• Gabapentin and Spasticity

      Carson, K (2011-03)
      Pediatric Pain Travelling Club
    • Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival.

      Pathology Service and Cancer Center, Massachusetts General Hospital, Boston, MA, , USA; Neuropathology Department, Beaumont Hospital, Dublin, Ireland; Department of, Pathology, Harvard Medical School, Boston, MA, USA Department of Biostatistics,, Harvard School of Public Health, Boston, MA; Neuropathology Department, Cork, University Hospital, Cork, Ireland. (2012-02-01)
      Aims: Atypical (WHO grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one-third will recur. Post-operative radiotherapy (RT) may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high-resolution array CGH to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumors show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression-free survival. This study aimed to validate and extend these findings in an independent sample. Methods: 86 completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow up was obtained. Utilizing a dual-colour interphase FISH assay, 1q gain was assessed using BAC probes directed against 1q25.1 and 1q32.1. Results: The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone complete surgical resection of atypical meningiomas. Conclusions: These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas.
    • Gait impairment in cervical spondylotic myelopathy: comparison with age- and gender-matched healthy controls.

      Malone, Ailish; Meldrum, Dara; Bolger, Ciaran; Physiotherapy Department, Beaumont Hospital, Dublin 9, Ireland. ailishmcd@gmail.com (2012-12)
      Gait impairment is a primary symptom of cervical spondylotic myelopathy (CSM); however, little is known about specific kinetic and kinematic gait parameters. The objectives of the study were: (1) to compare gait patterns of people with untreated CSM to those of age- and gender-matched healthy controls; (2) to examine the effect of gait speed on kinematic and kinetic parameters.
    • Galactosemia, a single gene disorder with epigenetic consequences.

      Coman, David J; Murray, David W; Byrne, Jennifer C; Rudd, Pauline M; Bagaglia, Paola M; Doran, Peter D; Treacy, Eileen P; National Centre for Inherited Metabolic Disorders, Children's University Hospital, Dublin 1, Ireland. (2010-03)
      Long-term outcomes of classic galactosemia (GAL) remain disappointing. It is unclear if the complications result mainly from prenatal-neonatal toxicity or persistent glycoprotein and glycolipid synthesis abnormalities. We performed gene expression profiling (T transcriptome) to characterize key-altered genes and gene clusters of four patients with GAL with variable outcomes maintained on a galactose-restricted diet, compared with controls. Significant perturbations of multiple cell signaling pathways were observed including mitogen-activated protein kinase (MAPK) signaling, regulation of the actin cytoskeleton, focal adhesion, and ubiquitin mediated proteolysis. A number of genes significantly altered were further investigated in the GAL cohort including SPARC (osteonectin) and S100A8 (S100 calcium-binding protein). The whole serum N-glycan profile and IgG glycosylation status of 10 treated patients with GAL were compared with healthy control serum and IgG using a quantitative high-throughput analytical HPLC platform. Increased levels of agalactosylated and monogalactosylated structures and decreases in certain digalactosylated structures were identified in the patients. The persistent abnormal glycosylation of serum glycoproteins seen with the microarray data indicates persisting metabolic dyshomeostasis and gene dysregulation in "treated" GAL. Strict restriction of dietary galactose is clearly life saving in the neonatal period; long-term severe galactose restriction may contribute to ongoing systemic abnormalities.
    • Gallbladder Carcinoma

      A Gillis, A; Cleary, S; Ridgway, PF (UOT Press, 2012)
    • Gallstone ileus in evolution.

      Larkin, John O; Moriarity, Andrew R; O'Mahony, Deirdre; Meaney, James; Ravi, Narayanasamy; Reynolds, John V; Department of Clinical Surgery, St. James's Hospital, Trinity College Dublin, Ireland. (2011-04)
    • Gastric applications of electrical field stimulation.

