Nuffield Orthopaedic Centre

About: Nuffield Orthopaedic Centre is a healthcare organization based out in Oxford, United Kingdom. It is known for research contribution in the topics: Population & Arthroplasty. The organization has 2082 authors who have published 2920 publications receiving 145718 citations.

The vascularity of atrophic non-unions.

Abstract: The objective of this study was to assess the vascularity of atrophic non-unions using an experimental animal model. Twenty skeletally mature female rabbits were randomly divided into control and experimental groups that were killed 1, 8, or 16 weeks after surgery. The experimental groups underwent surgery to induce an atrophic non-union whereas the control groups underwent a similar operation but which resulted in union. Using immunocytochemical techniques blood vessels were identified in histological sections obtained from the osteotomy site. The concentration of the vessels within the osteotomy gaps was measured, as was the serum concentration of an important angiogenic factor: endothelial cell-stimulating angiogenesis factor (ESAF). The results demonstrated a significant difference between the control and the experimental groups in the concentration of vessels within the gap at 1 week but there was no significant difference between those groups at 8 weeks. There were no significant differences in the ESAF concentration between the groups at any time points. We concluded that established atrophic non-unions can be well vascularised and that measurements of serum levels of ESAF could not distinguish between those osteotomies that would unite and those that would progress to non-union.

Prolonged activation of virus-specific CD8+T cells after acute B19 infection.

Abstract: Background Human parvovirus B19 (B19) is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The phenotype of CD8+ T cells in acute B19 infection has not been studied previously. Methods and Findings The number and phenotype of B19-specific CD8+ T cell responses during and after acute adult infection was studied using HLA–peptide multimeric complexes. Surprisingly, these responses increased in magnitude over the first year post-infection despite resolution of clinical symptoms and control of viraemia, with T cell populations specific for individual epitopes comprising up to 4% of CD8+ T cells. B19-specific T cells developed and maintained an activated CD38+ phenotype, with strong expression of perforin and CD57 and downregulation of CD28 and CD27. These cells possessed strong effector function and intact proliferative capacity. Individuals tested many years after infection exhibited lower frequencies of B19-specific cytotoxic T lymphocytes, typically 0.05%–0.5% of CD8+ T cells, which were perforin, CD38, and CCR7 low. Conclusion This is the first example to our knowledge of an “acute” human viral infection inducing a persistent activated CD8+ T cell response. The likely explanation—analogous to that for cytomegalovirus infection—is that this persistent response is due to low-level antigen exposure. CD8+ T cells may contribute to the long-term control of this significant pathogen and should be considered during vaccine development.

Fibrodysplasia Ossificans Progressiva, a Heritable Disorder of Severe Heterotopic Ossification, Maps to Human Chromosome 4q27-31 *

Abstract: Fibrodysplasia ossificans progressiva (FOP) is a severely disabling, autosomal-dominant disorder of connective tissue and is characterized by postnatal progressive heterotopic ossification of muscle, tendon, ligament, and fascia and by congenital malformation of the great toes. To identify the chromosomal location of the FOP gene, we conducted a genomewide linkage analysis, using four affected families with a total of 14 informative meioses. Male-to-male transmission of the FOP phenotype excluded X-linked inheritance. Highly polymorphic microsatellite markers covering all human autosomes were amplified by use of PCR. The FOP phenotype is linked to markers located in the 4q27-31 region (LOD score 3.10 at recombination fraction 0). Crossover events localize the putative FOP gene within a 36-cM interval bordered proximally by D4S1625 and distally by D4S2417. This interval contains at least one gene involved in the bone morphogenetic protein–signaling pathway.

Idiopathic juvenile osteoporosis: experience of twenty-one patients

Abstract: The features and outcome of 21 children (12 boys, nine girls) with idopathic juvenile osteoporosis (IJO) followed for up to 23 yr are described. The mean age of onset was 7 yr (range 1-13 yr) with no sex difference; the main presenting symptoms were long bone fractures, pain in the back and difficulty in walking. Typically, radiographs demonstrated compression of the vertebrae and metaphyses of the long bones; bone histology sometimes showed an excess of osteocytes associated with woven bone; routine biochemistry was normal for age; and with three exceptions no abnormalities of extracted dermal collagen or collagen synthesized by fibroblasts were detected. Where circulating vitamin D metabolites were measured they were within the normal range; and hip and spine bone mineral density (measured by DXA) was strikingly low. Five patients are still growing and two are currently untraceable. Of the remaining 14 who are now adults, 11 have substantially or completely recovered and three are disabled. Since spontaneous recovery occurs it remains impossible to assess the many forms of treatment given.