• Accuracy of whole-body low-dose multidetector CT (WBLDCT) versus skeletal survey in the detection of myelomatous lesions, and correlation of disease distribution with whole-body MRI (WBMRI).

      Gleeson, T G; Moriarty, J; Shortt, C P; Gleeson, J P; Fitzpatrick, P; Byrne, B; McHugh, J; O'Connell, M; O'Gorman, P; Eustace, S J; et al. (Skeletal radiology, 2009-03)
      The aim of the study is to assess the feasibility of whole-body low-dose computed tomography (WBLDCT) in the diagnosis and staging of multiple myeloma and compare to skeletal survey (SS), using bone marrow biopsy and whole-body magnetic resonance imaging (WBMRI; where available) as gold standard.
    • ACTH deficiency, higher doses of hydrocortisone replacement, and radiotherapy are independent predictors of mortality in patients with acromegaly.

      Sherlock, M; Reulen, R C; Alonso, A Aragon; Ayuk, J; Clayton, R N; Sheppard, M C; Hawkins, M M; Bates, A S; Stewart, P M; Centre for Endocrinology, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TH, United Kingdom. (The Journal of clinical endocrinology and metabolism, 2009-11)
      A number of retrospective studies report that patients with acromegaly have increased morbidity and premature mortality, with standardized mortality ratios (SMR) of 1.3-3. Many patients with acromegaly develop hypopituitarism as a result of the pituitary adenoma itself or therapies such as surgery and radiotherapy. Pituitary radiotherapy and hypopituitarism have also been associated with an increased SMR.
    • Acute serum amyloid A induces migration, angiogenesis, and inflammation in synovial cells in vitro and in a human rheumatoid arthritis/SCID mouse chimera model.

      Connolly, Mary; Marrelli, Alessandra; Blades, Mark; McCormick, Jennifer; Maderna, Paola; Godson, Catherine; Mullan, Ronan; FitzGerald, Oliver; Bresnihan, Barry; Pitzalis, Costantino; et al. (Journal of immunology (Baltimore, Md. : 1950), 2010-06-01)
      Serum amyloid A (A-SAA), an acute-phase protein with cytokine-like properties, is expressed at sites of inflammation. This study investigated the effects of A-SAA on chemokine-regulated migration and angiogenesis using rheumatoid arthritis (RA) cells and whole-tissue explants in vitro, ex vivo, and in vivo. A-SAA levels were measured by real-time PCR and ELISA. IL-8 and MCP-1 expression was examined in RA synovial fibroblasts, human microvascular endothelial cells, and RA synovial explants by ELISA. Neutrophil transendothelial cell migration, cell adhesion, invasion, and migration were examined using transwell leukocyte/monocyte migration assays, invasion assays, and adhesion assays with or without anti-MCP-1/anti-IL-8. NF-kappaB was examined using a specific inhibitor and Western blotting. An RA synovial/SCID mouse chimera model was used to examine the effects of A-SAA on cell migration, proliferation, and angiogenesis in vivo. High expression of A-SAA was demonstrated in RA patients (p < 0.05). A-SAA induced chemokine expression in a time- and dose-dependent manner (p < 0.05). Blockade with anti-scavenger receptor class B member 1 and lipoxin A4 (A-SAA receptors) significantly reduced chemokine expression in RA synovial tissue explants (p < 0.05). A-SAA induced cell invasion, neutrophil-transendothelial cell migration, monocyte migration, and adhesion (all p < 0.05), effects that were blocked by anti-IL-8 or anti-MCP-1. A-SAA-induced chemokine expression was mediated through NF-kappaB in RA explants (p < 0.05). Finally, in the RA synovial/SCID mouse chimera model, we demonstrated for the first time in vivo that A-SAA directly induces monocyte migration from the murine circulation into RA synovial grafts, synovial cell proliferation, and angiogenesis (p < 0.05). A-SAA promotes cell migrational mechanisms and angiogenesis critical to RA pathogenesis.
    • Adipophilin distribution and colocalization with lipid droplets in skeletal muscle.

