bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspirin, hydroxychloroquine, and hepatic enzyme abnormalities with methotrexate in rheumatoid arthritis
Authors: Fries James F. , Singh Gurkirpal , Lenert Leslie , Furst Daniel E.
Published: February 2007

Levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in patients with rheumatoid arthritis from 5 centers involved in the Arthritis, Rheumatism, and Aging Medical Information System were correlated with the use of specific antirheumatic medications. Elevated levels of SGOT and SGPT were most frequent in patients taking salicylates and methotrexate (MTX) and least frequent in patients taking hydroxychloroquine. The combination of MTX and salicylates greatly increased the frequency of abnormal liver enzyme values. In contrast, the addition of hydroxychloroquine to a regimen of either MTX or aspirin essentially eliminated the SGOT and SGPT abnormalities. Results from all 5 centers were consistent and remained so after adjustment for age, sex, and disease duration. Knowledge of these important drug interactions may permit continuation of MTX therapy in patients in whom the drug might otherwise be discontinued.
Diffusing capacity of the lung and nifedipine in systemic sclerosis
Authors: Sfikakis Petros P. , Kyriakidis Michael , Vergos Constantine , Papazoglou Sotirios , Georgiakodis Fotis , Toutouzas Pavlos , Sfikakis Paul
Published: February 2007

Lung involvement in systemic sclerosis may be due in part to a functional abnormality of the pulmonary vasculature. To investigate the possible role of a pulmonary vasospastic process in this disorder, 21 non‐smoking patients who had no evidence of cardiac disease or pulmonary hypertension were evaluated with pulmonary function tests prior to administration of nifedipine, 30 minutes after a single oral dose of nifedipine (20 mg), and after 4 weeks of treatment with nifedipine (10 mg 3 times daily). Treatment with nifedipine did not significantly change any of the pulmonary function values, except for the carbon monoxide diffusing capacity (DLCO). The linear trend between the individual DLCO values at baseline and their changes immediately following the initial 20‐mg dose of nifedipine (r = −0.603, P = 0.02) and after 4 weeks of treatment (r = −0.636, P = 0.01) showed that the lower the DLCO value at baseline, the greater the improvement caused by nifedipine. These findings support the hypothesis of a potentially reversible pulmonary vasospasm in systemic sclerosis and suggest that nifedipine may be useful in the treatment of lung disease in these patients; however, further studies are needed.
Evidence for impaired t cell dna methylation in systemic lupus erythematosus and rheumatoid arthritis
Authors: Richardson Bruce , Scheinbart Lee , Strahler John , Gross Laura , Hanash Samir , Johnson Marcia
Published: February 2007

Procainamide and hydralazine inhibit T cell DNA methylation and induce autoreactivity in cloned CD4+ T cells. These drugs also induce an autoimmune syndrome, suggesting a possible relationship between DNA hypomethylation, T cell autoreactivity, and certain autoimmune diseases. To test this relationship, DNA methylation was studied in T cells from patients with rheumatoid arthritis and patients with systemic lupus erythematosus, and was found to be impaired. These results support a relationship between DNA hypomethylation and some forms of autoimmune disease.
Spontaneous rheumatoid‐like arthritis in a line of mice sensitive to collagen‐induced arthritis
Authors: Bouvet Jean‐Pierre , Couderc Jacques , Bouthillier Yolande , Franc Brigitte , Ducailar Annie , Mouton Denise
Published: February 2007

Twenty‐eight percent of 13‐month‐old male mice of the high antibody responder line of Biozzi's selection I (HI) spontaneously developed a long‐lasting inflammatory arthritis. This disease was clinically and histologically similar to human rheumatoid arthritis. The synovium of joints and some tendons was hypertrophied, with thickening of the synovial cell layer and infiltration by polymorphonuclear and mononuclear leukocytes. In some cases, synovial pannus formation led to destructive damage of articular cartilage and bone. Rheumatoid factor and antinuclear, anti‐DNA, and anti‐type II collagen (CII) antibodies were often found in the sera of both arthritic mice and clinically normal littermates. The presence of CII autoantibodies in this line of mice suggests that a potentially harmful anti‐CII T cell autoimmunity can also develop spontaneously and lead to joint damage. Moreover, HI mice are also susceptible to collagen‐induced arthritis, while a closely related mouse line (HII) is resistant to both diseases. These data support the hypothesis that collagen‐induced arthritis is pathogenetically related both to this spontaneous arthritis and to rheumatoid arthritis.
Treatment of psoriatic arthritis with oral 1,25‐dihydroxyvitamin D3: a pilot study
Authors: Huckins David , Felson David T. , Holick Michael
Published: February 2007

