Thymopentin (TP-5) in the treatment of rheumatoid arthritis.

A randomized control trial of TP-5 in rheumatoid arthritis is reported. In a multicentre study, 76 patients were treated with TP-5 50 mg or placebo three times a week for 3 weeks as a slow intravenous injection, and followed for 7 weeks. Clinical parameters such as the Ritchie index and sum score of swollen joints improved significantly on TP-5 compared to placebo. Laboratory parameters did not change but an increased skin test score to common recall antigens was observed. Toxicity was minimal. TP-5 is a potentially useful agent in the treatment of rheumatoid arthritis, although further studies are required to determine the optimal treatment regimen.

Azathioprine in 50 rheumatoid arthritic patients intolerant or unresponsive to gold or penicillamine.

This is a retrospective review of 50 rheumatoid patients who had experienced side effects with gold and/or penicillamine and who were treated with azathioprine in routine clinical practice. The mean duration of the disease at commencement of azathioprine was 9.4 years; despite attempts to maintain the dose at 2.5 mg/kg.d because of minor side effects the average daily dose was 1.68 mg/kg.d. By one year, 11 (22%) had discontinued the drug due to side effects; 6 (12%) had not improved in any respect, 20 (40%) had a reduction in the total number of active joints with maintenance of function and in 13 (26%) the total number of active joints had been reduced by more than a half. During year 2 a further 4 discontinued therapy for adverse reactions. No further formal analysis has been performed though 31 patients were still on the drug with a mean duration of therapy for a period of 5 years. Ten of these had less than half their originally affected joints still active; this condition was usually associated with a fall in ESR and rise in haemoglobin but this was not invariable.

Glycosylated haemoglobin in rheumatoid arthritis.

Shortened red cell survival has a role in the anaemia of rheumatoid arthritis (RA), but direct measurement of it is difficult. Glycosylated haemoglobin (HbA1) provides an index of red cell life span in normoglycaemic patients, because glycosylation depends on both the concentration of blood glucose and the duration of erythrocyte survival. HbA1 was significantly lower in 30 patients with RA (5.6 +/- 0.7%, mean +/- SD) than in 15 healthy controls (7.3 +/- 0.7%) and 14 patients with osteoarthritis (7.4 +/- 0.7%, p less than 0.001). HbA1 was depressed less in active RA than during remission, which is consistent with diminished red cell production in active RA. These data on HbA1 confirm that shortened red cell survival is common in RA, and point to diminished red cell production in active disease. Determination of HbA1 should prove to be of clinical value in the assessment of normoglycaemic patients with RA but is an inadequate index of glucose homoeostasis in diabetics with RA.

Naproxen and sulindac in the treatment of osteoarthritis of the hip and knee.

Thirty patients with osteoarthritis of the hip or knee were entered into a double-blind, cross-over study of naproxen (750 mg/day) and sulindac (400 mg/day) both given in twice-daily regimens. Patients received each drug for four weeks. Both drugs produced improvements in the patients' overall condition. There were no statistically significant differences between the effects of the two drugs. There were few side-effects. Overall, both drugs proved beneficial and safe.

A double-blind study of benorylate and chlormezanone in musculoskeletal disease.

In a double-blind, cross-over study of 90 patients with degenerative disease of the hip, knee, cervical or lumbar spine, and capsulitis of the shoulder the analgesic drug benorylate (either alone or in combination with chlormezanone, a muscle relaxant anxiolytic drug) favourably modified pain, stiffness, quality of sleep and ability to work. Chlormezanone significantly reduced the number of breaks in sleep. There was no significant difference in the number of patients reporting side-effects on each of the four treatments, but drowsiness occurred significantly more in the chlormezanone weeks. There appeared to be no advantage in adding chlormezanone in patients suffering from osteoarthritis of the hip or knee, lumbar spondylosis or capsulitis of the shoulder, but there was significant improvement in both pain relief and quality of sleep in those patients with neck pain.

A comparative study of Butacote and Naprosyn in ankylosing spondylitis.

A double-blind, cross-over comparison of Naprosyn (naproxen) 750 mg daily and Butacote (enteric-coated phenylbutazone) 300 mg daily was carried out in a multi-centre trial. Twenty-five patients, mostly male and under 40 years of age, were entered. After a 2-week period in which any existing anti-inflammatory drugs were tailed off, patients were entered into the trial and treated for 1 month with each drug. Patients were assessed at 4-weekly intervals. Both drugs significantly reduced morning stiffness. Morning pain and discomfort and wall-tragus distance were also significantly reduced by both drugs during the trial. Results of the Schober test showed improvement during both treatment periods. There were no overall statistically significant differences between the effects of the 2 drugs on objective parameters. However, overall subjective assessment of symptoms showed a greater improvement on Butacote. Treatment preferences by physician and subjective assessment by the patient both favoured Butacote but the difference between the 2 drugs was not statistically significant. Side effects were mostly of a minor nature. One patient had to discontinue the trial, due to indigestion while taking Butacote.

Comparative study of salsalate and aspirin in osteoarthrosis of the hip or knee.

