Oxford Eprints
(1.101 recursos)
Oxford E-prints is a cross-disciplinary digital archive for research articles written by Oxford University authors. The repository has been developed as part of the SHERPA (Securing a Hybrid Environment for Research Preservation and Access) project and is running on eprints.org open archives software.
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The insulin-like growth factor system as a therapeutic target in colorectal cancer - Hassan, A. B.; Macaulay, V. M.
The purpose of this review is to examine recent evidence that investigates the role of the insulin-like growth factor (IGF) system in colorectal cancer. We concentrate on the evidence that makes the case for the investigation of strategies that might be used to disrupt the IGF system in prevention and treatment. Even though the weight of evidence suggests that components of the IGF system may be appropriate targets, there are a lack of studies that make a systematic characterisation of all the system components in human colorectal cancer. It is anticipated that this information, and the new therapeutic molecules which...
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Childhood cancer survival in Europe - Gatta, G.; Corazziari, I.; Magnani, C.; Peris-Bonet, R.; Roazzi, P.; Stiller, C.; EUROCARE Working Group, The
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Linkage analysis of candidate genes as susceptibility loci for osteoarthritis - suggestive linkage of COL9A1 to female hip osteoarthritis - Mustafa, Z.; Chapman, K.; Irven, C.; Carr, A. J.; Clipsham, K.; Chitnavis, J.; Sinsheimer, J. S.; Bloomfield, V. A.; McCartney, M.; Cox, O.; Sykes, B.; Loughlin, J.
Objective. To examine 11 candidate genes as susceptibility loci for osteoarthritis (OA).Methods. A total of 481 families have been ascertained in which at least two siblings have had joint replacement surgery of the hip, or knee, or hip and knee for idiopathic OA. Each candidate gene was targeted using one or more intragenic or closely linked microsatellite marker. The linkage data were analysed unstratified and following stratification by sex and by joint replaced (hip or knee).Results. The analyses revealed suggestive linkage of the type IX collagen gene COL9A1 (6q12-q13) to a subset of 132 families that contained affected females who...
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Linkage analysis of chromosome 2q in osteoarthritis - Loughlin, J.; Mustafa, Z.; Smith, A.; Irven, C.; Carr, A. J.; Clipsham, K.; Chitnavis, J.; Bloomfield, V. A.; McCartney, M.; Cox, O.; Sinsheimer, J. S.; Sykes, B.; Chapman, K. E.
Background In independent linkage studies chromosome 2q11-q24 and chromosome 2q23-35 have previously been implicated as regions potentially harbouring susceptibility loci for osteoarthritis (OA).Objective. To test chromosome 2q for linkage to idiopathic osteoarthritis.Methods. Using a cohort of 481 OA families that each contained at least one affected sibling pair with severe end-stage disease (ascertained by hip or knee joint replacement surgery), we conducted a linkage analysis of chromosome 2q using 16 polymorphic microsatellite markers at an average spacing of one marker every 8.5 cM.Results. Our results provide suggestive evidence for a locus at 2q31 with a maximum multipoint logarithm of the...
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Evidence from clinical trials and long-term observational studies that disease-modifying anti-rheumatic drugs slow radiographic progression in rheumatoid arthritis: updating a 1983 review - Pincus, T.; Ferraccioli, G.; Sokka, T.; Larsen, A.; Rau, R.; Kushner, I.; Wolfe, F.
Earlier reports, including a comprehensive 1983 review, had indicated that slowing of radiographic progression was relatively unusual in treatment of rheumatoid arthritis (RA) using traditional disease modifying anti-rheumatic drugs. However, in recent years, slowing of radiographic progression has been documented in a number of clinical trials, as well as long-term observational studies, with use of (in alphabetical order) adalimumab, anakinra, corticosteroids, cyclophosphamide, cyclosporin, etanercept, gold salts, infliximab, leflunomide, methotrexate and sulphasalazine. At this time, disease modification is a realistic goal in the clinical care of patients with RA. Documentation of improved long-term outcomes requires long-term observational data over 5-20 yr...
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Rheumatoid arthritis susceptibility and interleukin 10: a study of two ethnically diverse populations - MacKay, K.; Milicic, A.; Lee, D.; Tikly, M.; Laval, S.; Shatford, J.; Wordsworth, P.
Introduction. IL-10 is an immunoregulatory cytokine which may modulate disease expression in rheumatoid arthritis (RA). The IL-10 gene is highly polymorphic with a number of single nucleotide polymorphisms in the promoter region and two microsatellite loci, IL10.R and IL10.G, 4 kb and 1.1 kb 5' of the transcription initiation site. It has been reported that allele 2 of the IL10.R microsatellite (IL10.R2) is associated with increased IL-10 secretion and IL10.R3 with reduced secretion. Subsequently, over-representation of IL10.R2 and under-representation of IL10.R3 in three independent RA groups has been reported. The aim of the current study is to determine whether there...
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Osteoclast formation and activity in the pathogenesis of osteoporosis in rheumatoid arthritis - Hirayama, T.; Danks, L.; Sabokbar, A.; Athanasou, N. A.
Objective. Rheumatoid arthritis (RA) is often complicated by generalized osteopenia due to increased bone resorption by osteoclasts. We analysed a number of cellular and humoral factors that influence osteoclast formation from circulating precursors in RA patients.Methods. Monocytes isolated from RA patients and normal controls were cultured with macrophage colony-stimulating factor (M-CSF) and nuclear factor-?B ligand (RANKL), or with RANKL-expressing UMR106 cells and 1,25 dihydroxyvitamin D3 [1,25(OH)2D3]. Osteoclast differentiation was assessed by expression of tartrate-resistant acid phosphatase (TRAP) and vitronectin receptors (VNR) and lacunar resorption.Results. Osteoclasts formed from RA patients exhibited increased resorptive activity but there was no difference in the...
