Scintimetric assessment of synovitis activity during treatment with disease modifying antirheumatic drugs.

In a double blind trial of 36 patients with rheumatoid arthritis a new scintimetric method was applied to three comparable patient groups before and after eight months' treatment with levamisole, penicillamine, or azathioprine. Technetium-99m pyrophosphate scintigraphy of both hands was performed on a gammacamera with a computer attached, immediately after the administration of the tracer. The uptake ratio of each proximal interphalangeal (PIP) joint and the mid-half of the adjacent proximal phalanx was calculated from the activity counted for one minute. A scintimetric index was expressed as the sum of eight uptake ratios. This index was higher for each of the three patient groups before start of treatment than that for 10 age matched controls. After eight months of treatment the index, the number of PIP joints with clinical signs of synovitis, and the total circumference of the PIP joints decreased in the penicillamine and azathioprine groups. The scintimetric method reliably reflected local synovitis activity and its changes but, like grip strength and PIP circumference, was not a representative measure of the overall activity of the disease.

The effect of physical training on patients with rheumatoid arthritis: changes in disease activity, muscle strength and aerobic capacity. A clinically controlled minimized cross-over study.

For decades, physical training of rheumatoid arthritis (RA)-patients has been controversial, especially for patients with active disease. The aim of this study was to investigate whether RA-patients could receive graduated training without increasing the activity of the disease. In a controlled cross-over study the effect of graduated progressive training has been evaluated in 18 RA-patients with moderately active disease. The training was performed twice weekly with aerobic conditioning and strength exercises progressing to strenuous exercises over an 8-week period. The design was a crossover project with two groups obtained by minimisation. After training the patients had significantly fewer swollen joints than before. Training of the muscles acting over the swollen joints resulted in more than a 35% decrease in the number of swollen joints. The hemoglobin level increased significantly after the training period. The erythrocyte sedimentation rate, the complement factor C3d, and the number of sore joints remained unchanged. A decrease in the need for medicine was non-significant. From this study it appears that RA-patients with some activity are trainable without aggravating the disease, even in the chronically swollen joints. The rheumatoid arthritis activity decreased with fewer swollen joints and higher hemoglobin level after training.

Acute phase proteins and clinical synovitis activity in patients with rheumatoid arthritis.

A number of laboratory variables, including Hb., ESR and several phase proteins, fluctuated in concord with the clinical signs of synovitis activity in patients with rheumatoid arthritis during a controlled study of 3 disease-modifying anti-rheumatic drugs (DMARD). The correlation between laboratory variables and clinical synovitis was significant in a large patient population but the correlation coefficients were not of such magnitude that any of the laboratory variables reflected clinical synovitis activity in a reliable manner in the individual patients. In patients treated with azathioprine, the response of the Hb, (and consequently of the ESR), was reduced compared to patients given other DMARD. This phenomenon was caused by the bone marrow suppressing effect of azathioprine. However, the effect of azathioprine on the clinical synovitis activity did not differ from that of the 2 other drugs. Similar results were found by reviewing the literature about controlled trials of DMARD. In the present trial the clinical evaluation was performed under optimal conditions. In daily clinical practice the evaluations of the joints may be less than optimal since they may be performed by different rheumatologists with varying experience. Consequently, it may be difficult to do without the unreliable laboratory variables mentioned in the routine assessments of disease activity, unless the quality of routine evaluations of synovitis activity is improved considerably.

Influence of previous gold treatment and other patient variables on outcome of treatment with disease modifying anti-rheumatic drugs (DMARD) in patients with rheumatoid arthritis.

Based on a 2-year controlled double-blind trial of levamisole, penicillamine, and azathioprine (L, P, and A), a computer aided search for predictive factors of outcome was instituted. Already at month 4 several indicators of synovitis activity were able to discriminate between patients staying in the trial for 24 months and patients whose treatment was discontinued before that time. Patients who had previously received gold therapy responded less favourably to L, P, and A than those who had not received gold. This reduction of response was more pronounced in gold resistant patients than in patients whose gold treatment had been discontinued for other reasons. The only phase protein (of several) with a predictive value was haptoglobin. If, after 4 months of treatment, haptoglobin did not normalize, this finding indicated a lack of response to treatment or a deterioration of synovitis activity during the following 4 months. The response to treatment was not influenced by HLA-types, sex, age, or clinical synovitis, disease duration, functional or anatomical aberrations at the start of treatment. The shape of the response curve as reflected by means of monthly measurements of serum-albumin and ESR was not related to disease duration, HLA-types, or previous gold treatment.