      Shaw, Christopher S; Sherlock, Mark; Stewart, Paul M; Wagenmakers, Anton J M; Exercise Metabolism Research Group, School of Sport and Exercise Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. c.s.shaw@bham.ac.uk (Histochemistry and cell biology, 2009-05)
      Intramyocellular lipids (IMCL) are stored as discrete lipid droplets which are associated with a number of proteins. The lipid droplet-associated protein adipophilin (the human orthologue of adipose differentiation-related protein) is ubiquitously expressed and is one of the predominant lipid droplet-proteins in skeletal muscle. The aim of this study was to investigate the subcellular distribution of adipophilin in human muscle fibres and to measure the colocalization of adipophilin with IMCL. Muscle biopsies from six lean male cyclists (BMI 23.4 +/- 0.4, aged 31 +/- 2 years, W (max) 346 +/- 8) were stained for myosin heavy chain type 1, IMCL, adipophilin and mitochondria using immunofluorescence and viewed with widefield and confocal fluorescence microscopy. The present study shows that like IMCL, the adipophilin content is ~twofold greater in type I skeletal muscle fibres and is situated in the areas between the mitochondrial network. Colocalization analysis demonstrated that 61 +/- 2% of IMCL contain adipophilin. Although the majority of adipophilin is contained within IMCL, 36 +/- 4% of adipophilin is not associated with IMCL. In conclusion, this study indicates that the IMCL pool is heterogeneous, as the majority but not all IMCL contain adipophilin.
    • Alcohol, drug misuse and suicide attempts: unrecognised causes of out of hospital cardiac arrests admitted to intensive care units.

      McLaughlin, A M; Hardt, J; McKay, A P; Fitzpatrick, G J; Donnelly, M B; Department of Intensive Care, Adelaide & Meath Hospital incorporating The National Children's Hospital, Tallaght, Dublin 24, Ireland. annemmclaughlin@gmail.com (Irish journal of medical science, 2009-03)
      To assess the contribution of alcohol, drug abuse and suicide attempts to out of hospital cardiac arrests (OHCA) who are admitted to our intensive care unit (ICU).
    • Alzheimer disease: functional abnormalities in the dorsal visual pathway.

      Bokde, Arun L W; Lopez-Bayo, Patricia; Born, Christine; Ewers, Michael; Meindl, Thomas; Teipel, Stefen J; Faltraco, Frank; Reiser, Maximilian F; Moller, Hans-Juergen; Hampel, Harald; et al. (2012-02-01)
      PURPOSE: To evaluate whether patients with Alzheimer disease (AD) have altered activation compared with age-matched healthy control (HC) subjects during a task that typically recruits the dorsal visual pathway. MATERIALS AND METHODS: The study was performed in accordance with the Declaration of Helsinki, with institutional ethics committee approval, and all subjects provided written informed consent. Two tasks were performed to investigate neural function: face matching and location matching. Twelve patients with mild AD and 14 age-matched HC subjects were included. Brain activation was measured by using functional magnetic resonance imaging. Group statistical analyses were based on a mixed-effects model corrected for multiple comparisons. RESULTS: Task performance was not statistically different between the two groups, and within groups there were no differences in task performance. In the HC group, the visual perception tasks selectively activated the visual pathways. Conversely in the AD group, there was no selective activation during performance of these same tasks. Along the dorsal visual pathway, the AD group recruited additional regions, primarily in the parietal and frontal lobes, for the location-matching task. There were no differences in activation between groups during the face-matching task. CONCLUSION: The increased activation in the AD group may represent a compensatory mechanism for decreased processing effectiveness in early visual areas of patients with AD. The findings support the idea that the dorsal visual pathway is more susceptible to putative AD-related neuropathologic changes than is the ventral visual pathway.
    • Analysis of routine EEG usage in a general adult ICU.

      McHugh, J C; Downey, T; Murphy, R P; Connolly, S; Department of Neurology, AMNCH, Tallaght, Dublin 24, Ireland. drjohnmchugh@ireland.com (Irish journal of medical science, 2009-09)
      Non-convulsive seizures and status epilepticus are common in brain-injured patients in intensive care units. Continuous electroencephalography (cEEG) monitoring is the most sensitive means of their detection. In centres where cEEG is unavailable, routine EEG is often utilized for diagnosis although its sensitivity is lower.
    • An analytic observational study on complaints management in the general practice out of hours care setting: who complains, why, and what can we do about it?

