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Biomedical subjects

D L Scott

Publications and source records attributed to D L Scott.

At least 55 records · Page 3Linked to original sources
PubMed2000

Factors contributing to rapid wear and osteolysis in hips with modular acetabular bearings made of hylamer.

There have been several reports of osteolysis associated with rapid wear of Hylamer. A detailed analysis of retrieved implants and tissues can identify factors contributing to rapid wear and osteolysis. The mean linear wear rate of 12 liners was 0.49 mm/y, and 11 of 12 hips had progressive retroacetabular osteolysis. The average patient age was 50 years, and the mean implantation time was 50 months. All liners were sterilized by gamma irradiation in air. There was an 11-month difference in the average shelf-life of the 3 liners that were white and those that were darker in color. The volumetric wear rate of the white liners was 30% less than that of the others, suggesting a difference in the wear resistance of the liners as a function of shelf life. The mean average surface roughness (Ra) and the mean maximum surface roughness (R(max)) of the femoral heads were increased 3-fold and 50-fold compared with typical values for unused femoral heads. Evidence of 3-body wear, such as metal particles embedded in the liners, was commonly present. The pattern of backside liner deformation and burnishing was consistent with relative motion between the liner and the shell. In addition to generating Hylamer wear particles, repetitive axial motion between the liner and shell could generate fluid pressure, which transmitted through holes in the acetabular shell could cause or contribute to the development of retroacetabular osteolysis. Hylamer particles of variable shape and size, consistent with generation by several wear modes, were isolated from periprosthetic tissues.

Acetabulum↗
PubMed2000

Care giver perception of children's obesity-related health risk: a study of African American families.

OBJECTIVE: To examine care giver perception of children's weight-related health risk in African American families. RESEARCH METHODS AND PROCEDURES: One-hundred and eleven families (representing 48 boys and 63 girls) screened for participation in a diabetes prevention study participated. Care givers completed a health awareness questionnaire that assessed their perception of the child's weight, eating habits, appearance, exercise habits, and health risk. The care givers also reported each subject's family history of obesity, diabetes, and other chronic diseases. After a physical examination, height and weight were used to compute an age- and sex-adjusted body mass index for each child. RESULTS: Despite the fact that a substantial number of children were obese (57%) and super-obese (12%), only 44% of the care givers perceived the child's weight to be a potential health problem. Regression analysis showed that 21% of the variance in parental perception of obesity-related health risk could be predicted by child age, body mass index, perception of frame size, and perception of exercise habits. DISCUSSION: A number of reasons for the apparent minimization of child health risk are discussed, including cultural differences in the acceptance of a large body habitus, lack of knowledge about the connection between childhood obesity and future health risk, and an optimistic bias in the perception of personal health risk.

Adult↗
PubMed2000

Safety and efficacy of nabumetone in osteoarthritis: emphasis on gastrointestinal safety.

AIM: To compare the efficacy and gastrointestinal (GI) safety of nabumetone with two comparator non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac SR and piroxicam. METHODS: Two randomized, double-blind, multicentre, parallel group trials were carried out in patients with moderate to severe osteoarthritis of the hip or knee. During the 6 month treatment phase, the safety and efficacy of nabumetone (1500-2000 mg/day) was compared to diclofenac SR (100 mg/day) or piroxicam (20-30 mg/day). GI safety was evaluated by reviewing all adverse events reported during the trials and presenting all cases of ulcers (complicated and uncomplicated), as well as other bleeding events that may have been associated with NSAID administration. RESULTS: Most of the efficacy parameters showed no significant differences between the NSAIDs, although diclofenac SR was significantly better than nabumetone in one of 18 efficacy parameters. Nabumetone-treated patients experienced significantly fewer ulcer and bleeding events compared to patients treated with the comparator NSAIDs [1.1% (4/348) vs. 4.3% (15/346), P = 0.01]. Bleeding events, including outright upper or lower GI bleeding or a significant decline in haemoglobin, occurred in significantly fewer patients treated with nabumetone than with the comparator NSAIDs [1.1% (4/348) vs. 3.5% (12/346), P < 0.05]. More importantly, complications associated with either ulcers (perforation) or bleeding (leading to hospitalization or withdrawal) occurred in significantly fewer patients receiving nabumetone [0% (0/348)] than with comparator NSAIDs [1.4% (5/346), (P < 0.05)]. CONCLUSION: The results suggest that nabumetone was similar in efficacy by most criteria to diclofenac SR and piroxicam in relieving the symptoms of osteoarthritis; however, nabumetone's GI safety profile was generally superior to that of both comparator NSAIDs. In the pooled analysis, nabumetone was associated with a significantly lower total incidence of ulcers and bleeding events, and a significantly lower incidence of complications associated with these events.

