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Biomedical subjects

J Ledingham

Publications and source records attributed to J Ledingham.

At least 19 recordsLinked to original sources

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↗

Association between synovial fluid levels of inorganic pyrophosphate and short term radiographic outcome of knee osteoarthritis.

OBJECTIVE: To test the hypothesis that high concentrations of extracellular inorganic pyrophosphate (PPi), which associate with increased cell synthesis and turnover in cartilage, may act as a marker for structural outcome in knee osteoarthritis (OA). METHOD: One hundred and thirty five consecutive patients referred to hospital with knee OA (59 men, 76 women; mean age 71 years, range 41-88) were followed prospectively for a median of 2.5 years (interquartile range 1.75-3.0). Synovial fluid (SF) aspirated at presentation (202 OA knees: 68 bilateral, 66 unilateral) was assessed for PPi content by radiometric assay. Knee radiographs at presentation and at final review were assessed for change in global (Kellgren) and individual features (narrowing, osteophyte, sclerosis, cyst, attrition) of OA. RESULTS: The median SF PPi level was 10.5 mumol (range 0.07-72.4). At baseline, high PPi was significantly associated with presence of calcium pyrophosphate crystals, chondrocalcinosis, and bone attrition. Radiographic change was observed in 164 knees. High PPi levels were negatively associated with change in Kellgren and Lawrence grade, further narrowing, and increase in osteophyte, but positively associated with development of attrition. In the 68 patients from whom bilateral data were obtained, there was correlation between right and left knees for PPi levels, all baseline radiographic scores, and changes in radiographic features. Multiple logistic regression analysis for PPi as a continuous variable (age, gender, and patient number included in model) showed a negative correlation with change in global Kellgren and Lawrence grade (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.95 to 0.99) and a positive correlation with attrition (OR 1.04, 95% CI 1.02 to 1.07). CONCLUSION: High SF levels of PPi are associated with favourable radiographic outcome in terms of progressive change in Kellgren grade. Such elevated PPi levels, however, may inhibit new bone formation and remodelling in knee OA.

Adult↗

Factors affecting radiographic progression of knee osteoarthritis.

OBJECTIVES: To evaluate the prognostic significance of patient characteristics and radiographic features at the knee for outcome of knee osteoarthritis. METHODS: This was a prospective observational study of 350 osteoarthritic knees. Clinical and radiographic data were obtained on 188 hospital referred patients (mean age 70, range 34-91 years). RESULTS: Median duration of follow up was two years (range 1-5 years). The majority of patients (48%) reported deterioration, but 23% experienced improvement in symptoms during the study period. Reported exercise tolerance remained unchanged in the majority (62%) and deteriorated in 35%. Change in at least one individual radiographic feature of osteoarthritis was seen in 252 (72%) knees: increase in joint space narrowing occurred in 52%, osteophyte in 32%, cysts in 19%, sclerosis in 14%, and attrition in 30%. Increase in Kellgren grade occurred in 137 (39%) knees. Knee effusion, osteoarthritis at multiple joint sites, and nodal change associated with change in Kellgren grade (odds ratios 1.03, 2.39, and 1.80; 95% confidence intervals (CI) 1.01 to 1.05, 1.16 to 4.93, and 1.02 to 3.17, respectively); warmth at the knee associated with change in any radiographic feature (odds ratio 2.22; 95% CI 1.19 to 4.14). Development of, or increase in, attrition and joint space narrowing associated with worsening symptoms and function and occurred with increased frequency in knees with effusions, clinical warmth and calcium pyrophosphate crystals in synovial fluid (p < 0.05). CONCLUSIONS: A high rate of change, radiographic more than clinical, was seen in osteoarthritic knees during this study. Poor clinical and radiographic outcome associated with calcium pyrophosphate crystal deposition and clinical inflammation as reflected by knee effusion and warmth.

Adult↗

Intra-articular triamcinolone hexacetonide in knee osteoarthritis: factors influencing the clinical response.

