The effect of preoperative exercise on total knee replacement outcomes.

This study compared the effects of preoperative physical therapy of general cardiovascular conditioning exercises with the routine procedure of no preoperative physical therapy on patients undergoing primary total knee replacement. Thirty patients were randomly assigned to 1 of 3 groups. Group 1 was the control group. Group 2 participated in a physical therapy program designed to strengthen the upper and lower limbs and improve knee range of motion. Group 3 participated in a cardiovascular conditioning program, consisting of arm ergometry, cycle ergometry, aquatic exercises, and aerobic activity. All patients were evaluated preoperatively and postoperatively using the Hospital for Special Surgery Knee Rating, the Arthritis Impact Measurement Scale, and the Quality of Well Being instrument. Both experimental groups tolerated their respective exercise protocols extremely well. All 3 groups showed significant improvement postoperatively as measured by the Hospital for Special Surgery Knee Rating, the Arthritis Impact Measurement Scale and the Quality of Well Being measurement scales. However, neither type of preoperative exercise added to the degree of improvement after surgery at any of the postoperative evaluations.

Reflex sympathetic dystrophy syndrome.

There has been increasing interest in reflex sympathetic dystrophy syndrome (RSDS) over the past decade. This trend has continued over the past 2 years with the publication of a number of reports and studies, many of which are reviewed here. Progress has been made in understanding RSDS, with the demonstration of increased alpha-adrenergic receptor activity in peripheral nerves following injury. Release of alpha-adrenergic agonists from sympathetic nerve terminals may then cause nociceptor activation and pain. Use of phentolamine, an alpha-adrenergic receptor inhibitor, in a diagnostic test may provide a more specific method for recognizing RSDS.

Factors affecting unprescribed remedy use among people with self-reported arthritis.

OBJECTIVE: The purpose of the study is to determine the frequency and consequences of use of unprescribed remedies by people with self-reported osteoarthritis, and to find methods for predicting such use. METHODS: A random digit telephone survey was used to contact respondents. A 90-item questionnaire evaluated demographic characteristics, type of disorder, area affected, severity of problem, and symptoms encountered. RESULTS: Among 1,811 contacts, 21% had musculoskeletal complaints. Of those with self-reported musculoskeletal disorders, 84% had used at least one unprescribed remedy during the past 6 months. People with self-reported rheumatoid arthritis used more such remedies than those with self-reported osteoarthritis, and those with a greater degree of disability used more unprescribed remedies than those who were less affected. Unprescribed remedies were rated as effective as prescribed remedies. CONCLUSIONS: Unprescribed remedies are used frequently, particularly by those with painful and disabling arthritis. These remedies may be effective. Harmful and expensive remedies are used rarely.

Reflex sympathetic dystrophy syndrome: a review.

Reflex sympathetic dystrophy syndrome is a serious and potentially disabling condition. Early diagnosis and treatment are essential to control the disorder and restore the patient's quality of life. The cardinal clinical features, radiological changes, etiopathologic advances, and current approaches to proper diagnosis and treatment will be discussed.

Genetic analysis of self-associating immunoglobulin G rheumatoid factors from two rheumatoid synovia implicates an antigen-driven response.

Although much has been learned about the molecular basis of immunoglobulin M (IgM) rheumatoid factors (RFs) in healthy individuals and in patients with mixed cryoglobulinemia and rheumatoid arthritis, little is known about the genetic origins of the potentially pathogenic IgG RFs in the inflamed rheumatoid synovia of patients. Recently, we generated from unmanipulated synovium B cells several hybridomas that secreted self-associating IgG RFs. To delineate the genetic origins of such potentially pathogenic RFs, we adapted the anchored polymerase chain reaction to rapidly clone and characterize the expressed Ig V genes for the L1 and the D1 IgG RFs. Then, we identified the germline counterparts of the expressed L1 IgG RF V genes. The results showed that the L1 heavy chain was encoded by a Vh gene that is expressed preferentially during early ontogenic development, and that is probably located within 240 kb upstream of the Jh locus. The overlap between this RF Vh gene and the restricted fetal antibody repertoire is reminiscent of the natural antibody-associated Vh genes, and suggests that at least part of the "potential pathogenic" IgG RFs in rheumatoid synovium may derive from the "physiological" natural antibody repertoire in a normal immune system. Indeed, the corresponding germline Vh gene for L1 encodes the heavy chain of an IgM RF found in a 19-wk-old fetal spleen. Furthermore, the comparisons of the expressed RF V genes and their germline counterparts reveal that the L1 heavy and light chain variable regions had, respectively, 16 and 7 somatic mutations, which resulted in eight and four amino acid changes. Strikingly, all eight mutations in the complementarity determining regions of the V gene-encoded regions were replacement changes, while only 6 of 11 mutations in the framework regions caused amino acid changes. Combined with L1's high binding affinity toward the Fc fragment, these results suggest strongly that the L1 IgG RF must have been driven by the Fc antigen.

