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Biomedical subjects

D White

Publications and source records attributed to D White.

At least 19 recordsLinked to original sources
PubMed2006

Longitudinal study of magnetic resonance imaging and standard X-rays to assess disease progression in osteoarthritis.

OBJECTIVE: To investigate, over 1-year, the relationship between X-ray and magnetic resonance imaging (MRI) findings in patients with knee osteoarthritis (OA). METHODS: Sixty-two osteoarthritic patients (46 women) were followed for 1 year. At baseline and after 1 year, volume and thickness of cartilage of the medial tibia, the lateral tibia and the femur were assessed by MRI. A global score from the multi-feature whole-organ MRI scoring system (WORMS) was calculated for each patient at baseline and after 1 year. This score combined individual scores for articular cartilage, osteophytes, bone marrow abnormality, subchondral cysts and bone attrition in 14 locations. It also incorporated scores for the medial and lateral menisci, anterior and posterior cruciate ligaments, medial and lateral collateral ligaments and synovial distension. Lateral and medial femoro-tibial joint space width (JSW) measurements, performed by digital image analysis, were assessed from fixed-flexion, postero-anterior knee radiographs. RESULTS: One-year changes in medial femoro-tibial JSW reach 6.7 (20.5) % and changes in medial cartilage volume and thickness reach 0.4 (16.7) % and 2.1 (11.3) %, respectively. Medial femoro-tibial joint space narrowing (JSN) after 1 year, assessed by radiography, was significantly correlated with a loss of medial tibial cartilage volume (r=0.25, P=0.046) and medial tibial cartilage thickness (r=0.28, P=0.025), over the same period. We found also a significant correlation between the progression of the WORMS and radiographic medial JSN over 1 year (r=-0.35, P=0.006). All these results remained statistically significant after adjusting for age, sex and body mass index. CONCLUSION: This study shows a moderate but significant association between changes in JSW and changes in cartilage volume or thickness in knee joint of osteoarthritic patients.

Aged↗
PubMed2006

The dentinal caries experience of children in the United Kingdom, 2003.

BACKGROUND: The 2003 Children's Dental Health Survey is the fourth in a series of decennial national children's dental health surveys. AIMS: This paper reports the survey-derived estimates of dentinal caries experience of children aged five, eight, 12 and 15 years, considering the trends over recent decades and the position in 2003 following changes in disease presentation and the use of additional criteria. METHODOLOGY: A representative UK sample of children in the four specified age groups were invited to participate in a clinical dental examination in school. A total of 12,698 children were sampled and 10,381 were examined (82%). Examinations were undertaken in school by trained and calibrated examining teams using reclining chairs and portable lights, the criteria were visual, limited to dentine caries and no diagnostic aids were employed. In order to compare trend data with 1993 and earlier surveys the criteria allowed the re-classification of the full 2003a results (those including cavities and visual dentine caries - D(3cv)MFT/d(3cv)mft) according to the previous criteria to produce results labelled 2003b (those restricted to dentinal cavities--D(3c)MFT/d(3c)mft). RESULTS AND CONCLUSIONS: The experience of obvious dentinal caries in children within the UK has continued to change over the last decade and patterns are different for the two dentitions. While continuing overall improvements are evident for permanent teeth across the UK (D(3c) for 15-year-old children falling from 42% in 1983, via 30% in 1993 to 13% in 2003 for example), trends amongst those experiencing dentinal caries are more concerning and there have been no statistically significant improvements for primary teeth (the mean number of teeth with obvious dentine decay (d(3c)) at age five years being 1.3 in 1983 and 1.4 in both 1993 and 2003). The inclusion in the criteria of visual dentinal caries resulted in higher estimates of mean caries and mean caries experience in the permanent dentition (at age 15 years D(3) increasing from 0.2 to 0.8, D(3)MFT increasing from 1.6 to 2.0 for example) but not the primary dentition (where the estimates for % d(3)mft at age five years were identical at 43%). Geographic variations also persist across the UK (% with D(3cv)MFT at 12 years being 41% for England, 54% Wales, 73% Northern Ireland and 43% for the UK; % with d(3cv)mft at age 5 years: 41% for England, 52% Wales, 61% Northern Ireland and 43% for the UK). These survey results have implications for planning and for daily practice, but must be interpreted carefully acknowledging the specific survey conditions and diagnostic criteria employed.

Adolescent↗
PubMed2006

Osteoarthritis, magnetic resonance imaging, and biochemical markers: a one year prospective study.

