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It has been postulated that autoantibody formation occurs as a consequence of a depression of function of certain thymus-derived lymphocytes (T cells). We have examined cell-mediated immunity, a T-cell function, in infectious mononueleosis, a condition in which autoantibodies are known to-develop. We have shown some evidence of depressed cell-mediated immunity in patients with infectious mononueleosis but have been unable to correlate this with autoantibody production. These results do not support the hypothesis that depression of T-cell function leads to autoantibody formation. [ABSTRACT FROM AUTHOR]

In vivo and in vitro animal experiments have been performed to clarify the role of ultraviolet light denatured DNA (UV DNA) and ultraviolet light (UVL) in the pathogenesis of the dermal lesions of human SLE. Rabbits immunized with UV DNA show deposition of immunoglobulin at the dermal-epidermal junction following exposure to UVL. We have also shown that UV DNA appears concomitantly with the antibody at the dermal-epidermal junction subsequent to the UVL exposure. Both n DNA and UV DNA have been shown to bind to the dermal-epidermal junction in vitro which could result in the persistence of these antigens at this site. These studies lend further support to the hypothesis that the release of UV DNA and its subsequent deposition at the dermal-epidermal junction may result in binding of both immunoglobulin and complement, leading to the development of histological lesions of SLE. [ABSTRACT FROM AUTHOR]

Twenty-four patients had abnormal sacroiliac joints detected by quantitative sacroiliac scintigraphy but no radiological evidence of sacroiliitis on original investigation. We studied them again after intervals of 12 to 36 months. Four patients developed radiological change. Two young, HLA B27-positive men had undoubted ankylosing spondylitis, and a young woman had possible ankylosing spondylitis. A middle-aged man had changes that could be attributed to post-traumatic osteoarthrosis. Of the remaining 20 cases 15 had symptoms and signs suggestive of inflammatory disease of the axial skeleton (and peripheral arthropathy in 5 cases). The sexes were affected equally (8 females, 7 males), and only 2 of the 15 were B27-positive. The response to anti-inflammatory medication was generally good to excellent, and scintiscans tended to improve. Of the remaining 5 patients, 3 had mechanical or traumatic problems, and in 2 there was no explanation for the abnormal sacroiliac scintiscan. We conclude that quantitative sacroiliac scintigraphy may detect ankylosing spondylitis prior to the develpment of radiological change and that it can identify an organic basis for backache in patients with a spondylitis-like syndrome. The clinical circumstances must be taken into account, as scintigraphic abnormalities are not diagnostic of any specific disease entity. [ABSTRACT FROM AUTHOR]

Narrowing of the intervertebral disc space with sclerosis of the adjacent vertebral bodies may occur as a consequence of infection, neoplasia, trauma, or rheumatic disease. Some patients have been described with backache and these radiological appearances without any primary cause being apparent. The lesions were almost always of 1 or, at most, 2 vertebrae and most frequently involved the inferior margin of L4. We describe 3 patients with far more extensive vertebral involvement and present the clinical, radiological, scintiscan, and histological findings. The only patient we have seen with the better known, isolated L4/5 lesion was shown on biopsy to have staphylococcal osteomyelitis. For this reason we would still recommend a biopsy of all such sclerotic vertebral lesions if they occur in the absence of other rheumatic disease. [ABSTRACT FROM AUTHOR]

In vitro tests of lymphocyte function have been performed in 61 patients with ;classical' or ;definite' rheumatoid arthritis. In vitro lymphocyte function was assessed by lymphocyte transformation responses to phytohaemagglutinin (PHA), Pokeweed mitogen (PWM), Candida antigen, and herpes simplex type I (HSV1). Follow up data were available after 6 months of treatment in 32 of these patients. Spontaneous lymphocyte transformation was assessed in all patients. Results obtained in patients with rheumatoid arthiritis were compared to those seen in a normal control population. Disease activity of patients with rheumatoid arthritis was assessed using standard clinical methods. Lymphocytes from patients with rheumatoid arthritis showed a similar degree of spontaneous transformation to that seen in normal subjects. In contrast, lymphocytes from patients with rheumatoid arthritis responded less well to PHA and Candida and HSV1 antigens when compared to normal patients. In patients with rheumatoid arthritis the response to PWM was markedly enhanced compared to normals. Clinical improvement was noted in 19 of the 32 patients seen at follow up, all of whom had received gold or penicillamine therapy. The abnormal responses of PHA and PWM seen before treatment became normal in those patients who improved clinically. The responses to Candida and HSV1 antigens not only returned to normal following treatment but were increased above those seen in normal controls. A statistically significant association was seen between clinical improvement and improvement of in vitro tests of lymphocyte function. [ABSTRACT FROM AUTHOR]