We conducted a 6‐month open‐label trial in which 10 patients with active psoriatic arthritis received 2 m̈g of oral 1,25‐dihydroxyvitamin D3 daily. Statistically significant improvement was noted in the tender joint count and physician global impression. Of these 10 patients, 4 had substantial (≥50%) improvement, and 3 had moderate (≥25%) improvement in the tender joint count. Two patients were unable to receive therapeutic doses because of hypercalciuria. High‐dose vitamin D may be a useful therapeutic agent for psoriatic arthritis.
Clinical and pathologic studies of twenty‐six patients with penetrating foreign body injury to the joints, bursae, and tendon sheaths
Authors: Reginato Antonio J. , Ferreiro Jose Luis , RiesterO'Connor Carolyn , Barbasan Ceferino , Arasa Javier , Bednar John , Soler Juan
Published: February 2007

Foreign body synovitis has been neglected in the rheumatology literature. We describe 26 patients in whom arthritis, bursitis, or tenosynovitis appeared within 1 day to 7 years after an initial injury by a penetrating foreign body. Twenty‐two patients presented with acute synovitis, which was followed by chronic or recurrent inflammation mimicking septic arthritis, osteomyelitis, monarticular juvenile rheumatoid arthritis, bone tumor, or apatite deposition disease. Foreign bodies were not seen in 5 inflammatory synovial fluids studied, but were seen in the synovium or periarticular tissues of 17 patients. Excisional biopsy was required in most patients for precise diagnosis and treatment.
Autoantibody to th ribonucleoprotein (nucleolar 7–2 rna protein particle) in patients with systemic sclerosis
Authors: Okano Yutaka , Medsger Thomas A.
Published: February 2007

We studied sera of 371 consecutive new patients with systemic sclerosis (SSc; scieroderma) who were first evaluated during 1984–1988. All sera were tested for antinuclear antibodies by immunofluorescence staining using HEp‐2 cells as substrate. We excluded 219 sera showing dark nucleoli and screened for antibodies to Th in the remaining 152 sera by immunoprecipitation of a 32P‐labeled HeLa cell extract. Fifteen (4.0%) of 371 sera were anti‐Th+. Anti‐Th antibodies were present in 14 (8.4%) of 167 SSc patients with limited cutaneous involvement, in 1 of 167 with diffuse cutaneous involvement, and in 0 of 37 with SSc overlap syndrome. Among 244 controls with other connective tissue diseases, anti‐Th was detected in only 3 patients, all having primary Raynaud's phenomenon of 2 years duration. In the subgroup with SSc with limited cutaneous involvement, the 14 anti‐Th+ patients had a significantly greater frequency of puffy fingers, small bowel involvement, and hypothyroidism, and a significantly lower frequency of arthralgia and/or arthritis. Their cumulative survival rate from the time of onset of symptoms was lower than that for anti‐Th— patients (78% versus 91% at 10 years), primarily due to 3 deaths from pulmonary arterial hypertension (2 from primary pulmonary hypertension and 1 from pulmonary hypertension secondary to pulmonary interstitial fibrosis). Serum anti‐Th antibodies are present almost exclusively in patients with SSc with limited cutaneous involvement or in those with primary Raynaud's phenomenon whose disease may evolve to SSc with limited cutaneous involvement, and these antibodies may identify those patients who are at greater risk for reduced survival.
Increased expression of type VI collagen genes in systemic sclerosis
Authors: Peltonen Juha , Kähäri Leena , Uitto Jouni , Jimenez Sergio A.
Published: February 2007

The expression of type VI collagen genes in affected skin from patients with systemic sclerosis (SSc) was examined by in situ hybridizations with a human α2(VI) collagen sequence‐specific complementary DNA. Five patients with diffuse, rapidly progressive SSc of recent onset (less than 12 months) were studied. The results showed increased expression of α2(VI) collagen messenger RNA transcripts in the skin of scleroderma patients compared with that in the skin of normal subjects. These findings indicate that alterations in the expression of type VI collagen genes, similar to those previously described for types I and III collagen, are present in the affected skin of SSc patients. These alterations may result in excessive tissue accumulation of type VI collagen and may play a role in the progressive skin induration and sclerosis that are prominent features of SSc.
Androgen replacement therapy in male patients with rheumatoid arthritis
Authors: Cutolo Maurizio , Balleari Enrico , Giusti Massimo , Intra Ettore , Accardo Silvano
Published: February 2007

