Synergy between adjuvant arthritis and collagen-induced arthritis in rats.

Adjuvant arthritis (AA) in rats is susceptible to cell-mediated passive transfer. Collagen-induced arthritis (CIA) in rats is susceptible to passive transfer with antibody to type II collagen. We report here the development of strikingly severe arthritis in Lewis rats as the result of synergy between passively transferred antibody to type II collagen from rats with CIA and concanavalin A (Con A)-stimulated lymph node or spleen cells from syngeneic rats with AA. Similar synergy was seen in rats with AA given anticollagen antibody, in rats with CIA given Con A-stimulated adjuvant spleen cells, and in rats actively immunized with CII and complete Freund's adjuvant. The synergistic process caused a very severe polyarthritis, characterized by marked swelling and erythema in all the joints of the distal extremities, with histologic and radiographic evidence of early, extensive erosion of articular cartilage. Synergy was apparent if the lymphoid cells from AA rats were given up to 1 mo after a single injection of anticollagen antibody. No synergy was seen when normal rat immunoglobulin or anti-ovalbumin antibody was substituted for anticollagen antibody, when Con A-stimulated lymphoid cells from normal rats or donors with CIA were used, or when Con A-stimulated AA lymphoid cells were irradiated before transfer. Synergy between separate immune effector mechanisms may represent a general phenomenon in the pathogenesis of inflammatory joint disease.

Coxsackievirus B 1-induced polymyositis. Lack of disease expression in nu/nu mice.

Chronic inflammatory myositis similar to human polymyositis occurs in mice after infection with a strain of Coxsackievirus B 1 (CVB 1). To investigate the role of T cells in the pathogenesis of this disorder, we compared disease expression in T cell-deficient athymic nude (nu/nu) mice and heterozygotes (nu/+) with normal T cell function. Acute infectious myositis occurred in nu/nu and nu/+ mice. Chronic (greater than 21 d postinfection) weakness and myositis, however, developed only in nu/+. Resistance to disease in nu/nu mice was not explained by insusceptibility to infection; the amount of virus lethal for 50% of mice and virus replication were comparable in both groups. Additionally, anti-CVB 1 antibody production was similar in both groups. Reconstitution of infected nu/nu mice with spleen cells from normal mice resulted in disease. These results demonstrate that chronic weakness after infection with this virus is not simply a sequela of acute myonecrosis and suggest that T cells play a pivotal role in the pathogenesis of chronic myositis.

Long term effects of intra-articular botulinum toxin A for refractory joint pain.

UNLABELLED: The purpose of this case series review is to describe our 12 month clinical experience with intra-articular injections of Botulinum toxin Type A (BoNT/A) for refractory joint pain. Eleven patients with chronic arthritis who had failed treatment with oral and/or intra-articular medications and were not surgical candidates were referred to us for management of moderate to severe refractory joint pain in 15 joints. The use of BoNT/A to treat joint pain is a non-FDA approved "off label" treatment with potential side effects. After a detailed explanation of the joint injection procedure, signed informed consent was obtained for the procedure. Fifteen joints were injected with BoNT/A (Allergan, Inc): six lower extremity joints (3 knees, 3 ankles) with 25-50 units and nine shoulders with 50-100 units. Patients were followed for one year or longer. Maximum relief of pain was measured by comparing baseline pain on a numeric rating scale (0-10) to pain at the time of maximum relief (paired t-test). Maximum improvement in function was assessed using paired t-tests for improvement in active flexion and abduction for the shoulder joint, and by the time to perform sit to stand ten times (the timed stands test, TST) for the lower extremity joints. RESULTS: Two patients were female and nine were male, aged 42-82 years. Five had osteoarthritis (OA), five had rheumatoid arthritis (RA) and one had psoriatic arthritis. All patients were on analgesic and/or anti-inflammatory medications and all joints had previous intra-articular steroid or viscosupplement injections with inadequate or unsatisfactory benefit. A clinically and statistically significant improvement was noted after IA-BoNT/A injections. The mean maximum decrease in lower extremity joint pain was 55% (p =0.02) and the 36% (p =0.044) improvement in the Timed Stands Test was noted at four to ten weeks after injection. There was a 71% mean maximum reduction in shoulder pain severity from 8.2 +/- 1.1 to 2.4 +/- 1.9 (p <0.001). Active range of motion increased 67% in flexion (from 67.8 +/- 27.6 to 113.3 +/- 46.6 degrees, p =0.001) and 42% in abduction (from 50 +/- 18.5 degrees to 71.1 +/- 23.1 degrees p =0.01). No immediate or delayed adverse effects related to BoNT/A were noted after the injection. Duration of pain relief was variable and ranged from 3 to 12 months. Five joints were re-injected with IA-Bont/A and had a similar decrease in joint pain that lasted 3 to 12 months. CONCLUSIONS: This is the first report of the long term effects of intra-articular BoNT/A injections to treat chronic joint pain and the efficacy of repeated injections. Although this study was small, and uncontrolled the results suggest that IA-BoNT/A injections are an effective and safe treatment for chronic joint pain disorders.

