bluuebunny/crossref_metadata_2025 huggingface dataset:
The public's perceptions and misperceptions of arthritis
Authors: Price James H. , Hillman Kathy S. , Toral Michael E. , Newell Susan
Published: February 2007

A telephone survey of a random sample of 300 respondents indicated that the respondents relied mainly on the mass media for their information about arthritis. Almost half of the respondents believed arthritis could be caused by “poor diet” or “cold, wet climates.” Furthermore, quack or unproven “treatments” for arthritis, such as bee venom (83%), vitamins (76%), copper bracelets (74%), special diets (57%), and DMSO (54%) were all supported by more than half of the respondents. However, a followup to the random survey, using only diagnosed arthritis patients as respondents, did not reveal as high a level of actual use of unproven treatments. Numerous factors were found which imply that the lay public is not as well informed about arthritis as arthritis patients are, and that sustained, community‐wide educational efforts about arthritis are greatly needed.
Immunohistologic and cytochemical studies of temporal arteritis
Authors: Banks Peter M. , Cohen Marc D. , Ginsburg William W. , Hunder Gene G.
Published: February 2007

Arteritic lesions from 14 patients with temporal arteritis were studied by cytochemical and immunohistochemical methods to identify the nature of the inflammatory cell infiltrate and to demonstrate immunoglobulin deposition. The infiltrating cells typically seen were histiocytes, giant cells, monocytes, and lymphocytes. The lymphocytes were mainly T cells and the majority of them were of the helper/inducer (Leu‐3a) T cell subset, as indicated by monoclonal antibody reactivity. Immunoglobulin deposits on the internal elastica were identified in only 6 patients and neutrophils were either very sparse or absent. These findings are consistent with the hypothesis that cell‐mediated immunity may be important in the pathogenesis of temporal arteritis.
Comparison of auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis
Authors: Ward John R. , James Williams H. , Egger Marlene J. , Reading James C. , Boyce Eric , Altz‐Smith Mary , Samuelson Cecil O. , Willkens Robert F. , Solsky Marilyn A. , Hayes Stanley P. , Blocka Kenneth L. , Weinstein Arthur , Meenan Robert F. , Guttadauria Maria , Kaplan Stanley B. , Klippel John
Published: February 2007

A prospective controlled, double‐blind multi‐center trial compared placebo, auranofin (an orally administered gold complex), and parenteral gold sodium thiomalate (GST) in patients with active rheumatoid arthritis (RA). Of 193 patients who received any treatment, the only important improvement identified for either auranofin or GST was for pain/tenderness scores. When 161 patients who completed 20 weeks of treatment were examined, both auranofin and GST treatments were superior to placebo as measured by improvement in number of painful and/or tender joints, joint pain/tenderness scores, physician's assessment of disease activity, and decrease in erythrocyte sedimentation rate when elevated at entry. GST was superior to placebo in improvement of joint swelling scores, anemia, thrombo‐cytosis, and rheumatoid factor. No drug‐related remissions were observed. The only statistically significant advantages of GST over auranofin for efficacy were an increase in hemoglobin concentration and decrease of thrombocytosis with GST. Withdrawals for adverse effects were 5 times more frequent with GST treatment. Thrombocytopenia, proteinuria, elevated liver enzymes, “nitritoid” reactions, and “gold pneumonitis” were observed only in the GST treatment group. These results confirm that both parenteral and oral gold may be effective for the treatment of RA, that GST tends to show greater efficacy than auranofin, and that auranofin has fewer significant adverse effects than GST. However, long‐term benefits, tolerability, and safety cannot be inferred from this study.
The role of hypertension in the vascular disease and myocardial infarcts associated with murine systemic lupus erythematosus
Authors: Hang Leming , Stephens‐Larson Patricia , Henry James P. , Dixon Frank J.
Published: February 2007

The several kinds of mice that spontaneously develop acute systemic lupus erythematosus (SLE)—BXSB males, MRL/I males and females, and (NZB x W)F1 females—have a 15–20% incidence of degenerative vascular disease (DVD) and myocardial infarcts (MI) in which the affected coronaries contain deposits of immunoreactants, presumably in the form of immune complexes. Among the F1 hybrid crosses of SLE mice, only the (NZW x BXSB)F1, (W x B)F1 male has a significantly higher incidence of DVD/MI (80%). Search for possible causes of this high incidence of myocardial infarcts revealed several unique features of this mouse: hypertension, thrombocytosis, and early onset of circulating immune complexes and glomerulonephritis. Our attempts to prevent this DVD/MI focused on: reduction of hypertension, prevention of thrombosis, and immunosuppression. Immunosuppression by Cytoxan resulted in almost complete prevention of both the SLE disease and DVD/MI. Administration of bretylium, an antihy‐pertensive and anti‐arrhythmic agent, resulted in reduction of blood pressure and the severities of glomerulonephritis, DVD, and MI; phritis, DVD, and MI; it also slightly reduced the levels of circulating immune complexes and leukocytosis. Of the 4 antithrombotic agents used, only aspirin showed some reduction in the incidence of DVD/MI and delay of glomerulonephritis‐associated mortality.
Effect of lymphoplasmapheresis on clinical indices and t cell subsets in rheumatoid arthritis a double‐blind controlled study
Authors: Verdickt Wilfried , Dequeker Jan , Ceuppens Jan L. , Stevens Erik , Gautama Koo , Vermylen Carl
Published: February 2007

