The inflammatory component of mechanical back problems.
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Biomedical subjects
Publications and source records attributed to M I Jayson.
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The collagenolytic enzyme systems in the human, normal, and prolapsed intervertebral discs have been studied. Normal discs obtained postmortem contained a novel collagenase with specificity toward Type II collagen and gelatin but with little or no activity against Type I collagen. A method whereby enzymes are detected quantitatively in extracts of human tissue using specific substrates, without prior chromatographic separation of the enzymes, has been developed and used to study 14 normal discs and 35 surgically excised prolapsed discs. No differences were observed between annulus and nucleus extracts of normal discs either in the pattern of enzymes or the quantity. The intermediate zone between nucleus and annulus was excised and was not tested. Highly significant differences were observed between the enzyme patterns of the normal and prolapsed discs. The major collagenolytic activity of normal discs is against Type II collagen and 1 alpha 2 alpha 3 alpha collagen, there is little activity toward Type I collagen and virtually none toward elastin. Conversely, the prolapsed disc is more highly active against the substrates elastin and Type I collagen than against Type II collagen or 1 alpha 2 alpha 3 alpha collagen. The individual patterns of enzymes of the 35 prolapsed discs were virtually identical. Similarly there was little internal variation between the patterns of enzymes extracted from discs, obtained postmortem, which were apparently normal. The striking difference between the normal and prolapsed disc could be an important factor in the pathogenesis of disc prolapse.
The families of 65 patients with systemic sclerosis were examined clinically and serum samples from each subject were tested for antinuclear antibodies (ANA) by immunofluorescence on HEp2 cells and for precipitating antibodies to soluble cellular antigens including Scl-70. Of 217 blood relatives, 58 (27%) had ANA (42 speckled, 13 nucleolar, one centromere, two homogeneous); 22 (10%) had precipitins, one anti-Scl-70, one anti-PM-Scl, one anti-nRNP, two anti-Ro(SSA), the remainder unidentified). Family members tended to share ANA patterns. Of 38 spouses, nine (24%) had ANA (all speckled) and two showed unidentified precipitins. This compares with an incidence of ANA and precipitins in a control population of 8% and 1% respectively. Antibodies were more common in female than male relatives (particularly in mothers and sisters of probands). Twenty one of the 58 family members with ANA had clinical features of connective tissue disease; the remainder were asymptomatic. The presence of genetic factors influencing autoimmunity is suggested by the incidence of autoantibodies in first degree relatives. Similar observations in spouses, however, indicate that environmental factors may also have a role in these immune abnormalities.
The effect of a glucocorticoid on protein synthesis in human polymorphonuclear leucocytes (PMNLs) was investigated by two-dimensional gel electrophoresis. In the peripheral blood PMNLs of healthy laboratory personnel, the rate of incorporation of L-[35S]methionine into a least nine polypeptides was consistently influenced by dexamethasone in a dose-dependent manner, being increased in the case of seven polypeptides and decreased in the remainder.
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Plasma concentrations of [met]enkephalin (ME) and beta-endorphin (beta E) were measured in samples obtained immediately before and after physiotherapeutic exercises for patients with ankylosing spondylitis (AS), osteoarthritis (OA), or knee injuries. Correlations were sought between opioid peptide concentrations or changes therein, and nature, severity and duration of disease, age, severity of pain reported and pain threshold. No correlation was found with any of the pain parameters. However, there was a possible relationship between age or duration of disease and changes in ME concentrations.
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Ketanserin, 40 mg b.i.d., or matching placebo were administered for 8 weeks each in a randomised double-blind crossover design to 23 patients with Raynaud's phenomenon. Ketanserin had no effect on Doppler arterial patency or blood flow at rest, 37 degrees C, 15 degrees C, or during recovery after cold challenge. Red cell deformability index and whole blood viscosity were not significantly affected by ketanserin treatment. In vivo bleeding time was prolonged on ketanserin (p less than 0.05) but beta-thromboglobulin and platelet factor 4 were unaffected. There was a nonsignificant decrease in platelet aggregation response to serotonin but no change at all with other aggregating agents on treatment with ketanserin.
Parotid and submandibular gland secretions collected from patients with rheumatoid arthritis or systemic sclerosis have been analysed and the results compared with those obtained from a matched group of healthy individuals. Flow rates were measured and the saliva samples assayed for amylase, kallikrein, protein, and salivary IgA concentration. The results showed that only patients with rheumatoid arthritis had a reduced salivary flow, especially parotid flow, with a significantly increased concentration of salivary IgA in both parotid and submandibular saliva. Patients with systemic sclerosis did not show significantly altered salivary flow rates, but there was a marked depletion of salivary IgA content in both parotid and submandibular saliva. Neither disease states appeared to alter the kallikrein or amylase content of saliva. The possible clinical value of these findings is discussed.