A case is presented of pigmented villonodular synovitis involving three joints in a 7-year-old girl. The diagnosis was confirmed at surgery and by histology. The patient also exhibited a haemangioma of the upper lip and a congenital pulmonary stenosis of mild degree. Subtotal synovectomy of the right knee and of both ankles was performed. The lesion recurred in both ankles after 6 months. Review of the literature failed to reveal any previous report of multiple joint involvement by pigmented villonodular synovitis in childhood and it appears that simultaneous involvement of three joints has not previously been described. Scintiscanning with 99mTc stannous pyrophosphate showed increased vascularity of the involved joints immediately after injection, but no increased osteoblastic activity was seen on the delayed scan. This radionuclide scanning technique is therefore helpful in distinguishing pigmented villonodular synovitis from other arthropathies. [ABSTRACT FROM PUBLISHER]

Use of modern materials and methods has given bone scintiscanning a larger role in clinical medicine, The safety and ready availability of newer agents have led to its greater use in investigating both benign and malignant disease of bone and joint. Present evidence suggests that abnormal accumulation of 99mTc-polyphosphate and its analogues results from ionic deposition at crystal surfaces in immature bone, this process being facilitated by an increase in bone vascularity. There is, also, a component of matrix localization. These factors are in keeping with the concept that abnormal scintiscan sites represent areas of increased osteoblastic activity, although this may be an oversimplification. Increasing evidence shows that the bone scintiscan is more sensitive than conventional radiography in detecting focal disease of bone, and its ability to reflect the immediate status of bone further complements radiographic findings. The main limitation of this method relates to nonspecificity of the results obtained. [ABSTRACT FROM AUTHOR]

Sera were tested from 23 patients with systemic lupus erythematosus followed over a period of 1 to 5 years. Antibodies to native DNA were measured and correlated retrospectively with clinical evidence of disease activity. The overall degree of correlation between the presence of DNA antibodies and evidence of disease activity was good (P less than 0-001). Of 206 sera tested, only 4 had a normal DNA antibody at a time when significant clinical activity was noted. In contrast, 34 sera had mild to moderately raised DNA antibody levels at times of clinical remission. Although DNA antibodies are a useful investigation in the monitoring of disease activity, changes in therapy should not necessarily be made on DNA antibody levels alone. [ABSTRACT FROM PUBLISHER]

This study was designed to determine whether abnormalities in individual or group activation of the knee extensors might be associated with the development of osteoarthrosis of the knee with varus deformity. The study consisted of nine healthy women with normal tibial alignment, nine agematched healthy women with genu varum and nine women with osteoarthrosis (OA) of the knee and genu varum. The outcome measures were normalized quadriceps femoris surface EMG amplitude parameters, recorded during maximal voluntary static and dynamic knee extension movements at 0° and 90° s(-1), expressed as a percentage and peak torque and rate of tension development at 0° s(-1). Under static conditions, the normalized EMG amplitudes, peak torque and rate of tension development of the knee extensors in those with OA differed significantly from the same parameters recorded for the healthy controls (P < 0.001). Although not significantly different under dynamic conditions (P = 0.1), there was a large effect size of f = 0.40 between the EMG amplitudes of the knee extensors of the two healthy groups, with a neglible effect size between the EMG amplitudes as well as a trend towards reduced tension-generating capacity of the knee extensors in those with varus deformity, irrespective of joint status. The latter findings suggest that the neural integration mechanisms governing the contractural pattern of the extensors surrounding a varus knee may abnormally reflect various aspects of the disease process of osteoarthrosis., (Copyright © 1994. Published by Elsevier Ltd.)

The purpose of this study was to compare the electromyographic (EMG) activity of the quadriceps femoris (QF) muscles of women with osteoarthrosis (OA) of the knee with the EMG activity of the QF muscles of healthy women. To this end, a total of 14 subjects attended a single test session during which full-wave rectified surface electromyograms were recorded from the rectus femoris (RF), vastus lateralis (VL) and vastus medialis (VM) muscles during maximum voluntary isometric quadriceps contractions performed at knee angles of 30 degrees and 60 degrees flexion. A comparison of the resultant normalized peak EMG ratios using independent t-tests demonstrated significantly higher composite QF muscle activation for the osteoarthrotic subjects (p < 0.05). A higher RF activation also differentiated the two groups. The findings raise the possibility of a direct correlation between abnormal activation of the QF and joint status. They also suggest that patients with knee OA may benefit functionally from rehabilitation designed to improve QF coordination and endurance, and not merely strength.