A hypogonadic condition characterized by low serum testosterone levels has been identified in male patients with rheumatoid arthritis (RA). Seven men with active RA were treated daily for 6 months with oral testosterone undecanoate plus a nonsteroidal antiinflammatory drug in an attempt to evaluate the immunologic response, the overall clinical response, and the sex hormone response to such replacement therapy. At the end of the 6 months, there was a significant increase in serum testosterone levels (P < 0.05), an increase in the number of CD8+ T cells, and a decrease in the CD4+ :CD8+ T cell ratio. The IgM rheumatoid factor concentration decreased significantly (P < 0.05). There was a concurrent significant reduction in the number of affected joints (P < 0.05) and in the daily intake of nonsteroidal antiinflammatory drugs (P < 0.01). The well‐known immunosuppressive action of androgens probably contributed to our findings in these RA patients.
Relationship of clinical features with psychological status in primary fibromyalgia
Authors: Yunus Muhammad B. , Ahles Tim A. , Aldag Jean C. , Masi Alfonse T.
Published: February 2007

Clinical features and psychological status determined by the Minnesota Multiphasic Personality Inventory (MMPI) in 103 patients with primary fibromyalgia syndrome (PFS) were analyzed by univariate and multivariate techniques to determine if clinical features were related to psychological status or were intrinsic to PFS per se. The central features of PFS, e.g., number of pain sites, number of tender points, fatigue, and poor sleep, were independent of psychological status. However, discriminant analysis identified 4 variables—patient‐reported depression, anxiety, stress, and pain severity—which together predicted 3 MMPI subgroups with an accuracy of 55% (P < 0.001); the only musculoskeletal feature—pain severity—alone provided an accuracy of only 34% (P > 0.05). These data suggest a new concept, that the central features of fibromyalgia are independent of the psychological status and are more likely related to the PFS itself. However, pain severity may be influenced by psychological factors.
Restoration of the DNA binding activity of estrogen receptor in MRL‐lpr/lpr mice by a polyamine biosynthesis inhibitor
Authors: Thomas Thresia , Gunnia Uma B. , Seibold James R. , Thomas T. J.
Published: February 2007

Diverse data link estrogen influences to both the frequency and severity of systemic lupus erythematosus in humans and to murine lupus. A fundamental mechanism of action of estrogen involves the interaction of the hormone with its receptor protein, which is then transformed into the DNA binding form. We measured the concentration of uterine estrogen receptor and its DNA binding in normal BALB/c mice, lupus‐prone MRL‐lpr/lpr mice, and MRL‐lpr/lpr mice that had been treated with 1% difluoromethylornithine (DFMO). Uterine estrogen receptor levels in 20‐week‐old mice from the 3 groups were not significantly different. In contrast, DNA binding activity was significantly higher in BALB/c mice (mean ± SD 775 ± 100 fmoles/mg of DNA) than in untreated MRL‐lpr/lpr mice (80 ± 16 fmoles/mg of DNA) (P < 0.001). Treatment with 1% DFMO was associated with an increase in uterine estrogen receptor DNA binding (1,100 ± 218 fmoles/mg of DNA) in MRL‐lpr/lpr mice (P < 0.001). Polyamine levels were 2–6‐fold higher in the uterine tissues of untreated MRL‐lpr/lpr mice compared with the BALB/c mice and were significantly reduced by DFMO treatment. Our results link uterine polyamine production to a dysfunction of the estrogen receptors in MRL‐lpr/lpr mice. Reduction of the polyamine level by the irreversible inhibition of ornithine decarboxylase with DFMO restores estrogen receptor function.
Septic arthritis of the C1–C2 lateral facet joint and torticollis: Pseudo‐Grisel's syndrome
Authors: Halla James T. , Bliznak Johnny , Hardin Joe G. , Finn Sam
Published: February 2007