Adult↗
PubMed2000

The use of biomagnetic separation to recover DNA suitable for PCR from Claviceps species.

DNA analysis of agriculturally important fungi using polymerase chain reaction (PCR)-based methods is becoming routine in research and for diagnostic purposes. Rapid, small-scale DNA isolation methods that take advantage of the sensitivity, speed and automation potential of PCR technology are needed for timely analysis of important plant pathogens. DNA isolated from Claviceps africana (causal agent of ergot of sorghum) using several standard DNA extraction protocols was found to be unamplifiable using PCR. The standard methods apparently failed to separate DNA from substances inhibitory to the Taq polymerase enzyme. We obtained DNA amenable to PCR analysis using a novel method involving magnetic beads and high salt extraction buffer. The biomagnetic purification method allowed us to obtain reliable PCR amplification of the internal transcribed spacer (ITS) regions of rDNA of Claviceps africana, making genetic comparisons possible.

Claviceps↗
PubMed2000

Quality of life measures: use and abuse.

Health status and quality of life measures are widely used in the clinical assessment of rheumatoid and other forms of arthritis. A range of measures is available, mainly as self-administered instruments. Most of these are reliable, valid and sensitive to change. They can be used to assess clinical status, evaluate effectiveness in randomized trials, define outcome and help to plan for health-care needs for people with arthritis. The instruments form a continuum with assessments of disease activity and functional disability. Some instruments are specifically designed for use in rheumatoid arthritis, other instruments are generic and can be used across a range of conditions including arthritis, and some generic instruments can be specifically scored to reflect the problems most prominent in arthritis. There are trade-offs between simplicity and sensitivity and between using familiar and unusual instruments. Against this background, the most widely used disease-specific measure remains the health assessment questionnaire (HAQ), and the most commonly employed generic measure is the SF-36. Evidence currently suggests focusing on these well-known and widely used measures. In both cases, the pain score is the predominant clinical assessment associated with poor health status measured using either instrument. HAQ scores also reflect unchanging aspects of patients' overall status, such as their degree of deprivation. It is sensible for all future clinical trials to include one disease-specific and one generic measure of health status.

Arthritis, Rheumatoid↗
PubMed2000

Prognostic factors in early rheumatoid arthritis.

The current paradigm for rheumatoid arthritis suggests that persistent synovitis leads to erosive joint damage, progression of which results in functional disability. Studies of X-ray progression followed for 1-9 yr have shown that 40-83% of subsequent progression can be predicted by a combination of prognostic factors such as joint involvement, high levels of C-reactive protein and rheumatoid factor (RF) positivity. There are similar findings for predictors of functional disability in studies followed for 2-15 yr. The most consistent prognostic feature is RF positivity, which is equally important in predicting joint damage and functional disability. Immunoglobulin A RF and the co-presence of RF with anti-keratin or anti-filaggrin antibodies may increase levels of prediction. Added value of genetic predictors over that of RF remains inconclusive. Therefore, therapeutic management should be individualized. Cases with active disease and seropositive RF tests merit aggressive therapy; conversely, cases with little synovitis and seronegative tests require conservative management.