The effects of lymphoplasmapheresis on immunologic indices, including T cell subsets, and on clinical parameters of rheumatoid arthritis were evaluated in a controlled double‐blind trial. Twenty patients were randomized to receive either 6 lymphoplasmapheresis sessions or a seemingly identical control procedure over a 3‐week period. Lymphoplasmapheresis produced significant reduction in serum levels of total lymphocytes, erythrocyte sedimentation rate, C‐reactive protein, and IgG. These serologic measures returned to baseline 5 weeks after lymphoplasmapheresis. No change in the imbalance of T cell subsets (increased helper/suppressor ratio) was observed. No changes in the serologic measures, except IgA, were observed in the control group. An improvement in some of the clinical parameters was observed in both the lymphoplasmapheresis and control groups. A rebound above baseline values for several parameters was observed in both the lymphoplasmapheresis and the sham apheresis groups.
Association of HLA‐DR4/Dw4 and DR2/Dw2 with radiologic changes in a prospective study of patients with rheumatoid arthritis
Authors: Young Adam , Jaraquemada Dolores , Awad Juliette , Festenstein Hilliard , Corbett Mary , Hay Frank C. , Roitt Ivan M.
Published: February 2007

Patients admitted to a prospective study within a year of onset of suspected rheumatoid arthritis showed a positive correlation between HLA‐Dw4 and the eventual severity of peripheral radiologic changes. Dw4 and DR4 were strongly associated with severity of erosions when analysis was restricted to each of the following: patients with erosions, those under 50 at onset, and all females. Relationships were consistently stronger with Dw4 than with DR4. Another D‐related specificity, MT3, was positively correlated and Dw2/DR2 negatively correlated with erosions.
Clonal heterogeneity in the fibroblast response to mononuclear cell derived mediators
Authors: Korn Joseph H. , Torres Daria , Downie Elaine
Published: February 2007

Human dermal fibroblasts were examined for heterogeneity in proliferation and prostaglandin E2 (PGE2) synthetic response to supernates of mitogen activated mononuclear cell cultures. Eleven substrains from a single neonatal foreskin culture displayed marked clonal heterogeneity in the fibroblast response to mononuclear cell derived mediators. Supernates of mononuclear cell cultures stimulated fibroblast PGE2 synthesis and suppressed proliferation. Substrains displayed tenfold differences in PGE synthesis and the extent of growth suppression. Release of immunologic mediators at sites of inflammatory lesions could lead to alterations in the clonal composition and phenotypic expression of connective tissue cells.
Metalloproteinases and collagenase inhibitors in rheumatoid synovial fluid
Authors: Cawston T. E. , Mercer E. , Silva M. De , Hazleman B. L.
Published: February 2007

The levels of metalloproteinases and metalloproteinase inhibitors were measured in rheumatoid synovial fluid. Reliable estimates of total enzyme and inhibitor levels in the synovial fluids were obtained only after hyaluronidase treatment and gel filtration. Three latent metalloproteinases were found which, after activation, degraded collagen, proteoglycan, and gelatin. These enzymes closely resembled the metalloproteinases secreted into connective tissue culture medium. In addition to α2 macroglobulin, an Mr 30,000 collagenase inhibitor was detected which closely resembled the tissue inhibitor of metalloproteinase found in tissue culture medium.
Neutral proteases capable of proteoglycan digesting activity in osteoarthritic and normal human articular cartilage
Authors: Martel‐Pelletier Johanne , Pelletier Jean‐Pierre , Cloutier Jean‐Marie , Howell David S. , Ghandur‐Mnaymneh Latifa , Frederick Jr J. Woessner
Published: February 2007

Proteases have been postulated to account for the progressive disappearance of matrix proteoglycans in osteoarthritic (OA) cartilage. The digestion of endogenous proteoglycans by neutral proteases in human OA cartilage homogenates has been measured and compared with that of normal age‐matched controls. Cartilage was obtained from 16 patients at the time of knee arthroplasty and from 7 accident victims. Tissue blocks were cut from the tibial plateau; part was used for histologic grading of the severity of OA and part was homogenized for the quantification of neutral metallo‐and serine protease activities, based on the release of digested products from endogenous proteoglycans. Total metalloprotease activity (latent plus active forms) was elevated 3‐ to 10‐fold in all diseased cartilage. This elevation was already significant in mild disease, but was greatest in samples of moderate to severe disease. The active form of the enzyme was highest at the center of erosions and decreased in the margins of the plateau. The digestion of proteoglycans, as distinct from their mere release from the tissue, was demonstrated by chromatography on Sepharose‐CL2B and by large pore electrophoresis. Serine protease activity on proteoglycans was much lower than that of metalloprotease. The mean activity was highest in mild disease and declined in the severe disease samples, but the difference between these 2 groups and the controls was not statistically significant. The results of this study are consistent with the hypothesis that the neutral metalloproteases of cartilage are involved in the degradation of proteoglycans in osteoarthritis.
Does Hyperuricemia Protect from Rheumatoid Inflammation?
Authors: Agudelo Carlos A. , Turner Robert A. , Panetti Marguerite , Pisko Edward
Published: February 2007

The negative association between gout and rheumatoid arthritis is well accepted. The reason for this mutual exclusion is not clear; a protective immunosuppressive effect of hyperuricemia has been included among possible explanations. To test this hypothesis, we reviewed the charts of 160 rheumatoid arthritis patients on whom clinical information and followup for at least a year were available. We selected those patients with persistent hyperuricemia as defined by serum urate levels averaging above 7.5 mg% for at least 6 months. We found 12 patients fulfilling such criteria, and 11 of these were judged to have quiescent, minimally active, or inactive disease during hyperuricemic periods. In 2 patients, flares of the rheumatoid process coincided with normalization of serum urate levels. We propose that persistent hyperuricemia may protect against or decrease the expression of rheumatoid inflammation.
Systemic lupus erythematosus with paraproteinemia
Authors: Rubin Laurence , Urowitz Murray B. , Pruzanski Waldemar
Published: February 2007