We present the case of a 76‐year‐old man who experienced the sudden development of fever, right‐sided neck pain and stiffness, and torticollis. A soft tissue mass was noted on the right side of his neck, but his head was tilted to the left. Computed tomography scans (with reformatted sagittal and coronal images) of the patient's cervical spine revealed destructive changes of the right lateral masses of C1 and C2 and the clivus, and a well‐delineated periodontoid soft tissue mass (confirmed by magnetic resonance imaging). After the second episode of right‐sided hemiparesis, he underwent transoral surgical exploration, with anterior decompression and odontoidectomy. Histologic examination of the surgical material revealed granulation tissue, fibrosis, and chronic inflammation, consistent with abscess formation with invasion and compression of the spinal cord and bone. This case suggests that nonreducible rotational head tilt to the side opposite the side of lateral mass collapse should raise the suspicion of a possible infection.
Persistence of monosodium urate crystals and low‐grade inflammation in the synovial fluid of patients with untreated gout
Authors: Pascual Eliseo
Published: February 2007

Synovial fluid (SF) from 74 asymptomatic knees of patients with gout was analyzed. These patients had never been treated with serum uric acid‐lowering agents. SF samples were analyzed for the presence of crystals and for cell counts, using undiluted SF directly in a Niebauer cell counting chamber. Thirty‐seven of the aspirated knees had previously been inflamed, and monosodium urate (MSU) crystals were seen in SF aspirates from 36 of them (97%). Of the 37 knees that had never been inflamed, only 8 contained MSU crystals (P < 0.00001). After reaching the joint, MSU crystals will persist in the SF as long as the serum uric acid level has not been lowered by appropriate treatment. In this situation, analysis of SF is an excellent diagnostic test for the intercritical gout. The mean cell count in the 44 SF samples that contained MSU crystals was 449/mm3 (95% confidence interval 310–589); the mean cell count in the 30 SF without MSU crystals was 64/mm3 (95% confidence interval 34–95) (P < 0.00002). The SF samples that contained MSU crystals also had a higher percentage of polymorphonuclear leukocytes than those without MSU crystals (P < 0.002). These data suggest that there is a low‐grade inflammation present in the knees of patients with MSU crystals, the consequences of which should be investigated.
Local infectious complications following large joint replacement in rheumatoid arthritis patients treated with methotrexate versus those not treated with methotrexate
Authors: Perhala Robert S. , Wilke William S. , Clough John D. , Segal Allen M.
Published: February 2007

We performed a 10‐year retrospective analysis of the frequency of local postoperative infectious complications in methotrexate (MTX)‐treated rheumatoid arthritis patients who underwent total joint arthroplasty. Sixty patients, who had a total of 92 joint arthroplasties, were receiving MTX. A comparison group of 61 patients with a combined total of 110 total joint arthroplasties were not receiving MTX. The 2 groups were compared for the occurrence of local postoperative infectious complications and poor wound healing. Eight patients in the MTX group experienced a total of 8 complications (8.7% of procedures). In comparison, 5 patients in the non‐MTX group experienced a total of 6 complications (5.5% of procedures), a difference that was not statistically significant (χX2 = 0.816, P = 0.366). Statistical analysis of many other variables revealed none that could be identified as risk factors for postoperative complications. These results suggest that treatment in the perioperative period with weekly low‐dose pulse MTX does not increase the risk of local postoperative infectious complications or poor wound healing in rheumatoid arthritis patients who undergo total joint arthroplasty.
In vivo effects of nonsteroidal antiinflammatory drugs on rat skin and synovial mast cell–induced vasopermeability
Authors: Malone Daniel G. , Vikingsson Arnor , Seebruch Jane Servi , Verbsky James W. , Dolan Patricia W.
Published: February 2007

Using our animal model of synovial mast cell‐mediated arthritis in rats, we tested the effects of 3 nonsteroidal antiinflammatory drugs (NSAIDs) (aspirin, indomethacin, and ketoprofen) and an H1 and an H2 histamine receptor antagonist (diphenhydramine and cimetidine, respectively) on synovial and dermal mast cell‐induced vasopermeability. Drug effects were assessed by quantifying the leakage of radiolabeled albumin into tissues following specific antigen‐initiated activation of passively sensitized dermal and synovial mast cells. The 3 NSAIDs tested had different effects on synovial and dermal mast cell‐induced vasopermeability. Aspirin and indomethacin significantly increased dermal and synovial plasma exudation (P ⩽ 0.008). Ketoprofen decreased dermal (P = 0.015), but had no effect on synovial, vascular exudation. Complete histamine H1 and H2 receptor blockade with diphenhydramine and cimetidine, respectively, substantially decreased (P ⩽ 0.0008), but did not completely inhibit, dermal and synovial mast cell‐induced vasopermeability. However, the addition of indomethacin to the combined antihistamine regimen resulted in an increase in the leakage of the radiolabel into skin and synovium (back to control levels), despite the complete blockade of H1 and H2 receptors. Results of experiments with antihistamines and indomethacin suggest that mediators other than histamine are involved in synovial mast cell‐induced inflammation. Furthermore, the differential response to ketoprofen indicates that the specific antigen‐stimulated mediator release profiles of dermal and synovial mast cells are different. Our finding of enhanced synovial vascular leakage in animals treated with some NSAIDs, and no such effect by other NSAIDs, perhaps explains in part the diverse effects of these agents in humans with arthritis.
Spontaneous degenerative polyarthritis in male new zealand black/kn mice
Authors: Nakamura Kunie , Kashiwazaki Sadao , Takagishi Kenji , Tsukamoto Yukio , Morohoshi Yasuo , Nakano Takeshi , Kimura Masaaki
Published: February 2007

