• Kinetics of host immune responses and cytomegalovirus resistance in a liver transplant patient.

      Schaffer, Kirsten; Moran, Julie; Duffy, Margaret; McCormick, Aiden P; Hall, William W; Hassan, Jaythoon; Department of Microbiology, St. Vincent's University Hospital, Elm Park, Dublin, , Ireland. kirsten.e.schaffer@ucd.ie (2012-02-01)
      Among solid organ transplant (SOT) recipients, donor-seropositive/recipient-seronegative (D+/R-) cytomegalovirus (CMV) status is associated with the highest risk of ganciclovir-resistant CMV disease, which has been reported for patients receiving oral ganciclovir but not valganciclovir prophylaxis. We report a case of CMV breakthrough infection in a D+/R- liver transplant patient while he was receiving oral valganciclovir. Forty samples collected over 6 months were analyzed for the CMV viral load, lymphocyte counts, cytokine levels, and lymphocyte differentiation status. Genotypic resistance testing of the viral UL97 gene was performed when the patient failed to respond. CMV viremia occurred on day 50 post-transplant, and 5 samples taken between days 50 and 85 showed the wild-type UL97 genotype. The appearance of deletion 594-595 was observed from day 114 post-transplant. Viral loads declined when foscarnet was commenced and remained below 10,000 copies/mL when the lymphocyte count was greater than 1000/microL (P = 0.02). T cell responses revealed significant expansion of CD8+ terminal effector memory cells. CD4+ cells were largely populations of naive and central memory cells. Circulating interleukin 10 (IL-10) levels correlated with the viral load (P < 0.0001). Seroconversion occurred on day 230. The CMV viral load in combination with lymphocyte counts and IL-10 may be a predictive marker for the risk of development of resistant CMV disease in D+/R- SOT patients.
    • Knobloch syndrome: novel intra-oral findings.

      O'Connell, Anne C; Toner, Mary; Murphy, Sinead; Division of Public and Child Dental Health, Dublin Dental School and Hospital, Lincon Place, Dublin, Ireland. anne.oconnell@dental.tcd.ie (2009-05)
    • Knowledge and behaviour of parents in relation to the oral and dental health of children aged 4-6 years.

      ElKarmi, R; Shore, E; O'Connell, A; Division of Public and Child Dental Health-Dublin Dental University Hospital-Trinity College-Dublin, Lincoln Place, Dublin2, Ireland, rawankarmi@yahoo.com. (European archives of paediatric dentistry : official journal of the European Academy of Paediatric Dentistry, 2014-11-04)
      To evaluate baseline knowledge and behaviour of parents with regard to the oral and dental health of their young children.
    • Knowledge, attitudes and practices in the provision of nutritional care.

      Fletcher, Antoinette; Carey, Eileen; St Vincent's University Hospital Dublin. (2012-02-01)
      The nutritional care of patients is one of the primary responsibilities of all registered nurses (Persenius et al, 2008). A poor nutritional status can lead to malnutrition, which can have serious consequences for an individual's quality of life (Field and Smith, 2008). This paper commences with an introduction to the concept of nutrition, provides an overview of nutritional guidelines and nutritional screening tools which identify those at risk of malnutrition. It reviews the literature on nurses' knowledge, attitudes and practices in the provision of nutritional care and debates challenges and opportunities encountered to help nurses ensure adequate patient nutrition.
    • Knowledge, Skills and Experience Managing Tracheostomy Emergencies: A Survey of Critical Care Medicine trainees

      Nizam, AA; Ng, SC; Kelleher, M; Hayes, N; Carton, E (Irish Medical Journal, 2016-10)
      Since the development of percutaneous tracheostomy, the number of tracheostomy patients on hospital wards has increased. Problems associated with adequate tracheostomy care on the wards are well documented, particularly the management of tracheostomy-related emergencies. A survey was conducted among non-consultant hospital doctors (NCHDs) starting their Critical Care Medicine training rotation in a university affiliated teaching hospital to determine their basic knowledge and skills in dealing with tracheostomy emergencies. Trainees who had received specific tracheostomy training or who had previous experience of dealing with tracheostomy emergencies were more confident in dealing with such emergencies compared to trainees without such training or experience. Only a minority of trainees were aware of local hospital guidelines regarding tracheostomy care. Our results highlight the importance of increased awareness of tracheostomy emergencies and the importance of specific training for Anaesthesia and Critical Care Medicine trainees.
    • Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.