Genetic studies of four highly homologous rheumatoid factor-associated Vk genes in rheumatoid arthritis patients and normal individuals.

Rheumatoid factors (RFs) are autoantibodies directed against IgG molecules. They are present in increased quantity in most patients with rheumatoid arthritis (RA), and are implicated in tissue damage in this disease. Paradoxically, recent studies of RFs have revealed that these autoantibodies are likely a physiological component of the immune system, and may play a role in the development and function of the B cell repertoire. Previously, we found that a significant fraction of RA patients express RF bearing the 6B6.6 cross-reactive idiotype, which is a phenotypic marker of the Humkv328-like genes. In order to elucidate the possible genetic factors that may contribute to the abnormal production of RFs in RA patients, we studied restriction fragment length polymorphisms (RFLP) of four highly homologous RF-related kappa light chain variable region (Vk) genes (i.e. Humkv328, Humkv328h2, Humkv328h5 and Humkv329) in RA patients and normal controls. The results show that kv328, kv328h2 and kv329 are likely to be alleles of the kv328 locus, while kv328h5 is a highly homologous Vk gene residing in a separate locus; and that deletion in one copy of either the kv328 or the kv328h5 loci, but not both loci, occurs in several individuals. However, the frequencies of various RFLP patterns of these two Vk gene loci are similar in patients and normals.

Medical and surgical treatment of seronegative spondyloarthropathies.

Advances in the treatment of the seronegative spondyloarthropathies are reviewed here. The search for effective disease-modifying agents in this group of disorders has continued. Recent attention has focused primarily on sulfasalazine and different immunosuppressive agents. Sulfasalazine has been evaluated by several groups of investigators in ankylosing spondylitis and psoriatic arthritis. Results have been variable, but data suggest that sulfasalazine is less effective for spinal disease than for peripheral joint involvement. Preliminary studies have shown that cyclosporine and other immunosuppressive agents are beneficial in patients with psoriasis and Behçet's disease. Azathioprine appears to be highly effective in Behçet's disease.

Molecular basis of an autoantibody-associated restriction fragment length polymorphism that confers susceptibility to autoimmune diseases.

Recently, combined serological and molecular studies of autoantibodies have revealed that these antibodies play an important role in the normal function of the immune system and in the development of the B cell repertoire. Accordingly, we hypothesized that a homozygous deletion of a critical autoantibody-associated Ig variable (V) gene may alter the immune system and thus predispose the host to autoimmune disorders. Initial experiments revealed several restriction fragment length polymorphisms (RFLP) of the Humhv3005 gene, that is likely to encode heavy chains of rheumatoid factors, and the closely related 1.9III gene. By probing EcoR1-digested DNA with the Humhv3005/P1 probe, we found that one of the four major hybridizing bands was missing in approximately 20% of patients with either rheumatoid arthritis or systemic lupus erythematosus, but only 2% of normal subjects. To delineate the genetic basis of this polymorphism, we have now employed the PCR to amplify and analyze hv3005, 1.9III, and homologous genes in individuals with characteristic RFLP genotypes. Our results indicate that the human Vh gene repertoire contains several hv3005- and 1.9III-like genes, and that a complete deletion of the hv3005-like genes is relatively restricted to a subset of autoimmune patients. These findings provide initial evidence for deletion of developmentally regulated autoreactive V genes in autoimmune diseases.