Aged↗
PubMed2000

The long-term effects of non-steroidal anti-inflammatory drugs in osteoarthritis of the knee: a randomized placebo-controlled trial.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat osteoarthritis (OA), though their long-term efficacy is uncertain. We report a comparison of the symptomatic responses to therapy with tiaprofenic acid, indomethacin and placebo over 5 yr. METHODS: A parallel-group, randomized, single-blind trial of patients with knee OA recruited 812 patients from 20 centres; 307 patients received tiaprofenic acid (300 mg b.d.), 202 indomethacin (25 mg t.d.s.) and 303 matching placebo for up to 5 yr. At the end of the parallel-group study, patients receiving tiaprofenic acid or placebo entered a 4-week blinded cross-over study of tiaprofenic acid or placebo, both given for 2 weeks. Assessments were at baseline, 4 weeks, then at 6-month intervals for up to 5 yr in the parallel group study and at 2-week intervals in the cross-over study. They comprised pain scores, duration of morning stiffness, patients' global assessments, paracetamol consumption, adverse reactions, withdrawals and functional outcomes. RESULTS: There were significant falls in overall pain scores in patients receiving NSAIDs compared with placebo at 4 weeks in the parallel-group phase. Thereafter there were no advantages favouring active therapy. In the cross-over phase, pain scores were significantly lower in patients receiving tiaprofenic acid than placebo. Patients who had been receiving long-term tiaprofenic acid showed significant rises in their pain scores when receiving placebo therapy and vice versa. Adverse events were reported by 61% of patients receiving tiaprofenic acid, 63% on indomethacin and 51% on placebo. Potentially severe side-effects were rare; for example, there were only three cases of gastrointestinal bleeding on NSAIDs. The pattern of withdrawal was similar in patients taking NSAIDs and placebo in the parallel-group study; at 48 weeks 53% of the patients remained on tiaprofenic acid, 50% on indomethacin and 54% on placebo. CONCLUSIONS: NSAIDs significantly reduce overall pain over 4 weeks. This short-term responsiveness is retained, and even after several years of therapy with tiaprofenic acid pain scores increased over 2 weeks when it was changed to placebo. Our results do not show long-term benefits from the use of NSAIDs in OA and the majority of patients had persisting pain and disability despite therapy.

Adult↗
PubMed2000

The links between joint damage and disability in rheumatoid arthritis.

OBJECTIVE: The characteristic joint damage and disability of rheumatoid arthritis (RA) increase slowly over 10-20 yr. Although it is generally believed that persisting inflammatory synovitis causes joint damage and subsequent disability, the strength of their relationship has not been systematically evaluated. This review describes their progression and interrelationship in treated RA. METHODS: MEDLINE and Current Contents databases were searched for the combined terms of rheumatoid arthritis AND X-rays, Health Assessment Questionnaire, slow-acting anti-rheumatic drugs and all identifiable synonyms. This search identified 1303 articles and from these we evaluated in detail 23 reports on the progression of joint damage, 12 reports on the progression of disability and 25 reports dealing with their interrelationship. Additional information was obtained from four data sets comprising 725 RA patients studied cross-sectionally and 33-126 cases followed prospectively for 1-5 yr. X-ray damage was primarily assessed by Larsen and Sharp indices, and disability by the Health Assessment Questionnaire (HAQ). RESULTS: Joint damage and disability both increase throughout the duration of RA. Although disability (HAQ score) is correlated with disease duration (correlation coefficients between 0.27 and 0.30), the link between X-ray damage and disability is stronger (correlation coefficients between 0.30 and 0.70). In the earliest phases of RA, X-ray damage and HAQ scores are not related. By 5-8 yr, there are significant correlations with correlation coefficients between 0.30 and 0.50. In late RA (>8 yr), most studies show highly significant correlations between 0.30 and 0.70. CONCLUSIONS: Joint damage progresses constantly over the first 20 yr of RA. It accounts for approximately 25% of disability in established RA. The link between damage and disability is strongest in late (>8 yr) RA. However, avoiding or reducing joint damage in both early and established/late RA is likely to maintain function.