A comparative study of procedures for sheep erythrocyte-human-T-lymphocyte rosette formation.

A comparative study of several published methods for sheep red blood cell-T-lymphocyte rosette formation was performed. Maximum SRBC-rosette formation occurred with AET treated SRBC in medium supplemented with 20% FCS or with untreated SRBC in 100% FCS. Prolongation of the 4 degrees C incubation period from 4 to 18 h enchanced rosette formation. Fluorescein diacetate staining significantly increased calculated percentage of rosette formation. Fluorescein diacetate staining significantly increased calculated percentage of rosette-forming lyphocytes by allowing accurate indentification of the central lymphocytes in morulas.

Immediate and short-term effects of three commercial wrist extensor orthoses on grip strength and function in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the immediate and short-term effects of 3 commercial wrist orthoses on grip strength and function. METHODS: Thirty-six patients with definite rheumatoid arthritis participated in the randomized, controlled, cross-over design study of 3 commercial wrist extensor orthoses. Dominant-hand dynamometric grip strength was assessed at both initial and followup sessions while splinted and nonsplinted. Functional impact was assessed using a written questionnaire. RESULTS: All 3 commercial orthoses reduced grip strength when first donned. After a 1-week adjustment period, one orthosis, the Smith and Nephew Roylan D-Ring (Roylan), afforded splinted grip strength equal to that of the nonsplinted grip strength. The other 2 orthoses continued to reduce grip strength, and afforded splinted grip strength significantly below that of the Roylan. The Roylan was deemed comfortable by more subjects than the other orthoses. CONCLUSIONS: The belief that commercial orthotic use increases grip strength, either immediately or after 1 week, is not supported by this study's data. Different styles of commercial wrist orthoses appear to have differing influence on splinted grip strength.

Finger dexterity and hand function: effect of three commercial wrist extensor orthoses on patients with rheumatoid arthritis.

OBJECTIVE: To investigate the effect of 3 commercial wrist orthoses on finger dexterity and hand function of patients with rheumatoid arthritis (RA). METHODS: Forty-two patients with definite RA participated in the cross-over study comparing 3 styles of commercial wrist orthoses. Finger dexterity and hand function of the dominant hand were assessed while splinted and unsplinted, at the initial session and after 1 week of intermittent orthosis use. Finger dexterity was assessed using two subtests from the Purdue Pegboard Test (Purdue) and hand function was assessed using the Jebsen-Taylor Hand Function Test (Jebsen-Taylor). RESULTS: Both finger dexterity and hand function were reduced by splinting; men and women were affected similarly. There was no difference in finger dexterity or hand function afforded by the 3 orthoses. Results on both the Purdue and Jebsen-Taylor tests showed a significant learning effect across time. CONCLUSIONS: The 3 commercial wrist orthoses studied reduce dexterity similarly and significantly. When commercial wrist orthoses are to be used during tasks that require maximum dexterity, this reduction should be weighed against the known benefits of splinting.

Commercial wrist extensor orthoses: a descriptive study of use and preference in patients with rheumatoid arthritis.

OBJECTIVE: To describe patients' functional uses of 3 commercial wrist orthoses, to describe patients' preference patterns for the orthoses, and to clarify orthotic attributes that are viewed positively and negatively. METHODS: Using a cross-over design, 42 patients with definite rheumatoid arthritis used each of 3 commercial orthoses for one week. There was a one-week wash-out between each week of use. At the end of the study, private semi-structured interviews were conducted with each participant. Data from close-ended questions were tabulated. Open-ended data were analyzed using qualitative methods. RESULTS: Patients reported that the 3 commercial wrist orthoses reduced wrist pain similarly, but that comfort and a sense of security during functional tasks were only found if the orthoses were comfortable and well-fitting. Most subjects preferred the padded, short forearm orthosis, though a small number found it uncomfortably warm, and many complained that it was difficult to use when wearing long-sleeved garments. Common complaints about the two elastic orthoses included chafing at the thumb webspace and chafing at the proximal closures. Longer forearm length was often perceived as providing unnecessarily high levels of wrist support. CONCLUSIONS: No single orthosis suited all subjects. Satisfaction with an orthosis appears to be based not only on its therapeutic effect, but also the comfort and ease of its use. To maximize patient satisfaction and improve the likelihood of appropriate fit and comfort, several styles of commercial orthoses should be available. The current trend toward restricted clinic stocks appears contrary to both therapeutic goals and patient satisfaction.