Nine patients (2.2%) in a group of 415 who were followed in a longitudinal prospective study of systemic lupus erythematosus (SLE) were found to have various monoclonal (M) proteins in their blood (IgG [6 patients], IgA [2 patients], IgM [1 patient]). No other findings compatible with plasmacytic dyscrasia were found. Bence Jones proteinuria was absent. Bone marrow aspirates and skeletal radiographs did not reveal any associated features of malignancy. Four of the 9 patients were under the age of 50. From the point of view of the M components, 3 groups emerged: transient (2 patients), persistently stable (6 patients), and increasing serum concentrations (1 patient). Using current measures of disease status, no correlation was apparent between the presence, type, and concentration of the M protein and the clinical and laboratory variables of lupus activity. Thus, M proteins were found in 2% of our SLE patients, but their relationship to the polyclonal B cell activation seen in this disorder, or perhaps to therapeutic modalities used in its treatment, remains to be elucidated.
Misuse of statistical methods in arthritis and rheumatism
Authors: Felson David T. , Adrienne Cupples L. , Meenan Robert F.
Published: February 2007

Articles published in Arthritis and Rheumatism in 1982 were compared with those from 1967–68 to evaluate trends in statistical methods and in the quantity and character of statistical misuse. Results show that among articles in 1982 using statistics, 66% contained methodologic errors. The percentage was similar in 1967–68, although fewer articles used statistics. In 1967–68 the most common error was failure to identify the statistical method used, whereas in 1982 multiple testing errors predominated, specifically, use of the t‐test to compare 3 or more groups and comparison of 2 groups on multiple variables. The availability of calculators and computers which readily perform complex data analysis may underly the emergence of multiple testing errors. To compare multiple groups, we suggest using analysis of variance instead of the t‐test. To avoid multiple testing errors, we recommend limiting the number of tests performed, lowering the alpha (significance) level, or using multivariate techniques.
Erosive azotemic osteoarthropathy
Authors: Rubin Laurence A. , Fam Adel G. , Rubenstein Joel , Campbell John , Saiphoo Carl
Published: February 2007

Fifty‐nine patients with end‐stage renal disease undergoing long‐term dialysis were studied prospectively for joint disease. Radiographic assessment allowed division of patients into 3 groups: group 1 included 12 patients with renal osteodystrophy and erosions of the metacarpophalangeal, proximal interphalangeal, distal interphalangeal, shoulder, wrist, and knee joints; group 2 had 11 patients with renal osteodystrophy without articular erosions; group 3 included 36 patients without osteodystrophy or erosions. Clinical manifestations were frequent in patients of group 1 and included episodes of arthralgias of the metacarpophalangeal, wrist, proximal interphalangeal, and knee joints. Patients of groups 1 and 2, particularly those of group 1, had a longer mean duration of dialysis and a higher mean serum alkaline phosphatase level compared with group 3 patients. The study indicates that there is a relatively high incidence (20%) of erosive arthropathy in dialysis patients. Renal osteodystrophy, more specifically, secondary hyperparathyroidism, and duration of dialysis are important factors in the development of this articular disorder.
Anticollagen antibodies and immune response gene products in rheumatoid arthritis
Authors: Collier David H. , Kerwar S. S. , Garovoy Marvin R. , Fye Kenneth H. , Stobo John D.
Published: February 2007

Circulating antibodies to native and denatured types I and II human and bovine collagens were assayed in patients with rheumatoid arthritis (RA), patients with other rheumatic diseases, and normal individuals. A subgroup of this population was also assayed for reactivity with typing reagents which detect determinants (MT and HLA‐DR) present in human immune response gene products. The mean titers of antibodies to each collagen tested were not significantly higher in RA patients when compared with patients who had other rheumatic diseases. Although both MT3 and MT4 were significantly associated with RA, there was no significant association between the anticollagen antibodies and any MT type or HLA‐DR4. These studies raise a question concerning the role of collagen antibodies in the pathogenesis of RA and suggest that genes distinct from those coding for HLA‐DR may play a role in the expression of the disease.
Small airways function in nonsmokers with rheumatoid arthritis
Authors: Sassoon Catherine S. H. , Mcalpine Samuel W. , Tashkin Donald P. , Baydur Ahmet , Quismorio Frank P. , Mongan Edward S.
Published: February 2007

To evaluate the possible relationship between rheumatoid arthritis (RA) and airways dysfunction independent of cigarette smoking, we studied 19 lifetime nonsmokers with RA and 47 healthy nonsmokers. Ten tests of small airways function were administered to the subjects. In addition, diffusing capacity and static lung compliance were measured, and upstream airway conductance at mid‐to‐low lung volumes was calculated. Mean values were not significantly lower in the RA group than in the control group in any of the tests of small airways function. Three of the 19 (16%) patients with RA versus 15 of the 47 (32%) control subjects had abnormal findings on >2 tests of small airways function (P > 0.1). Although mean diffusing capacity and static lung compliance were both within normal limits in each group, the former tended to be lower, while the latter was significantly lower, in the RA subjects. We conclude that airways dysfunction in RA, if present, is probably related to factors other than the underlying disease; if an association between RA and small airways abnormality is present in some patients, its prevalence is too small to have been detected in our sample.
IgG and IgM antibody to native type ii collagen in rheumatoid arthritis serum and synovial fluid evidence for the presence of collagen‐anticollagen immune complexes in synovial fluid
Authors: Clague Roy B. , Moore Lindsey J.
Published: February 2007

