Publications by authors named "Darrah C"

The bacterial cell-division protein FtsZ has been a promising antibiotic target for over a decade now, but there is still a need for more work in this area. So far there are no FtsZ targeting drugs commercially available. We have analyzed a wide variety of prospective drugs and their interactions with multiple FtsZ species using both free and directed docking simulations.

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Although the plant kingdom provides an enormous diversity of metabolites with potentially beneficial applications for humankind, a large fraction of these metabolites and their biosynthetic pathways remain unknown. Resolving metabolite structures and their biosynthetic pathways is key to gaining biological understanding and to allow metabolic engineering. In order to retrieve novel biosynthetic genes involved in specialized metabolism, we developed a novel untargeted method designated as qualitative trait GWAS (QT-GWAS) that subjects qualitative metabolic traits to a genome-wide association study, while the conventional metabolite GWAS (mGWAS) mainly considers the quantitative variation of metabolites.

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Background: Self-administration of medicines by patients whilst in hospital is being increasingly promoted despite little evidence to show the risks and benefits. Pain control after total knee replacement (TKR) is known to be poor. The aim of the study was to determine if patients operated on with a TKR who self-medicate their oral analgesics in the immediate post-operative period have better pain control than those who receive their pain control by nurse-led drug rounds (Treatment as Usual (TAU)).

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We assessed the results of long cemented stems in patients over 65 undergoing a first time revision hip arthroplasty for aseptic loosening. 103 patients were followed up for a minimum of five years after revision surgery; 45% had EndoKlinik C grade preoperative bone loss. At final follow-up 31 patients had died, all but one with the prosthesis in situ.

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Background: In 2009, 665 patients underwent total knee replacements (TKRs) at the Norfolk and Norwich University Hospitals NHS Foundation Trust (NNUH), representing nearly 1% of the national total. Pain control following the operation can be poor, and this can cause poor mobilization and potential long-term adverse events. Although high levels of pain are not associated with patient dissatisfaction, brief periods of pain may lead to neuronal remodeling and sensitization.

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Lignin, a phenolic polymer in the secondary wall, is the major cause of lignocellulosic biomass recalcitrance to efficient industrial processing. From an applications perspective, it is desirable that second-generation bioenergy crops have lignin that is readily degraded by chemical pretreatments but still fulfill its biological role in plants. Because plants can tolerate large variations in lignin composition, often without apparent adverse effects, substitution of some fraction of the traditional monolignols by alternative monomers through genetic engineering is a promising strategy to tailor lignin in bioenergy crops.

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Preoperative psychological distress has been reported to predict poor outcome and patient dissatisfaction after total hip arthroplasty (THA). The purpose of this study was to investigate if pre-operative psychological distress was associated with adverse functional outcome after primary THR. We analysed the database of a prospective multi-centre study undertaken between January 1999 and January 2002.

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Background: There are concerns that pre-operative psychological distress might be associated with reduced patient satisfaction after total hip replacement (THR).

Methods: We investigated this in a multi-centre prospective study between January 1999 and January 2002. We dichotomised the patients into the mentally distressed (MHS ≤ 56) and the not mentally distressed (MHS > 56) groups based on their pre-operative Mental Health Score (MHS) of SF36.

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Metal-on-metal total hip replacement has been targeted at younger patients with anticipated long-term survival, but the effect of the production of metal ions is a concern because of their possible toxicity to cells. We have reviewed the results of the use of the Ultima hybrid metal-on-metal total hip replacement, with a cemented polished tapered femoral component with a 28 mm diameter and a cobalt-chrome (CoCr) modular head, articulating with a 28 mm CoCr acetabular bearing surface secured in a titanium alloy uncemented shell. Between 1997 and 2004, 545 patients with 652 affected hips underwent replacement using this system.

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The rate and mode of early failure in 463 Birmingham hip resurfacings in a two-centre, multisurgeon series were examined. Of the 463 patients two have died and three were lost to follow-up. The mean radiological and clinical follow-up was for 43 months (6 to 90).

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Introduction: The molecular mechanisms underlying cartilage destruction in osteoarthritis are poorly understood. Proteolysis is a key feature in the turnover and degradation of cartilage extracellular matrix where the focus of research has been on the metzincin family of metalloproteinases. However, there is strong evidence to indicate important roles for other catalytic classes of proteases, with both extracellular and intracellular activities.