OBJECTIVE: To assess the efficacy of a single intra-articular injection of triamcinolone hexacetonide (THA) in knee osteoarthritis (OA) and examine factors which may relate to treatment efficacy. METHODS: Eighty four patients with clinical and radiographic evidence of knee OA were recruited and randomly allocated to receive either THA (20 mg in 1 ml) or placebo (0.9% normal saline, 1 ml). Follow up assessments evaluated the following outcome variables: patient opinion of overall change in the treated knee, visual analogue pain score (VAS), distance walked in one minute (WD), and Health Assessment Questionnaire modified for lower limb function (HAQ). RESULTS: Seventy eight percent of THA and 49% of placebo treated patients reported overall improvement at week 1 (p < 0.05). At week 6, improvement was reported in 57% and 55% of patient groups, respectively. VAS improved in both groups at week 1 (THA, p < 0.001; placebo, p < 0.05) and week 6 (both p < 0.01). Improvement in VAS was significantly greater among THA treated patients at week 1 only (p < 0.01). Subgroup analysis of THA treated patients revealed greater improvement in VAS among patients with clinical evidence of an effusion (p < 0.05), and those who had synovial fluid successfully aspirated at the time of injection (p < 0.01). WD improved in THA treated patients at week 1 (p < 0.001), and in both groups at week 6 (THA, p < 0.001; placebo, p < 0.01). Improvements in HAQ were seen in THA patients only at weeks 1 and 6 (p < 0.05). Regression analysis did not identify any additional clinical, radiographic, or synovial fluid characteristics which influenced the response. CONCLUSIONS: THA provided short term pain relief in knee OA. Increased benefit was associated with both clinical evidence of joint effusion and successful aspiration of synovial fluid at the time of injection.

Administration, Topical↗

Risk factors for ischaemic heart disease and stroke mortality in young and old hypertensive patients.

We investigated the predictors of cardiovascular mortality at different ages in a longitudinal study of 10186 hypertensive patients attending clinics in the UK. There were 7374 patients (51% were men) < 60 years of age and 2799 patients (44% men) were > or = 60 years. For IHD death the age-adjusted relative risks (RRs) and 95% confidence intervals (CI) for a 1 mmol/l increase in cholesterol were RR = 1.17 (1.07, 1.27) (men) and RR = 1.22 (1.12, 1.33) (women). The RRs for stroke were 0.99 (men) and 1.07 (women). In men and younger women, urea and smoking were important predictors of IHD and stroke death. Age differences were present in women for both urea and smoking. For IHD in women, smoking: RR = 2.65 (1.80, 3.89) (< 60 years) and RR = 1.38 (1.01, 1.88) (> or = 60 years). For stroke in women, smoking: RR = 2.03 (1.23, 3.35) (< 60 years) and RR = 1.06 (0.70, 1.61) (> or = 60 years). We conclude that urea and smoking are important risk factors for stroke and IHD death in hypertensive women aged < 60 years, but are less important in those aged over 60 years. Cholesterol predicted IHD death in all men and women, but did not predict stroke death.

Adult↗

Six-year follow-up of multiple joint replacement surgery to the lower limbs.

We report a 6-yr follow-up study of an original population of 50 patients who had three or more major joints (hips and knees) replaced. Thirty-one of 32 surviving patients were still ambulant in the community, and all patients described significant pain relief. No RA patient was requiring permanent inpatient or residential care and the family remained the main social support. They remained a very disabled group with a median Health Assessment Questionnaire score of 2.75. Ten required revision surgery: three hips and seven knees; four patients required their fourth lower limb joint (hip/knee) replaced and seven patients required surgery to the upper limbs and nine feet during the follow-up period. The median 10-yr survival of hip and knee arthroplasties in multiple joint replacement (MJR) patients with RA was 90.5 and 78.6% respectively. There was an increased incidence of cervical myelopathy in MJR patients 16.9%. The mortality rate was higher than expected (standardized mortality ratio = 590) but the actual surgery was not implicated. MJR therefore appears to be a worthwhile policy, even at long-term follow-up.

Arthritis, Rheumatoid↗

Primary fibromyalgia syndrome--an outcome study.