Levels of IgG and IgM antibody to native type II collagen, a component of articular cartilage, were measured by a specific solid‐phase radioimmunoassay, in 48 rheumatoid arthritis patients. Good correlations were found between the levels in sera and those in synovial fluids. Collagenase digestion caused a significant rise in specific antibody levels in synovial fluids, indicating the presence of intraarticular collagen‐anticollagen complexes. These immune complexes may be one mechanism for perpetuation of inflammation in some rheumatoid arthritis patients.
Hereditary joint disorder in progressive ankylosis (ank/ank) mice I. association of calcium hydroxyapatite deposition with inflammatory arthropathy
Authors: Hakim Frances T. , Cranley Robert , Brown Kenneth S. , Eanes Edward D. , Harne Leslie , Oppenheim Joost J.
Published: February 2007

Progressive ankylosis (ank), a murine autosomal recessive mutation, produces an inflammatory joint disorder associated with intraarticular calcium hydroxyapatite deposition and culminates in fusion of the joints. Joints in the feet become stiffened and swollen with milky white fluid containing polymorphonuclear leukocytes, large mononuclear macrophage‐like cells, and calcium hydroxyapatite. The joints develop a proliferative synovitis, sometimes associated with marginal erosions of the articular cartilage and periosteal bone. Subsequently, cartilaginous osteophytes, extending outward from the subchondral bone, bridge the margins of the joint and undergo ossification. The progressive ankylosis mutation provides a useful system for investigating calcium hydroxyapatite‐associated arthropathies.
Quantitative histologic studies on the pathogenesis of periarticular osteoporosis in rheumatoid arthritis
Authors: Shimizu Shinichi , Shiozawa Shunichi , Shiozawa Kazuko , Imura Shigeaki , Fujita Takuo
Published: February 2007

The pathogenesis of periarticular osteopenia in rheumatoid arthritis (RA) was investigated by histomorphometry on juxtaarticular bone removed during joint surgery. Twenty areas from 12 RA patients were compared with 14 areas from 6 osteoarthritis (OA) patients. There was no difference between the 2 groups in the percent of total bone volume. However, increased bone formation was suggested by an increase in the percent of active osteoid surface in RA compared with that in OA. Bone resorption was also increased in RA, as evidenced by increases versus OA in percent total resorptive surface, percent active resorptive surface, and number of osteoclasts. These results demonstrate increased turnover of bone in RA, especially in the resorptive phase of the periarticular trabecular bone. It is proposed that soluble factor(s) synthesized in the contiguous rheumatoid synovium may be transferred to the periarticular bone space, stimulating osteoclasts to resorb bone.
Atrophic gastritis in sjögren's syndrome. Morphologic, biochemical, and immunologic findings
Authors: Maury C. P. J. , Törnroth T. , Teppo A‐M.
Published: February 2007

Gastric studies were carried out in 16 patients with well‐documented Sjögren's syndrome (SS), 43 matched rheumatic disease patients without SS, and 7 patients with chronic atrophic gastritis not associated with SS. Chronic atrophic gastritis was a much more common finding in the SS patients than in the rheumatic disease control patients. Significant hypopepsinogenemia was present in 11 of 16 SS patients. In 6 patients this was combined with hypergastrinemia, a combination highly specific for chronic atrophic gastritis. The lowest pepsinogen levels were seen in patients with primary SS associated with high levels of SS‐B antibody. On a histologic and biochemical basis, it was not possible to distinguish the gastric findings in primary SS from those in secondary SS, nor to distinguish chronic atrophic gastritis associated with SS from that not associated with SS. We conclude that chronic atrophic gastritis is a prominent feature in SS and that the severity of the gastritis appears to correlate with some serologic parameters of SS.
A longitudinal study of high and low avidity antibodies to double‐stranded DNA in systemic lupus erythematosus
Authors: McGrath Hugh , Biundo Joseph J.
Published: February 2007

The role of avidity in the pathogenicity of double‐stranded DNA/anti–double‐stranded DNA immune complexes in systemic lupus erythematosus (SLE) has been controversial. We used polyethylene glycol to identify low avidity antibodies and the standard Farr assay to detect high avidity antibodies against double‐stranded DNA in a longitudinal study of sera from 19 patients with SLE. We found that high and low avidity antibodies to double‐stranded DNA did not move independently, but instead, rose and fell in a parallel and relatively fixed manner in these patients. The mechanisms responsible for the changes in titer of anti–double‐stranded DNA antibody appeared nondiscriminatory in regard to avidity. In addition, the humoral immune response in SLE depicted by these antibody measurements appeared atypical, lacking maturational features.
Role of synovial membrane inflammation in cartilage matrix breakdown in the Pond‐Nuki dog model of osteoarthritis
Authors: Pelletier Jean‐Pierre , Martel‐Pelletier Johanne , Ghandur‐Mnaymneh Latifa , Howell David S. , Woessner Jr. J. Frederick
Published: February 2007