OBJECTIVE: To investigate the relation between biochemical markers of bone, cartilage, and synovial remodelling and the structural progression of knee osteoarthritis. METHODS: 62 patients of both sexes with knee osteoarthritis were followed prospectively for one year. From magnetic resonance imaging (MRI), done at baseline and after one year, the volume and thickness of cartilage of the femur, the medial tibia, and the lateral tibia were assessed. A whole organ magnetic resonance imaging score (WORMS) of the knee was calculated for each patient at baseline and at the one year visits. This score consists in a validated, semiquantitative scoring system for whole organ assessment of the knee in osteoarthritis using MRI. Biochemical markers (serum hyaluronic acid, osteocalcin, cartilage glycoprotein 39 (YKL-40), cartilage oligomeric matrix protein (COMP), and C-telopeptide of type I collagen (CTX-I), and urine C-telopeptide of type II collagen (CTX-II)) were measured at baseline and after three months. RESULTS: Baseline markers were not correlated with one year changes observed in cartilage volume and thickness. However, an increase in CTX-II after three months was significantly correlated with a one year decrease in mean thickness of medial tibial and lateral tibial cartilage. Patients in the highest quartile of three month changes in CTX-II experienced a mean loss of 0.07 (0.08) mm of their medial thickness, compared with a mean increase of 0.05 (0.19) mm for patients in the lowest quartile (p = 0.04) Multiple regression analysis showed that high baseline levels of hyaluronic acid are predictive of a worsening in WORMS (p = 0.004). CONCLUSIONS: These results suggest that a single measurement of serum hyaluronic acid or short term changes in urine CTX-II could identify patients at greatest risk of progression of osteoarthritis.

Adipokines↗
PubMed2006

Immunomodulatory effects of Toll-like receptor-7 activation on chronic lymphocytic leukemia cells.

Weak immunogenicity of chronic lymphocytic leukemia (CLL) cells may contribute to disease progression and inhibit effective immunotherapy. Accordingly, agents that enhance the immunogenicity of CLL cells may be useful in immunotherapeutic approaches to this disease. Since Toll-like receptors (TLRs) are major regulators of innate immunity and initiation of adaptive immunity, we studied the effects of viral pathogen associated molecular pattern agonists (that are recognized by TLRs) on the costimulatory phenotype and function of CLL cells. CLL cells (especially those with high endogenous expression of CD38) responded to TLR7-activating imidazoquinolines and guanosine analogs by increasing costimulatory molecule expression, producing inflammatory cytokines, and becoming more sensitive to killing by cytotoxic effectors. Additional activation of protein kinase C pathways increased the ability to stimulate T-cell proliferation, blocked phosphorylation of the transcription factor, signal transducer and activator of transcription (STAT)3, and resulted in the acquisition of a dendritic cell surface phenotype by TLR7-activated CLL cells. Normal B cells also responded to TLR7 activation by increasing costimulatory molecule expression and cytokine production. These findings suggest a potential role for TLR7 agonists in CLL immunotherapy.

Adult↗
PubMed2006

Montelukast in the treatment of HIV associated immune reconstitution disease.

The pathogenesis of immune reconstitution disease (IRD) is not well understood and it can be difficult to manage. Leukotrienes exert proinflammatory effects, have an important role in the innate immune response, and are relatively deficient in HIV infection. Montelukast is a leukotriene receptor antagonist (LTRA) currently licensed for the treatment of asthma. We report a series of three patients with severe HIV associated IRD (cases 1 and 2 associated with starting HAART and unresponsive to steroids), who obtained clinically dramatic responses to treatment with montelukast. The first case is of IRD to secondary syphilis and the second and third to tuberculosis. Cases 1 and 3 both relapsed after a temporary break from montelukast and resolved on restarting. Montelukast should be considered in HIV associated IRD as an alternative to steroids and where these are not effective. Leukotriene overactivity may be implicated in IRD.

Acetates↗
PubMed2004

Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis.

OBJECTIVES: To describe a semi-quantitative scoring method for multi-feature, whole-organ evaluation of the knee in osteoarthritis (OA) based on magnetic resonance imaging (MRI) findings. To determine the inter-observer agreement of this scoring method. To examine associations among the features included in the scoring method. METHODS: Nineteen knees of 19 patients with knee OA were imaged with MRI using conventional pulse sequences and a clinical 1.5 T MRI system. Images were independently analyzed by two musculoskeletal radiologists using a whole-organ MRI scoring method (WORMS) that incorporated 14 features: articular cartilage integrity, subarticular bone marrow abnormality, subarticular cysts, subarticular bone attrition, marginal osteophytes, medial and lateral meniscal integrity, anterior and posterior cruciate ligament integrity, medial and lateral collateral ligament integrity, synovitis/effusion, intraarticular loose bodies, and periarticular cysts/bursitis. Intraclass correlation coefficients (ICC) were determined for each feature as a measure of inter-observer agreement. Associations among the scores for different features were expressed as Spearman Rho. RESULTS: All knees showed structural abnormalities with MRI. Cartilage loss and osteophytes were the most prevalent features (98% and 92%, respectively). One of the least common features was ligament abnormality (8%). Inter-observer agreement for WORMS scores was high (most ICC values were >0.80). The individual features showed strong inter-associations. CONCLUSION: The WORMS method described in this report provides multi-feature, whole-organ assessment of the knee in OA using conventional MR images, and shows high inter-observer agreement among trained readers. This method may be useful in epidemiological studies and clinical trials of OA.

