Mechanical properties of wrist extensor tendons are altered by the presence of rheumatoid arthritis.

The in vitro mechanical properties of 14 wrist extensor tendons salvaged at surgery from patients with inflammatory (rheumatoid) arthritis and noninflammatory arthrosis were measured in uniaxial tension and compared. The rheumatoid tendons had higher extensibility at low stresses, lower stiffness in the linear portion of the stress-strain curve, greater rates of stress relaxation, and lower ultimate strengths than did the nonrheumatoid tendons. Differences in tangent modulus, stress remaining at 100 seconds, and ultimate tensile strength were significant at the 95% confidence level. In vivo, mechanically impaired tendons may play an important role in destabilization of the wrist in patients with rheumatoid arthritis.

Validation of a 3D optoelectronic motion analysis system for the wrist joint.

OBJECTIVE: A study was undertaken to determine the experimental accuracy of a non-invasive optoelectonic 3-dimensional tracking system in assessing wrist joint motion. DESIGN: This was an in vivo experimental study involving volunteer subjects performing prescribed wrist motions. BACKGROUND: Current clinical practice does not include routine kinematic analysis for evaluating arthritic disease state, although motion disorders are common. METHODS: Surface markers were applied to 24 subjects assigned two hand postures in a test-retest factorial design for the expected range of motion. The marker positions were measured optoelectronically and using calibrated stereoradiography, to determine the positions of the surface markers and of key bone landmarks. Alignment and motion were compared for the three measurement techniques. Standard kinematic analyses were performed to extract Euler angles and equivalent screw displacement axes for paired postures. RESULTS: The three measurement techniques were highly correlated for wrist flexion-extension. Uncertainties were less than 6 degrees, similar to uncertainties from bone landmark identification errors when implanted markers cannot be used. Measures of motion exhibited higher correlations than those for alignment. Equivalent screw displacement axis orientations had poor intraclass correlations, reflecting sensitivity to coordinate system definitions. CONCLUSIONS: For motion analysis in the wrist in vivo, a non-invasive optoelectronic measurement system is as accurate as stereoradiographic analysis of bone segments.

Femoral fracture mimicking acute arthritis in Down's syndrome.

We describe a 38-year-old white woman with Down's syndrome with a history of chronic arthritis and hyperuricemia who presented with acute left knee pain, patellar tenderness and patello-femoral instability. Findings appeared due to a fracture of the lateral femoral condyle, which responded to conservative therapy with a spica cast. Patellofemoral instability in Down's syndrome can be associated with significant morbidity including femoral condyle fracture. Patients with Down's syndrome who present with acute knee arthritis responding poorly to antiinflammatory agents and other conventional therapy should be assessed for fractures related to patellar dislocation, as treatments for the 2 disorders differ.

Clinical features of osteoarthritis in the elderly.

Osteoarthritis (OA), the commonest form of arthritis, is an important cause of chronic morbidity. Assessment of patients with OA can be improved by the recognition of several patterns with which this disorder can present. When these patterns are delineated by a careful history, physical examination, appropriate radiographs and laboratory tests, it often leads to a more precise diagnosis and ultimately better management of these patients. The standard classification of primary and secondary OA, while useful, should be expanded to include clinically relevant patterns of disease.

Plasmapheresis therapy in rheumatoid arthritis. A controlled, double-blind, crossover trial.

Twenty-six patients with rheumatoid arthritis (average age, 57 years; average duration of disease, 11 years) who were unresponsive to antiinflammatory and slow-acting antirheumatic drug therapy were entered into a controlled, double-blind, crossover study to assess the efficacy of plasmapheresis therapy. All patients received 10 true and 10 sham aphereses as outpatients and continued to take their usual drugs. Twenty patients completed the study, and six were withdrawn--three because of poor venous access. Standard clinical and laboratory measures were assessed by personnel blinded to the therapy administered. Paired t-test analysis of seven clinical measures failed to show significant differences between the true and sham procedures (P = 0.36 to 0.96), although transient, mild improvement did occur during both cycles of apheresis, probably because of a placebo response. Significant reductions in the erythrocyte-sedimentation rate, rheumatoid factor titer, and levels of hemoglobin, IgM, and C3 occurred only with true therapy (P = 0.001, 0.01, 0.03, 0.045, and 0.005, respectively). We conclude that plasmapheresis does not have clinical benefit in chronic rheumatoid arthritis, in spite of impressive laboratory changes.

Efficacy and toxicity of D-penicillamine for rheumatoid disease in the elderly.

