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Biomedical subjects

J Highton

Publications and source records attributed to J Highton.

65 records · Page 4Linked to original sources

Fall in immune complex levels during gold treatment of rheumatoid arthritis.

Prior to starting gold treatment 30 patients with rheumatoid arthritis had an elevated mean level of circulating immune complexes measured by Clq binding activity. Gold treatment led to an improvement in disease reflected by significant falls in erythrocyte sedimentation rate (p less than 0.001), C-reactive protein (p less than 0.01), Ritchie articular index (p less than 0.001), and duration of morning stiffness (p less than 0.05). Concurrently immune complex levels fell, and this change first reached significance after 3 months' treatment (p less than 0.05). Serum Clq binding activity was not related to clinical and laboratory measurements of joint inflammation. This suggested to us that there is no direct immunopathological relationship between circulating immune complexes and joint inflammation in rheumatoid arthritis. Serum Clq binding activity was strongly related to IgM-RF levels measured at latex titre (r - 0.7, p less than 0.001). Removal of immune complexes from serum with Sepharose 4B-staph A (staphylococcal protein A) led to a fall in IgM-RF from 2 mg/ml (2 g/l) to 0.4 mg/ml (0.4 g/l). This suggests that the reason for the relationship between Clq BA and IgM-RF is that, on average 80% of serum IgM-RF exists as part of immune complexes containing IgG.

Adult↗

Improvement in peripheral blood lymphocyte response to concanavalin A and pokeweed mitogen during gold treatment of rheumatoid arthritis.

Peripheral blood lymphocyte mitogen responsiveness was studied in 21 patients with rheumatoid arthritis being treated with sodium aurothiomalate. There was a significant increase in lymphocyte response to concanavalin A and pokeweed mitogen but not to phytohaemagglutinin. This observed increase in lymphocyte response contrasts with the suppressive effect of gold salts in vitro. We propose that this apparent contradiction may be explained by the relatively low serum gold levels measured in our patients, compared with expected levels in synovial membrane. Thus gold could suppress rheumatoid inflammation in the "target tissue" while having little suppressive action in the peripheral blood compartment, where a removal of suppressive influences due to active disease might then be seen as a net improvement in lymphocyte responsiveness.

Adult↗

Renal impairment and gout.

A study of renal function of 51 patients with gout and an equal number of normouricaemic controls revealed significant differences. A relative impairment of the glomerular filtration rate and urine concentrating ability in the gouty subjects could not be wholly explained on the basis of aging or hypertension. Renal dysfunction was generally mild and was not associated with specific clinical characteristics higher levels of uric acid excretion, or hypertriglyceridaemia. Gout patients excreted urine with a significantly lower pH. This was associated with a relatively high excretion of titratable acid and a deficit of ammonium excretion, which was accentuated by ingestion of an acid load. Urate clearance was significantly reduced in gout, even when expressed as a fraction of the glomerular filtration rate.

Adult↗

Benoxaprofen in the treatment of osteoarthritis--a comparison with ibuprofen.

A double-blind within-patient crossover trial compared the new nonsteroidal antiinflammatory agent benoxaprofen with ibuprofen in the treatment of osteoarthritis in 31 patients. Both benoxaprofen (600 mg once daily) and ibuprofen (400 mg qid) improved measurements of pain, stiffness, range of movement, mobility, patient preference, and overall assessment. However, the improvement was statistically significant only for pain at rest and range of knee movement for both drugs and for range of hip movement (N = 8) for ibuprofen. There was no statistically significant difference between treatments with the 2 drugs. Six patients taking benoxaprofen reported skin irritation on exposure to sunlight.

Adult↗

Multiple epiphyseal dysplasia: a family study.

Three generations of a single family exhibited evidence of multiple epiphyseal dysplasia. The distribution of involvement was entirely consistent with an autosomal dominant mode of inheritance. The family was characterized by premature osteoarthrosis of the hips developing in adolescence or early adulthood. In most patients there were no obvious signs of an underlying anomaly and the diagnosis was not recognized for a long time. Eventual diagnosis of the disorder allowed easy genetic counselling.

Adolescent↗

Hypertension, renal function and gout.