Blood fibrinolytic activity was measured in 18 subjects with severe chronic back pain and 18 age and sex matched controls. The patients showed evidence of defective fibrinolysis--namely, significant prolongation of the euglobulin clot-lysis time, reduction in fibrin-plate lysis-area and plasminogen levels, and increase in levels of the fibrinolytic inhibitors, alpha 2 antiplasmin and alpha 2 macroglobulin. This defect could be associated with fibrin deposition and scar formation and be responsible for the development and/or perpetuation of chronic inflammation and scarring at sites of damage in the spine. Enhancement of fibrinolytic activity may offer a new approach to the management of these back problems, and a double-blind controlled trial is in progress.
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A 10-year study of the management of rheumatoid arthritis was conducted to compare a programme consisting of rest and anti-inflammatory and antirheumatic drugs with one consisting of maintenance of activity, anti-inflammatory and antirheumatic drugs, and systemic steroids where necessary. During this period subjects who did not respond to the treatment allocated went on to a combined treatment programme of rest, anti-inflammatory and antirheumatic drugs, and steroids. Among those who remained in the trial for the 10 years, there was little difference between the two groups in morning stiffness, number of inflamed joints, functional capacity, grip strength, number of American Rheumatism Association criteria present, and whether they remained on their original treatment programme or switched to the combined programme. However, in those who started in the steroid group, the condition of several joints tended to be better clinically and radiologically than in those of the other group during and at the end of 10 years of the original treatment programme, at time of transfer to the combined programme, and at the completion of the combined programme. Both groups had as many complications of disease and treatment, and adverse effects attributable to steroids seemed to be restricted to those with severe disease who had not responded to their original programme. A policy of maintaining physical activity plus the judicious use of steroids where required produces, in the long term, results as good as or probably better than a regimen of bed rest and no steroids.
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Human umbilical vein endothelial cells grew equally well in sera from scleroderma patients and in sera from rheumatic controls. Using two independent methods of assessing cell growth, no evidence of a previously described endothelial cell cytotoxic factor could be found in heat inactivated sera from 23 scleroderma patients. The system used was sensitive in detecting growth inhibition due to five batches of foetal calf serum and low concentrations of homocysteine and 2-mercaptoethanol.
Intraperitoneal injection of pristane induced a clinical peripheral arthritis and/or tenosynovitis in 40% of 40 Balb/cJ/Ola mice. Hind paws were always affected first and fore paws were frequently involved. Involvement of knee joints was only apparent histologically. Some clinically unaffected animals and apparently uninvolved joints from arthritic mice were also shown to have a synovitis histologically. The time of onset and pattern of arthritis was variable. The development of arthritis was not related to plasmacytoma or ascites induction, which occurred in a similar percentage of mice over a similar period. The earliest change was synoviocyte hyperplasia and polymorphonuclear infiltration in the subintima. There was no obvious mononuclear cell infiltration. In the later stages there was erosion of cartilage and sclerosis of underlying bone. These features resemble the joint changes seen in osteoarthritis.
Studies of both intensity and Doppler shifted linewidths of light scattered from skin tissue have been made using photon correlation spectroscopy and optical fibre techniques. Measurements as a function of the separation of input and detecting fibre positions show characteristic features. These features are interpreted in terms of the positions of the scattering red blood cells and the tissue structure. Evidence is given for an interpretation of the differences in the scattered light for scattering from superficial vessels including capillary loops and from deeper lying larger vessels and shunts. Measurements using various laser wavelengths are discussed. The results of this study are important in the development of laser light scattering instruments for the measurement of peripheral blood flow and microcirculation.
The HLA antigens were determined in 54 Caucasoid patients with scleroderma (ARA criteria). All were assessed for extent of skin and organ involvement, anticentromere (ACA), and scleroderma 70 (Scl 70) antibodies. The antigens DR1, DR3 and DR5 were raised in the patient group, and DR2 was lowered. Of these only the increase in DR5 was significant (chi 2 = 5.2; p = 0.02). The increased frequency of DR3 was attributable to a rise in the A1, B8, DR3 haplotype (chi 2 = 3.9; p = 0.05). Patients with non-diffuse disease showed a significant increase in the DR1 and DR5 antigens (chi 2 = 3.7, p = 0.05; chi 2 = 8.0, p = 0.01). No association was found between the HLA antigens and specific organ involvement. Anticentromere antibodies were present in 15 of the HLA-DR typed patients. Thirteen of these 15 patients were either DR1 or DR5. No relationship was found between the frequencies of HLA antigens and anti-Scl 70 antibodies.