Histopathologic studies and radiographic analysis revealed that male New Zealand black/KN (NZB/KN) mice develop degenerative polyarthritis in the joints of the forepaw and hindpaw beginning at age 2 months. Deposits of autoantibodies were observed on proliferating collagen fibers, nuclei of chondrocytes, and epidermal cells. Increases in the frequency of positivity for rheumatoid factor and anti‐type II collagen antibodies and in the level of serum oxidation activity were noted in these mice. The joint disease in male NZB/KN mice was transferable to female NZB/KN mice and male BALB/c mice by intraperitoneal injection of spleen cells from the male NZB/KN mice. This animal model of arthritis will be extremely useful for analyzing not only the pathogenesis of rheumatoid arthritis, but also new strategies for its treatment, since NZB/KN mice, unlike MRL/lpr mice, do not develop severe lupus nephritis or lymphadenopathy, and therefore have a longer survival period.
Clinical correlations with serum C1q levels in patients with rheumatoid arthritis
Authors: Olsen Nancy J. , Ho Edward , Barats Lev
Published: February 2007

Previous studies have suggested that serum C1q levels measured during the first 5 years of rheumatoid arthritis (RA) may be predictive of the extent of subsequent joint damage. To further evaluate the clinical significance of this marker in RA, levels of C1q were measured by radial immunodiffusion in serum samples from 107 well‐characterized patients with RA. Mean levels of C1q were higher in patients with a disease duration ⩽5 years (173 μg/ml) than in patients with a disease duration >5 years (148 μg/ml) (P = 0.032). Serum C1q levels were correlated with total joint counts and activities of daily living scores, but no correlation was observed with erythrocyte sedimentation rates or with radiographic scores. The results suggest that C1q may be a useful early marker of disease activity in patients with RA.
Wegener's granulomatosis presenting as temporal arteritis
Authors: Small Peter , Brisson Marie‐Laure
Published: February 2007

A granulomatous giant cell vasculitis of the temporal artery was observed in a biopsy specimen from a patient with corresponding clinical symptoms. Within weeks, the new onset of pulmonary infiltrates and renal failure prompted biopsy of the patient's kidney. A necrotizing glomerulonephritis, compatible with a diagnosis of Wegener's granulomatosis, was present. Vasculitis of the temporal artery may be a feature of Wegener's granulomatosis.
Effects of lobenzarit disodium on human endothelial cells. Lobenzarit disodium inhibits proliferative response, HLA–DR antigen expression, and T cell adherence toward endothelial cells
Authors: Kawakami Atsushi , Eguchi Katsumi , Ueki Yukitaka , Migita Kiyoshi , Ida Hiroaki , Nakao Hideto , Kurata Akihiko , Fukuda Takaaki , Nagataki Shigenobu , Ishimaru Tadayuki , Kurouji Kenichi , Fujita Nagatoshi
Published: February 2007

