Lancet
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Up to 40% of patients with rheumatoid arthritis treated with anti-tumour necrosis factor (TNF) drugs do not respond because of primary inefficacy or loss of response. Although one explanation is that immunogenicity leads to the development of anti-drug antibodies and low drug concentrations, the clinical usefulness of pharmacological monitoring is debated. Our aim was to assess whether the presence of anti-drug antibodies and non-trough drug concentrations could predict treatment response in patients with rheumatoid arthritis treated with anti-TNF drugs. ⋯ MJ is a MRC Clinical Training Fellow supported by the North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics, which is funded by the UK Medical Research Council (grant number G1000417/94909), ICON, GlaxoSmithKline, AstraZeneca, and the Medical Evaluation Unit. Arthritis Research UK (grant ref 20385).
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Implementation of the National Early Warning Score in the National Health Service (NHS) has renewed focus on prompt identification and referral of the deteriorating ward patient. A large body of published work suggests that delay in both referral and admission to critical care can be associated with poor outcomes. We sought to explore factors associated with early provision of respiratory support in a cohort of deteriorating ward patients referred to the critical care team. ⋯ Wellcome Trust, National Institute for Health Service Support Costs, Intensive Care National Audit & Research Centre.
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Obesity is an emergent epidemic associated with morbidity, mortality, and psychosocial effects. One of the key gut hormones that controls appetite is peptide tyrosine-tyrosine 3-36 (PYY3-36) whose circulating half-life is only 8 min. A long-acting analogue of PYY3-36 would therefore have great potential as an antiobesity agent. The aims of this study were to investigate the effect of various aminoacid modifications of PYY3-36 on pharmacokinetics and their ability to suppress food intake. ⋯ UK Medical Research Council, Biotechnology and Biological Sciences Research Council, National Institute for Health Research (NIHR), an Integrative Mammalian Biology (IMB) Capacity Building award, an FP7-HEALTH-2009-241592 EuroCHIP grant, NIHR Imperial Biomedical Research Centre Funding Scheme.
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Memory T cells are known to reside in peripheral non-lymphoid tissue, but how their presence within solid organ allografts affects transplant outcomes is not known. We have previously described how graft-versus-host (GVH) allorecognition by passenger CD4 T cells within MHC class II-mismatched bm12 heart grafts provokes antinuclear humoral autoimmunity in C57BL/6 recipient mice. Here we aimed to examine how such GVH recognition affects the alloresponse to allografts with greater mismatching. ⋯ Wellcome Trust Clinical Research Training Fellowship.
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Increased expression of antimicrobial peptides including human beta defensins (HBD) has been reported in the amniotic fluid and vaginal secretions of women who deliver preterm. We have previously shown that these women have increased first trimester serum HBD2. The gene encoding HBD2, DEFB4A, is part of a defensin beta (DEFB) cluster on chromosome 8 that is variable in copy number. Increased serum HBD2 is associated with increased DEFB copy number. We aimed to test the hypothesis that variation in DEFB copy number is associated with preterm birth. ⋯ Wellcome Trust, Wellbeing of Women.