Hypertension was found in 18% of 65 patients with untreated gout, a lower prevalence than that previously reported. The clinical characteristics and renal function of these patients were compared with those of age matched groups of both normotensive gouty subjects and normouricaemic patients. The hypertensive patients had significantly greater body weights than their controls and also had a lower glomerular filtration rate. Other aspects of renal function were not significantly different between the three groups. The association of hypertension with gout and impaired renal function is complicated by many possible contributory factors and a simple cause and effect relationship is unlikely.

Adult↗

A comparative trial of benoxaprofen and naproxen.

A double-blind within-patient trial in rheumatoid arthritis comparing the new anti-inflammatory drug benoxaprofen with naproxen is reported. Patients received naproxen 250 mg b.d. for two weeks and benoxaprofen 200 mg b.d. for three weeks. Both drugs demonstrated efficacy. There was no statistically significant difference between them, except for grip strength which favoured naproxen. Side-effects were mild, infrequent and similar for both drugs. Evidence is presented which confirms the long duration of action of benoxaprofen, a fact which may be of clinical significance.

Administration, Oral↗

A trial of clodronate-liposomes as anti-macrophage treatment in a sheep model of arthritis.

OBJECTIVE: Our previous research has concerned the role of macrophages in joint inflammation in rheumatoid arthritis. We have therefore been interested in liposomes containing clodronate as an antimacrophage treatment for arthritis. We have used the antigen-induced arthritis model in sheep to evaluate the effect of clodronate liposomes. METHODS: Arthritis was induced in the right hock joint (day 0). We were able to demonstrate uptake of liposomes into macrophages within the inflamed joint lining. On day 7, sheep were given a single intra-articular injection of clodronate liposomes (group 1, n = 10) or saline liposomes (group 2, n = 10). A further 6 sheep (group 3) had no arthritis and no treatment. RESULTS: No difference in joint diameter was observed between the sheep in group 1 (clodronate) and group 2 (saline treated). Both groups had joint swelling which persisted until the end of the trial (day 20). Histologic scoring was also similar in group 1 and group 2 animals, and both were worse than group 3. CONCLUSION: In vitro studies have shown that interaction of liposomes with neutrophils and monocytes stimulates a respiratory burst. Despite this possible pro-inflammatory effect we did not observe any increase in joint diameter following liposome injection. Thus we were unable to demonstrate a therapeutic effect of a single dose of clodronate liposomes in this large animal model of antigen-induced arthritis.

Analgesics, Non-Narcotic↗

Non-steroidal anti-inflammatory drugs in combination. Experimental observations.

Diflunisal in combinations with oxaprozin, indomethacin and sodium meclofenamate produced significant synergistic suppression of carrageenan-induced oedema of the rat foot-pad. Oxaprozin, benoxaprofen, indomethacin, diflunisal, sodium meclofenamate and auranofin in some paired combinations but not in others were associated with a greater effect than the component drugs used alone. Antagonism was demonstrated with other combinations of these drugs.

Animals↗

Antigen-induced (Dumonde Glynn) arthritis in the sheep: a large joint animal model of arthritis.

OBJECTIVE: To determine if the Dumonde Glynn model of arthritis can be established in sheep since a larger model would facilitate injection and the measurement of joints. METHODS: Three groups of sheep were immunised with ovalbumin in Freund's adjuvant. Arthritis was induced in group 1 (n = 10, by the injection of 5 mg ovalbumin in 0.5 ml to the right hock joint. Control groups received saline (n = 10) or no treatment (n = 6). RESULTS: Following joint injection the mean AP diameter increased so that there was a 32% difference between the right and left joints at 24 hr (p < 0.001) declining gradually to 12% (p < 0.01) 19 days after the induction of arthritis. The level of haptoglobin in group 1 prior to the induction of arthritis was 0.04 +/- 0.01. Haemoglobin binding capacity (mg/ml) peaked on day 3 at 0.33 +/- 0.13 (p < 0.01), and was 0.110 +/- 0.05 thirteen days after joint injection. Features observed included proliferation of the joint lining, fibrin deposition and early erosion of cartilage. Synovial membrane showed an infiltrate of inflammatory cells identified as monocytes/macrophages and lymphocytes. Synovial histology scores were 1.8 +/- 0.2 for the left joint and 9.3 +/- 0.73 for the arthritic right joint. CONCLUSION: We conclude that this is a model of mono-arthritis particularly useful when a larger joint is required for intra-articular injection or repeated joint measurements such as in a clinical trial.

Animals↗