Possible deletion of a developmentally regulated heavy-chain variable region gene in autoimmune diseases.

Several autoantibody-associated variable region (V) genes are preferentially expressed during early ontogenic development, suggesting strongly that they are of developmental and physiological importance. As such, it is possible that polymorphisms in one or more of these genes may alter susceptibility to autoimmune disease. We have searched extensively for a probe related to a developmentally regulated V gene that has the power to differentiate among highly homologous V genes in human populations. Using such a probe (i.e., Humhv3005/P1) related to both anti-DNA and anti-IgG autoantibodies, we studied restriction fragment length polymorphisms in patients with rheumatoid arthritis and systemic lupus erythematosus and found an apparent heavy-chain V (VH) gene deletion that was nearly restricted to the autoimmune patients. These data suggest that deletions of physiologically important VH genes may increase the risk of autoimmunity through indirect effects on the development and homeostasis of the B-cell repertoire.

Autoantibody production by severe combined immunodeficient mice reconstituted with synovial cells from rheumatoid arthritis patients.

In an attempt to characterize the heterogeneity of the human autoantibody response, mice with severe combined immunodeficiency were reconstituted with synovial or blood lymphocytes from patients with rheumatoid arthritis (RA). Mononuclear cells extracted from synovial fluid or tissue (SMC) were a greatly enriched source of IgM rheumatoid factor (RF)-producing cells compared to the peripheral blood mononuclear cells (PBMC) of rheumatoid arthritis patients or normal donors. Six to nine weeks after reconstitution of mice with synovial mononuclear cells, 0%-39.3% (mean = 11.4%) of total IgM consisted of IgM RF compared to 0%-0.15% (mean = 0.02%) in mice given RA PBMC and 0%-1.2% (mean = 0.34%) in mice given normal PBMC. Detectable levels of IgM RF were maintained in some mice for as long as 20 weeks after transfer. Mice reconstituted with synovial membrane or synovial fluid lymphocytes produced a heterogeneous mixture of immunoglobulins. These included other autoantibodies, such as anti-nuclear and anti-cytoplasmic antibodies, and antibodies to exogenous antigens such as the Epstein-Barr virus nuclear antigen-1 (EBNA-1). This heterogeneity is further illustrated by the demonstration that the sera from mice given synovial cells also contained IgG antibodies possessing all three major VH families (VH1, VH3 and VH4) and the four major V kappa families (V kappa 1 to V kappa 4). Autoantibody production gradually decreased with time even under circumstances where total immunoglobulin levels increased, and elevated production could not be induced by antigenic stimulation. These findings describe a new model for the analysis of human autoantibody production.

The incidence of a new human cross-reactive idiotype linked to subgroup VHIII heavy chains.

Cross-reactive idiotypes (CRI) on human rheumatoid factors (RF), which are identified by murine monoclonal antibodies (mAb), have proved useful in defining both the incidence and the structural characteristics of these autoantibodies. In this study, a new murine anti-idiotypic reagent, mAb B6, has been used to identify and define the expression of a distinct heavy chain CRI. The B6 CRI was found on 20% of monoclonal IgM (16 of 81), but on only 5% of monoclonal IgA (1 of 20) and on no monoclonal IgG. In addition, this CRI was expressed exclusively on a subset of Ig derived from the VHIII protein variable region subgroup. In immunoblotting experiments, the mAb B6 bound directly to the heavy (H) chains of CRI positive proteins. The B6 CRI was found frequently on monoclonal IgM-RF molecules, and the mAb B6 could inhibit the binding of the RF to its IgG antigen. It was also demonstrated that Staphylococcus aureus protein A (SpA), which has recently been shown to bind to the F(ab) region of VHIII molecules, could block the interaction of some B6 CRI positive IgM to the anti-CRI. These experiments suggest that the B6 CRI is a marker for one or a few VHIII genes and that it is expressed commonly on IgM paraproteins, many of which have RF activity.

Prevalence of the use of unconventional remedies for arthritis in a metropolitan community.

