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Biomedical subjects

S E Edwards

Publications and source records attributed to S E Edwards.

10 recordsLinked to original sources

Flexible intramedullary nailing of displaced diaphyseal forearm fractures in children.

INTRODUCTION: This study analyses the results of 50 displaced diaphyseal forearm fractures in children treated with flexible intramedullary nailing. METHODS: Between 1999 and 2002 we treated 50 children aged between 5 and 15 years, with diaphyseal fractures of the forearm using Flexible intramedullary nailing (FIN). Both bones were fractures in 45 patients, radius only in 4 and ulna only in 1. The indications for fixation were instability (26), re-displacement (20), and open fractures (4). RESULTS: 24 patients were reduced closed, followed by nailing, while 26 fractures required open reduction of either one bone(16 cases) or both bones(10 cases) prior to nailing. Bony union of all fractures was achieved by an average of 7 weeks (range 6 weeks to 4 months) with one delayed union. Pronation was restricted by an average of 20 degrees in 9 patients. Two patients developed post operative compartment syndrome requiring fasciotomy. Three patients were lost to follow-up. INTERPRETATION: FIN led to early bony union with acceptable bony alignment in all 47 patients available at final follow-up. We therefore recommend FIN for the treatment of unstable diaphyseal forearm fractures in children.

Adolescent↗

Processing of radical prostatectomy specimens for correlation of data from histopathological, molecular biological, and radiological studies: a new whole organ technique.

AIMS: To develop a method of processing non-formalin fixed prostate specimens removed at radical prostatectomy to obtain fresh tissue for research and for correlating diagnostic and molecular results with preoperative imaging. METHODS/RESULTS: The method involves a prostate slicing apparatus comprising a tissue slicer with a series of juxtaposed planar stainless steel blades linked to a support, and a cradle adapted to grip the tissue sample and receive the blades. The fresh prostate gland is held in the cradle and the blades are moved through the cradle slits to produce multiple 4 mm slices of the gland in a plane perpendicular to its posterior surface. One of the resulting slices is preserved in RNAlater. The areas comprising tumour and normal glands within this preserved slice can be identified by matching it to the haematoxylin and eosin stained sections of the adjacent slices that are formalin fixed and paraffin wax embedded. Intact RNA can be extracted from the identified tumour and normal glands within the RNAlater preserved slice. Preoperative imaging studies are acquired with the angulation of axial images chosen to be similar to the slicing axis, such that stained sections from the formalin fixed, paraffin wax embedded slices match their counterparts on imaging. CONCLUSIONS: A novel method of sampling fresh prostate removed at radical prostatectomy that allows tissue samples to be used both for diagnosis and molecular analysis is described. This method also allows the integration of preoperative imaging data with histopathological and molecular data obtained from the prostate tissue slices.

Biomedical Research↗

LUCA-15-encoded sequence variants regulate CD95-mediated apoptosis.

Using an expression cloning system to discover novel genes involved in apoptosis, we identified a 326 bp bone marrow cDNA fragment (termed Je2) that suppresses, upon transfection, CD95-mediated apoptosis in Jurkat T cells. Sequence homology revealed that Je2 maps to 3p21.3, to an intronic region of the candidate TSG LUCA-15 locus. It represents, in fact, an antisense transcript to the 3'-UTR of two novel splice variants of this gene. Overexpression of sequence representing one of these splice variants (a 2.6 kb cDNA termed Clone 26), inhibited proliferation of Jurkat cells and sensitized them to CD95-mediated apoptosis. This study therefore implicates the LUCA-15 gene locus in the control of apoptosis.

Alternative Splicing↗

Mutation of cytochrome bd quinol oxidase results in reduced stationary phase survival, iron deprivation, metal toxicity and oxidative stress in Azotobacter vinelandii.

Azotobacter vinelandii cydAB mutants lacking cytochrome bd lost viability in stationary phase, irrespective of temperature, but microaerobiosis or iron addition to stationary phase cultures prevented viability loss. Growth on solid medium was inhibited by a diffusible factor from neighbouring cells, and by iron chelators, In(III) or Ga(III); microaerobic growth overcame inhibition by the extracellular factor. Siderophore production and total Fe(III)-chelating activity were not markedly affected in Cyd(-) mutants, and remained responsive to iron repression. Cyd(-) mutants were hypersensitive to Cu(II), Zn(II), and compounds exerting oxidative stress. Failure to synthesise haemoproteins does not explain the complex phenotype since mutants retained significant catalase activity. We hypothesise that Cyd(-) mutants are defective in maintaining the near-anoxic cytoplasm required for reductive iron metabolism and nitrogenase activity.

Azotobacter vinelandii↗

Acute phase proteins in cattle: discrimination between acute and chronic inflammation.

Acute phase proteins such as serum amyloid A, haptoglobin, and alpha 1-acid glycoprotein have been identified as markers of inflammation in cattle because they are produced by the liver in response to pro-inflammatory cytokines. This study was designed to assess whether they could be used to discriminate between acute and chronic inflammation. Their concentrations were measured in serum samples from 81 cattle in which inflammation was classified by thorough clinical examination, supported by postmortem findings, as being acute in severity in 31 and chronic in 50. The classical haematological markers of inflammation were also determined in blood from the animals. Serum amyloid A had a maximum (100 per cent) clinical sensitivity in discriminating between the acute and chronic cases, and haptoglobin had the highest clinical specificity of 76 per cent; counts of neutrophils and band neutrophils had sensitivities of 71 per cent and 42 per cent and specificities of 30 per cent and 72 per cent, respectively. It was concluded that serum amyloid A and haptoglobin may be used to discriminate between acute and chronic inflammatory conditions.