The close relationship between ankylosing spondylitis and the presence of the transplantation antigen HL-A 27 is well recognized. An attractive explanation for this has been that the gene coding for this antigen exists in marked linkage disequilibrium with an abnormal immune response gene. We have suggested, in contrast, that HL-A 27 may have a more direct importance because of a defective epistatic interaction between the gene coding for this antigen and a distinct disease susceptibility gene for AS, which may therefore be situated some distance from the major histocompatibility complex.

One hundred and twelve patients with classical or definite rheumatoid arthritis (RA) were randomly assigned to receive either sodium aurothiomalate (GSTM) or auranofin (AF). Monthly clinical assessments (morning stiffness, grip strength, articular index, pain, quality of life) and concurrent hematological, biochemical, and urine studies were performed to monitor the efficacy/toxicity (E/T) ratio. Ninety-two patients have completed 3 months; 65, 6 months; 47, 9 months; and 30, 12 months. The groups were numerically balanced at each time period. Analysis of the 0-6 month period suggests that both drugs were equally and significantly beneficial after 3 months and that this was maintained at 6 months. Toxicity was as frequent in both groups but more serious in the GSTM group. The main side effects were gastrointestinal (diarrhea) in the AF group and mucocutaneous in the GSTM group. Half of the withdrawals (14 in each group) were because of side effects in the GSTM group and for inadequate therapeutic efficacy in the AF group. This study suggests that after 6 months of treatment the E/T ratio of AF is greater than or equal to that of GSTM. These conclusions will need to be confirmed during the ongoing longer observation period. A significant clinical difference between the 2 drugs is that in a given patient treated with GSTM, the onset of toxicity coincides with a good therapeutic effect. This relationship does not appear to exist during AF treatment.

Antibodies to native DNA have been assessed by three separate radioimmunoassay methods: the Millipore filter technic, the Farr ammonium sulfate precipitation test, and a commercially available kit method. Although each method was found to be reliably reproducible, the different units by which results are expressed made comparison difficult because of the technical variations inherent in each test. The correlation between tests was, however, high. To allow for interlaboratory standardization, it is suggested that the assay method used be clearly specified. Results are best expressed in terms of mg of DNA bound per deciliter of test serum. It appears that the centrally standardized radioimmunoassay kit is the most convenient method by which these antibodies can be measured in routine laboratories.

The development of antinuclear antiboides, proteinuria and cumulative mortality has been studied in four groups of NZB/W mice. Two groups were exposed to different amounts of ultraviolet light [UVL] and one group were bred and raised in total darkness. The fourth group served as a control. No significant difference was noted bwtween the groups in the development of antinuclear antibodies, proteinuria or in cumulative mortality. This study failed to show any major role of UVL as an environmental factor in the development of this disease.

One hundred and sixty-nine patients, 82 with acute anterior uveitis (AAU) only, 48 with AAU and ankylosing spondylitis (AS), and 39 with AS only were studied. The HLA antigen A2 was present in 44/82 AAU only, 31/48 AAU + AS, and 23/39 AS only. Where haplotype analysis was possible by virtue of family studies, A2 B27 was present in 7/16 AAU only, 9/15 AAU and AS and 14/29 AS only. These figures do not differ significantly from the expected values of control populations. Alpha-1-antitrypsin (alpha-1-AT) phenotypes were obtained on 30/82 AAU only, 29/48 AAU + AS, and 27/39 AS only patients. The MZ phenotype appeared in 8/86 patients tested; 4/30 with AAU only and 4/29 AAU + AS patients. This is higher than the expected value for control populations. Therefore, MZ alpha-1-AT phenotype but not HLA-A2 appears increased in patients with AAU.

In vivo, gold salts have been shown to induce disease remission in rheumatoid arthritis. In some patients, this is associated with a return to normal of suppressed lymphocyte responses to mitogens and antigens. This study demonstrates that gold salts will suppress lymphocyte transformation in vitro but do not affect antibody dependent cell-mediated cytotoxicity. This suppression appears to be dose-related. In contrast to previous studies, evidence is provided to suggest that the suppression of lymphocyte responses by gold may at least in part be due to a direct toxic effect of myochrisine on the cultured cells.