Aged↗
PubMed2003

Quantitative trait loci for low aflatoxin production in two related maize populations.

Aflatoxin B(1) formed by Aspergillus flavus Fr:Link has been associated with animal disease and liver cancer in humans. We performed genetic studies in progenies derived from maize inbred Tex6, associated with relatively low levels of aflatoxin production, crossed with the historically important inbred B73. (Tex6 x B73) x B73 BC(1)S(1) and Tex6 x B73 F(2:3) mapping populations were produced and evaluated in 1996 and 1997 in Champaign, Ill. Ears were inoculated 20 to 24 days after midsilk using a pinboard method and a mixture of conidia of A. flavus Link:Fr. isolates. Aflatoxin B(1) levels in harvested ears were determined using an indirect competitive ELISA. Molecular markers were assayed on the populations and used to generate maps. Molecular marker - QTL associations for lower levels of aflatoxin production were determined using multiple regression (MR) and composite interval analysis with multiple regression (CIM MR). MR revealed sets of markers associated with lower aflatoxin production in 1996 and 1997, and CIM MR detected a smaller subset of loci significant in 1997. QTLs for lower aflatoxin were attributed to both Tex6 and B73 parental sources. Environment strongly influenced the detection of QTLs for lower aflatoxin production in different years. There were very few chromosome regions associated with QTLs in more than 1 year or population with MR analysis, and none with CIM MR analysis. In 1997, QTLs for lower aflatoxin were detected with CIM MR in bins 5.01-2 and 5.04-5 in the BC(1)S(1) population, and in bins 3.05-6, 4.07-8 and 10.05-10.07 in the F(2:3) population. These QTL associations appear the most promising for further study.

Aflatoxins↗
PubMed2003

Metallic artefacts in MR imaging: effects of main field orientation and strength.

AIM: To determine the effect of metallic implant positioning on magnetic resonance (MR) imaging artefacts, and to determine the optimal imaging parameters for minimization of metallic artefacts. MATERIALS AND METHODS: In a phantom and in three joints with non-ferromagnetic metallic implants imaged at 1.5 and/or at 0.2 T, we examined the influence of the static magnetic field (B(0)) strength and orientation, frequency-encoding direction, and type of imaging sequence on metallic artefacts. RESULTS: The impact of artefacts caused by metallic objects depends mainly on the relationship between the anatomy of interest and the orientation of the object relative to the direction of B(0). The main field strength plays a less important role, but its orientation depends on the type of MR imager. CONCLUSION: MR artefacts can be easily minimized by optimally positioning patients with metallic implants in the magnet. Knowledge of how this influences MR imaging is helpful in patient selection and guiding limb positioning.

Artifacts↗
PubMed2003

Successful peripheral blood stem cell mobilisation with filgrastim in patients with chronic myeloid leukaemia achieving complete cytogenetic response with imatinib, without increasing disease burden as measured by quantitative real-time PCR.

Imatinib mesylate (Glivec) is a selective inhibitor of bcr-abl tyrosine kinase, the product of the Philadelphia chromosome, which is the hallmark of chronic myeloid leukaemia (CML). With imatinib, complete cytogenetic response (CCR) can be achieved in over 70% of newly diagnosed patients with CML. However, the optimal long-term management of patients who achieve CCR after imatinib is unknown. With longer follow-up, it is anticipated that some patients are likely to progress and become candidates for autologous transplantation. We studied filgrastim (r-metHuG-CSF) mobilisation of peripheral blood stem cells (PBSC) in 32 patients who have achieved CCR with imatinib. Our data demonstrate that (1) the target CD34(+) cell yields of >/=2.0 x 10(6)/kg were attained with filgrastim 10 microg/kg/day, in 9/18 (50%) of patients during uninterrupted imatinib therapy, and in 10/14 (70%) when imatinib was temporarily withheld. The median CD34(+) cell yield per aphaeresis was 0.70 x 10(6)/kg (range 0.14-2.18) and 2.90 x 10(6)/kg (range 0.15-8.71) in the two groups, respectively (P&<0.005). (2) The cell yields did not correlate with the duration of imatinib administration. (3) There was no impact of the mobilisation procedure on the level of leukaemia as measured by serial blood bcr-abl levels using real-time quantitative PCR with either protocol. (4) bcr-abl remained detectable at low levels in the harvests in most but not all patients. In conclusion, filgrastim can safely be used to mobilise PBSC in patients who have achieved CCR with imatinib, but CD34(+) cell yields are significantly improved when imatinib is temporarily withheld.