The therapeutic action of lobenzarit disodium (CCA) on the function of endothelial cells (EC) isolated from human umbilical cord veins was investigated. CCA suppressed 3H‐thymidine incorporation into EC in a dose‐dependent manner. Significant inhibition was detected at a concentration of 50 μg/ml. The expression of HLA–DR antigen on the surface of EC was increased when EC were cultured with recombinant interferon‐γ (rIFNγ). Treatment of EC with either IFNγ or interleukin‐1 enhanced the adhesion of T cells to EC. The kinetics of HLA–DR antigen expression by EC cultured with IFNγ was different from the kinetics of T cell‐EC adhesion, however. Neither anti–HLA–DR nor anti–HLA–ABC monoclonal antibody inhibited T cell binding to EC monolayers. CCA suppressed the expression of HLA–DR antigen by EC cultured with rIFNγ. In an EC monolayer adhesion assay, CCA also inhibited T cell adhesion to EC in the presence of either IFNγ or interleukin‐1. Significant inhibition was observed at a CCA concentration of 10 μg/ml, a level that is easily attainable in serum. These results suggest that CCA may suppress rheumatoid synovitis by reducing the angiogenesis and emigration of chronic inflammatory cells from the blood into the synovium.
Crystal‐induced neutrophil activation. I. Initiation and modulation of calcium mobilization and superoxide production by microcrystals
Authors: Naccache Paul H. , Grimard Marléne , Roberge Charles J. , Gilbert Caroline , Poubelle Patrice E. , Lussier André , De Médicis Rinaldo
Published: February 2007

The effects of monosodium urate and calcium pyrophosphate dihydrate crystals on the levels of cytoplasmic free calcium and on the oxidative burst in normal human blood neutrophils were examined. The pattern of sensitivity to granulocyte–macrophage colony‐stimulating factor, colchicine, cytochalasin B, pertussis toxin, diglyceride kinase, and protein kinase C inhibitors differentiated the mechanism(s) of neutrophil activation by the crystals from that involved in the responses to soluble chemotactic factors and indicated that individual crystals can use several activation pathways.
Hip arthropathy in genetic hemochromatosis. Radiographic and histologic features
Authors: Axford J. S. , Revell P. , Watt I. , Bomford A. , Williams R. , Hamilton E. B. D.
Published: February 2007

Genetic hemochromatosis, a disorder of iron metabolism, results in the deposition of massive amounts of iron in the tissues. Arthropathy is one of a number of clinical features associated with the disease. Characteristic radiographic features in the wrist and hand have been reported, and an increased incidence of severe hip disease has been observed. In this study, hip radiographs of 112 patients with genetic hemochromatosis and arthritis were reviewed, and histologic examination of 2 femoral heads was performed. Twenty‐eight of the 112 patients (25%) had evidence of arthritis of the hip joint. In 23 (82%) of the 28 patients, this feature was thought to be associated with osteoarthritis; 2 of these patients had an atypical arthropathy associated with radiolucency of the femoral head and histologic features of atypical stripping of the cartilage from the subchondral bone. These atypical features were not thought to be due to avascular necrosis, pyrophosphate‐associated arthropathy, apatite‐associated deposition arthritis, or osteoarthritis, but may be typical of genetic hemochromatosis and possibly the result of increased susceptibility to shearing forces at the bone–cartilage interface. In 5 of the 28 patients (18%), chondrocalcinosis was the sole abnormal finding on radiography. Ten of the 28 patients eventually required hip surgery, which confirms the severity of the hip disease associated with genetic hemochromatosis.
Eosinophil activation in systemic sclerosis
Authors: Gustafsson Rolf , Hällgren Roger , Fredens Kjeld , Nettelbladt Otto
Published: February 2007

Circulating levels of eosinophil cationic protein (ECP) were increased 4‐fold in patients with systemic sclerosis (SSc) compared with those in healthy control subjects. There was no correlation between the ECP concentrations and laboratory indices of inflammatory activity or visceral involvement. Mean ECP levels were higher in patients with a history of occupational exposure to silica, even though patients who had no such history also had ECP levels higher than normal. The patients had increased bronchoalveolar levels of ECP, which correlated with impaired lung functioning. Skin infiltration with activated eosinophils and extracellular deposits of ECP were present in skin biopsy samples from the SSc patients. We conclude that eosinophil activation is part of the inflammatory process in SSc.
Elimination of soluble 123I‐labeled aggregates of IgG in patients with systemic lupus erythematosus. Effect of serum IgG and numbers of erythrocyte complement receptor type 1
Authors: Halma Cornelis , Daha Mohamed R. , Evers‐Schouten Jeannette H. , van Es Leendert A. , Breedveld Ferdinand C. , Blok Dik , Hermans Jo , Pauwels Ernst K. J.
Published: February 2007