A review of 27 cases of temporomandibular joint arthritis in patients with psoriasis reveals the main pathologic features to be condylar erosions, condylar osteoporosis, calcification of the articular disc, and subchondral cyst formation. We present another pathological process, temporomandibular joint bony ankylosis in a patient with psoriasis. Surgical management consisted of a high condylectomy, with a silastic implant to maintain the vertical dimension of the ramus. A very good functional result was obtained and 21/2 years later her incisive distance is 44 mm.

The effects of auranofin (AF) and sodium aurothiomalate (GSTM) on the production of specific arachidonic acid metabolites by chemotactic tripeptide activated polymorphonuclear leukocytes has been investigated using radioimmunoassay techniques. AF insignificantly enhanced the production of leukotrienes B4 and C4 at a concentration of 0.5 microgram Au/ml. However, at increasing concentrations, this drug suppressed the production of these metabolites in a dose dependent manner. In contrast, GSTM did not affect the production of either leukotriene at the concentrations tested. Of particular interest, prostaglandin E2 production was not affected by either gold compound. Both leukotrienes and prostaglandins are metabolized from arachidonic acid and are potent mediators of inflammation. The inhibition of leukotriene production may be another mechanism by which AF manifests its antiinflammatory effects in patients with rheumatoid arthritis.

Improved laboratory investigative techniques now foster an increased clinical interest in and awareness of the rheumatologic disease. This review is a discussion of the relevance of laboratory tests used in the more common rheumatologic disorders and of their role in both the diagnosis and assessment of these diseases from the standpoint of the practising clinician.

Three patients who received antithymocyte globulin therapy for severe aplastic anemia due to gold therapy are described. In 2 patients the hemoglobin, white blood cell count and neutrophils were normal and platelet counts exceeded 100 X 10(9)/1 more than 2 years after treatment. The 3rd patient did not respond to antithymocyte globulin or to cyclosporine therapy; subsequent allogeneic bone marrow transplantation resulted in satisfactory engraftment at 12 months. In all 3 patients the arthritis was improved after the episode of marrow aplasia and its treatment. Including these 3 patients, 12 reported patients with severe aplastic anemia due to gold have now been treated with antithymocyte globulin; 8 have shown significant improvement. These results are better than those reported for any other treatment. Antithymocyte globulin may be optimal initial treatment for this serious disorder.

Bone scans and radiographic skeletal surveys have been done in 41 patients who had Paget's disease. The scintigraphic findings are consistent with what is known of the pathophysiology of Paget's disease. Diseased bone demonstrates increased vascularity, an increased degree of uptake of bone-seeking radiotracers and, in appropriate bones, evidence of marrow replacement. The bone scintiscan is a more sensitive indicator of the extent of polyostotic Paget's disease than conventional radiograph, demonstrating 34% more lesions. Because it reflects shorter term changes in osteoblastic activity the bone scan is of some value in providing immediate objective evidence of the therapeutic effectiveness of Mithramycin which has been used in this study in the treatment of the minority of patients with pain in Pagetoid bone. A technique for documenting alterations in uptake by diseased bone numerically is presented. Upon treatment with Mithramycin the ratio of abnormal uptake in relation to normal bone fell from 8.7 to 3.9.

An attempt has been made to improve diagnostic precision in a group of diseases associated with inflammation of the sacroiliac joints, by using a 99mTechnetium stannous pyrophosphate bone scan. Inflammation of these joints is associated with osteoblastic activity and is reflected by an increase in the uptake of radionuclide, which can be precisely quantitated. The uptake was markedly above the range of normal in patients with active ankylosing spondylitis (AS), and also in a number of patients with possible AS, psoriasis, and Reiter's syndrome. However, patients with Grade 4 radiological changes of the sacroiliac joints frequently had normal scans. This technique may be useful in the early diagnosis of sacroiliitis, and the nosological implications of the changes in patients with Reiter's syndrome and psoriasis are of interest.

Hepatic toxicity is rarely associated with gold therapy. Three patients with rheumatoid arthritis who developed jaundice during the course of chrysotherapy are described. Jaundice occurred both early and late in the course of therapy. differing grades of severity of dysfunction were encountered. Liver biopsy revealed intrahepatic cholestasis. Significance of jaundice occurring during gold therapy is discussed.

Forty-seven patients receiving gold therapy for rheumatoid arthritis were observed sequentially at 6-monthly intervals. When the disease was in remission, and remained so, the in vitro responses of lymphocytes to phylohemagglutinin stimulation tended to be normal. Improvement in the disease were associated with improvement in lymphocyte response and deterioration associated with depression of response. Our observations suggest that these changes are a reflection of disease activity and their relationship to gold therapy is indirect.