A short-term, double-blind controlled crossover study was carried out in 20 patients with osteoarthrosis of the hip or knee to compare the effectiveness and tolerance of salsalate and aspirin. After a 1-week placebo washout period, patients received either 3 g salsalate per day or 3.6 g soluble aspirin per day for 2 weeks before being crossed over to the alternative treatment. Paracetamol was used as a rescue analgesic. The results of clinical assessments of pain, stiffness and sleep disturbance, using visual analogue scales, showed that salsalate produced a comparable clinical improvement to that with aspirin, and similar serum salicylate levels. Salsalate, however, was significantly superior to aspirin with regard to side-effects and faecal occult blood loss.

Multicentre trial of naproxen and phenylbutazone in acute gout.

Naproxen 750 mg as a single dose followed by 250 mg three times daily has been compared with phenylbutazone 200 mg four times daily for 48 hours followed by 200 mg three times daily for treatment of acute gout in an open study on 41 patients. The drugs were equally effective with few and relatively mild side effects. Naproxen is a useful alternative agent for the treatment of acute gout.

Multi-centre trial of naproxen and phenylbutazone in acute gout.

Naproxen 750 mg as a single dose followed by 250 mg three times daily has been compared with phenylbutazone 200 mg four times daily for 48 hours followed by 200 mg three times daily for the treatment of acute gout in an open study on 41 patients. The drugs were equally effective with few and relatively mild side effects. Naproxen is a useful alternative agent for the treatment of acute gout.

Tolmetin in osteoarthrosis of the hip and knee: double-blind crossover trials.

A double-blind crossover study was carried out in 24 patients with osteoarthrosis of the hip or knee to compare the efficacy of a 1200 mg tolmetin daily dose with a 600 mg daily dose, each given for 2 weeks. Both regimens were well tolerated and appeared to give satisfactory relief of pain, but no differences in response between the two dosages were noted either because the number of patients involved were small or because the methods of monitoring clinical improvement were not sufficiently sensitive. A further double-blind crossover study was carried out in 40 patients to compare the efficacy of 1200 mg tolmetin daily with 150 mg ketoprofen daily, each drug being given for 2 weeks after an initial 1-week period on placebo. Pain was monitored using a visual analogue line technique and significant differences were found between both active and placebo periods. Analysis of the biochemical monitoring of both trials showed statistically significant rises in blood urea for all active treatment periods. There were no concomitant changes in serum creatinine, suggesting this effect to be extra-renal in origin. In general, side-effect incidence was low; 1 patient withdrew from ketoprofen treatment because of weight increase and urine retention.

Azathioprine and penicillamine in treatment of rheumatoid arthritis: a controlled trial.

Sixty-five patients, 33 receiving azathioprine and 32 receiving penicillamine, took part in a one-year, single-blind external-observer trial designed to compare the efficacy and toxicity of these two drugs in the treatment of rheumatoid arthritis. By six months there was a significantly greater rise in haemoglobin and fall in erythrocyte sedimentation rate among those receiving penicillamine, and by one year this difference remained only in the increase in haemoglobin levels. Fifteen patients, 10 on azathioprine and 5 on penicillamine, had to stop treatment because of side effects; 90 single side effects occurred, 48 in those on penicillamine and 42 in those on azathioprine. After one year both drugs were similar in efficacy and toxicity, but longer-term trials are needed. Both drugs were effective.

Large subarticular cysts (geodes) adjacent to the knee-joint in rheumatoid arthritis.

Two patients with rheumatoid arthritis are described, who developed very large bone cysts or geodes adjacent to the knee-joint. The existence of cysts adjacent to joints involved by rheumatoid arthritis is well recognised, but the occurrence of very large cysts is unusual and may present diagnostic difficulties. Possible aetiological factors are discussed.

Adjuvant arthritis in the rat. Distribution of fluorescent material after footpad injection of rhodamine-labelled tubercle bacilli.

Adjuvant disease in the rat may represent a cell-mediated response to tuberculous material disseminated from the original injection site, but previous studies have provided only indirect evidence for this dissemination. In the present experiments tubercle bacilli labelled in vitro with rhodamine isothiocyanate (RITC) were injected into a footpad as Freund's complete adjuvant. Serial studies showed two varieties of fluorescent material in the tissues (1) intracellular and extracellular intact and fragmented bacilli, and (2) amorphous intracellular material. Both types of material were identified in the injected foot and draining lymph nodes. Bacilli were also identified in the contralateral knee joint, peritoneum, pleura, lung, and liver, while amorphous material alone appeared in the spleen. The presence of intact bacilli was confirmed by positive Ziehl-Nielsen staining of the organisms, but the amorphous intracellular material did not stain positively by this method. The use of RITC-labelled organisms considerably reduced the severity of adjuvant disease. Most of the organisms identified in sites distant from the injected limb were not situated within foci of inflammation. Marked differences in processing of the tuberculous material (and lack of dissemination of intact bacilli) were noted when labelled organisms were injected in saline instead of in oil.

Influence of tubercle aggregate size on severity of adjuvant arthritis in the rat.

Incorporation into Freund's complete adjuvant of tuberculous aggregates smaller than 90 mum in size is essential to produce adjuvant arthritis in the rat, and this correlates with a significantly greater degree of cell-mediated immunity to tuberculous antigens produced by small aggregates (smaller than 90 mum), when compared with large (larger than 90 mum) aggregates. This requirement for small aggregates to render Freund's complete adjuvant arthritogenic is not paralleled by detectable differences in antimycobacterial humoral antibody production nor by a size-dependent requirement for a conventional adjuvant effect.