      Hogan, Aisling M; Gallagher, Tom K; Kennelly, Rory; Baird, Alan W; Winter, Desmond C; Department of General Surgery, Institute of Clinical Outcomes Research and, Education (iCORE), St Vincent's University Hospital, Dublin, Ireland., Aislinghogan@yahoo.com (2012-02-01)
      Advances in clinical applications of electricity have been vast since the launch of Hayman's first cardiac pacemaker more than 70 years ago. Gastric electrical stimulation devices have been recently licensed for treatment of gastroparesis and preliminary studies examining their potential for use in refractory obesity yield promising results.
    • Gastrointestinal Erdheim-Chester disease

      Tevlin, R; Cahalane, AM; Larkin, JO; Treacy, A; Connaghan, D; Winter, DC (Irish Medical Journal, 2014-05)
      We report a rare case of Erdheim-Chester Disease, a non-Langerhans cell histiocytosis. A 60-year old female presented with a seven-month history of vague abdominal symptoms. A large retroperitoneal mass was detected on computed tomography (CT), but multiple CT-guided biopsy samples were inconclusive. Laparoscopy revealed a mass in the distal ileum, which was resected. Histology and immuno-histochemistry supported a diagnosis of Erdheim-Chester Disease.
    • Gastrointestinal perforation in metastatic carcinoma: a complication of bevacizumab therapy.

      Collins, D; Ridgway, P F; Winter, D C; Fennelly, D; Evoy, D; Department of Surgery, St Vincent's University Hospital, Elm Park, Dublin 4,, Dublin, Ireland. daniellecollins@rcsi.ie (2012-02-01)
    • Gastrointestinal stromal tumors.

      O'Sullivan, Maureen J; Consultant Paediatric Pathologist, Our Lady's Children's Hospital, Crumlin,, Dublin 12, Ireland. Maureen.osullivan@tcd.ie (2012-02-01)
    • Gelastic seizures without hypothalamic hamartoma

      O'Connor, G; Chaila, E; Mullins, G; Delanty, N (Wiley-Blackwell, 2011-08)
      Purpose: Gelastic epilepsy is a well recognized epilepsy syndrome, and is associated in almost all cases with the presence of a hypothalamic hamartoma. However, the epileptologist should be alert to alternative causes for such presentations. We present two cases from our service of gelastic seizures in the absence of hypothalamic hamartoma. Method: We reviewed the clinical features in both cases. Both patients were male and right-handed. The duration of epilepsy was similar in both cases, with onset in late adolescence. In both cases, epilepsy was refractory to treatment with antiepileptic medications. Clinical examination was unremarkable in both men. Both patients were investigated with video EEG monitoring and imaging to localize a seizure focus. Results: Video EEG monitoring in both cases suggested a right frontal focus for seizure onset. MRI in one patient revealed a right frontal mass lesion, and in the other, a right frontal cortical dysplasia. There was no evidence of a hypothalamic lesion in either case. After discussion, both cases were felt to be suitable for neurosurgical intervention. Conclusion: Gelastic epilepsy without hypothalamic hamartoma is rare, but some cases reported have had a right frontal focus for seizure onset. Causes reported in such cases have included tumors and cortical dysplasia. Many of the cases reported have had a good response to surgical intervention. In gelastic epilepsy, the clinician should be aware of causes other than hypothalamic hamartomata. Investigations should be directed towards confirming a seizure focus with a view to offering surgical intervention.
    • Gender differences in outcome at 2-year follow-up of treated bipolar and depressed alcoholics.

      Farren, Conor K; Snee, Laura; McElroy, Sharon; Department of Addiction Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, Dublin 8, Ireland. cfarren@stpatsmail.com (2011-09)
      Alcohol dependence and affective disorders are significant health problems, and their co-occurrence is mutually detrimental. There are few long-term studies on the impact of treatment on the prognosis of these comorbid disorders. We wished to study if the impact of effective inpatient integrated treatment for these co-occurring disorders was maintained 2 years after discharge from the hospital.
    • Gender differences in the association between childhood abuse and psychosis.

      Fisher, Helen; Morgan, Craig; Dazzan, Paola; Craig, Thomas K; Morgan, Kevin; Hutchinson, Gerard; Jones, Peter B; Doody, Gillian A; Pariante, Carmine; McGuffin, Peter; et al. (2009-04)
      Studies demonstrating an association between childhood trauma and psychosis in adulthood have not systematically explored gender differences.
    • Gender identity disorder.