      Arsov, Todor; Smith, Katherine R; Damiano, John; Franceschetti, Silvana; Canafoglia, Laura; Bromhead, Catherine J; Andermann, Eva; Vears, Danya F; Cossette, Patrick; Rajagopalan, Sulekha; et al. (2011-05-13)
      The molecular basis of Kufs disease is unknown, whereas a series of genes accounting for most of the childhood-onset forms of neuronal ceroid lipofuscinosis (NCL) have been identified. Diagnosis of Kufs disease is difficult because the characteristic lipopigment is largely confined to neurons and can require a brain biopsy or autopsy for final diagnosis. We mapped four families with Kufs disease for whom there was good evidence of autosomal-recessive inheritance and found two peaks on chromosome 15. Three of the families were affected by Kufs type A disease and presented with progressive myoclonus epilepsy, and one was affected by type B (presenting with dementia and motor system dysfunction). Sequencing of a candidate gene in one peak shared by all four families identified no mutations, but sequencing of CLN6, found in the second peak and shared by only the three families affected by Kufs type A disease, revealed pathogenic mutations in all three families. We subsequently sequenced CLN6 in eight other families, three of which were affected by recessive Kufs type A disease. Mutations in both CLN6 alleles were found in the three type A cases and in one family affected by unclassified Kufs disease. Mutations in CLN6 are the major cause of recessive Kufs type A disease. The phenotypic differences between variant late-infantile NCL, previously found to be caused by CLN6, and Kufs type A disease are striking; there is a much later age at onset and lack of visual involvement in the latter. Sequencing of CLN6 will provide a simple diagnostic strategy in this disorder, in which definitive identification usually requires invasive biopsy.
    • L-2-hydroxyglutaric aciduria diagnosed in an adult presenting with acute deterioration.

      Saidha, Shiv; Murphy, Sinead; McCarthy, Peter; Mayne, Philip D; Hennessy, Michael (Journal of neurology, 2010-01)
    • Laboratory assessment of iron status in pregnancy.

      Walsh, Thomas; O'Broin, Sean D; Cooley, Sharon; Donnelly, Jennifer; Kennedy, John; Harrison, Robert F; McMahon, Corinna; Geary, Michael; Rotunda Hospital, Dublin, Ireland. (2012-02-01)
      BACKGROUND: Efforts to improve maternal nutrition during pregnancy prompted an observational study of the occurrence of maternal iron deficiency and its laboratory diagnosis in almost 500 pregnancies. METHODS: In this longitudinal study, the biochemical and haematological iron indices of women (n=492) attending a prenatal clinic in a Dublin maternity hospital were assessed at first booking (mean 15.9 weeks), and after 24 weeks, and 36 weeks of gestation. Full blood counts were measured. Serum ferritin (SF), zinc protoporphyrin (ZPP), and transferrin receptor (sTfR) concentrations were assayed and transferrin receptor index (sTfR-Index) was calculated. The occurrence of low values and their diagnostic values were considered. RESULTS: A high occurrence iron deficiency (ID) at first booking (SF<12 mug/L) had increased over six-fold by 24 weeks, and all biochemical iron indices reflected progressive iron depletion right up to term. The WHO recommended anaemia "cut-off" (Hb<110 g/L) was insensitive to biochemical iron deficiency at booking, missing over 90% of the low SF values (SF<12 mug/L) which were mostly associated with much higher Hb levels. CONCLUSIONS: This study stresses the importance of including a biochemical index of iron status in prenatal screening and supports SF as the best indicator of biochemical ID overall. sTfR was insensitive to iron deficiency in early pregnancy, whereas the sTfR-Index, as a ratio, has the potential to distinguish between ID and physiological anaemia, and may offer stability in the assessment of iron stores from early pregnancy to full term. A policy of early screening of both Hb and SF concentrations is recommended as the minimum requirement for surveillance of maternal iron status in pregnancy.
    • Laboratory assessment of iron status in pregnancy.