      Barragry, Ruth A; Varadkar, Leo E; Hanlon, David K; Bailey, Ken F; O'Dowd, Tom C; O'Shea, Brendan J (BioMed Central, 2016)
      General Practice Co-Operatives provide most out of hours care in communities in Ireland. Limited data exists on patient complaints. This study reports on complaints at Kildare and West Wicklow Doctors on Call ('K Doc'), a GP Co-Operative in Ireland, examining the impact of a formal risk reduction strategy implemented (2010-2013). The aim of the study was to determine if it was possible to reduce the rate of written complaints per 1000 consultations through a formal approach encompassing evaluation of complaints, improved communication in relation to complaints, and more direct use of insights gained from complaints analysis in continuing professional development at the Co-Operative.
    • Answer to case of the month #149 alveolar soft-part sarcoma.

      Ward, Emily; Doody, Orla; d'Adhemar, Charles; Swan, Niall; Torreggiani, William C; Department of Radiology, The Adelaide and Meath Hospital, Tallaght, Dublin,, Ireland. (2012-02-01)
    • Anti Ma2-associated myeloradiculopathy: expanding the phenotype of anti-Ma2 associated paraneoplastic syndromes.

      Murphy, Sinéad M; Khan, Usman; Alifrangis, Constantine; Hazell, Steven; Hrouda, David; Blake, Julian; Ball, Joanna; Gabriel, Carolyn; Markarian, Pierre; Rees, Jeremy; et al. (Journal of neurology, neurosurgery, and psychiatry, 2012-02)
    • Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles.

      Hong, Ying; Eleftheriou, Despina; Hussain, Abdullah A K; Price-Kuehne, Fiona E; Savage, Caroline O; Jayne, David; Little, Mark A; Salama, Alan D; Klein, Nigel J; Brogan, Paul A; et al. (2012-01)
      The mechanisms by which anti-neutrophil cytoplasmic antibodies (ANCAs) may contribute to the pathogenesis of ANCA-associated vasculitis are not well understood. In this study, both polyclonal ANCAs isolated from patients and chimeric proteinase 3-ANCA induced the release of neutrophil microparticles from primed neutrophils. These microparticles expressed a variety of markers, including the ANCA autoantigens proteinase 3 and myeloperoxidase. They bound endothelial cells via a CD18-mediated mechanism and induced an increase in endothelial intercellular adhesion molecule-1 expression, production of endothelial reactive oxygen species, and release of endothelial IL-6 and IL-8. Removal of the neutrophil microparticles by filtration or inhibition of reactive oxygen species production with antioxidants abolished microparticle-mediated endothelial activation. In addition, these microparticles promoted the generation of thrombin. In vivo, we detected more neutrophil microparticles in the plasma of children with ANCA-associated vasculitis compared with that in healthy controls or those with inactive vasculitis. Taken together, these results support a role for neutrophil microparticles in the pathogenesis of ANCA-associated vasculitis, potentially providing a target for future therapeutics.
    • An antipodean infection.

      Cafferkey, A; Collins, J; Kane, D; Gibney, J; Fennell, J P (Irish medical journal, 2012-04)
    • Arhgap24 inactivates Rac1 in mouse podocytes, and a mutant form is associated with familial focal segmental glomerulosclerosis.

      Akilesh, Shreeram; Suleiman, Hani; Yu, Haiyang; Stander, M Christine; Lavin, Peter; Gbadegesin, Rasheed; Antignac, Corinne; Pollak, Martin; Kopp, Jeffrey B; Winn, Michelle P; et al. (2011-10)
      The specialized epithelial cell of the kidney, the podocyte, has a complex actin-based cytoskeleton. Dynamic regulation of this cytoskeleton is required for efficient barrier function of the kidney. Podocytes are a useful cell type to study the control of the actin cytoskeleton in vivo, because disruption of components of the cytoskeleton results in podocyte damage, cell loss, and a prototypic injury response called focal segmental glomerulosclerosis (FSGS). Searching for actin regulatory proteins that are expressed in podocytes, we identified a RhoA-activated Rac1 GTPase-activating protein (Rac1-GAP), Arhgap24, that was upregulated in podocytes as they differentiated, both in vitro and in vivo. Increased levels of active Rac1 and Cdc42 were measured in Arhgap24 knockdown experiments, which influenced podocyte cell shape and membrane dynamics. Consistent with a role for Arhgap24 in normal podocyte functioning in vivo, sequencing of the ARHGAP24 gene in patients with FSGS identified a mutation that impaired its Rac1-GAP activity and was associated with disease in a family with FSGS. Thus, Arhgap24 contributes to the careful balancing of RhoA and Rac1 signaling in podocytes, the disruption of which may lead to kidney disease.
    • Association of central obesity with early Carotid intima-media thickening is independent of that from other risk factors.