      De Gascun, C; Kelly, J; Salter, N; Lucey, J; O'Shea, D; Department of Endocrinology, St Columcilles Hospital, Dublin. (2006-05)
      Gender Identity Disorder (GID) is a relatively rare condition of atypical gender development in which there is a psychological perception of self as masculine or feminine which is incongruent with ones phenotype. GID replaced the term Transsexualism in DSM-IV in 1994. The demographics of GID in Ireland have not been established. Since 2000 we have received 52 referrals of individuals with confirmed GID to our endocrine service for consideration for hormonal treatment (HT). Of the 52 patients 45 have male to female (MTF) GID (mean age 38.9 years) and 7 have female to male (FTM) GID (mean age 30.7 years). The age at presentation in this group is approximately 9 years older than in international series for both MTF (39 years v 30yrs) and FTM (31 yrs v 22yrs). The karyotype where analysed has been normal for their phenotypic sex. Twenty-three of the patients had received HT prior to attending our clinic that in only one case had been prescribed by a specialist. A number of patients had obtained HT via the internet or from overseas sources without medical review. Eighteen of the patients have been or are married and 14 of the group have children. The scale of referrals confirms that GID exists in the Irish population to a significant degree. Thus an appropriate care pathway for people with the condition needs to be established. This will facilitate optimum medical management of the patient group and a coherent approach to the many difficult social issues faced individuals with this disorder.
    • Gene expression analysis in prostate cancer: the importance of the endogenous control.

      Vajda, Alice; Marignol, Laure; Barrett, Ciara; Madden, Stephen F; Lynch, Thomas H; Hollywood, Donal; Perry, Antoinette S; Prostate Molecular Oncology, Academic Unit of Clinical and Molecular Oncology, Institute of Molecular Medicine, Trinity College Dublin, Ireland. vajdaa@tcd.ie (2013-03)
      Aberrant gene expression is a hallmark of cancer. Quantitative reverse-transcription PCR (qRT-PCR) is the gold-standard for quantifying gene expression, and commonly employs a house-keeping gene (HKG) as an endogenous control to normalize results; the choice of which is critical for accurate data interpretation. Many factors, including sample type, pathological state, and oxygen levels influence gene expression including putative HKGs. The aim of this study was to determine the suitability of commonly used HKGs for qRT-PCR in prostate cancer.
    • Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer.

      Perry, Antoinette S; O'Hurley, Gillian; Raheem, Omer A; Brennan, Kevin; Wong, Simon; O'Grady, Anthony; Kennedy, Anne-Marie; Marignol, Laure; Murphy, Therese M; Sullivan, Linda; et al. (2013-04-15)
      Aberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes SFRPs (Secreted Frizzled-Related Proteins) is a frequent oncogenic event. The significance of this is not known in prostate cancer. The objectives of our study were to (i) profile Wnt signaling related gene expression and (ii) investigate methylation of Wnt antagonist genes in prostate cancer. Using TaqMan Low Density Arrays, we identified 15 Wnt signaling related genes with significantly altered expression in prostate cancer; the majority of which were upregulated in tumors. Notably, histologically benign tissue from men with prostate cancer appeared more similar to tumor (r = 0.76) than to benign prostatic hyperplasia (BPH; r = 0.57, p < 0.001). Overall, the expression profile was highly similar between tumors of high (≥ 7) and low (≤ 6) Gleason scores. Pharmacological demethylation of PC-3 cells with 5-Aza-CdR reactivated 39 genes (≥ 2-fold); 40% of which inhibit Wnt signaling. Methylation frequencies in prostate cancer were 10% (2/20) (SFRP1), 64.86% (48/74) (SFRP2), 0% (0/20) (SFRP4) and 60% (12/20) (SFRP5). SFRP2 methylation was detected at significantly lower frequencies in high-grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), p = 0.0096), tumor adjacent benign areas (8.82%, (7/69), p < 0.0001) and BPH (11.43% (4/35), p < 0.0001). The quantitative level of SFRP2 methylation (normalized index of methylation) was also significantly higher in tumors (116) than in the other samples (HGPIN = 7.45, HB = 0.47, and BPH = 0.12). We show that SFRP2 hypermethylation is a common event in prostate cancer. SFRP2 methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer.
    • Gene expression profiling in cervical cancer: identification of novel markers for disease diagnosis and therapy.