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We report the follow-up at 12 years of the use of the Elite Plus total hip replacement (THR). We have previously reported the results at a mean of 6.4 years.

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Metal-on-metal hip replacements are the subject of much current debate. There is some evidence that there may be a hypersensitivity reaction, specific to metal-on-metal total hip replacements (THRs), which is associated with early failure of these prostheses. It has to date only been described in total replacements and not in metal-on-metal hip resurfacing.

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A retrospective analysis of patients who underwent knee arthroscopy was undertaken to determine the accuracy of clinical diagnosis when compared with arthroscopic findings, and to see whether any specific pathologies were difficult to diagnose. The preoperative diagnosis was compared with the operative findings and the accuracy, sensitivity and specificity of the clinical diagnosis calculated. Six hundred ninety-eight patients were included.

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Generating and identifying transformants is essential for many studies of gene function. In Arabidopsis thaliana, a revolutionary protocol termed floral dip is now the most widely used transformation method. Although robust, it involves a number of relatively time-consuming and laborious steps, including manipulating an Agrobacterium tumefaciens culture and aseptic procedures for the selection of plant lines harboring antibiotic-selection markers.

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Introduction: The objective of this study was to investigate how patients, general practitioners (GPs) and orthopaedic trainees, feel about the proposed governmental changes to reduce orthopaedic out-patient clinics by having GPs and specialist nurses follow-up postoperative orthopaedic patients in the community.

Subjects And Methods: The design was a cross-sectional questionnaire study including a teaching hospital and general practitioners in the Norfolk primary care trust. Participants were 73 orthopaedic postoperative patients who attended out-patients over a 1-week period in July 2007 who all responded.

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A cohort of 109 consecutive patients with a tibial fracture who underwent continuous compartment pressure monitoring of the anterior compartment of the leg were reviewed and compared to a historical control group of the immediate previous 109 patients who were clinically monitored. Of these patients 33 underwent fasciotomies for acute compartment syndrome in association with tibial diaphyseal fractures. Seventeen patients had continuous compartment pressure monitoring and 16 clinical assessments alone.

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Objectives: To characterise the catabolic response of osteoarthritic chondrocytes to Toll-like receptor (TLR) ligands.

Methods: Induction of the collagenases, matrix metalloproteinase (MMP)1 and MMP13, by TLR ligands was assessed in chondrocytes by real-time reverse transcriptase (RT)-PCR. TLR signalling pathway activation and their involvement in collagenase induction were confirmed by immunoblotting and use of pathway inhibitors and siRNA.

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Aim: To perform a retrospective review of all the conventional radiographic and magnetic resonance imaging (MRI) studies performed in patients with early postoperative pain following cobalt-chrome metal-on-metal total hip arthroplasty.

Methods: A retrospective review of the radiology, surgical findings and histology in nineteen patients who had undergone a total of 20 hip arthroplasties using a cobalt-chromium on cobalt-chromium alloy prosthesis was undertaken.

Results: Measures of implant placement on the immediate postoperative radiographs were all within the normal ranges (n=20).

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Cartilage destruction in osteoarthritis (OA) is thought to be mediated by two main enzyme families; the matrix metalloproteinases (MMPs) are responsible for cartilage collagen breakdown, whereas enzymes from the 'a disintegrin and metalloproteinase domain with thrombospondin motifs' (ADAMTS) family mediate cartilage aggrecan loss. Tissue inhibitors of metalloproteinases (TIMPs) regulate the activity of these enzymes. Although cartilage destruction in OA might be driven by the chondrocyte, low-grade synovitis is reported in patients with all grades of this disease.

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There has been a debate amongst orthopaedic surgeons about which plain radiographs are required in common knee conditions and this is a 5-year review assessing the influence of recent publications on the use of radiographs. A postal survey of all members of the British Orthopaedic Association was performed. The response rate was 60% (990/1,650).

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In response to exogenous rhythms of light and temperature, most organisms exhibit endogenous circadian rhythms (i.e. cycles of behavior and gene expression with a periodicity of approximately 24 h).

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Ten subjects with cruciate ligament rupture (five ACL and five PCL), and four normal subjects underwent magnetic resonance imaging (MRI) with a novel splint that stresses the knee. The splint acted as a fulcrum to translate the tibia in an anterior and posterior direction, depending on application. The MRI images showed that translation of the tibial plateaux occurred but not in a simple manner.

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