidic Acid-induced up-regulation of adhesion molecules and eosinophil chemoattractant in nerve cells.

      Costello, Richard W; Maloney, Michael; Atiyeh, Mazin; Gleich, Gerald; Walsh, Marie-Therese; Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland; E-Mails: rcostello@rcsi.ie (R.W.C.); micmaloney@rcsi.ie (M.M.); matiyeh@rcsi.ie (M.A.). (2011-05)
      The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via G-protein coupled receptors S1P(1-5) and LPA(1-3) respectively, and are implicated in allergy. Eosinophils accumulate at innervating cholinergic nerves in asthma and adhere to nerve cells via intercellular adhesion molecule-1 (ICAM-1). IMR-32 neuroblastoma cells were used as an in vitro cholinergic nerve cell model. The G(i) coupled receptors S1P(1), S1P(3), LPA(1), LPA(2) and LPA(3) were expressed on IMR-32 cells. Both S1P and LPA induced ERK phosphorylation and ERK- and G(i)-dependent up-regulation of ICAM-1 expression, with differing time courses. LPA also induced ERK- and G(i)-dependent up-regulation of the eosinophil chemoattractant, CCL-26. The eosinophil granule protein eosinophil peroxidase (EPO) induced ERK-dependent up-regulation of transcription of S1P(1), LPA(1), LPA(2) and LPA(3), providing the situation whereby eosinophil granule proteins may enhance S1P- and/or LPA- induced eosinophil accumulation at nerve cells in allergic conditions.
    • Mechanisms of protein misfolding in conformational lung diseases.

      McElvaney, N G; Greene, C M; Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland. (2012-08)
      Genetic or environmentally-induced alterations in protein structure interfere with the correct folding, assembly and trafficking of proteins. In the lung the expression of misfolded proteins can induce a variety of pathogenetic effects. Cystic fibrosis (CF) and alpha-1 antitrypsin (AAT) deficiency are two major clinically relevant pulmonary disorders associated with protein misfolding. Both are genetic diseases the primary causes of which are expression of mutant alleles of the cystic fibrosis transmembrane conductance regulator (CFTR) and SERPINA1, respectively. The most common and best studied mutant forms of CFTR and AAT are ΔF508 CFTR and the Glu342Lys mutant of AAT called ZAAT, respectively. Non-genetic mechanisms can also damage protein structure and induce protein misfolding in the lung. Cigarette-smoke contains oxidants and other factors that can modify a protein's structure, and is one of the most significant environmental causes of protein damage within the lung. Herein we describe the mechanisms controlling the folding of wild type and mutant versions of CFTR and AAT proteins, and explore the consequences of cigarette-smoke-induced effects on the protein folding machinery in the lung.