Seventy-two patients (65 F, 7 M; mean age 52, range 18-81 years) fulfilling criteria for primary fibromyalgia syndrome (PFS) were reviewed at a mean of 4 years (range 1.5-6) following diagnosis. Ninety-seven per cent still had symptoms typical of PFS (60% worse, 26% better than at presentation); 85% had multiple hyperalgesic tender sites and still fulfilled criteria for PFS; 8% had more limited, and 7% had no tender sites at review. Many had significant disability (median score 1.0, range 0-2.75, on the Health Assessment Questionnaire; median 2, range 1-3 on the Steinbrocker index) and 92% scored highly (> 12) on the Hospital Anxiety and Depression index. In no patient did screening investigations reveal development of inflammatory, metabolic, endocrine or muscle disease. This study confirms a poor outcome for PFS patients and association with often marked functional disability and high levels of anxiety and depression. Contrary to one previous study there was no evidence that PFS predates the onset of other disease.

Adolescent↗

Radiographic progression of hospital referred osteoarthritis of the hip.

Various factors have been considered important in the rate of progression of osteoarthritis of the hip, though few data are available from large longitudinal studies. One hundred and thirty six patients referred to hospital (85 women, 51 men; mean age 65 years, range 29-86 years) with osteoarthritis of the hip (192 affected hips) were followed up for a median of 27 (range 3-72) months. One hundred and six patients (144 affected hips) were reviewed for a minimum of one year (median 28, range 12-72 months). Fifty three per cent of all osteoarthritic hips required an operation at a median of 14 (range 3-48) months from entry. All radiographs before and after entry were examined (median four films for each patient over a median of three years, range 0.5-19 years). Hips showing rapid radiographic progression on prospective films more often had superior migration, or an atrophic bone response; those with no progression more often had an indeterminate, medial, or axial migration pattern, protrusio or mild osteoarthritis at presentation. A higher occurrence of rapid progression was seen in women, in those of older age at symptom onset, and in hips with a higher Kellgren grade at entry; men more often showed no progression. Age at presentation, body mass index, symptom duration, or presence of chondrocalcinosis, hand osteoarthritis/nodes, or Forestier's disease did not influence progression. This study supports the contention that, at the time of hospital referral, certain patient characteristics and radiographic features at the hip may help to identify those at high risk of rapidly progressive hip osteoarthritis.

Adult↗

Radiographic patterns and associations of osteoarthritis of the knee in patients referred to hospital.

OBJECTIVES: To investigate differing patterns and associations of osteoarthritis of the knee in patients referred to hospital. METHODS: Two hundred and fifty two consecutive patients (161 women, 91 men; mean age 70 years, range 34-91 years) referred to hospital with osteoarthritis of the knee underwent clinical, radiographic, and synovial fluid screening. RESULTS: Radiographic changes of osteoarthritis of the knee (definite narrowing with or without osteoarthritic features) were bilateral in 85% of patients. Of 470 knees affected, 277 (59%) were affected in two compartments and 28 (6%) in three compartments. Unilateral and isolated medial tibiofemoral osteoarthritis were more common in men. Calcium pyrophosphate crystal deposition was common (synovial fluid identification in 132 (28%) knees; knee chondrocalcinosis in 76 (30%) patients) and associated with disability, bilateral, multicompartmental and severe radiographic osteoarthritis, marked osteophytosis, attrition, and cysts. Multiple clinical nodes (58 (23%) patients) and radiographic polyarticular interphalangeal osteoarthritis (66 (26%) patients) were associated with a higher frequency of inactivity pain, disability, multicompartmental and severe radiographic change. Forestier's disease predominated in men but showed no other associations. CONCLUSIONS: In a group of patients referred to hospital osteoarthritis of the knee is usually bilateral and affects more than one compartment. Severe and multicompartmental radiographic changes are associated with calcium pyrophosphate crystal deposition, nodal change, and polyarticular interphalangeal osteoarthritis.

Adult↗

Radiographic assessment of patellofemoral osteoarthritis.