Using soluble 123I‐labeled aggregates of human IgG (123I‐AHIgG) as a probe, we examined the function of the mononuclear phagocyte system in 22 patients with systemic lupus erythematosus (SLE) and 12 healthy controls. In SLE patients, a decreased number of eryth‐rocyte complement receptor type 1 was associated with less binding of 123I‐AHIgG to erythrocytes and a faster initial rate of elimination of 123I‐AHIgG (mean ± SEM half‐maximal clearance time 5.23 ± 0.2 minutes, versus 6.58 ± 0.2 minutes in the controls), with possible spillover of the material outside the mononuclear phagocyte system of the liver and spleen. However, multiple regression analysis showed that serum concentrations of IgG were the most important factor predicting the rate of 123I‐AHIgG elimination. IgG concentration may thus reflect immune complex clearance, which in turn, would influence the inflammatory reaction, in SLE.
Enhanced CD3‐mediated T lymphocyte proliferation in patients with systemic lupus erythematosus
Authors: Stekman Ivan L. , Blasini Ana M. , Leon‐Ponte Matilde , Baroja Miren L. , Abadi Isaac , Rodriguez Martin A.
Published: February 2007

Nonfractionated peripheral blood lymphocytes from patients with systemic lupus erythematosus (SLE) showed enhanced proliferative responses when stimulated via the CD3 pathway. In contrast, proliferative responses induced by phytohemagglutinin were diminished in SLE patients. Levels of CD3‐induced interleukin‐2 production and interleukin‐2 receptor expression were comparable with normal levels. Highly purified T cells also showed augmented CD3 responses, but only in the presence of phorbol myristate acetate or a combination of phorbol myristate acetate plus calcium ionophore A23187, and not with calcium ionophore alone. The data suggest integrity of the T cell receptor/CD3 pathway for T cell activation in patients with SLE, as examined in cultures stimulated with specific anti‐CD3 monoclonal antibodies rather than with multivalent lectins. An increased response via the CD3 complex could contribute to the autoimmune activity in human SLE.
The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip
Authors: Altman R. , Alarcón G. , Appelrouth D. , Bloch D. , Borenstein D. , Brandt K. , Brown C. , Cooke T. D. , Daniel W. , Feldman D. , Greenwald R. , Hochberg M. , Howell D. , Ike R. , Kapila P. , Kaplan D. , Koopman W. , Marino C. , McDonald E. , McShane D. J. , Medsger T. , Michel B. , Murphy W. A. , Osial T. , Ramsey‐Goldman R. , Rothschild B. , Wolfe F.
Published: February 2007

Clinical criteria for the classification of patients with hip pain associated with osteoarthritis (OA) were developed through a multicenter study. Data from 201 patients who had experienced hip pain for most days of the prior month were analyzed. The comparison group of patients had other causes of hip pain, such as rheumatoid arthritis or spondylarthropathy. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop different sets of criteria to serve different investigative purposes. Multivariate methods included the traditional “number of criteria present” format and “classification tree” techniques.

Clinical criteria: A classification tree was developed, without radiographs, for clinical and laboratory criteria or for clinical criteria alone. A patient was classified as having hip OA if pain was present in combination with either 1) hip internal rotation ≥15º, pain present on internal rotation of the hip, morning stiffness of the hip for ≤60 minutes, and age >50 years, or 2) hip internal rotation <15º and an erythrocyte sedimentation rate (ESR) ≤45 mm/hour; if no ESR was obtained, hip flexion ≤115º was substituted (sensitivity 86%; specificity 75%).

Clinical plus radiographic criteria: The traditional format combined pain with at least 2 of the following 3 criteria: osteophytes (femoral or acetabular), joint space narrowing (superior, axial, and/or medial), and ESR <20 mm/hour (sensitivity 89%; specificity 91%). The radiographic presence of osteophytes best separated OA patients and controls by the classification tree method (sensitivity 89%; specificity 91%).

The “number of criteria present” format yielded criteria and levels of sensitivity and specificity similar to those of the classification tree for the combined clinical and radiographic criteria set. For the clinical criteria set, the classification tree provided much greater specificity. The value of the radiographic presence of an ostophyte in separating patients with OA of the hip from those with hip pain of other causes is emphasized.
Defective CD2 pathway T cell activation in systemic lupus erythematosus
Authors: Fox David A. , Millard Jo Ann , Treisman Jonathan , Zeldes Wendy , Bergman Alice , Depper Joel , Dunne Robert , McCune W. Joseph
Published: February 2007

