Royal Devon and Exeter Hospital

About: Royal Devon and Exeter Hospital is a healthcare organization based out in Exeter, United Kingdom. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 2282 authors who have published 2526 publications receiving 78866 citations. The organization is also known as: RD&E.

CD20+inflammatory T-cells are present in blood and brain of multiple sclerosis patients and can be selectively targeted for apoptotic elimination.

Abstract: Background A subset of T-cells expresses the B-cell marker CD20 and in rheumatoid arthritis secretes Interleukin (IL)-17. IL-17 secreting T-cells (Th17) have also been implicated in the inflammatory response in the central nervous system in multiple sclerosis (MS) and may be a potential target for elimination by biologic therapeutics. ScFvRit:sFasL comprises of a rituximab-derived antibody fragment scFvRit genetically fused to human soluble FasL that specifically eliminated T-cells. Objective To determine the presence and phenotype of CD20+T-cells in blood and brain of MS patients. Second, to determine whether scFvRit:sFasL can selectively eliminate CD20+T-cells. After CD20-selective binding, scFvRit:sFasL is designed to trigger FasL-mediated activation-induced cell death of T-cells, but not B-cells. Methods Flow cytometry and immunohistochemistry were used to screen for CD20+inflammatory T-cells in MS blood and brain tissue. ScFvRit:sFasL pro-apoptotic activity was evaluated by Annexin-V/PI staining followed by flow cytometry assessment. Results Peripheral blood ( n =11) and chronic but not active lesions of MS patient brains ( n =5) contained CD20+inflammatory T-cells. Activated CD20+T-cells were predominantly CD4+and secreted both IL-17 and INF-γ. ScFvRit:sFasL triggered CD20-restricted FasL-mediated activation-induced cell death in peripheral blood CD20+T-cells, but not CD20+B-cells. Conclusion CD20+inflammatory T-cells are present in blood and chronic brain lesions of MS patients. ScFvRit:sFasL selectively eliminated CD20+T-cells and may eliminate pathogenic T-cells without B-cell depletion.

Necrotizing renal vasculopathy resulting in chronic renal failure after ingestion of methamphetamine and 3,4-methylenedioxymethamphetamine ('ecstasy')

Abstract: renal failure and C serology were negative. Anti-neutrophil cyto-plasmic antibody titres (p and c) were negative. Chest X-ray confirmed pulmonary oedema. He commenced haemodialysis via a temporary double lumen subcla

Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight

Abstract: Importance Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain. Objective To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight. Design, Setting, and Participants Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30 487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included. Exposures Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level. Main Outcome and Measure Offspring birth weight from 18 studies. Results Among the 30 487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele ( P = .008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele ( P = 7 × 10 −14 ) and −4 g (95% CI, −6 to −2g) per SBP-raising allele ( P = 1×10 −5 ), respectively. A 1-SD ( ≈ 4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD ( ≈ 7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD ( ≈ 10 mm Hg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95% CI, −394 to −21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions. Conclusions and Relevance In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.

Phacovitrectomy for primary retinal detachment repair in presbyopes.

Abstract: PURPOSE To review the results of phacovitrectomy for primary retinal detachment repair in presbyopes. METHODS The outcome and complications of surgery were examined in a retrospective case series of 93 presbyopic patients who underwent phacoemulsification and vitrectomy for primary rhegmatogenous retinal detachment. RESULTS Eighty-two patients (88.2%) had reattachment with a single procedure. The final reattachment rate with further procedures was 97.8%. Two patients (2.2%) in whom final reattachment did not occur declined further surgery after the primary repair. All redetachments were due to proliferative vitreoretinopathy. The median Snellen converted logMAR visual acuity improved from 1.00 preoperatively to 0.30 postoperatively (P < 0.001, Wilcoxon test). Postoperative complications included transient intraocular pressure rise (29%), fibrinous uveitis (16.2%), and iris/intraocular lens capture (8.6%). One of the eight patients with iris/intraocular lens capture required surgical reintervention. All cases of fibrinous uveitis and intraocular pressure rise resolved within a few days with medical treatment. Posterior capsular opacification occurred in 23 patients (24.7%). CONCLUSION Combined surgery with phacoemulsification, lens extraction, and vitrectomy offers significant advantages to both patient and surgeon in the management of primary retinal detachment. We believe that it should be considered for presbyopes even in the absence of significant lens opacity. Fibrinous uveitis and intraocular pressure rise may occur in a few patients in the immediate postoperative period but are transient and resolve with medical treatment. Further prospective studies are required, in particular to examine the rate of postoperative proliferative vitreoretinopathy, which may be higher than with vitrectomy alone.

Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration

Abstract: The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.