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Non-inherited maternal HLA alleles are associated with rheumatoid arthritis - Harney, S.; Newton, J.; Milicic, A.; Brown, M. A.; Wordsworth, B. P.
Background. Rheumatoid arthritis (RA) is strongly associated with a series of HLA-DRB1 alleles that encode a conserved sequence of amino acids (70Q/R K/R R A A74) in the DR?1 chain, known as the shared epitope (SE). However 30% of patients are negative for DRB1*04 and 15% are SE-negative. Exposure to these alleles as non-inherited maternal antigens (NIMA) might explain this discrepancy. We undertook a family study to investigate the role of NIMA in RA.Methods. One hundred families, including the RA proband and both parents, were recruited. HLA-DRB1 genotyping was performed using an allele-specific polymerase chain reaction by standard methods. The...
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Remission induction in Behçet's disease following lymphocyte depletion by the anti-CD52 antibody CAMPATH 1-H - Lockwood, C. M.; Hale, G.; Waldman, H.; Jayne, D. R. W.
Objective. Behçet's disease (BD) is a multisystem vasculopathy of unknown cause with variable clinical presentation and the outcome of current treatments is often unsatisfactory. There is evidence for T-cell autoreactivity in BD and this study explores the therapeutic response to lymphocyte depletion with a humanized anti-CD52 antibody, CAMPATH-1H.Methods. Eighteen patients with active BD received a single course of 134 mg of CAMPATH-1H. Immunosuppressives were withdrawn and prednisolone reduced according to clinical status. Treatment response was assessed by remission of clinical features of disease activity, erythrocyte sedimentation rate, C-reactive protein, prednisolone dose, the need for subsequent immunosuppressives and disease relapse.Results. By...
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Hormone replacement therapy: patterns of use studied through British general practice computerized records - Lawrence, M; Jones, L; Lancaster, T; Daly, E; Banks, E
Objective: We aimed to describe the longitudinal pattern of hormone replacement therapy (HRT) consumption in a cohort of long-term users (defined as use for >1 year).Method: We carried out longitudinal analysis of prescription data derived from GPs' computer records. Subjects were recruited through 15 general practices in the former Oxford, South West and North West Thames Regions that contributed to the VAMP/OPCS general practice research database. All women in the practices aged 45-64 years in September 1991 were identified. Of these, the analysis concerned the 1224 long-term users and 1154 non-user controls who remained in the practices from September 1991...
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The 'new genetics' and primary care; GPs' views on their role and their educational needs - Watson, EK; Shickle, D; Qureshi, N; Emery, J; Austoker, J
Background: Given the limited specialist resources available to cope with the rising demand for genetic services, it has been proposed that at least some of these services are provided by primary care in the future.Objective: We aimed to explore GPs' attitudes towards new developments in genetics, to establish the role they envisage for primary care and to clearly define the education, information and training needed to support them in this role.Methods: We carried out a qualitative study with GPs using four focus groups (26 GPs) and 15 individual semi-structure interviews.Results: GPs perceived genetics as an important and increasingly relevant topic...
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A study of GP referrals to a family cancer clinic for breast/ovarian cancer - Watson, Eila; Austoker, Joan; Lucassen, Anneke
Objectives.The aim of this study was to investigate the appropriateness of primary care referrals to the Oxford Regional Genetics Service on account of a family history of breast and/or ovarian cancer and to explore GPs' expectations following a referral.Methods.Fifty consecutive GP referrers were sent a questionnaire post-referral, and their referral letters were reviewed.Results.The study achieved a high response rate (94%) and showed that many GPs did not know which patients warrant referral to the genetics service and that they had unrealistic expectations of what happens at the clinic.Conclusions.If GPs are to fulfil their gatekeeper role effectively, and possibly become more...
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Guidelines for referral to a regional genetics service: GPs respond by referring more appropriate cases - Lucassen, Anneke; Watson, Eila; Harcourt, Jean; Rose, Peter; O'Grady, Jane
Objectives. The aim of this study was to see whether guidelines on whom to refer to a regional genetics service could improve the appropriateness of referrals to the service. It also aimed to assess whether the genetic clinic assessment of risk agreed with that described in the GP letter.Methods. Referral guidelines were sent to all Oxfordshire GPs and the subsequent content of the referral letters was analysed. A retrospective assessment of referral letters sent during the 6 months before dissemination was also made.Results. The study showed that post-guidelines, fewer 'lower risk' referrals were made and that the description of the...
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New developments in genetics-knowledge, attitudes and information needs of practice nurses - Bankhead, Clare; Emery, Jon; Qureshi, Nadeem; Campbell, Harry; Austoker, Joan; Watson, Eila
Background.In response to increased referrals to geneticists and the predicted patient demand for genetic counselling, it has been proposed that some genetics services should be provided in primary care. Practice nurses are ideally placed to collect family history information and advise patients accordingly in new patient, family planning, well women/men and chronic disease clinics, but little is known about their knowledge, skills and attitudes towards providing genetic advice.Objectives.The survey aimed to measure the current situation with regard to: the prevalence of family history recording by practice nurses; confidence in collecting and acting upon family history; and practice nurses' knowledge about...
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