The Minnesota Arthritis Training Program: emphasis on self-management, not compliance.

Based on a needs assessment of our ambulatory patients and review of available arthritis education programs, we developed an innovative education and exercise program, the Minnesota Arthritis Training Program (MATP). Patients are taught self-management skills including how to: (1) interpret changing physical symptoms and limitations caused by joint inflammation and apply modifications to their individualized exercise program; (2) recognize common drug toxicites and use a decision analysis schema to manage side effects to decrease the risk of serious toxicity and decrease dependency on professionals safely; (3) develop strategies to modify activity schedules to make the most of limited stamina; (4) recognize and understand psychological problems produced by rheumatoid arthritis (RA) including sexual dysfunction, depression and breakdown of communication; and (5) reconstitute social support systems.

Animal models of infectious arthritis.

The results from animal studies of bacterial joint infection have demonstrated pathogenic changes in synovium, cartilage, and bone which lead to joint destruction. Mechanisms responsible for the changes in these articular components remain to be more completely defined in order to develop methods to prevent articular destruction. Eradication of the active infectious process with early institution of antibiotics and adequate drainage is required but is not sufficient to prevent chronic destructive processes initiated by the acute bacterial infection. Biochemical effects of changes in the anabolic and catabolic functions of the cells in bone, cartilage, and synovium and the control mechanisms for these functions undoubtedly hold the key to prevention of destruction in infectious arthritis. Much less is understood about the pathogenic changes and mechanisms in infections caused by anaerobic bacteria, mycobacteria, fungi or viruses. Application of advances in immunological, morphological and biochemical techniques to animal models of infectious arthritis provides the opportunity to increase understanding of pathogenic mechanisms and to develop innovative methods of treatment.

Transient inhibition of murine progressive ankylosis by indomethacin.

Murine progressive ankylosis (MPA) is an heritable disorder which produces acute arthritis and ankylosis of peripheral and axial joints similar to ankylosing spondylitis. Because indomethacin inhibits heterotopic bone formation in vivo, we studied its effects on MPA. Indomethacin was administered for 6 weeks beginning at weaning to litters from heterozygote breeder pairs. Progression curves for peripheral, spinal and thoracic joint ankylosis in treated and untreated ank/ank animals wer compared. There was no delay in ankylosis of peripheral or spinal joint ankylosis in MPA animals treated with indomethacin. interestingly, transient delay of thoracic ankylosis occurred in indomethacin treated MPA animals.

Calcergy in murine progressive ankylosis.

Murine progressive ankylosis (MPA) is characterized by periarticular ossification and joint ankylosis. We studied calcergy and calciphylaxis in MPA. Calcergy represents a chemical attraction between heavy metal salts and apatite followed by hydroxyapatite deposition around collagen. Mice were injected subcutaneously with FeCl2, PbAcetate, and saline, and sacrificed at intervals between 5 minutes and 14 days. Section of skin and subcutaneous tissues were stained with Von Kossa's stain. No mice developed calcifylaxis. PbAcetate produced calcergy in all mice. MPA mice exhibited calcergy qualitatively and quantitatively the same as normal mice suggesting abnormal calcergy is not responsible for joint ankylosis in MPA.

Lymphocyte destruction by antibody-dependent cellular cytotoxicity mediated in vitro by antibodies in serum from patients with systemic lupus erythematosus.

Sera from patients with systemic lupus erythematosus (SLE) were tested for the presence of IgG antilymphocyte antibodies that are capable of mediating antibody-dependent cellular cytotoxicity (ADCC) of peripheral blood lymphocytes (PBL) from normal donors. The effector cells employed were PBL autologous with the target PBL. Positive ADCC responses were obtained with serum from 5 SLE patients with severe active diseases. It is possible that ADCC is a mechanism by which IgG antilymphocyte antibodies in patients with SLE may mediate in-vivo lymphocytolysis.

A case of Wegener's granulomatosis presenting with jaw claudication.

The major manifestations of Wegener's granulomatosis have been well described. Jaw claudication has not been recognized as one of the symptoms associated with this disease. We report the first case of Wegener's granulomatosis presenting with jaw claudication. Documentation of different histological types of vasculitis producing similar symptoms broadens our concepts of systemic vasculitis and emphasizes the need for tissue biopsy for diagnosis.

