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Biomedical subjects

M Doherty

Publications and source records attributed to M Doherty.

At least 37 records · Page 2Linked to original sources
PubMed1997

Chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluronan in progressive versus non-progressive osteoarthritis.

OBJECTIVE: To determine if a single time point estimation of chondroitin sulphate (CS) or keratan sulphate (KS) epitopes, hyaluronan (HA), or total glycosaminoglycans (GAG) in knee synovial fluid at time of hospital referral can predict subsequent radiographic progression of knee osteoarthritis. METHODS: Two groups of hospital referred patients with knee osteoarthritis were compared: (1) a "progressive" group (n = 45), showing further reduction in radiographic joint space of at least one grade (0-3) in at least one compartment; and (2) a "non-progressive" group (n = 25) in whom radiographs showed no change during the mean follow up period of 2.3 years (median 2, range 1 to 5 years). Knee synovial fluid obtained at the first visit was examined by ELISA for: CS epitopes, using monoclonal antibodies 3B3 and 7D4; KS epitope, using monoclonal antibody 5D4; and HA, using biotinylated HA binding region of cartilage proteoglycan. Total sulphated GAG were measured by dye binding with 1:9 dimethylmethylene blue. RESULTS: In patients with bilateral synovial fluid data right and left knee values were closely correlated for all variables. There were no significant differences between CS and KS epitopes, HA, total sulphated GAG, or ratios of individual CS or KS epitopes to total GAG, between progressive and non-progressive groups. CONCLUSIONS: Single time point estimation of CS, KS, HA, or total GAG in synovial fluid does not distinguish radiographically progressive and non-progressive knee osteoarthritis patients followed for two years.

Aged↗
PubMed1997

Synovial fluid chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluronan in arthritic and normal knees.

OBJECTIVES: To determine concentrations of chondroitin sulphate (CS) and keratan sulphate (KS) epitopes, glycosaminoglycans (GAGs) and hyaluronan (HA) in knee synovial fluid (SF) from normal subjects and patients with osteoarthritis (OA) or rheumatoid arthritis (RA), to test whether these variables may be used as markers of the OA process. METHODS: OA was subdivided into large joint OA (LJOA), nodal generalised OA (NGOA), and OA with calcium pyrophosphate crystal deposition (CPA). Clinical assessment of inflammation (0-6) was undertaken on OA and RA knees. Knee SF was examined by enzyme linked immunosorbent assay for: CS epitopes, using monoclonal antibodies 3-B-3 and 7-D-4; KS epitope using monoclonal antibody 5-D-4; and HA, using biotinylated HA binding region of cartilage proteoglycan. Total sulphated GAGs were measured by dye binding with 1:9 dimethylmethylene blue. RESULTS: Increased SF 3-B-3 concentrations and 3-B-3/GAG ratio were found in OA, compared with RA or normal knees, with higher 3-B-3 and 3-B-3/GAG in LJOA and NGOA than in CPA. SF 7-D-4 and 7-D-4/GAG were reduced in RA, compared with normal and OA; SF 5-D-4 was reduced in OA compared with normal. GAG and HA concentrations were decreased in both OA and RA. No correlations with radiographic scores were observed, but SF 7-D-4 was lower in 'inflamed' compared with 'non-inflamed' RA and OA knees. In patients with bilateral samples there were strong correlations between right and left knees for all SF variables. CONCLUSIONS: Changed concentrations of SF CS and KS can be detected in OA with a profile that differs from that seen in RA. Clinical subgrouping and local joint inflammation may influence these measures, supporting different pathogenesis within OA subgroups and requirement for careful patient characterisation in SF studies.

Adult↗
PubMed1997

Comparison of lung volume in Greek swimmers, land based athletes, and sedentary controls using allometric scaling.

OBJECTIVE: To compare lung volumes in a large cross sectional sample of Greek swimmers, land based athletes, and sedentary controls by means of allometric scaling. METHODS: Four hundred and fifty nine asymptomatic Greek children and young adults (age 10-21 years), including 159 swimmers, 130 land based athletes, and 170 sedentary controls, performed forced expiratory manoeuvres into a portable spirometer. Measurements included forced vital capacity, forced expiratory volume in one second (FEV1.0), and peak expiratory flow. Body mass and stature were also measured using standardised anthropometric techniques. RESULTS: Logarithmic transformations showed that in FEV1.0 was highly related to in stature in males and females (r = 0.93 and 0.86 respectively, P < 0.001) and were used to determine the exponent in an allometric equation which also included age and age. Resulting power functions, FEV1.0/stature, were 0.64 (0.18) litres/m2.69 and 0.33 (0.24) litres/m2.32 for males and females respectively (mean (SE)). The male and female swimming groups had larger FEV1.0 than both land based athletes and sedentary controls (one way analysis of variance, P < 0.001). In addition, male national standard swimmers (n = 38) had superior FEV1.0 in comparison with male non-national standard swimmers (n = 24; t test, P < 0.05). However, when years of swimming training was controlled for by analysis of covariance, the difference in FEV1.0 between the two groups was no longer evident. CONCLUSIONS: Swimmers have superior FEV1.0 independent of stature and age in comparison with both land based athletes and sedentary controls. In addition, male national standard swimmers have superior FEV1.0 independent of stature and age in comparison with male non-national standard swimmers. When years of training is controlled for, the difference in FEV1.0 between the two groups is no longer evident. This suggests that the years of swimming training and/or the earlier age at which training begins may have a significant influence on subsequent FEV1.0 and swimming performance. However, because of the cross sectional nature of this study, the results do not exclude genetic endowment as a major determinant of the superior lung volume observed in swimmers.

