Adjuvant arthritis 50 years on: The impact of the 1956 article by C. M. Pearson, 'Development of arthritis, periarthritis and periostitis in rats given adjuvants'.

The Science Citation Index (Web of Science) has now accumulated over 700 citations to this report published in Proc Soc exp Biol Med 1956; 91: 95-101, including several in 2006. This memoire is a tribute to its author for revealing the opportunities for so much subsequent research in experimental pharmacology and toxicology. For half a century, the adjuvant disease in rats has enormously aided research on drugs to control arthritis and other chronic inflammatory disorders. The adjuvant also triggers many systemic responses beyond the articular tissues. So we are given simultaneously a window to explore the converse phenomenon: namely, how a chronic disease can affect drug efficacy and toxicity. This phenomenon has been variously described as patho-pharmacodynamics, conditional pharmacology/toxicology and 'a right nuisance' ! Nevertheless it has enormous heuristic value for clinical therapeutics.

[Features of occupational fluorosis course]. / Osobennosti techeniia professional'nogo fliuoroza.

Analysis of X-ray signs in 397 patients suffering from fluorosis revealed degenerative and dystrophic lumbar disorders in 94%, calcified anterior longitudinal ligament in 65%, various changes (epicondylosis, periarthrosis and arthrosis deformans) in 91%. Locomotory disorders appeared systemic, multiple and symmetrical.

Recovery process of arthritis induced by 6-sulfanilamidoindazole (6SAI) in rats.

6-Sulfanilamidoindazole (6SAI) is known to induce not only an acute arthritis but also serositis and arteritis which resemble those induced by some vasodilators in rats. In this study, the recovery process of ankle lesions was examined histopathologically for up to 12 weeks of recovery period in rats bearing arthritis induced by administration of 6SAI (500 mg/kg) for 2 weeks. At 2 weeks of 6SAI-treatment, exudative synovitis and exudative/edematous periarthritis with marked formation of granulation tissues and periosteal reactive bone formation were noted in the ankles, but no remarkable neutrophil infiltration was detected in those lesions. The ankle swelling induced by 6SAI diminished by 4 weeks of recovery period, and the elevated plasma fibrinogen levels were normalized by 2 weeks of recovery period. Although fibrosis and newly-formed periosteal bone were still observed after 2 weeks of recovery period, no inflammatory lesion was detected at that point. At 4 or 12 weeks of recovery periods, the ankles showed an almost normal appearance. These results indicate that 6SAI-induced arthritis is reversible in nature and does not develop into chronic phase.

Periarthritis promotes gait disturbance in zymosan-induced arthritis in rats.

OBJECTIVE AND DESIGN: We studied the contribution of periarthritis and synovitis to gait disturbance in zymosan (Zy)-induced arthritis. METHODS: Sixty Wistar rats were subjected to injection of Zy (1 mg) into their right knee joints. A first group of animals (GI) had Zy injected through the intact skin. A second group (GII) had Zy injected directly into the articular cavity after excision of the skin and subcutaneous tissue surrounding the joint. Gait disturbance was evaluated using the rat-knee joint incapacitation test. Increase in vascular permeability and cell influx were assessed in joint fluids and joint histology was performed. RESULTS: Zy injection induced a dose-dependent gait disturbance which was maximal at the third/fourth hour of arthritis, being significantly greater in GI rats, whereas cell influx (neutrophils > or = 80%) was maximal at the sixth hour. Cell influx and increase in vasopermeability did not differ between both groups. Histology revealed no significant difference between GI and GII. A third group (GIII), subjected to immune-complex arthritis, that received anti-bovine serum albumin (BSA) antibodies intra-articularly and BSA i.v., did not present gait disturbance, despite the increase in cell counts. CONCLUSIONS: Vascular permeability increase and cell influx are phenomena independent of gait disturbance. Neutrophils do not seem to contribute to development of gait disturbance in Zy arthritis. Sensitization of specific pain receptors in periarticular rather than in synovial tissue is responsible for gait disturbance in Zy-induced arthritis.

Human recombinant erythropoietin in anaemic patients on maintenance haemodialysis. Secondary effects of the increase of haemoglobin.

Twelve anaemic patients on haemodialysis were treated with recombinant human erythropoietin, starting with 72 IU/kg/week. The dose was doubled after 2 weeks until an increase of 2 g/dl of haemoglobin was observed. The effects on various parameters were studied during a 3-month period. Haemoglobin increased from 6.70 +/- 0.74 to 10.49 +/- 1.04 g/dl (mean +/- SD, P less than 0.001), potassium from 5.51 +/- 0.50 to 6.06 +/- 0.65 mmol/l (P less than 0.005), phosphate from 1.78 +/- 0.40 to 2.17 +/- 0.40 mmol/l (P less than 0.001) and the calcium phosphorus product from 4.3 to 5.2 (P less than 0.001). Three patients developed marked periarticular inflammation due to calcified deposits with a high calcium-phosphorus product of 6.8. An increase in arterial blood pressure was observed in three previously well-controlled hypertensive patients, one of whom developed hypertensive encephalopathy. We conclude that recombinant human erythropoietin is very effective in treating the anaemia of end-stage renal failure on haemodialysis. Regular estimations of serum potassium and phosphate are mandatory. In hypertensive individuals a further increase in blood pressure is possible.

Apatite-associated arthropathy: a clinical study of 14 cases and of 2 patients with calcific bursitis.

Fourteen cases of acute calcific periarthritis and 2 cases of acute calcific bursitis are described. All patients had radiologic periarticular calcific deposits. Synovial fluid was available from 8 patients. Hydroxyapatite crystals were positively identified in 1 by x-ray diffraction analysis and by scanning and transmission electron microscopy. Apatite-associated arthropathy likely represents a form of crystal-induced inflammation. Three articular syndromes can be recognized; acute calcific periarthritis, acute (calcific) arthritis and a subacute-to-chronic arthritis resembling osteoarthritis. To improve patient classification, diagnostic criteria are proposed.

A musculoskeletal syndrome in intravenous heroin users: association with brown heroin.

During a recent 5-month period, 16 intravenous heroin users were hospitalized with a previously unrecognized complication of drug abuse. The characteristic symptoms were similar in all patients and included fever, paraspinal myalgias, and periarthritis. There was no evidence of bacterial infection, hepatitis, or drug abstinence as the cause of these musculoskeletal symptoms. Continued heroin use was associated with progressive musculoskeletal symptoms, while discontinuation of heroin use resulted in complete recovery. Antibiotics did not affect the outcome, and the syndrome was self-limited in all hospitalized patients. The pathogenesis of this syndrome is unknown but may be related to the heroin, which was described as brown by the patients, or an adulterant.

6-Sulfanilamidoindazole arthritis of the rat: complement activity and sulfhydryl group concentration of the serum in three different phases of inflammation.

In 6-sulfanilamidoindazole (6-SAI) arthritis the total haemolytic complement activity of the serum was significantly increased by 69% in developing arthritis at day 4, and by 42% in fully developed arthritis at day 8. In declining arthritis at day 12, 5 days after the last administration of the prophlogistic agent 6-SAI, no difference of the serum complement activity between arthritic rats and non-arthritic controls could be determined. The serum SH group concentration was significantly decreased by 31% at day 4 and by 54% at day 8, but it was nearly normalized at day 12. There was no close correlation between increase of paw diameter and serum complement activity in 6-SAI-arthritic rats. It is suggested that investigations on the role that complement components might play in 6-SAI arthritis could be interest.