Clinical synovitis and radiological lesions in rheumatoid arthritis. A prospective study of 25 patients during treatment with remission-inducing drugs.

The joints of hands and feet of 25 patients (1150 joints) with rheumatoid arthritis were compared, joint by joint, clinically and radiologically, over 2 years of treatment with remission-inducing drugs. Joints with clinical signs of synovitis decreased from 47% to 17% (p less than 0.001), while the number of joints with radiological lesions increased from 23% to 27% (p less than 0.01). Definite radiological progression of bone lesions was seen in 7% of the joints. Joints with clinical synovitis had a higher risk of progressive bone damage than joints without clinical synovitis (p less than 0.001) and joints in which the clinical signs of synovitis persisted during the study had a higher risk of progressing bone lesions than joints in which the clinical synovitis subsided (p less than 0.001). Progressive bone damage was seen more often in swollen joints than in tender joints without swelling or joints without clinical signs of synovitis (p less than 0.001), the difference in radiological progression between the latter two groups being non-significant. Twenty-one per cent of the joints with progressive bone lesions had no clinical signs of synovitis during the period.

Skeletal muscle phosphagen and lactate concentrations in ischaemic dynamic exercise.

Five young males performed dynamic, submaximal contractions to exhaustion with the quadriceps muscle under arterial occlusion. The work load was 14.7 Watt (W). After 10 min rest with intact arterial circulation, the subjects commenced another bout to exhaustion; this process was repeated until a total of 10--16 bouts had been performed. Muscle biopsies were obtained immediately after the second, fifth, eighth, and last bout as well as 30 min after the last bout. The concentrations of adenosine triphosphate (ATP), creatine phosphate (CP), lactate, and glycogen were measured in each sample and some material underwent histochemical analysis. Muscle lactate was highest following the second work bout [22.9 mmol/kg wet weight (ww)] and gradually declined to 7.0 mmol/kg ww by the end of the last bout. CP level was low in all postexercise samples with the exception of a remarkably high CP (11.7 mmol/kg ww) after the last bout. Glycogen utilization tended to parallel muscle lactate levels, the rate of depletion being most rapid initially. Histochemical staining for glycogen depletion revealed that both type I and II fibres were low in glycogen, although type I was depleted most uniformly. In the first work bouts the high lactate and low CP levels in the total muscle could be responsible for the fatigue; none of these factors seem adequate to explain the development of the fatigue experienced in the later work bouts. It is concluded that muscle fatigue in this type of exercise is not related to substrate depletion or accumulation of metabolites, further that the fibre recruitment pattern is determined by the type and relative severity of performed work rather than local metabolic factors.

Adaptation to peripheral muscle training.

Ten healthy subjects underwent a 6-week dynamic exercise program designed to put a high relative load on individual muscle groups while maintaining low central circulatory stress levels. This was done to test the hypothesis that such "peripheral" training could produce skeletal muscle adaptation at low levels of myocardial work. Such a program may be useful in rehabilitating patients whose myocardial disease prevents adequate levels of participation in the traditional types of large muscle training. Strength testing, muscle biopsies and both submaximal and maximal bicycle ergometry were done to assess the effects of "peripheral" training. Heart rate during the training sessions decreased progressively over the 6 weeks (p less than 0.001). Quadriceps strength increased (p less than 0.02) with training as did both quadriceps (p less than 0.03) and gastrocnemius (p less than 0.008) fiber areas. Fiber composition was unchanged. Succinic dehydrogenase concentrations were unchanged while phosphorylase activity decreased in both muscle groups (p less than 0.03). Submaximum and maximum bicycle ergometry results were unchanged with training. The data show that dynamic training of small groups of muscles sequentially can produce significant skeletal muscle adaptation with little central circulatory stress. The effects of "peripheral" training in cardiac patients remain to be determined.