      Walsh, Thomas; O'Broin, Sean D; Cooley, Sharon; Donnelly, Jennifer; Kennedy, John; Harrison, Robert F; McMahon, Corinna; Geary, Michael; Rotunda Hospital, Dublin, Ireland. (2011-07)
      Efforts to improve maternal nutrition during pregnancy prompted an observational study of the occurrence of maternal iron deficiency and its laboratory diagnosis in almost 500 pregnancies.
    • Lack of awareness of risk factors for primary toxoplasmosis in pregnancy.

      Ferguson, W; Mayne, P D; Cafferkey, M; Butler, K; Department of Paediatrics, The Rotunda Hospital, Parnell Square, Dublin 1, Ireland. wferguson@rotunda.ie (2011-12)
      The overall seroprevalence of toxoplasma antibodies in women of childbearing age in Ireland is 25% [1]. Hence, 75% of women remain susceptible to primary toxoplasma infection during pregnancy, which if transmitted to the foetus can cause ocular, neurological and other sequelae. Toxoplasma exposure during pregnancy can be avoided if there is an awareness of the potential sources of infection, mainly contaminated food, water, soil and cat faeces.
    • Lack of benefit for the addition of androgen deprivation therapy to dose-escalated radiotherapy in the treatment of intermediate- and high-risk prostate cancer.

      Krauss, Daniel; Kestin, Larry; Ye, Hong; Brabbins, Donald; Ghilezan, Michel; Gustafson, Gary; Vicini, Frank; Martinez, Alvaro; Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073,, USA. dkrauss@beaumont.edu (2012-02-01)
      PURPOSE: Assessment of androgen deprivation therapy (ADT) benefits for prostate cancer treated with dose-escalated radiotherapy (RT). METHODS AND MATERIALS: From 1991 to 2004, 1,044 patients with intermediate- (n = 782) or high-risk (n = 262) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital. Patients received external-beam RT (EBRT) alone, brachytherapy (high or low dose rate), or high dose rate brachytherapy plus pelvic EBRT. Intermediate-risk patients had Gleason score 7, prostate-specific antigen (PSA) 10.0-19.9 ng/mL, or Stage T2b-T2c. High-risk patients had Gleason score 8-10, PSA >/=20, or Stage T3. Patients were additionally divided specifically by Gleason score, presence of palpable disease, and PSA level to further define subgroups benefitting from ADT. RESULTS: Median follow-up was 5 years; 420 patients received ADT + dose-escalated RT, and 624 received dose-escalated RT alone. For all patients, no advantages in any clinical endpoints at 8 years were associated with ADT administration. No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately. Patients with palpable disease plus Gleason >/=8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT. Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given. CONCLUSION: Benefits of ADT in the setting of dose-escalated RT remain poorly defined. This question must continue to be addressed in prospective study.
    • Lack of cytotoxicity by Trustwater Ecasol™ used to maintain good quality dental unit waterline output water in keratinocyte monolayer and reconstituted human oral epithelial tissue models.

      Boyle, M A; O'Donnell, M J; Russell, R J; Coleman, D C; Microbiology Research Unit, Division of Oral Biosciences, Dublin Dental School & Hospital, University of Dublin, Trinity College Dublin, Lincoln Place, Dublin 2, Ireland. (2010-11)
      We previously showed that residual treatment of dental chair unit (DCU) supply water using the electrochemically-activated solution Trustwater Ecasol™ (2.5 ppm) provided an effective long-term solution to the problem of dental unit waterline (DUWL) biofilm resulting in DUWL output water quality consistently superior to potable water.
    • Lack of differential pattern in central adiposity and metabolic syndrome in Barrett's esophagus and gastroesophageal reflux disease.