Using the Pond‐Nuki procedure, osteoarthritis was induced in 26 crossbred dogs. Their right knees were subjected to anterior cruciate ligament sectioning, and their left knees received a sham operation. The unoperated knees of 7 additional dogs served as controls. Cartilage and synovial membranes were excised 2, 4, and 8 weeks after surgery. Collagenolytic activity, determined by direct tissue assay, was higher at all times tested in osteoarthritic cartilage and synovia than in sham operated and control specimens. The increased collagenolytic activity of the cartilage did not correlate with the collagenolytic activity of the synovium, but it did correlate (r = 0.57) with the degree of synovial inflammation, which was graded histologically. Treatment for 4 weeks with prednisone (0.20–0.25 mg/kg/day) blocked the increased collagenolytic activity of the cartilage. Our results indicate that stimulating factors may, but collagenolytic enzymes probably do not, diffuse from the synovium to the cartilage and modulate tissue breakdown. Prednisone may also suppress cartilage breakdown by either acting at the level of the synthesis or by acting on the release/action of the stimulating factors.
The immunoreactivity, ligand, and cell binding characteristics of rheumatoid synovial fluid fibronectin
Authors: Carsons Steven , Lavietes Beverly B. , Diamond Herbert S. , Kinney Sandra G.
Published: February 2007

Fibronectin promotes macrophage adherence and expression of Fc receptors, is chemotactic for fibroblasts, and is an opsonin for fibrin and denatured collagen. These properties suggest a role for fibronectin in the modulation of joint inflammation. Since structural modification of the fibronectin molecule has been shown to result in loss or de novo acquisition of opsonic and chemotactic activity, we determined the functional and immunochemical properties of fibronectin isolated from the inflamed joint. Eighty‐six percent of synovial fluids obtained from patients with active rheumatoid arthritis (RA) contained fibronectin fragments, and 39% of the fluids no longer displayed the dimeric form. Compared with native fibronectin, RA peptides were as active in promoting synoviocyte chemotaxis and in glycosaminoglycan binding, but displayed lower affinity for fibrin and gelatin. Although comparable with intact protein in augmenting monocyte attachment to gelatin, the RA synovial fluid peptides did not augment monocyte attachment to fibrin. Analysis of whole synovial fluid and isolated fibronectins by enzyme immunoassay showed that the increased fibronectin immunoreactivity, previously reported in RA synovial fluid, measures intact and nearly intact protein and does not measure extensively degraded fragments.
Cricopharyngeal obstruction in inflammatory myopathy (polymyositis/dermatomyositis). Report of three cases and review of the literature
Authors: Kagen Lawrence J. , Hochman Raymond B. , Strong Elliot W.
Published: February 2007

Three adults, 2 of whom had polymyositis and 1 with dermatomyositis, developed dysphagia during the course of their illness. Results of esophageal manometry supplemented with esophageal radiography indicated the presence of cricopharyngeal achalasia. Because of the severity of this disorder, which is associated with aspiration of esophageal contents into the airways, surgery to divide the cricopharyngeal musculature was performed in 2 patients, giving complete relief of their symptoms. Prednisone dosage was not increased to treat this condition since it arose not from weakness but from obstruction. A biopsy specimen taken from 1 patient demonstrated inflammatory changes in the obstructing muscle. A review of these 3 patients and 3 previously reported cases indicates that cricopharyngeal obstruction can be a dominant cause of dysphagia in patients with myositis. The recognition of this entity is important in the management of patients with myositis because: 1 it has serious and potentially life‐threatening implications; and 2 in certain cases, it can be effectively treated with surgery.
Decreased coronary reserve in primary scleroderma myocardial disease
Authors: Kahan Andréa , Nitenberg Alain , Foult Jean‐M. , Amor Bernard , Menkes Charles‐J. , Devaux Jean‐Y. , Blanchet Fraņloise , Perennec Jeannine , Lutfalla Geneviève , Roucayrol Jean‐C.
Published: February 2007

We assessed coronary reserve, by measuring the increase in coronary sinus blood flow (CSBF) after intravenous administration of dipyridamole (0.14 mg/kg/minute for 4 minutes), in 7 patients with primary scleroderma myocardial disease (PSMD) and in 7 control subjects. Coronary reserve was greatly impaired in PSMD: before administration of dipyridamole, CSBF was similar in patients with PSMD (89 ± 32 ml/minute/100 gm, mean ± SD) and in controls (100 ± 15 ml/minute/100 gm); after dipyridamole infusion, CSBF was significantly lower in patients with PSMD (191 ± 45 ml/minute/100 gm) than in controls (399 ± 58 ml/minute/100 gm) (P < 0.01). Six of the 7 patients with PSMD had angiographically normal epicardial coronary arteries and normal left ventricular function. Decreased coronary reserve may be an important contributor to the pathogenesis of primary scleroderma myocardial disease.
Coronary arthritis in mice following the systemic injection of group b Lactobacillus casei cell walls in aqueous suspension
Authors: Lehman Thomas J. A. , Walker Sharyn M. , Mahnovski Vladimir , McCurdy Deborah
Published: February 2007