Adolescent↗
PubMed1997

Conservatively managed tibial shaft fractures in Nottingham, UK: are pain, osteoarthritis, and disability long-term complications?

OBJECTIVES: To investigate longterm pain and disability subsequent to a tibial shaft fracture treated conservatively. DESIGN AND SETTING: Subjects who had sustained a tibial shaft fracture more than 27 years ago were compared with those who had not. SUBJECTS: 572 fracture patients (identified from the records of the plaster room) aged over 16 at the time of injury were contracted and were compared with 2285 randomly selected subjects matched for age, sex, and general practice. MAIN OUTCOME MEASURES: Self reported knee pain; self reported GP's diagnosis of osteoarthritis; ability to climb stairs, walk 100 yards, to bend, kneel, or stoop; and SF-36 physical functioning score. RESULTS: Subjects were reviewed between 27 and 41 years after tibial shaft fracture (mean 35 years). Fracture patients were more likely to suffer chronic knee pain (odds ratio 1.23; 95% confidence interval (CI) 1.00, 1.51) and report being given a diagnosis of osteoarthritis by their GP (odds ratio 1.46; 95% CI 1.08, 1.97). The ability to climb stairs, walk 100 yards, and bend, kneel, or stoop was less in the fracture group than the other subjects. The SF-36 physical function score was significantly lower in the fracture group. CONCLUSIONS: More than 27 years after a tibial shaft fracture, subjects have more knee pain than the rest of the population. They also have greater difficulty performing everyday physical activities. The excess morbidity may be due to injury factors or treatment factors, and further research is needed to investigate this important association further.

Activities of Daily Living↗
PubMed1996

Intra-articular corticosteroids are effective in osteoarthritis but there are no clinical predictors of response.

OBJECTIVES: To show whether intra-articular steroid injections are effective in osteoarthritis; to determine factors that predict response; and to determine whether injection has a beneficial effect on muscle strength. METHODS: Double blind, placebo controlled, crossover study in 59 patients with symptomatic osteoarthritis of the knee. Outcome measure-Primary outcome measure: change in visual analogue score for pain at three weeks. Predictors of response analysed using logistic regression with a 15% decrease in pain score at three weeks defining response. RESULTS: Intra-articular methyl prednisolone acetate produced a significant reduction in visual analogue pain score at three weeks compared to both baseline (median change -2.0 mm, interquartile range -16.25 to 4.0) and placebo (median 0.0 mm, interquartile range -9.0 to 6.25). No clinical predictors of response could be identified. Muscle strength was not significantly improved in the short term by intra-articular injection. CONCLUSIONS: Intra-articular corticosteroids are effective for short term relief of pain in osteoarthritis but predicting responders is not possible. There may be a place for their more widespread use.

Aged↗
PubMed1996

Assessing progression of patellofemoral osteoarthritis: a comparison between two radiographic methods.

OBJECTIVE: To compare two plain radiographic methods for sensitivity to detect progression of patellofemoral osteoarthritis. METHODS: Two sets of paired skyline and lateral knee radiographs from 54 hospital referred patients (108 knees) with knee osteoarthritis were taken an average of 31 months apart (range 12-40). Films were examined separately in random order by a single observer blind to patient identity and time order. Minimum joint space was measured by metered caliper; individual features of osteoarthritis were graded 0-3 using an atlas. RESULTS: Intraobserver reproducibility assessed on 40 knees was to within +/- 0.5 mm for skyline lateral facet and +/- 0.7 mm for medial facet and lateral views. On the lateral view measured joint space decreased in 51% of knees but increased in 43%, with overall no significant mean group change with time (-0.2 mm, 95% confidence interval, 0.1 to -0.5). By contrast on the skyline view joint space decreased in at least one facet in 71% of knees, with significant decrease in mean joint space for both lateral facets (-0.4 mm, 95% CI, -0.2 to -0.6) and medial facets (-0.5 mm, 95% CI, -0.1 to -0.8). CONCLUSIONS: It is possible to detect significant joint space loss with time on the skyline view that is not apparent on the lateral view. The skyline view should be the method of choice to detect progression of patellofemoral osteoarthritis.