      Healy, L A; Ryan, A M; Pidgeon, G; Ravi, N; Reynolds, J V; Department of Clinical Surgery, St. James' Hospital and Trinity College, Dublin, , Ireland. (2012-02-01)
      Obesity is an established risk factor for esophageal adenocarcinoma, although the mechanism is unclear. A pathway from reflux to inflammation through metaplasia is the dominant hypothesis, and an added role relating to visceral adiposity and the metabolic syndrome has been mooted in Barrett's esophagus (BE) patients. Whether BE differs from gastroesophageal reflux disease (GERD) in obesity and metabolic syndrome profiles is unclear, and this was the focus of this study. Patients with proven BE or GERD were randomly selected from the unit data registry and invited to attend for metabolic syndrome screening, anthropometry studies including segmental body composition analysis, and laboratory tests including fasting lipids, insulin, and C-reactive protein. Metabolic syndrome was defined using the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) criteria. One hundred and eighteen BE patients and 113 age- and sex-matched GERD controls were studied. The incidence of obesity (body mass index >30 kg/m(2)) was 36% and 38%, respectively, with the pattern of fat deposition predominantly central and an estimated trunk fat mass of 13 and 14 kg, respectively. Using the NCEP criteria, metabolic syndrome was significantly more common in the BE cohort (30% vs 20%, P < 0.05), but there was no significant difference using IDF criteria (42% vs 37%, P= 0.340). Central obesity and the metabolic syndrome are common in both Barrett's and GERD cohorts, but not significantly different, suggesting that central obesity and the metabolic syndrome does not per se impact on the development of BE in a reflux population. In BE, the importance of obesity and the metabolic syndrome in disease progression merits further study.
    • Lack of National Consensus for the Molecular Investigation of Myeloproliferative Neoplasms

      Langabeer, SE (Irish Medical Journal, 2015-06)
      The discovery of the JAK2 V617F mutation ten years ago revolutionised the molecular diagnosis of the classical myeloproliferative neoplasms (MPN) of polycythaemia vera, essential thrombocythaemia and primary myelofibrosis with presence of this mutation now considered a major criteria for the diagnosis of these malignancies according to the World Health Organization classification of tumours. 1 Despite these advances, current guidelines maintain the requirement for bone marrow aspirate and biopsy necessary for assessment of morphology and degree of fibrosis critical for therapeutic decisions. While presence or absence of this mutation is beneficial in differentiating between a reactive haematological response (causes include infection, inflammation, tissue damage, hyposplenism, haemorrhage, iron deficiency, malignancy, haemolysis and drug therapy) and a clonal MPN, testing for the JAK2 V617F mutation is becoming an advance test in the initial work up of patients for whom the aforementioned secondary causes have not been fully excluded. The year upon year increase in requests for JAK2 V617F mutation status, despite consistency in the annual number of newly diagnosed MPN patients, has been previously documented. 2
    • Lack of significant metabolic abnormalities in mice with liver-specific disruption of 11β-hydroxysteroid dehydrogenase type 1.

      Lavery, Gareth G; Zielinska, Agnieszka E; Gathercole, Laura L; Hughes, Beverly; Semjonous, Nina; Guest, Phillip; Saqib, Khalid; Sherlock, Mark; Reynolds, Gary; Morgan, Stuart A; et al. (Endocrinology, 2012-07)
      Glucocorticoids (GC) are implicated in the development of metabolic syndrome, and patients with GC excess share many clinical features, such as central obesity and glucose intolerance. In patients with obesity or type 2 diabetes, systemic GC concentrations seem to be invariably normal. Tissue GC concentrations determined by the hypothalamic-pituitary-adrenal (HPA) axis and local cortisol (corticosterone in mice) regeneration from cortisone (11-dehydrocorticosterone in mice) by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme, principally expressed in the liver. Transgenic mice have demonstrated the importance of 11β-HSD1 in mediating aspects of the metabolic syndrome, as well as HPA axis control. In order to address the primacy of hepatic 11β-HSD1 in regulating metabolism and the HPA axis, we have generated liver-specific 11β-HSD1 knockout (LKO) mice, assessed biomarkers of GC metabolism, and examined responses to high-fat feeding. LKO mice were able to regenerate cortisol from cortisone to 40% of control and had no discernible difference in a urinary metabolite marker of 11β-HSD1 activity. Although circulating corticosterone was unaltered, adrenal size was increased, indicative of chronic HPA stimulation. There was a mild improvement in glucose tolerance but with insulin sensitivity largely unaffected. Adiposity and body weight were unaffected as were aspects of hepatic lipid homeostasis, triglyceride accumulation, and serum lipids. Additionally, no changes in the expression of genes involved in glucose or lipid homeostasis were observed. Liver-specific deletion of 11β-HSD1 reduces corticosterone regeneration and may be important for setting aspects of HPA axis tone, without impacting upon urinary steroid metabolite profile. These discordant data have significant implications for the use of these biomarkers of 11β-HSD1 activity in clinical studies. The paucity of metabolic abnormalities in LKO points to important compensatory effects by HPA activation and to a crucial role of extrahepatic 11β-HSD1 expression, highlighting the contribution of cross talk between GC target tissues in determining metabolic phenotype.
    • Lafora disease: epidemiology, pathophysiology and management.