We describe the induction of an asymmetric, focal, inflammatory coronary arteritis by a single intraperitoneal injection of group B Lactobacillus casei cell wall fragments in various inbred mouse strains. This coronary arteritis resembles the arteritis which is responsible for the 1–2% fatality rate among children with mucocutaneous lymph node syndrome. Coronary arteritis developed in 18 of 26 C57BL/6, 14 of 26 A/J, 7 of 15 Balb/c, and 8 of 15 C3Heb/FeJ mice injected. It also developed in 2 of 4 „nude”︁ A/J background mice and 3 of 4 „nude”︁ C57BL/6 mice, but in 0 of 15 C3H/HeJ mice. Lesions were evident as early as 3 days following injection. The development of arteritis was accompanied by disruption of the arterial intima and media with true aneurysm formation. Measurement of serial IgG and IgM titers indicated no relationship between the development of coronary arteritis and immunoglobulin response to L casei cell walls or the development of antibodies cross‐reactive with normal myocardium. The absence of disease in only the C3H/HeJ mice, which are known to have defective macrophages, suggests that macrophages may play an essential role in the pathogenesis of coronary arteritis.
IgG and IgM rheumatoid factor synthesis in rheumatoid synovial membrane cell cultures
Authors: Wernick Richard M. , Lipsky Peter E. , Marban‐Arcos Eusebio , Maliakkal John J. , Edelbaum Dale , Ziff Morris
Published: February 2007

The detection of rheumatoid factors (RFs) in synovial membranes and fluids of patients with rheumatoid arthritis (RA) has suggested that local production of these antiimmunoglobulin autoantibodies may have a role in the pathogenesis of synovitis. To quantitate RF synthesis in the rheumatoid synovial membrane, 12 synovial specimens were obtained from patients with seropositive RA, 5 from patients with seronegative RA, and 6 from patients with other arthritides. Single cell suspensions were cultured, and supernatants were analyzed for IgG, IgM, IgG‐RF, and IgM‐RF by solidphase radioimmunoassays. IgM‐RF was detected in all of the 12 seropositive culture supernatants, and IgG‐RF was detected in 8 of the 12. Addition of cycloheximide to the cultures resulted in a ⩾40% decrease in the amount of IgM‐RF. A similar decrease in IgG‐RF occurred in the 4 cultures in which the largest amounts of IgG‐RF were detected. IgM‐RF synthesis represented 7.3 ± 0.7% (mean ± SEM) of the total IgM produced, and IgG‐RF represented 2.6 ± 1.1% (mean ± SEM) of the IgG synthesized in those cultures with detectable IgG‐RF. Cultures of synovial membrane cells (SMC) from seronegative RA patients or patients with other arthritides did not contain detectable amounts of IgM‐RF or IgG‐RF. Selective synthesis of RF by seropositive synovium was suggested by the observation that the fractions of synthesized IgM with RF activity were greater in the SMC supernatants than in paired sera in all cases, and the fractions of IgG with RF activity were greater in the SMC supernatants of 3 of the 4 cases in which substantial amounts of IgG‐RF were produced. Comparison of the percentages of newly synthesized IgM with RF activity in paired cultures of SMC and peripheral blood mononuclear cells similarly indicated selective synthesis of IgM‐RF by the synovium. These results demonstrate active and selective synthesis of both IgG‐RF and IgM‐RF by seropositive SMC. However, RFs account for only a minor fraction of the total Ig produced.
Cellular immunity to collagen and laminin in scleroderma
Authors: Huffstutter J. Eugene , Delustro Frank A. , LeRoy E. Carwile
Published: February 2007

Peripheral blood mononuclear cells (PBMC) obtained from scleroderma patients and normal controls were cultured in the presence of types I and IV collagen, intima collagen, laminin, and phytohemagglutinin. PBMC from 9 of 19 patients (47%) demonstrated lymphocyte transformation in response to laminin, and those from 2 of 17 patients (12%) demonstrated reactivity to type IV collagen. None of the patient PBMC were responsive to type I collagen or to intima collagen. Healthy controls failed to demonstrate lymphocyte transformation in response to laminin or collagens. Analysis of clinical data, including age, disease duration, and degree of skin thickening and internal organ involvement, failed to predict the response to laminin or type IV collagen. The significance and disease specificity of this cellular immunity to laminin and, with lower frequency, to type IV collagen, that occurs in some scleroderma patients are unknown.
Inspiratory muscle dysfunction and unexplained dyspnea in systemic lupus erythematosus
Authors: Jacobelli Sergio , Moreno Rodrigo , Massardo Loreto , Rivero Santiago , Lisboa Carmen
Published: February 2007

The role of inspiratory muscle dysfunction in lung volume restriction and unexplained dyspnea was studied in 16 consecutive patients with systemic lupus erythematosus. Maximal mouth inspiratory pressure (PIM) and maximal transdiaphragmatic pressure (Pdi max) were measured. Pdi and its components were determined during quiet breathing. No significant association was found between the activity of the disease, several serologic markers, and the inspiratory muscle dysfunction. No specific anti‐skeletal muscle antibody was found in these patients. Significant correlations were found between the degree of dyspnea and PIM (r = −0.69, P < 0.01) and Pdi max (r = −0.75, P < 0.001); however, dyspnea did not correlate with specific lung compliance. Vital capacity correlated significantly with the degree of dyspnea (r = −0.813, P < 0.001) and with Pdi max (r = 0.544, P < 0.05). No correlation was found between vital capacity and specific lung compliance. We conclude that inspiratory muscle dysfunction can be an important mechanism in the pathogenesis of the lung volume restriction and dyspnea in patients with systemic lupus erythematosus.
Antiarthritic drugs containing thiol groups scavenge hypochlorite and inhibit its formation by myeloperoxidase from human leukocytes. A therapeutic mechanism of these drugs in rheumatoid arthritis?
Authors: Cuperus Roelck A. , Muijsers Anton O. , Wever Ron
Published: February 2007