OBJECTIVES: To determine the feasibility of assessing patellofemoral osteoarthritis using the 'skyline' view and to compare its reproducibility with the standard lateral view. METHODS: Fifty patients attending a rheumatology outpatient department with osteoarthritis of the knee had standard radiographs taken of both knees: standing weightbearing anteroposterior; lateral supine radiograph in 30 degrees of flexion; and a skyline view of the patellofemoral joint. After an initial training period using 20 sets of films the remaining 30 sets were read blind by five observers. Intraobserver and interobserver variability was assessed using the kappa statistic. The minimum joint space in each compartment was measured using a ruler. Two views of a single normal subject were measured to determine the effect of knee flexion. RESULTS: The final 30 study films were from 20 women and 10 men, median age 72.5, range 18-91 years. A grading system comprising assessment of osteophytosis, joint space narrowing, sclerosis, cysts, and attrition could easily be applied to the skyline patellofemoral view. Intraobserver reproducibility was better than the interobserver reproducibility for all features. The skyline view performed more reproducibly and over a wider range of categorisation for joint space narrowing than the lateral radiograph. Measurement using a ruler was easy to perform and precise to within 1 mm for the medial tibiofemoral and lateral facet of the patellofemoral joint. In normal knees the degree of flexion significantly affected the measurement. CONCLUSIONS: Radiographic grading of the skyline patellofemoral view is readily achieved, is more reproducible than assessment of the lateral view, and allows more precise localisation of change. Such views should be considered in radiological surveys of osteoarthritis of the knee.

Adolescent↗

Radiographic patterns and associations of osteoarthritis of the hip.

A number of patterns of osteoarthritis of the hip are described, though studies are conflicting with respect to the frequency of such patterns and their associations. Two hundred and eleven patients (133 women, 78 men; mean age 66 years, range 29-86) referred to hospital with osteoarthritis of the hip were studied. Involvement was unilateral in 108 (51%) and bilateral in 89 (42%); 14 (7%) had undergone arthroplasty and were presenting with osteoarthritis hips). Sixty one per cent of hips had severe, 28% moderate, and 11% mild changes (Kellgren grade). Superior pole migration occurred in 82% (46% superolateral, 25% intermediate, 11% superomedial), medial/axial migration occurred in only 8%, and in 10% the pattern was indeterminate. In bilateral osteoarthritis of the hip the pattern was generally symmetrical. Superomedial and medial/axial patterns were proportionately more common in women, whereas superlateral osteoarthritis predominated in men. No association was found between multiple clinical nodes, radiographic polyarticular interphalangeal or first carpometacarpal osteoarthritis and any migration pattern. Any interphalangeal osteoarthritis was negatively associated with medial migration. Only 40% of hips could be categorised as hypertrophic or atrophic; chondrocalcinosis at any site was associated with atrophic osteoarthritis; no associations were seen with Forestier's disease. This large survey confirms the association between chondrocalcinosis and atrophic osteoarthritis of the hip. Importantly it suggests that gender, rather than associated osteoarthritis at other sites, is a major determinant of the pattern of osteoarthritis of the hip.

Adult↗

A proposed minimal rheumatological screening history and examination. The joint answers back.

We have developed a rapid, reliable locomotor screening procedure to identify regional locomotor problems. An initial screen was tested in general medical inpatients and modified in the light of this experience. The revised screen was subsequently retested in a similar group of patients and new referrals to a rheumatology outpatient clinic. The revised screen proved sensitive, quick, and acceptable to both patients and doctors. Such a screen could readily be adopted by undergraduates: its routine use should improve detection and awareness of rheumatological problems and form the foundation for development of rheumatological clinical skills.

Adult↗

Hydroxyurea-induced acute alveolitis in a patient with chronic myeloid leukaemia.

A number of cytotoxic agents have been implicated in the production of widespread pulmonary alveolar damage. We present a case of life-threatening alveolitis in a patient on hydroxyurea for chronic myeloid leukaemia. The clinical course suggests that the alveolitis was induced by the hydroxyurea. This is the first reported case of hydroxyurea-induced pulmonary alveolitis.

Aged↗