Of 1,811 individuals sampled in a metropolitan community, 382 reported having a musculoskeletal complaint. Eighty-four percent of them had used an unconventional remedy within the previous 6 months. Most individuals used inexpensive, unharmful remedies such as exercise, prayer, and relaxation. This study indicates that people with musculoskeletal disorders often use unconventional remedies, but raises questions regarding the seriousness of this problem.

The Quality of Well-being Scale. Applications in AIDS, cystic fibrosis, and arthritis.

The Quality of Well-being (QWB) Scale combines preference-weighted measures of symptoms and functioning to provide a numerical point in-time expression of well-being that ranges from zero (0) for death to 1.0 for asymptomatic optimum functioning. The QWB includes three scales of function: mobility, physical activity, and social activity. Each step of these scales is associated with preference weights. Preference adjustments for symptoms are also included. This paper describes how this general system was used to evaluate outcomes in three different clinical conditions: acquired immune deficiency syndrome (AIDS), cystic fibrosis, and arthritis. In one study, the QWB was administered to 31 patients participating in evaluation of azidothymidine (AZT) treatment for AIDS. The QWB system demonstrated substantial benefits of AZT treatment in comparison to placebo. In a second study, the QWB and a series of pulmonary function measures were administered to 44 patients with cystic fibrosis. The QWB was demonstrated to be significantly correlated with measures of pulmonary function, including FEV1 and maximal midexpiratory flow rate (MMEFR). In addition, there were significant associations between the QWB and measures of exercise tolerance. In the third study, the QWB and an arthritis-specific measure were administered to 83 arthritis patients before and after their treatment. The QWB was at least as capable of detecting clinical change in this population as was the disease-specific measure. For all three conditions, the QWB considered side effects and benefits of treatment in a common unit. Clinical trial data are cited to suggest that the QWB is a valuable outcome measure in arthritis treatment evaluation. We conclude that the QWB has substantial validity as a general health outcome measure and that the system can be used with different populations.

Characterization of four homologous L chain variable region genes that are related to 6B6.6 idiotype positive human rheumatoid factor L chains.

A significant proportion of monoclonal IgM rheumatoid factors (RF) from patients with mixed cryoglobulinemia express a KIIIa L chain-associated cross-reactive idiotype, termed 6B6.6. Previously, we reported the isolation from a patient with a monoclonal RF of a Vk gene, termed Humkv328, whose deduced amino acid sequence differs by three and seven residues from the L chains of the 6B6.6-positive RF Les and Pom, respectively. To further delineate the genetic basis of the 6B6.6 cross-reactive idiotype, we isolated from the same patient another Vk gene, termed Humkv329, which differs from kv328 by only three bases over a stretch of 1331 nucleotides sequenced. However, kv329 has a stop codon at amino acid position 94, and is thus a pseudogene. Therefore, we screened a second genomic library from an unrelated individual and isolated two potential function Vk genes (i.e., Humkv328h2 and Humkv328h5) which are highly homologous to Humkv328. All three potential functional Vk genes differ from each other by one to six bases over a 1331-bp stretch and all encode the same Vk region amino acid sequence. Among the six bases by which Humkv328h5 differs from Humkv328, two are in the conserved pentadecanucleotide region, which is known to be important in the regulation of k L chain transcription. In the future it will be important to ascertain the potential association of polymorphisms in the conserved pentadecanucleotide region with RF associated autoimmune and lymphoproliferative diseases.

Sjögren's syndrome. Proposed criteria for classification.