Adult↗
PubMed1996

Screening for pain in knee osteoarthritis: which question?

OBJECTIVE: To compare three questions on knee pain with respect to determined prevalence and associations with disability and structural change. METHODS: Postal survey to 4057 men and women aged 40-79 years. Knee pain was defined by three questions: (A) "Have you ever had pain in or around the knee on most days for at least a month? If so, have you experienced any pain during the last year?" (B) "Have you had pain within the last year in or around the knee that occurred on most days for at least a month?" (C) "Have you had knee pain on most days of the last month?" [American College of Rheumatology (ACR) criteria for knee osteoarthritis]. Disability was assessed with the SF-36 health status questionnaire. Radiographs (AP weight bearing and skyline) were obtained on a proportion (n = 459) and graded for maximum osteophyte in any compartment. RESULTS: Prevalence of knee pain for questions A, B, and C were 28.3%, 25.3%, and 19.3% respectively. Highest rates of disability were observed for question C (71.3% compared with 60.9% for question A). There was no major difference between questions in terms of percentage with > or = grade 1 osteophyte or > or = grade 2 osteophyte. Sensitivity and specificity of each question for > or = grade 1 osteophyte did vary, with question A being most sensitive but least specific (58.7% and 59.1%) and question C most specific (72.7%) but least sensitive (45.4%). CONCLUSIONS: Estimates of knee pain and disability are influenced by even minor changes in question content. The ACR criteria question may be a better predictor of disability but is relatively insensitive for use in the community.

Adult↗
PubMed1996

Plasminogen activators and their inhibitors in synovial fluids from normal, osteoarthritis, and rheumatoid arthritis knees.

OBJECTIVES: To establish baseline concentrations of plasminogen activators and their inhibitors in normal knee synovial fluids, and to compare them with well characterised osteoarthritis (OA) and rheumatoid arthritis (RA) knee fluids. METHODS: A total of 26 normal subjects, 71 patients with OA, and 17 patients with RA underwent knee aspiration. Patients with OA were subclassified according to presence of nodal generalised OA (NGOA) and synovial fluid calcium pyrophosphate crystals. Clinical assessment of inflammation (graded 0-6) was undertaken in OA and RA patients. Plasminogen activator (PA), plasminogen activator inhibitor (PAI), and urokinase-type PA receptor (uPAR) antigen concentrations were determined by enzyme linked immunosorbent assay. The species of PAs present were determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. RESULTS: Concentrations of all antigens (uPA, tissue-type PA (tPA), uPAR, and PAI-1), were significantly greater in RA than OA; those in OA were significantly greater than normal. The concentrations showed no direct association with clinically assessed inflammation of the knee. In normal fluids, no associations with age were observed. Antigen concentrations (uPA, tPA, and uPAR) in NGOA differed from those in other subclasses of OA, but the species of PA present did not appear to vary between disease groups. The predominant PA appeared to have identity with uPA. CONCLUSION: Because of the greater concentrations of these antigens in OA compared with normal fluids, OA cannot be used as a surrogate normal control in studies of the PA/PAI system. Alteration of the PA/PAI system was confirmed in RA and OA knee fluids, with greater changes evident in RA. The finding of different concentrations of PA antigens in NGOA compared with other OA fluids further supports a different pathogenic mechanism in this subset.

Adult↗
PubMed1996

Association of two loci on chromosome 2q with nodal osteoarthritis.

OBJECTIVE: To search for genetic association between microsatellite marker loci and sibling pairs with nodal osteoarthritis (NOA). METHODS: Using the affected sibling pair method of analysis, genomic DNA from 66 sib pairs with NOA was analysed for association with highly polymorphic microsatellite marker loci. The microsatellite markers were amplified using polymerase chain reaction and typed on polyacrylamide gels. RESULTS: A significant association (p < 0.05) was identified between NOA and two loci on the short arm of chromosome 2 (2q 23-35). Candidate genes for osteoarthritis in this region include: fibronectin, a glycoprotein present in the extracellular matrix of normal cartilage; the alpha 2 chain of collagen type V, a major constituent of bone; and the interleukin-8 receptor, important in the regulation of neutrophil activation and chemotaxis. CONCLUSIONS: The chromosomal region 2q 23-35 requires further detailed study in NOA. Confirmation of these findings in large independent data sets and further analysis of candidate genes in this region will be important in unravelling the molecular basis for this common disease.

Adult↗