Arthritis, Rheumatoid↗
PubMed1999

2.0 A X-ray structure of the ternary complex of 7,8-dihydro-6-hydroxymethylpterinpyrophosphokinase from Escherichia coli with ATP and a substrate analogue.

The X-ray crystal structure of 7,8-dihydro-6-hydroxymethylpterinpyrophosphokinase (PPPK) in a ternary complex with ATP and a pterin analogue has been solved to 2.0 A resolution, giving, for the first time, detailed information of the PPPK/ATP intermolecular interactions and the accompanying conformational change. The first 100 residues of the 158 residue peptide contain a betaalpha betabeta alphabeta motif present in several other proteins including nucleoside diphosphate kinase. Comparative sequence examination of a wide range of prokaryotic and lower eukaryotic species confirms the conservation of the PPPK active site, indicating the value of this de novo folate biosynthesis pathway enzyme as a potential target for the development of novel broad-spectrum anti-infective agents.

Adenosine Triphosphate↗
PubMed1999

Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group.

BACKGROUND: Phase II trials of leflunomide, an inhibitor of de-novo pyrimidine synthesis, have shown efficacy in rheumatoid arthritis. This double-blind randomised trial compared leflunomide with placebo and sulphasalazine in active rheumatoid arthritis. METHODS: 358 patients were randomly assigned leflunomide (100 mg daily on days 1-3, then 20 mg daily), placebo, or sulphasalazine (0.5 g daily, titrated progressively to 2.0 g daily at week 4). The primary endpoints were tender and swollen joint counts and investigator's and patient's overall assessments. Analyses were by intention to treat. FINDINGS: The mean changes in the leflunomide, placebo, and sulphasalazine groups were -9.7, -4.3, and -8.1 for tender joint count; -7.2, -3.4, and -6.2 for swollen joint count; -1.1, -0.3, and -1.0 for physician's overall assessment; and -1.1, -0.4, and -1.1 for patient's overall assessment. Leflunomide and sulphasalazine were significantly superior to placebo (p=0.0001 for joint counts; p<0.001 for assessments). Radiographic disease progression was significantly slower with leflunomide and sulphasalazine than with placebo (p<0.01). Most common adverse events with leflunomide were diarrhoea (17%), nausea (10%), alopecia (8%), and rash (10%). Transiently abnormal liver function was seen in three leflunomide-group patients and five sulphasalazine-group patients. There were two cases of reversible agranulocytosis in the sulphasalazine group. INTERPRETATION: Leflunomide was more effective than placebo in treatment of rheumatoid arthritis and showed similar efficacy to sulphasalazine. Leflunomide was well tolerated. This drug may be a useful option as a disease-modifying antirheumatic drug.

Algorithms↗
PubMed1999

Leflunomide improves quality of life in rheumatoid arthritis.

Functional disability in rheumatoid arthritis (RA) interferes with activities of daily living and severely affects patient quality of life. It results in increased levels of work disability and high medical costs. A new goal of RA therapy is to reduce or prevent functional disability. Patients' perception of overall health status in RA was assessed using several instruments (HAQ, MHAQ, SF-36, and PET) in Phase III double-blind, placebo-controlled, randomized trials comparing the new DMARD, leflunomide to sulfasalazine and methotrexate. Leflunomide significantly improved patient quality of life compared to placebo in both the European (P = 0.0001) and North American (P = 0.0001) studies. Reduction in HAQ scores with leflunomide (-0.50 vs -0.29; P = 0.0086) was significantly greater than sulfasalazine. Leflunomide also significantly reduced MHAQ scores versus methotrexate (-0.29 vs -0.15; P < or = 0.05). These changes were seen as early as Week 4. These results highlight the efficacy of leflunomide in RA therapy.

Activities of Daily Living↗
PubMed1999

A patient-derived disease activity score can substitute for a physician-derived disease activity score in clinical research.

