• The detection of heterozygous familial hypercholesterolemia in Ireland.

      O'Kane, Maurice J; Menown, Ian B; Graham, Ian; Maher, Vincent; Tomkin, Gerald; Nicholls, Paul; Graham, Colin; Clinical Chemistry Laboratory, Altnagelvin Hospital, Londonderry, Northern Ireland. Maurice.OKane@westerntrust.hscni.net (Advances in therapy, 2012-05)
      Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant condition with a population prevalence of 1 in 500, and is associated with significant cardiovascular morbidity and mortality. It may be caused by mutations in the low-density lipoprotein (LDL) receptor, apolipoprotein B100 (Apo B100), or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes, with over 1,000 causative mutations described. Statin therapy in HeFH is considered effective and safe. Audit data suggest that approximately 80% of the putative HeFH population remains unidentified and, therefore, there is a need to develop a strategy for the identification of affected individuals so that early lipid-lowering treatment may be offered. There is good evidence showing the effectiveness and acceptability of HeFH screening programs in Europe. The authors describe a protocol for an all island approach to HeFH detection in the Republic of Ireland/Northern Ireland. Index cases will be identified by opportunistic screening using the Simon Broome, or Make Early Diagnosis to Prevent Early Death (MedPed) and World Health Organization (WHO) criteria. Patients identified as "definite," "probable," or "possible" HeFH criteria will be offered genetic testing. The authors expect causative mutations to be identified in approximately 80% of patients with "definite" HeFH but in only approximately 20% of patients with "possible" HeFH. Cascade screening will be undertaken in first-degree relatives of the index case using genetic testing (where a causative mutation has been identified), or otherwise using LDL cholesterol concentration. The establishment of a HeFH screening program on an all-island basis will require: expansion of the existing molecular genetics diagnostic services, the establishment of a cohort of nurses/genetic counselors, a HeFH database to support cascade testing, the development of a network of lipid clinics (in a primary or secondary care setting), and an educational initiative to raise awareness of HeFH among healthcare professionals and the general population.
    • Early diagnosis of bilateral sub-deltoid bursitis using clinic-based ultrasonography in a patient receiving infliximab therapy for ulcerative pouchitis.

      Veerappan, S G; Moinuddin, G; Kennedy, M; O'Morain, C A; Kane, D; Department of Gastroenterology, Adelaide & Meath Hospital, Tallaght, Dublin 24, Republic of Ireland. sveerappan@rcsi.ie (2010-12)
      Infliximab, a monoclonal chimeric antibody to tumour necrosis factor (TNF)α, is a novel therapy used in the management of chronic refractory pouchitis that is unresponsive to conventional medical therapy.
    • Enrichment of MCI and early Alzheimer's disease treatment trials using neurochemical and imaging candidate biomarkers.

      Hampel, H; Broich, K; Discipline of Psychiatry, School of Medicine, Trinity College, University of, Dublin, Trinity Center for Health Sciences, The Adelaide and Meath Hospital, incorporating the National Children's Hospital (AMiNCH), Tallaght, Dublin 24,, Ireland. harald.hampel@tcd.ie (2012-02-01)
      In the earliest clinical stages of Alzheimer's Disease (AD), when symptoms are mild, clinical diagnosis will still be difficult. AD related molecular mechanisms precede symptoms. Biological markers can serve as early diagnostic indicators, as markers of preclinical pathological change, e.g. underlying mechanisms of action (MoA). Hypothesis based candidates are derived from structural and functional neuroimaging as well as from cerebrospinal fluid (CSF) and plasma. Unbiased exploratory approaches e.g. proteome analysis or rater independent fully automated imaging post-processing methods yield novel candidates. Recent progress in the validation of core feasible imaging and neurochemical biomarkers for functions such as early detection, classification, progression and prediction of AD is summarized. Single core feasible biomarkers can already be used to enrich populations at risk for AD and may be further enhanced using distinct combinations. Some biomarkers are currently in the process of implementation as primary or secondary outcome variables into regulatory guideline documents, e.g. regarding phase II in drug development programs as outcome measures in proof of concept or dose finding studies. There are specific biomarkers available depending on the hypothesized mechanism of action of a medicinal product, e.g. impact on the amyloidogenic cascade or on tauhyperphosphorylation. Ongoing large-scale international controlled multi-center trials will provide further validation of selected core feasible imaging and CSF biomarker candidates as outcome measures in early AD for use in phase III clinical efficacy trials. There is a need of rigorous co-development of biological trait- and statemarker candidates facilitated through planned synergistic collaboration between academic, industrial and regulatory partners.
    • Small bowel angiodysplasia and novel disease associations: a cohort study.

      Holleran, Grainne; Hall, Barry; Hussey, Mary; McNamara, Deirdre; Department of Clinical Medicine, Adelaide and Meath Hospital, Trinity College Dublin, Dublin, Ireland. grainneholleran@gmail.com (2013-04)
      Gastrointestinal angiodysplasias recurrently bleed, accounting for 3-5% of obscure gastrointestinal bleeding. The advent of small bowel capsule endoscopy (SBCE) has led to an increased recognition of small bowel angiodysplasias (SBAs) but little is known about their etiology. Previous small cohorts and case reports suggest an equal gender incidence and associations with cardiovascular disease, renal impairment, and coagulopathies.