      Maher, V; O'Dowd, M; Carey, M; Markham, C; Byrne, A; Hand, E; Mc Inerney, D; Department of Cardiology and Radiology, Adelaide, Meath and National Children's Hospital, Tallaght, Dublin, Ireland. (International journal of obesity, 2009-01)
      We investigated whether anthropometric measurements or metabolic risk factors correlated more with vascular changes associated with obesity.
    • The association of plasma cysteine and gamma-glutamyltransferase with BMI and obesity.

      Elshorbagy, Amany K; Refsum, Helga; Smith, A David; Graham, Ian M; Department of Physiology, Anatomy and Genetics, Oxford University, Oxford, UK. amany.elshorbagy@dpag.ox.ac.uk (Obesity (Silver Spring, Md.), 2009-07)
      We recently reported a strong positive association of plasma total cysteine (tCys) with fat mass in over 5,000 subjects. As gamma-glutamyltransferase (GGT) enzyme increases cysteine availability by catalyzing glutathione breakdown and is positively associated with BMI and adiposity, we hypothesized that GGT might explain the association of tCys with adiposity. To study whether the associations of tCys and serum GGT with BMI and obesity were interrelated we conducted a cross-sectional study using data from 1,550 subjects recruited from nine European countries in the COMAC project. Multiple linear and logistic regression models and concentration-response curves were used. In age and sex-adjusted analyses, tCys showed strong positive associations with BMI (partial r = 0.19, P < 0.001), and obesity (odds ratio (OR) for 4th vs. 1st tCys quartile: 2.8; 95% confidence interval: 1.6-5.0, P < 0.001), both of which remained robust after adjustment for GGT and other metabolic and lifestyle confounders. Serum GGT was also a positive predictor of BMI (partial r = 0.17, P < 0.001) and obesity (OR for 4th vs. 1st GGT quartile: 4.8; 95% confidence interval: 2.5-9.2, P < 0.001), independent of tCys. However, the associations of GGT with BMI and obesity were weakened by adjustment for obesity-related factors such as serum lipids and blood pressure. These results indicate that tCys is a strong positive predictor of BMI and obesity, independent of GGT and other obesity-related factors. We also suggest that the association of serum GGT with BMI and obesity is unrelated to the role of GGT in cysteine turnover. The potential link between cysteine and fat metabolism should be further evaluated.
    • Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients.

      Anheim, M; Monga, B; Fleury, M; Charles, P; Barbot, C; Salih, M; Delaunoy, J P; Fritsch, M; Arning, L; Synofzik, M; et al. (Brain : a journal of neurology, 2009-10)
      Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. In patients with AOA2, median AFP serum level was 31.0 microg/l at diagnosis, which was higher than the median AFP level of AOA2 negative patients: 13.8 microg/l, P = 0.0004; itself higher than the normal level (3.4 microg/l, range from 0.5 to 17.2 microg/l) because elevated AFP was one of the possible selection criteria. Polyneuropathy was found in 97.5% of AOA2 patients, cerebellar atrophy in 96%, occasional oculomotor apraxia in 51%, pyramidal signs in 20.5%, head tremor in 14%, dystonia in 13.5%, strabismus in 12.3% and chorea in 9.5%. No patient was lacking both peripheral neuropathy and cerebellar atrophy. The age at onset and presence of occasional oculomotor apraxia were negatively correlated to the progression rate of the disease (P = 0.03 and P = 0.009, respectively), whereas strabismus was positively correlated to the progression rate (P = 0.03). An increased AFP level as well as cerebellar atrophy seem to be stable in the course of the disease and to occur mostly at or before the onset of the disease. One of the two patients with a normal AFP level at diagnosis had high AFP levels 4 years later, while the other had borderline levels. The probability of missing AOA2 diagnosis, in case of sequencing senataxin gene only in non-Friedreich ataxia non-ataxia-telangiectasia ataxic patients with AFP level > or =7 microg/l, is 0.23% and the probability for a non-Friedreich ataxia non-ataxia-telangiectasia ataxic patient to be affected with AOA2 with AFP levels > or =7 microg/l is 46%. Therefore, selection of patients with an AFP level above 7 microg/l for senataxin gene sequencing is a good strategy for AOA2 diagnosis. Pyramidal signs and dystonia were more frequent and disease was less severe with missense mutations in the helicase domain of senataxin gene than with missense mutations out of helicase domain and deletion and nonsense mutations (P = 0.001, P = 0.008 and P = 0.01, respectively). The lack of pyramidal signs in most patients may be explained by masking due to severe motor neuropathy.
    • Atrial fibrillation in a primary care population: how close to NICE guidelines are we?