OBJECTIVE: Joint counts have a central role in assessing disease activity in rheumatoid arthritis (RA). They are usually undertaken by physicians or nurses. We investigated whether joint counts can be devolved to patients and evaluated the use of a patient-derived Disease Activity Score (DAS). METHODS: One hundred RA patients attending a specialist unit were evaluated, comparing joint counts by a physician with patient-assessed joint counts and DAS derived from both methods. They were related to other measures of disease activity in the European League Against Rheumatism (EULAR) core data set and with the Rheumatoid Arthritis Disease Activity Index (RADAI; a validated patient self-assessment index). RESULTS: Regression analysis showed no significant differences between a physician's and patient's joint counts and DAS. There were middle to high correlations between patient and physician assessments of tender joints and swollen joints; using R2, this explained 70% of the variance for tender joints and 40% for swollen joints. Kappa analysis showed good agreement between physician and patient assessments of individual joint tenderness (kappa values 0.49-0.84). There was lower agreement for individual swollen joints (kappa values 0.02-0.61). Physician DAS and patient DAS had a similar correlation with the Health Assessment Questionnaire (HAQ) (r = 0.50 and r = 0.48, respectively). CONCLUSION: The agreements between physician and patient assessments are sufficient to allow patients' assessments to be used for clinical research. This is especially the case with a patient-derived DAS. However, the results are not directly interchangeable and further studies are needed before patients' assessments are used to guide clinical practice.

Arthritis, Rheumatoid↗
PubMed1999

Rheumatoid arthritis: new developments in the use of existing therapies.

Combination therapy with methotrexate may be the newest standard to which future therapies for rheumatoid arthritis are compared. Many questions remain to be answered regarding the appropriateness of such combination therapies for specific patients and clinical situations, and the optimal therapeutic combinations. Other unanswered questions regarding combination therapy include the need for appropriate monitoring, long-term safety and cost-benefit implications. Future research is needed to clarify the role of biological response modifiers (e.g. anti-tumour necrosis factor therapies) and matrix metalloproteinase inhibitors, both as components of and alternatives to methotrexate combination regimens.

Antirheumatic Agents↗
PubMed1998

Arthritis associated with venereal disease in nineteenth century London.

It is well known that arthritis can be associated with venereal disease. Nowadays septic arthritis and reactive arthritis (usually classified as Reiter's syndrome) are distinguished. To place current knowledge within its historical context we reviewed the medical literature on sexually acquired arthritis in the nineteenth century and examined the medical records of London teaching hospitals from this period. We used original sources of rheumatological literature at major London libraries, including the Heberden library of the Royal College of Physicians, and visited the archives at three London teaching hospitals to review original case records and examine diagnostic registers. The first clear description of arthritis associated with venereal disease was given by Swediaur (1798/1809) in French. It became relatively common in London from 1820 onwards with 13 cases described in the literature between 1818 and 1836. It accounts for 3% of admissions at University College and St Bartholomew's Hospitals between 1835 and 1839 and also 3% of admissions at the London Hospital from 1895 to 1900. In the 50 years after Swediaur's report, arthritis associated with venereal disease seemed quite common. This may have been related to the industrial revolution or other social diseases. Historical observations suggest its evidence may vary considerably with time.

Arthritis, Reactive↗
PubMed1998

The differentiation of Phytophthora species that are pathogenic on potatoes by an asymmetric PCR combined with single-strand conformation polymorphism analysis.

The goal of this study was to develop a polymerase chain reaction (PCR) capable of differentiating Phytophthora species that are pathogenic on potatoes using a single primer pair. To achieve this objective, primers were derived from conserved regions flanking variable sequences in the internal transcribed spacer 1 (ITS1) of Phytophthora species. One primer pair produced a 140 bp product from P. infestans, P. erythroseptica and P. nicotianae. The PCR products were purified and used in an asymmetric PCR (A-PCR) protocol to generate single-strand DNA (ssDNA). The ssDNA of the Phytophthora potato pathogens reproducibly migrated in non-denaturing polyacrylamide gels in a species-specific manner.

Base Sequence↗