We investigated the effect of antiarthritic drugs containing thiol groups, such as D‐penicillamine, tiopronin (N‐[2‐mercaptopropionyl]glycine), sodium aurothiomalate, and aurothioglucose, on the chlorinating activity of myeloperoxidase purified from human leukocytes. Hypochlorite, the reactive product of the reaction catalyzed by myeloperoxidase, was effectively scavenged by these antiarthritic drugs, and in addition, D‐penicillamine and tiopronin inhibited myeloperoxidase itself. The above‐mentioned effects of these drugs were observed at concentrations that occur in the serum of rheumatoid arthritis patients treated with these agents. We suggest that the therapeutic effect of these antiarthritic drugs may be due to the protection of tissues against the reactive HOCl released by activated granulocytes at inflamed sites.
Noninvasive evaluation of cardiac dysrhythmias, and their relationship with multisystemic symptoms, in progressive systemic sclerosis patients
Authors: Ferri Clodoveo , Bernini Luigi , Bongiorni Maria Grazia , Levorato Dianora , Viegi Giovanni , Bravi Prassede , Contini Carlo , Pasero Giampiero , Bombardieri Stefano
Published: February 2007

Fifty‐three patients (34 who had diffuse scleroderma, and 19 who had CREST syndrome [calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias]) were studied by noninvasive procedures, including resting electrocardiogram (ECG), continuous 24‐hour Holter ECG monitoring, M‐mode echocardiography, and 2‐dimensional echocardiography. Only 22 patients (42%) had abnormalities such as conduction defects, supraventricular or ventricular arrhythmias, or ST‐T changes detected on resting ECG. In contrast, using Holter monitoring, the number of conduction abnormalities seen increased from 10 to 16 patients and transient ST‐T changes increased from 2 to 18 patients. Forty‐eight patients had ventricular arrhythmias, with multiform ventricular premature beats in 21 (40%), pairs of runs of ventricular tachycardia in 15 patients (28%), and 1 or more runs of ventricular tachycardia in 7 (13%). Echocardiography detected asymmetric septal hypertrophy in 10 patients, impaired ventricular function in 9 patients, congestive cardiomyopathy in 2, mitral prolapse in 4, and pericardial effusion in 3 patients. Multiform and/or repetitive ventricular premature beats occurred more frequently in patients with echocardiographic abnormalities, but were also present in patients who had normal findings on echocardiographic examination. Cardiac involvement was not correlated with clinical variants of scleroderma (CREST syndrome or diffuse scleroderma), nor with other signs and symptoms of the disease. Thus, cardiac involvement is found much more frequently than would be expected from clinical symptoms or from results of resting ECG alone; therefore, Holter monitoring and echocardiography should be included in the routine workup of patients who have scleroderma.
The value of biopsy in patients with monarticular juvenile rheumatoid arthritis of recent onset
Authors: Konttinen Yrjö T. , Bergroth Ville , Kunnamo Ilkka , Haapasaari Jarkko
Published: February 2007

The histopathology of arthroscopic biopsy material from the knees of 8 patients with monarticular juvenile rheumatoid arthritis (JRA) of recent onset and of 4 control patients was examined using a histochemical method for acid α‐naphthyl acetate esterase and an avidin‐biotin‐peroxidase complex method for different cell subtype‐specific surface antigens. According to results of our prospective, single‐blind study, nonspecific synovitis was observed in those biopsy samples obtained early in the course of disease. The samples were also characterized by cellular changes that are quite distinct from those described in patients with chronic rheumatoid synovitis. JRA must be considered the cause of symptoms if no orthopedic or infectious disease is found at arthroscopy in children with monarticular symptoms of recent onset and if nonspecific synovitis is observed in the histopathologic specimen. This pathologic description, however, does not correspond to that of classic rheumatoid synovitis. In our studies, we found that mononuclear cells displaying diffuse cytoplasmic esterase and surface Ia formed a large proportion of all inflammatory cells in situ. There were comparatively few activated Ia+ T cells and plasma cells. These observations suggest that exudative features and nonspecific cellular inflammation are prominent at onset of JRA. The immune response, in the form of immunocompetent T and B cells, seems to be more extensively involved in chronic JRA and may represent secondary features of the disease.
Adult‐onset still's disease. Disease course and HLA associations
Authors: Wouters Jacques M. G. W. , Reekers Paul , van de Putte Levinus B. A.
Published: February 2007

Disease course and HLA antigens were determined in 29 patients with definite and 13 patients with probable adult‐onset Still's disease (AOSD). Twenty‐six patients had persistent disease with continuous disease activity for at least 1 year. Radiographic examination revealed evidence of joint destruction in 26 patients. In 15 patients, at least 1 root joint was impaired. The frequency of DR4 was increased in the total group of patients (35%, P = 0.03) and in the 29 patients with definite AOSD (41%, P = 0.02) compared with the frequency in normal controls (20%). None of the patients was positive for DR1, and only 1 was positive for Bw35. The frequency of DRw6 was increased in the patients with involvement of at least 1 root joint (40%, P = 0.03) compared with the patients without involvement of these joints (11%).
Dietary fish oil reduces progression of established renal disease in (NZB × NZW)F1 mice and delays renal disease in BXSB and MRL/1 strains
Authors: Robinson Dwight R. , Prickett James D. , Makoul Gregory T. , Steinberg Alfred D. , Colvin Robert B.
Published: February 2007