Inclusion body myositis and renal cell carcinoma. Report of two cases and review of the literature.

OBJECTIVE: To describe the clinical course of 2 patients with concurrent inclusion body myositis and renal cell carcinoma and review published reports of inclusion body myositis associated with malignancy. METHODS: Prospective followup of 2 patients. Review of published case reports and series of patients with inclusion body myositis. RESULTS: Our 2 patients with inclusion body myositis and renal cell carcinoma had no improvement of strength following nephrectomy. Seven previously reported cases of inclusion body myositis and malignancy were identified and are discussed. CONCLUSION: Findings in our 2 patients suggest that there is no etiopathologic relationship between inclusion body myositis and malignancy.

Validity and reliability of the timed-stands test for patients with rheumatoid arthritis and other chronic diseases.

The timed-stands test (TST) is a simple measure of lower extremity strength which correlates with age in healthy people. We validated the TST as a functional assessment tool against other measurements of functional capacity and comorbidity in 147 patients with rheumatoid arthritis (RA) or other chronic diseases. The TST was significantly impacted by RA disease activity and by comorbidity. Age affected TST only in patients without arthritis or life threatening disease. TST is a simple, reproducible measure of lower extremity function that was valid in this patient population.

Exercise for arthritis.

The data available indicate that ROM, strengthening and aerobic conditioning exercises are safe for patients with OA, RA or AS, despite earlier concerns that exercise might exacerbate joint symptoms or accelerate disease. Less clear are the therapeutic benefits of exercise. In patients with OA, stretching, strengthening, and aerobic conditioning programmes can improve the deficits observed in these patients. The improvements observed generally have been small, and the evidence that these individual improvements result in improved overall function is minimal. None the less, it is likely that exercise will reduce pain, improve endurance for physical activities and improve cardiovascular fitness. Study of the long-term effects of exercise in the geriatric population, for sustaining independent living and functioning, is critically important for future health care and social expenditures. In RA, strengthening and aerobic conditioning exercise programmes can increase muscle strength and cardiovascular fitness and probably improve physical function as well. Improvements demonstrated in patients with RA seem more convincing than those in patients with OA and AS; this probably represents their poorer physical status prior to exercising. For patients with AS, intensive physiotherapy brings statistically significant short-term improvements in spinal and hip ROM which are only modestly clinically significant. It is possible that spinal mobility exercises decelerate loss of mobility over the long term, but controlled studies are needed to confirm this. Improvement in respiratory function with exercise appears to be related to cardiopulmonary fitness and perhaps to improvements in diaphragmatic respiration rather than to changes in thoracic cage mobility. Given the overall safety and likely benefits of the described forms of exercise, exercise should be included in the overall treatment of patients with OA, RA or AS. Careful patient evaluation and education about exercise should be a part of the exercise programme.

Preparation of whole rabbit knee joints for microscopic examination.

A paraffin embedding method to prepare whole rabbit knee joints for histological examination is described. This method provides good quality microscopic sections thin enough for the study of cellular detail and does not require prolonged processing. When examining pathologic changes in experimental arthritis, it is advantageous to be able to examine the intact joint with the structural relations of the joint components preserved. Sections of the whole joint provide numerous areas where bone, cartilage and synovium are contiguous for examination. Having obtained poor results using methods recommended for small bony specimens, we modified several existing procedures to obtain a reliable method for preparing excellent microscopic sections of the whole rabbit knee joint.

The importance of identifying depression in patients with rheumatoid arthritis: evaluation of the beck depression inventory.

Depression is common in patients with chronic illness including rheumatoid arthritis (RA). Identifying depression accurately and treating it appropriately are important for helping to maintain function in patients with RA. Several self-administered screening tools are available that are sensitive for the detection of depression in medical outpatients and are easy to use in a clinic setting. There has been debate regarding the validity of some of these tools for detecting depression in RA patients because of "arthritis-biased" questions. In this study, we evaluated 77 patients with RA and measured their responses to one of these screening tools, the Beck Depression Inventory (BDI). We compared disease activity and severity measures and measures of functional status between patients who were designated as depressed by BDI score and patients without depressive symptoms.We were unable to demonstrate differences in specific objective measures of disease activity, severity, or objective functional measures between nondepressed and depressed RA patients. However, depressed patients reported greater disease activity and poorer physical function, and observer global assessment of depressed patients was poorer. We conclude that the "arthritis-biased" questions in the BDI did not interfere with the detection of depression in patients with RA and should not be a deterrent for its use. We found that the BDI can be used effectively in a clinic setting as a screening tool for depression in patients with RA.