Adult↗
PubMed2003

Selected CD34 blood cell allografts for older patients: low transplant-related mortality, graft failure and acute GvHD.

BACKGROUND: Early transplant mortality is related to acute GvHD, which this study in older patients (40 to 60 years) decreased by reducing the graft T-cell number while maintaining a high CD34 cell number--by positive CD34 cell selection. Potential increased risk of relapse is addressed by giving donor leucocyte infusion (DLI) post-transplant. METHODS: CD34 cells selected by Isolex devices from leukophereses obtained from Filgrastim-treated matched sibling donors were transplanted and DLI given later if there was no GvHD. RESULTS: Selection of CD34 cells achieved a median of 5.2 million cells/kg, with minimum target for transplantation achieved in 17 of 21 donors. Median CD3 cell number was 0.24 million/kg. Engraftment was rapid and graft failure rare. Transplant-related mortality was low (6% at 3 months). Acute GvHD of >or=Grade 2 occurred in only two patients (12.5%). DLI were given to only six patients who had resolved Grade 1 or no GvHD. Eight of the 17 patients relapsed, including three of the six who had DLI. Extensive chronic GvHD developed in six of 12 evaluable patients, two of these had received DLI. Seven of the 17 patients (41%) are alive at median follow-up of 56 months. CONCLUSION: CD34 selection allows transplantation of high numbers of CD34 cells with low CD3 cell count, reducing early mortality in patients 40-60 years old because of rapid hemopoietic reconstitution and low acute GvHD incidence. Administration of DLI was often precluded by low-grade acute GvHD.

Acute Disease↗
PubMed2003

Imaging in antiangiogenesis trial: a clinical trials radiology perspective.

Traditional approaches for treating cancer have largely focused on the ability of chemotherapy, and to a lesser extent radiation therapy, to destroy tumour cells. Recent developments in antiangiogenesis treatments require a fundamental shift in the radiological and imaging paradigms associated with evaluating response. Proper design and execution of any clinical trial involving imaging angiogenesis requires satisfactory consideration of a number of strategies and an in-depth understanding of different imaging techniques such as dynamic contrast enhanced MRI and CT, contrast-enhanced ultrasound and positron emission tomography. In particular, for imaging, the strategies can be divided into issues that need to be addressed during the protocol planning phase, and strategies that need to be addressed during the execution phase. Furthermore, clinical trials are usually subject to stringent regulations surrounding traceability and reproducibility that need to be followed before the regulatory authorities will accept the integrity of the data. This paper elaborates on the above strategies and outlines certain aspects, or tactics, that need to be considered while preparing for a multicentre clinical trial that involves imaging angiogenesis.

Angiogenesis Inhibitors↗
PubMed2003

The psychosocial impact of the implantable cardioverter defibrillator: a meta-analytic review.

OBJECTIVE: The implantable cardioverter defibrillator (ICD) has become the treatment of choice for ventricular arrhythmia (VA; abnormal heart rhythms) and the prevention of sudden cardiac death (SCD). Recent clinical trials have shown the ICD to be superior to anti-arrhythmic medication in reducing mortality; however, research has suggested that ICD recipients experience poor psychosocial adjustment following implantation of the device. This aim of this study was to identify the key psychological characteristics associated with ICD implantation and to establish whether poor psychosocial outcome can be attributed directly to the device and its therapy. METHOD: Studies which reported valid and reliable measures of psychological functioning in ICD patients and appropriate comparison groups were considered for inclusion in a meta-analytic review. A systematic search of electronic databases and reference lists identified 20 studies which fulfilled the inclusion criteria. RESULTS: There were no significant differences in psychosocial outcome between ICD patients and drug-maintained VA patients or between pre- and post-implant ICD patients. However, ICD patients reported significantly worse psychological functioning and physical functioning than other cardiac controls. CONCLUSION: These findings suggest that poor psychosocial outcome in ICD patients may occur as a result of variables associated with the underlying VA condition, rather than as a direct response to implantation of the device and its therapy. This holds important implications for the development and implementation of psychological interventions for patients experiencing VA, in preference to ICD-specific programmes.

Adaptation, Psychological↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