Acute Disease↗

Immunoepidemiology of the equine tapeworm Anoplocephala perfoliata: age-intensity profile and age-dependency of antibody subtype responses.

The equine intestinal cestode Anoplocephala perfoliata has been the subject of recent epidemiological and immunological studies because of its suspected association with intestinal disease in the horse. We have previously shown that the IgG(T) subtype antibody response to the 12/13 kDa component of the parasite excretory/secretory (E/S) antigen is positively correlated with parasite intensity. In this study, we utilize that correlation to examine the changes in natural infection intensity with age. Infection intensity based on IgG(T) responses showed a triphasic age-dependency pattern with peak mean worm burden in the 6 months-2 years age group, falling to a lower plateau level from 3 to 15 years, and rising again in older age groups. Anti-E/S total IgG was found to have a convex age-dependency curve, with maximal response in the 6 months-2 years old age group. IgG(a) showed a triphasic response similar to the age-intensity profile of IgG(T); IgG(c) showed steadily increasing levels of antibody with age. The IgG(b) age-dependency profile was intermediate between IgG(a) and IgG(c). Age-specific correlation coefficients between anti-12/13 kDa IgG(T) (as a measure of infection intensity) and IgG(a) and IgG(b) revealed statistically significant values for many age groups. The relative importance of exposure to infection and the development of acquired immunity as determinants of the observed age-intensity pattern is considered.

Age Factors↗

Polymerase chain reaction amplification analyses of clonality in T-cell malignancy including peripheral T-cell lymphoma.

Clonality in T-cell malignancy was investigated using T-cell receptor (TcR) V beta 1-20 family primers and polymerase chain reaction amplification (PCR) of cDNA prepared from tissue biopsies and blood involved with tumour. Secondary PCR amplification of the VDJ joints of primary PCR products was performed to distinguish clonal from polyclonal products, and clonal V beta gene products were confirmed by direct PCR sequencing in the majority of cases. In eight T-cell malignancies including T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell chronic lymphocytic leukaemia (T-CLL) shown to be clonal by Southern blot analysis, one or two primary PCR products were identified and shown to be clonal. In five cases of peripheral T-cell lymphoma (PTCL) all V beta 1-20 families were identified after primary PCR amplification, and clonal products were identified in two cases after secondary amplification; TcR V beta clonal families could not be demonstrated in the remaining three cases. These data were in agreement with previous Southern blot analysis of these cases, and confirmed the presence of reactive T cells in PTCL as well as providing further evidence for the genotypic heterogeneity of this entity. In the remaining case, a blood lymphocytosis, primary PCR amplification produced predominant TcR V beta 6 and V beta 12 family products, of which the V beta 6 family proved clonal after secondary PCR amplification. There was no evidence for overrepresentation of TCR V beta families by the tumour populations in this study, furthermore the data confirm the involvement of reactive cells in T-cell malignancy and the genetic heterogeneity of PTCL.

Base Sequence↗

Macrophage colony-stimulating factor production by murine and human keratinocytes. Enhancement by bacterial lipopolysaccharide.

CSF have a broad range of effects on differentiated cells outside the bone marrow. Site-specific elaboration of these factors may influence local immune reactions. Keratinocytes have been demonstrated to produce a number of immunoactive cytokines, including factors capable of modifying macrophage function. We have previously identified at least two products of keratinocytes that induce DNA synthesis by elicited peritoneal macrophages; one factor has been identified as granulocyte-macrophage CSF. In the present study, the second keratinocyte product has been characterized and identified as macrophage-CSF (M-CSF). Conditioned media from cultures of normal human keratinocytes and the transformed murine keratinocyte cell line PAM 212 induce formation of macrophage colonies in soft agar as well as dose-dependent proliferation of the M-CSF-dependent cell line BAC1.2F5. The bioactivity in both assays is blocked by neutralizing anti-M-CSF antibody. Western blot analysis of cell lysates from both PAM 212 and normal human keratinocytes demonstrates multiple molecular mass forms of M-CSF (45 to 98 kDa). Northern blot analysis (PAM 212 cells) and in situ hybridization (normal keratinocytes) demonstrate expression of M-CSF mRNA. Stimulation of keratinocytes with LPS increases M-CSF synthesis as measured both by bioactivity and level of mRNA expression. Thus, both murine and human keratinocytes produce M-CSF in vitro. Furthermore, production of keratinocyte-derived M-CSF is increased by bacterial LPS. CSF production by keratinocytes may play an important role in regulating the cutaneous immune response.

Animals↗

The value of radiography in the management of rheumatoid arthritis.

All radiographs of joints requested on 50 consecutive clinic patients with rheumatoid arthritis were reviewed; 1094 films were available. With few minor exceptions, all information relevant to diagnosis and medical management was provided by one view of each joint: postero-anterior hands, dorsi-planar feet, antero-posterior (AP) elbow, AP shoulder, AP pelvis and lateral flexion cervical spine. Norgaard's 'ballcatcher's' projection of the hands provided no extra information. Radiographs of the hands were consistently more sensitive in showing progression of erosion than those of the feet. Radiography of both hands and feet was required to avoid missing earliest erosions. Radiographs requested at times when drug treatment was under review did not consistently affect decisions, which were largely dependent on clinical findings.

Arthritis, Rheumatoid↗