      Martin, Cara M; Astbury, Katharine; McEvoy, Lynda; O'Toole, Sharon; Sheils, Orla; O'Leary, John J; Department of Pathology, Coombe Women's Hospital, Dublin, Ireland. (2012-02-01)
      Cervical cancer, a potentially preventable disease, remains the second most common malignancy in women worldwide. Human papillomavirus is the single most important etiological agent in cervical cancer. HPV contributes to neoplastic progression through the action of two viral oncoproteins E6 and E7, which interfere with critical cell cycle pathways, p53, and retinoblastoma. However, evidence suggests that HPV infection alone is insufficient to induce malignant changes and other host genetic variations are important in the development of cervical cancer. Advances in molecular biology and high throughput gene expression profiling technologies have heralded a new era in biomarker discovery and identification of molecular targets related to carcinogenesis. These advancements have improved our understanding of carcinogenesis and will facilitate screening, early detection, management, and personalised targeted therapy. In this chapter, we have described the use of high density microarrays to assess gene expression profiles in cervical cancer. Using this approach we have identified a number of novel genes which are differentially expressed in cervical cancer, including several genes involved in cell cycle regulation. These include p16ink4a, MCM 3 and 5, CDC6, Geminin, Cyclins A-D, TOPO2A, CDCA1, and BIRC5. We have validated expression of mRNA using real-time PCR and protein by immunohistochemistry.
    • Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency.

      McLean, Caitriona; Greene, Catherine M; McElvaney, Noel G; Respiratory Research Division, Dept. Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. (2009)
      Alpha-1 antitrypsin (A1AT) is a 52 kDa serine protease inhibitor that is synthesized in and secreted from the liver. Although it is present in all tissues in the body the present consensus is that its main role is to inhibit neutrophil elastase in the lung. A1AT deficiency occurs due to mutations of the A1AT gene that reduce serum A1AT levels to <35% of normal. The most clinically significant form of A1AT deficiency is caused by the Z mutation (Glu342Lys). ZA1AT polymerizes in the endoplasmic reticulum of liver cells and the resulting accumulation of the mutant protein can lead to liver disease, while the reduction in circulating A1AT can result in lung disease including early onset emphysema. There is currently no available treatment for the liver disease other than transplantation and therapies for the lung manifestations of the disease remain limited. Gene therapy is an evolving field which may be of use as a treatment for A1AT deficiency. As the liver disease associated with A1AT deficiency may represent a gain of function possible gene therapies for this condition include the use of ribozymes, peptide nucleic acids (PNAs) and RNA interference (RNAi), which by decreasing the amount of aberrant protein in cells may impact on the pathogenesis of the condition.
    • Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders.

      Anney, Richard J L; Kenny, Elaine M; O'Dushlaine, Colm; Yaspan, Brian L; Parkhomenka, Elena; Buxbaum, Joseph D; Sutcliffe, James; Gill, Michael; Gallagher, Louise; Buxbaum, Joseph D; et al. (2012-02-01)
      Recent genome-wide association studies (GWAS) have implicated a range of genes from discrete biological pathways in the aetiology of autism. However, despite the strong influence of genetic factors, association studies have yet to identify statistically robust, replicated major effect genes or SNPs. We apply the principle of the SNP ratio test methodology described by O'Dushlaine et al to over 2100 families from the Autism Genome Project (AGP). Using a two-stage design we examine association enrichment in 5955 unique gene-ontology classifications across four groupings based on two phenotypic and two ancestral classifications. Based on estimates from simulation we identify excess of association enrichment across all analyses. We observe enrichment in association for sets of genes involved in diverse biological processes, including pyruvate metabolism, transcription factor activation, cell-signalling and cell-cycle regulation. Both genes and processes that show enrichment have previously been examined in autistic disorders and offer biologically plausibility to these findings.