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Liverpool, United Kingdom

Arnold P.,Alder Hey Childrens Hospital
Paediatric Anaesthesia | Year: 2011

Bleeding is a considerable clinical problem during and after pediatric heart surgery. While the primary cause of bleeding is surgical trauma, its treatment is often complicated by the presence of coagulopathy. The principle causes of coagulopathy are discussed to provide a context for treatment. The role of laboratory and point of care tests, which aim to identify the cause of bleeding in the individual patient, is also discussed. An attempt is made to examine the current evidence for available therapies, including use of blood products and, more recently proposed, approaches based on human or recombinant factor concentrates. © 2010 Blackwell Publishing Ltd.

Summary The risk of accidental over-dosing of obese children poses challenges to anaesthetists during dose calculations for drugs with serious side-effects, such as analgesics. For many drugs, dosing scalars such as ideal body weight and lean body mass are recommended instead of total body weight during weight-based dose calculations. However, the complex current methods of obtaining these dosing scalars are impractical in the peri-operative setting. Arbitrary dose adjustments and guesswork are, unfortunately, tempting solutions for the time-pressured anaesthetist. The study's aim was to develop and validate an accurate, convenient alternative. A nomogram was created and its performance compared with the standard calculation method by volunteers using measurements from 108 obese children. The nomogram was as accurate (bias 0.12 kg vs -0.41 kg, respectively, p = 0.4), faster (mean (SD) time taken 2.8 (1.0) min (vs 3.3 (0.9) min respectively, p = 0.003) and less likely to result in mistakes (significant errors 3% vs 19%, respectively, p = 0.001). We present a system that simplifies estimation of ideal body weight and lean body mass in obese children, providing foundations for safer drug dose calculation. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

Curran A.L.M.,Alder Hey Childrens Hospital
Developmental Medicine and Child Neurology | Year: 2015

This commentary is on the original article by Kelly et al. on pages 241-247 of this issue Developmental Medicine and Child Neurology © 2014 Mac Keith Press.

Iyer A.,Walton Center for Neurology and Neurosurgery | Elsone L.,Walton Center for Neurology and Neurosurgery | Appleton R.,Alder Hey Childrens Hospital | Jacob A.,Walton Center for Neurology and Neurosurgery
Autoimmunity | Year: 2014

Neuromyelitis optica (NMO) is an immune-mediated neurological disorder characterised by recurrent episodes of optic neuritis and longitudinally extensive transverse myelitis. A serum biomarker, aquaporin-4 IgG, the autoantibody against aquaporin-4 water channel, has been specifically associated with NMO and has assisted early recognition and prediction of relapses. Less commonly, a monophasic course, associated with antibodies to myelin oligodendrocyte glycoprotein has been reported. Specific diagnostic criteria have been defined; however, some cases that do not fulfil these criteria (but are nevertheless associated with aquaporin-4 IgG) are classified as NMO spectrum disorder and follow the same relapsing course. An ever-growing list of autoimmune disorders, both organ-specific and non-organ-specific, have been associated in up to 20-30% of patients with NMO. These disorders, which may become symptomatic before or after the development of NMO, are often diagnosed long after the diagnosis of NMO, as symptoms may be wrongly attributed to NMO, its residual effects or medication side effects. In addition, autoantibodies can be found in patients with NMO without coexisting disease (up to 40% in some series) and maybe suggestive of a heightened humoral immune response. We present a comprehensive review of the current literature on autoimmune disorders co-existing with NMO and identified 22 autoimmune conditions (myasthenia gravis, coeliac disease, ulcerative colitis, sclerosing cholangitis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid antibody syndrome, Sjogren's syndrome, autoimmune hypothyroidism, immune thrombocytopenic purpura, pernicious anaemia, narcolepsy, pemphigus foliaceus, alopecia areata, psoriasis, scleroderma, dermatitis herpetiformis, polymyositis, chronic inflammatory demyelinating polyneuropathy, paraneoplastic disorders, insulin dependent diabetes mellitus and autoimmune encephalitis). © 2014 Informa UK Ltd. All rights reserved.

Zhang Q.,University of Liverpool | Leong S.C.,Alder Hey Childrens Hospital | McNamara P.S.,Institute of Child Health | Mubarak A.,University of Liverpool | And 2 more authors.
PLoS Pathogens | Year: 2011

Regulatory T cells (Treg) diminish immune responses to microbial infection, which may contribute to preventing inflammation-related local tissue damage and autoimmunity but may also contribute to chronicity of infection. Nasopharyngeal carriage of pneumococcus is common in young children and can persist for long periods but it is unknown whether the presence of Treg in the nasopharynx contributes to this persistence. We have investigated the numbers and activities of Foxp3+Treg in adenoidal tissues and their association with pneumococcal carriage in children. Expression of Treg cell-related markers including Foxp3, CD25, CD39, CD127 and CLTA4 were analysed by flow-cytometry in adenoidal mononuclear cells (MNC) and PBMC from children. Unfractionated MNC or Treg-depleted MNC were stimulated with a pneumococcal whole cell antigen (WCA) and T cell proliferation measured. Cytokine production by MNC was measured using a cytometric bead array. Higher numbers of CD25 highFoxp3 high Treg expressing higher CD39 and CTLA4 were found in adenoidal MNC than in PBMC. Children with pneumococcus positive nasopharyngeal cultures had higher proportions of Treg and expressed higher levels of CD39 and CTLA-4 than those who were culture negative (-). WCA induced adenoidal Treg proliferation which produce IL10 but not IL17, and CD4 T cell proliferation in Treg-depleted MNC was greater in pneumococcal culture positive than negative children. Significant numbers of Treg with an effector/memory phenotype which possess a potent inhibitory effect, exist in adenoidal tissue. The association of pneumococcal carriage with an increased frequency of adenoidal Treg suggests that Treg in nasal-associated lymphoid tissue (NALT) may contribute to the persistence of pneumococcus in children. Further studies to determine what component and mechanisms are involved in the promotion of Treg in NALT may lead to novel therapeutic or vaccination strategy against upper respiratory infection. © 2011 Zhang et al.

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