The term "Sjögren's syndrome" (SS) is frequently used to describe the occurrence of keratoconjunctivis sicca and xerostomia in association with an autoimmune disorder. However, well-defined criteria for the classification of SS have not been established, and this diagnosis is being applied to a wide spectrum of conditions, ranging from clear "autoimmune" disease in some patients, to sicca complaints without evidence of a systemic immune process in elderly patients. Here, we review the clinical and laboratory features of patients referred for evaluation of sicca symptoms. In particular, we emphasize the need for care in choosing the site for minor salivary gland biopsy, and we describe the histologic features that aid in the evaluation of these biopsy specimens. In an attempt to identify a population of patients whose conditions might have a common etiopathogenesis and, thus, a common treatment program, we propose the following criteria for a diagnosis of SS: 1) objective evidence of keratoconjunctivis sicca, as documented by rose bengal or fluorescein dye staining; 2) objective evidence of diminished salivary gland flow; 3) minor salivary gland biopsy, obtained through normal mucosa, with the specimen containing at least 4 evaluable salivary gland lobules, and having an average of at least 2 foci/4 mm2; 4) evidence of a systemic autoimmune process, as manifested by the presence of autoantibodies, such as rheumatoid factor and/or antinuclear antibody. The diagnosis of "definite SS" would be made when all 4 criteria are met; the diagnosis of "possible SS" would be made when 3 criteria are present. Specific exclusions for this diagnosis are preexisting lymphoma, graft-versus-host disease, sarcoidosis, and acquired immunodeficiency disease.(ABSTRACT TRUNCATED AT 250 WORDS)

The radiographic diagnosis of sacroiliitis. A comparison of different views with computed tomograms of the sacroiliac joint.

Conventional radiography is the standard method of objectively identifying sacroiliitis. Single views of the sacroiliac joints can be unequivocally interpreted in 70-80% of patients with low back pain. A series of views usually correctly resolves the ambiguity in the remaining 20-30% of patients (67% correct). Computed tomography will be helpful in the few patients in whom a series of views produces equivocal interpretation.

Plasma protein binding by monosodium urate crystals. Analysis by two-dimensional gel electrophoresis.

Using 2-dimensional O'Farrell gel electrophoresis, we have mapped the proteins from undiluted plasma and serum which bind to monosodium urate (MSU) crystals. More than 30 crystal-associated polypeptides were visualized, including anionic and cationic species. Proteins increased on the crystals relative to plasma included C1q, C1-r, C1-s, fibronectin, fibrinogen, and kininogen. Crystal-bound polypeptides derived from IgG, albumin, and transferrin were recovered in decreased amounts relative to plasma. Direct evidence for activation of the complement and coagulation systems in plasma was provided by the identification of crystal-associated activation fragments of C1 and kininogen. Plasmas deficient in selected proteins (e.g., C1q and IgG) were used to define the role of these proteins in such activation events and confirmed activation of C1 in immunoglobulin-deficient plasma by MSU crystals. In summary, we have described a high resolution, semiquantitative approach to analyze protein binding to crystals, have documented the complexity of crystal-plasma protein interaction, and have provided direct evidence for the binding of coagulation system proteins and binding and activation of complement by MSU crystals, in whole plasma and IgG-deficient plasma.

Two unique shoulder disorders. Adhesive capsulitis and reflex sympathetic dystrophy syndrome.

Adhesive capsulitis and reflex sympathetic dystrophy syndrome are unique, but not rare, shoulder disorders that occur most often in persons over 50 who have experienced recent trauma. Although the etiology and nature of the disorders are not fully understood, therapy is often effective when instituted early. Adhesive capsulitis is a self-limited disorder, and patients usually recover in time. Reflex sympathetic dystrophy syndrome, however, can cause serious impairment if not treated promptly. Early mobilization of persons at risk may help reduce the incidence of the disorders.

Kinetics of collagenase and neutral protease release by neutrophils exposed to microcrystalline sodium urate.

The rates of release of the various enzymes from PMN leukocytes exposed to MSU crystals were measured. Lysozyme and neutral protease appeared to be released simultaneously and release appeared to be essentially complete by 60 minutes. In contrast, collagenase was detected only after 30 minutes incubation, reached peak concentration at 90 minutes and dropped noticeably by 180 minutes. The presence of these enzymes was not due to cell lysis since only 10% of the total cellular LDH was present in the supernates. The levels of total and active collagenase in the supernatants were measured. In contrast to latent collagenase, active collagenase levels increased continually throughout the incubation period. The gradual increase in level of active collagenase may explain the corresponding drop of latent collagenase in the longer incubation (90 minutes or more) as the latter apparently is converted to active form. The effects of collagenase on Type I collagen were examined by SDS gel electrophoresis.