The efficacy and the toxicity pattern of D-penicillamine were studied in patients with rheumatoid disease followed up between April 1975 and March 1979. The population of patients was divided into an elderly group (greater than or equal to 60 years old, mean = 65 years) and a younger group (less than 60 years old, mean = 41 years). Patients with classic or definite rheumatoid disease not responsive to nonsteroidal drugs were eligible. The mean durations of disease prior to D-penicillamine therapy were five years in the elderly and seven years in the younger group. Overall, the mean follow-up time was 11 months. The average dosages of D-penicillamine were 461 mg/day in the elderly and 520 mg/day in the younger patients. Results indicated that D-penicillamine was efficacious in 75 per cent of the elderly during all time periods after three months, and in 75 per cent of the younger patients after three months until at least two years. Prior gold-salt therapy did not influence efficacy. Toxicity was significantly greater in the elderly for overall skin rash (P less than 0.01), severe skin rash (P less than 0.01), and marked abnormalities in the ability to taste (P less than 0.05). The incidence of hematologic toxicity was not increased in the elderly compared with the younger patients. Toxicity in either group was not influenced by prior gold-salt therapy. It is concluded that D-penicillamine was equally efficacious in both elderly and younger groups, and that the toxicity patterns were similar except for increased tendencies toward rashes and taste abnormalities in the elderly.

The toxicity pattern of D-penicillamine therapy. A guide to its use in rheumatoid arthritis.

One hundred and one patients with rheumatoid arthritis were followed prospectively to assess the efficacy and toxicity of therapy with D-penicillamine. After a mean total followup of 11.5 months (38 patients have completed 2 years of followup) there was a 70% overall improvement rate with 2 complete remissions. Sixty-one patients developed 84 separate toxic reactions, 36 of which required drug withdrawal. Skin rashes (27/84), proteinuria (15/84), low platelets (14/84), and taste abnormalities (10/84) were the most common side effects of therapy at a mean D-penicillamine dose of 463 mg/day. The majority of toxic reactions (85%) occurred in the first 6 months, but proteinuria and thrombocytopenia were more common in the 6 to 12 month treatment period. Previous gold toxicity was a risk factor for developing D-penicillamine toxicity (10/13). Our observations suggest that D-penicillamine related toxicity is a major problem even at 500 mg/day, but the drug can be used with an increased safety margin after 9 months of continuous therapy.

Leucapheresis in severe rheumatoid arthritis.

Two patients with severe seropositive rheumatoid arthritis previously unresponsive to conventional therapy have been treated with leucapheresis. This technique involves continuous cell separation daily to remove primarily lymphocytes. Clinical improvement was recorded with the use of standard rheumatological measures of inflammation. It is concluded that leucapheresis may help in the management of severely active rheumatoid arthritis when conventional therapy has been unsuccessful.

HLA B27 in rheumatoid factor-negative polyarthritis.

Eighty-three consecutive patients with rheumatoid factor-negative polyarthritis seen during a 1-year period were evaluated clinically, radiologically, and with the B27 test. Patients with definite spondylitis, juvenile chronic polyarthritis, a collagen disease, a known metabolic arthropathy, or primary generalized osteoarthritis were excluded. The patients could be classified into two groups independent of any knowledge of B27 testing. Twenty-five had a spondylitic "variant" syndrome. These could be diagnosed on clinical grounds, and included a male preponderance and a high frequency of B27 positivity. Fifty-eight patients, who could generally be classified by American Rheumatism Association criteria as having definite or classic rheumatoid arthritis, included a female preponderance and a normal prevalence of B27. Thus the B27 test was not more helpful than clinical diagnosis in the classic spondylitic variant syndromes, nor did it separate out a population of patients from among the seronegative rheumatoid arthritis group.

Azathioprine in early rheumatoid arthritis. Comparison with gold and chloroquine.

This study compares the effect of azathioprine with those of gold and chloroquine in early (Class II) rheumatoid arthritis (RA). Thirty-three similar patients with classic or definite RA of less than 5 years duration were randomly entered, 11 into each drug group. Assessment of standard clinical and laboratory measures at 12 and 24 weeks showed significant improvement in all three groups. In general, all three drugs were effective antirheumatic agents with low toxicity. However, because of serious potential toxicity, azathioprine could not be recommended over gold and chloroquine in early RA therapy.

Hip involvement in ankylosing spondylitis.