      Monaghan, Thomas S; Delanty, Norman; Department of Neurology and Neuroscience, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin 9, Ireland. (2010-07-01)
      Lafora disease is a rare, fatal, autosomal recessive, progressive myoclonic epilepsy. It may also be considered as a disorder of carbohydrate metabolism because of the formation of polyglucosan inclusion bodies in neural and other tissues due to abnormalities of the proteins laforin or malin. The condition is characterized by epilepsy, myoclonus and dementia. Diagnostic findings on MRI and neurophysiological testing are not definitive and biopsy or genetic studies may be required. Therapy in Lafora disease is currently limited to symptomatic management of the epilepsy, myoclonus and intercurrent complications. With a greater understanding of the pathophysiological processes involved, there is justified hope for future therapies.
    • Language processing abnormalities in adolescents with psychotic-like experiences: An event related potential study.

      Murphy, Jennifer; Blanchard, Mathieu M; Rawdon, Caroline; Kavanagh, Fergal; Kelleher, Ian; Clarke, Mary C; Roche, Richard A P; Cannon, Mary; Department of Psychology, National University of Ireland, Maynooth, Co. Kildare, Ireland; Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland. (2012-05)
      Language impairments are a well established finding in patients with schizophrenia and in individuals at-risk for psychosis. A growing body of research has revealed shared risk factors between individuals with psychotic-like experiences (PLEs) from the general population and patients with schizophrenia. In particular, adolescents with PLEs have been shown to be at an increased risk for later psychosis. However, to date there has been little information published on electrophysiological correlates of language comprehension in this at-risk group. A 64 channel EEG recorded electrical activity while 37 (16 At-Risk; 21 Controls) participants completed the British Picture Vocabulary Scale (BPVS-II) receptive vocabulary task. The P300 component was examined as a function of language comprehension. The at-risk group were impaired behaviourally on receptive language and were characterised by a reduction in P300 amplitude relative to the control group. The results of this study reveal electrophysiological evidence for receptive language deficits in adolescents with PLEs, suggesting that the earliest neurobiological changes underlying psychosis may be apparent in the adolescent period.
    • Laparoscopic adrenalectomy: Single centre experience.

      O'Farrell, N J; Collins, C G; Stafford, A T; Broe, P J; Department of General Surgery, Beaumont Hospital, Beaumont Road, Dublin 9,, Ireland. (2012-02-01)
      BACKGROUND: Laparoscopic adrenalectomy is an attractive alternative to the traditional open approach in the surgical excision of an adrenal gland. It has replaced open adrenalectomy in our institution and we review our experience to date. METHODS: All cases of laparoscopic adrenalectomies in our hospital over eight years (from 2001 to May 2009) were retrospectively reviewed. Patient demographics, diagnosis, length of hospital stay, histology and all operative and post-operative details were evaluated. RESULTS: Fifty-five laparoscopic adrenalectomies (LA) were performed on 51 patients over eight years. The mean age was 48 years (Range 16-86 years) with the male: female ratio 1:2. Twenty-three cases had a right adrenalectomy, 24 had a left adrenalectomy and the remaining four patients had bilateral adrenalectomies. 91% were successfully completed laparoscopically with five converted to an open approach. Adenomas (functional and non functional) were the leading indication for LA, followed by phaeochromocytomas. Other indications for LA included Cushing's disease, adrenal malignancies and rarer pathologies. There was one mortality from necrotising pancreatitis following a left adrenalectomy for severe Cushing's disease, with subsequent death 10 days later. CONCLUSION: Laparoscopic adrenalectomy is effective for the treatment of adrenal tumours, fulfilling the criteria for the ideal minimally invasive procedure. It has replaced the traditional open approach in our centre and is a safe and effective alternative. However, in the case of severe Cushing's disease, laparoscopic adrenalectomy has the potential for significant adverse outcomes and mortality.