Previous studies have shown that dietary marine lipids containing large quantities of n‐3 polyunsaturated fatty acids, administered to (New Zealand black × New Zealand white)F1 and MRL‐lpr/lpr mice before the development of renal disease, reduce the severity of glomerulonephritis in mice of these strains. The present study demonstrated that delayed administration of a marine lipid diet, 25% menhaden oil (MO) by weight, until after the onset of overt renal disease, also resulted in significant improvement in rates of mortality, proteinuria, and histologic evidence of glomerular injury, compared with control animals fed a diet that contained mostly saturated fatty acids, 25% beef tallow. The MO diet also reduced the histologic severity of renal disease in male BXSB/MpJ and male MRL‐lpr/lpr mice. In contrast, necrotizing vasculitis was more frequent in small and medium‐sized renal arteries of the MRL‐lpr/lpr mice fed MO than in those fed beef tallow (33.4% versus 7.6%, respectively).
Electron microscopic study of HLA‐DR and monocyte/macrophage staining cells in the rheumatoid synovial membrane
Authors: Iguchi Tetsuhiro , Kurosaka Masahiro , Ziff Morris
Published: February 2007

We examined synovial membrane samples from 6 rheumatoid arthritis (RA) and 3 osteoarthritis patients and from 1 normal subject, by an immunoelectron microscopic technique using anti‐HLA‐DR (anti‐Ia) and anti‐monocyte/macrophage (63D3) monoclonal antibodies. In the lining layer, the type A macrophage‐like cells were strongly DR+ and 63D3+, whereas the type B fibroblast‐like cells were almost completely negative. Lymphocyte‐rich areas (containing more than 90% densely packed lymphocytes) showed weak and patchy DR staining of the lymphocytes. In these areas, 3–5% of the cells were macrophage‐like cells which were 63D3‐, a type of staining compatible with that of the interdigi‐tating cell (IDC). In the plasma cell‐containing (transitional) areas, many strongly DR+ macrophage‐like cells were observed in close contact with lymphocytes and plasma cells. Ten to twenty percent of these cells were 63D3‐, which suggests that they were IDC. Cells with the structural appearance of IDC were most frequently seen in those transitional areas which contained elevated concentrations (50–70%) of lymphocytes. In uninfiltrated interstitial areas, approximately 50% of the cells stained strongly with both anti‐DR and 63D3 antibody, indicating that they were cells of monocyte/macrophage lineage, presumably histiocytes. This investigation has demonstrated the presence of the DR antigen in the RA synovial membrane on 1) phagocytic cells of the lining area, 2) lymphocytes and small numbers of IDC‐like cells in dense, lymphocyte‐rich areas, 3) large numbers of macrophage‐like cells, of which some had the morphologic appearance of IDC, in transitional or plasma cell‐containing areas, and 4) histiocytic cells in uninfiltrated interstitial areas. The observation of large numbers of DR+ macrophages and IDC‐like cells in close contact with lymphocytes and plasma cells in the RA synovial membrane emphasizes their role in an active immune response. The observation of substantial numbers of potentially immunocompetent, DR+ histiocytic cells in uninfiltrated regions of the synovial membrane suggests that such cells may play a role in the progression of the synovial inflammatory reaction.
Estimation of the relative avidity of 19S IgM rheumatoid factor secreted by rheumatoid synovial cells for human IgG subclasses
Authors: Robbins Dick L. , Skilling Jeffrey , Benisek William F. , Wistar Richard
Published: February 2007

19S IgM rheumatoid factors (RF) may play an important role in sustaining inflammation in rheumatoid arthritis (RA). As yet, no unique antigenic specificity for RF in RA has been identified. Because the synovium is central to the pathogenic changes in RA, RF produced therein might be pathogenically more important than serum RF. Therefore, we examined the reactivity and relative avidity of 19S IgM‐RF in serum and rheumatoid synovial cells (RSC) from 20 patients with seropositive RA. Reactivities were determined by competitive inhibition of serum RF hemolytic activity and RSC RF‐plaque‐forming cells (PFC) by added soluble antigen, i.e., monomeric human IgG subclasses. Estimation of relative avidities of RSC RF for human IgG subclasses was done by calculation of fractional RF expression in the RSC RF‐PFC assay following inhibition by IgG subclasses. RSC RF had greatest reactivity with IgG3 and IgG1, some reactivity with IgG2, and the least reactivity with IgG4. Serum RF reacted most with IgG1 and IgG2, reacted some with IgG4, but reacted poorly with IgG3. The antigenic determinants with which RSC RF reacted were common to many IgG3 molecules. The highest relative avidity of RSC RF was for IgG3. These observations indicate a selective deficiency of serum RF compared with RSC RF and suggest an important pathogenic role for these qualitatively different RSC RF molecules for in situ RF immune complex‐mediated inflammation in RA synovial tissue.
Reactivity of monoclonal anti‐type II collagen antibodies with cartilage and synovial tissue in rheumatoid arthritis and osteoarthritis
Authors: Klareskog Lars , Johnell Olof , Hulth Anders , Holmdahl Rikard , Rubin Kristofer
Published: February 2007

Monoclonal antibodies to 3 different epitopes on native type II collagen were used for immunohistochemical analysis of antigenic determinants that are exposed in the cartilage and synovial tissue obtained from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Two of the monoclonal antibodies reacted with cartilage from both OA and RA joints, but not with that from normal joints. The third monoclonal did not stain any of the cartilage sections. The 2 positive antibodies also reacted with cartilage fragments in the synovial tissue of both RA and OA joints, and in RA pannus tissue, the antibodies showed intracellular staining in many class II transplantation antigen‐expressing synovial cells lying close to the damaged cartilage.