Hip involvement in ankylosing spondylitis (AS) is a common and disabling problem. The clinical and x-ray records of 87 patients with definite AS (Rome criteria) were examined to define and characterize their hip disease. Clinical hip disease was present in 33 cases (38%), was usually bilateral (91%), and tended to begin early in the disease course; it was the cause of 50% of the Class III and IV disability in the entire study group. Typical findings included regional pain, limitation of motion, muscle atrophy, and flexion contractures. Radiologic hip abnormalities occurred in 42 cases (48%). The radiographic pattern was distinctive when compared to that in two control groups and included axial migration of the femoral head (63%), concentric joint space narrowing (50%), rufflike femoral osteophytosis (36%), and protrusio acetabuli (30%). Eight patients required bilateral hip surgery. Para-articular ossification occurred in 8 of 16 replaced hips; in 5 of 8 hips it caused clinical immobility. This potentially serious complication may limit the usefulness of hip arthroplasty in some AS patients.

Clinical and radiographic "reankylosis" following hip surgery in ankylosing spondylitis.

Eleven patients with ankylosing spondylitis underwent reconstructive hip surgery (21 hips). In 10 of these hips multiple surgical procedures had been performed. The final procedure included total hip arthroplasties (16 hips), femoral cup arthroplasties (four hips) and an Austin-Moore prosthetic replacement (one hip). A clinical and radiographic evaluation in the postoperative period revealed a high incidence of decreased joint motion and heterotopic ossification. Clinically moderate to severe restriction of motion was noted in 12 hips, and in six of these "reankylosis" was present. Radiographically moderate to severe new bone formation was seen in 11 hips, and in nine of these "reankylosis" was suggested. An association of excessive ossification and multiple surgical procedures was evident. It would appear that when the prime indication for hip surgery in patients with ankylosing spondylitis is restricted motion, the operation may not be beneficial.

Clinical and radiographic abnormalities in ankylosing spondylitis: a comparison of men and women.

A clinical and radiographic study of 98 patients with definite ankylosing spondylitis (Rome criteria) was undertaken to evaluate differences in men and women with the disease. Clinical manifestations which were atypical in the 18 female patients when compared to those of the men included older age of disease onset, higher incidence of initial and subsequent peripheral joint disease, more common cervical spine symptomatology, and milder disease course. Radiographic differences in the women included a high incidence of cervical spine abnormalities, a combination of cervical spine and sacroiliac joint alterations with a normal intervening thoracic and lumbar segment, and frequent and severe osteitis pubis.

Hypoxanthine-guanine phosphoribosyltransferase. Characterization of a mutant in a patient with gout.

The mutation in a young gouty male with a partial deficiency of hypoxanthine-guanine phosphoribosyltransferase has been evaluated. The serum uric acid was 11.8 mg/100 ml, and the urinary uric acid excretion was 1,279 mg/24 h. Erythrocyte hypoxanthine-guanine phosphoribosyltransferase was 34.2 nmol/h/mg, adenine phosphoribosyltransferase was 36.5 nmol/h/mg and phosphoribosylpyrophosphate was 2.6 muM. Hypoxanthine-guanine phosphoribosyltransferase from peripheral leukocytes and cultured diploid skin fibroblasts was within the normal range, but enzyme activity in rectal mucosa was below the normal range. Initial velocity studies of the normal enzyme and the mutant enzyme from erythrocytes with the substrates hypoxanthine, guanine, or phosphoribosylpyrophosphate showed that the Michaelis constants were similar. Product inhibition studies distinguished the mutant enzyme from the normal enzyme. Hyperbolic kinetics with increasing phosphoribosylpyrophosphate were converted to sigmoid kinetics by 0.2 mM GMP with the mutant enzyme but not with the normal enzyme. The mutant erythrocyte hypoxanthine-guanine phosphoribosyltransferase was inactivated normally at 80 degrees C and had a normal half-life in the peripheral circulation. The mol wt of 48,000 was similar to the normal enzyme mol wt of 47,000. With isoelectric focusing, the mutant erythrocyte enzyme had two major peaks with isoelectric pH's of 5.50 and 5.70, in contrast to the isoelectric pH's of 5.76, 5.82, and 6.02 of the normal isozymes. Isoelectric focusing of leukocyte extracts from the patient revealed the presence of the mutant enzyme. Cultured diploid fibroblasts from the propositus appeared to function normally, as shown by the inability to grow in 50-100 muM azaguanine and by the normal incorporation of [14C]hypoxanthine into nucleic acid. In contrast, erythrocytes from the patient displayed abnormal properties, including the increased synthesis of phosphoribosylphyrophosphate and elevated functional activity of orotate phosphoribosyltransferase and orotidylic decarboxylase. These unique kinetic, physical, and functional properties provide support for heterogeneous structural gene mutations in partial deficiencies of hypoxanthine-guanine phosphoribosyltransferase.