      Loo, Bryan; Parnell, Cath; Brook, Gerald; Southall, Ed; Mahy, Ian; South West Cardiothoracic Centre, Department of Cardiology, Derriford Hospital, Plymouth. bloo@nhs.net (Clinical medicine (London, England), 2009-06)
      The National Institute for Health and Clinical Excellence (NICE) guidelines for the management of atrial fibrillation were published in June 2006. It was anticipated that they would potentially lead to increased demand for echocardiography (ECHO), increased access to secondary care services (for example for cardioversion), and require additional resources for monitoring anticoagulation. A primary care survey was therefore initiated in South Devon, in advance of publication of the guidelines as a snapshot of existing practice, to determine any additional resources and education required to meet the new standards. The main aim was to determine what proportion of patients were managed exclusively in primary care, how frequently patients were investigated by ECHO and whether anticoagulation was being appropriately targeted at patients at high risk of thromboembolic events.
    • The benefit of an enhanced recovery programme following elective laparoscopic sigmoid colectomy.

      Al Chalabi, Hasan; Kavanagh, Dara O; Hassan, Lana; Donnell, Kate O; Nugent, Emmeline; Andrews, Emmet; Keane, Frank B V; O'Riordain, Diarmuid S; Miller, Andrew; Neary, Paul; et al. (2012-02-01)
      BACKGROUND: Enhanced recovery programmes (ERPs) have demonstrated reduced morbidity and length of hospital stay in patients undergoing open elective colorectal resections. The application of laparoscopic techniques to colorectal surgery is associated with shorter length of stay and morbidity compared to open resections. In the setting of laparoscopic surgery, it is unclear whether there is an additive effect on length of stay and morbidity by combining these. The current study addresses the benefit of an ERP (RAPID protocol) in a cohort of matched patients undergoing laparoscopic sigmoid colon resection MATERIALS AND METHODS: Consecutive patients over a 40-month period who underwent laparoscopic sigmoid colon resection were assigned either to the RAPID protocol (group 1) or traditional post operative care (group 2) in a non-randomised manner. Analysis was on an "intention to treat" basis. Primary and secondary endpoints were identified; primary endpoints included length of hospital stay and readmission rate. Secondary endpoints included morbidity and mortality rate. RESULTS: Seventy-three consecutive patients were included. Group 1 included 37 patients. Group 2 included 36 patients. Median length of hospital stay in groups 1 and 2 was 5 and 8 days, respectively (p = 0.01). Readmission rate in groups 1 and 2 was 8.1% and 8.3%, respectively (p = 0.98). Morbidity rate in groups 1 and 2 was 30% and 22%, respectively (p = 0.61); there was one mortality in each group. CONCLUSION: The application of the ERP (RAPID) to patients undergoing laparoscopic sigmoid colon resection results in a significant improvement in length of hospital stay, with comparable morbidity and readmission rates.
    • Bilateral uncemented ceramic-on-ceramic total hip arthroplasty in a 26-year-old man with Morquio syndrome.

      Leonard, Michael; Nicholson, Paul; Department of Orthopaedic Surgery, Adeladie and Meath Incorporating the National Childrens Hospital, Tallaght, Dublin, Ireland. mikeleonard77@gmail.com (American journal of orthopedics, 2011-11)
    • Blind bedside insertion of small bowel feeding tubes.

      Duggan, SN; Egan, S M; Smyth, N D; Feehan, S M; Breslin, N; Conlon, K C; Department of Nutrition and Dietetics & Centre for Pancreatico-Biliary Diseases, Adelaide & Meath Hospitals, Incorporating the National Children’s Hospital, Dublin, Ireland. sinead.duggan@amnch.ie (Irish journal of medical science, 2009-12)
      The use of Naso-Jejunal (NJ) feeding is limited by difficulty in feeding tube placement. Patients have traditionally required transfer to Endoscopy or Radiology for insertion of small bowel feeding tubes, with clear resource implications. We hypothesised that the adoption of a simple bedside procedure would be effective and reduce cost. Clinical nutrition and nurse specialist personnel were trained in the 10/10/10 method of blind bedside NJ insertion.