CD2 (T11; sheep erythrocyte receptor) is the surface component of an alternative, antigen‐independent pathway of human T cell activation. The response to certain anti‐CD2 antibodies is relatively independent of accessory cell signals and therefore provides a direct measurement of T cell function. The CD2 pathway may be important in the differentiation of thymocytes, on which the expression of CD2 precedes the appearance of the CD3–T cell receptor complex. In view of the impaired T cell regulation of immune responses in patients with systemic lupus erythematosus (SLE), we examined the activation of peripheral blood lymphocytes by anti‐CD2 antibodies in 57 SLE patients and 32 normal control subjects. The CD2 pathway response was lower in the SLE patients (P < 0.0001); 18 of the 57 SLE patients had a lower response than any of the control subjects. The SLE low‐responder patients did not differ from the normal‐responder patients in terms of disease activity or use of antiinflammatory and immunosuppressive medications. Low responses to anti‐CD2 were corrected to normal by the coaddition of a submitogenic amount of phorbol myristate acetate (1 ng/ml). In some low‐responder patients, the responses were normalized by the removal of non–T cells. The data indicate that some SLE patients have impaired responses to CD2 pathway activation and that this may reflect intrinsic T cell defects and/or regulatory influences of non–T cells.
In vivo effects of interleukin‐1 on articular cartilage. Prolongation of proteoglycan metabolic disturbances in old mice
Authors: van Beuningen Henk M. , Arntz Onno J. , Van den Berg Wim B.
Published: February 2007

We investigated the effects of intraarticular injections of interleukin‐1α (IL‐1α) into the knee joints of young (3‐month‐old) and old (18‐month‐old) C57B1/10 mice. In this in vivo study, 35S‐sulfate incorporation and release were used to compare the effects of IL‐1 on patellar cartilage proteoglycan metabolism. IL‐1–induced stimulation of proteoglycan degradation was confined to the first 24 hours after injection in both young and old animals, and was only slightly lower in old cartilage than in young. In old patellar cartilage, IL‐1–induced suppression of proteoglycan synthesis appeared to be more prolonged. Also, the amount of time needed to restore the cartilage matrix, characterized by proteoglycan synthesis above normal levels, was longer in old animals. Histologic analysis confirmed the retarded recovery in the cartilage of old mice. Autoradiography showed that the chondrocytes of the medial side of the femorotibial area were most vulnerable to IL‐1–induced suppression of proteoglycan synthesis, especially the medial tibial plateau. As with the patellar cartilage, IL‐1–induced suppression of proteoglycan synthesis in this area of articular cartilage was more prolonged in old animals. Our data indicate that the impact of IL‐1 on articular cartilage is higher in old mice and that, consistent with certain loci found to be at risk in experimental osteoarthritis, there are sites at which IL‐1 is more likely to act.
The progression of erosion and joint space narrowing scores in rheumatoid arthritis during the first twenty‐five years of disease
Authors: Sharp John T. , Wolfe Frederick , Mitchell Donald M. , Bloch Daniel A.
Published: February 2007

Erosions and cartilage destruction are nearly universal features in peripheral joints that have been chronically affected by rheumatoid arthritis. Scoring methods to measure the extent of these abnormalities in hands and wrists have been developed and have been thoroughly tested in several studies to establish their reproducibility. In this study, we utilized one of these scoring methods to examine the progression of radiologic damage as related to duration of disease. Two hundred ninety‐two patients from 3 different participating centers in the Arthritis, Rheumatism, and Aging Medical Information System were included. Six hundred fifty films of the hands and wrists, obtained from 210 patients, were scored for erosions and joint space narrowing. The average annual rate of progression of the total radiologic score, which sums erosion and joint space abnormalities and has a maximum possible score of 314, was approximately 4 units per year over the first 25 years after onset; this progression was more rapid in the earlier years of disease and slightly slower in the later years. Data were insufficient to accurately determine the progression rate in disease of more than 25 years duration.
Sera from patients with autoimmune disease recognize conformational determinants on the 60‐kd ro/ss‐a protein
Authors: Boire Gilles , Lopez‐Longo Francisco‐Javier , Lapointe Sylvie , Ménard Henri‐A.
Published: February 2007

Anti‐Ro antibodies are found in a large proportion of patients with systemic lupus erythematosus and primary Sjögren's syndrome. These antibodies also characterize neonatal lupus, subacute cutaneous lupus erythematosus, and vasculitis associated with Sjögren's syndrome and rheumatoid arthritis. Anti‐Ro‐positive sera may contain either or both of 2 sets of antibodies, recognizing either a 60‐kd or a 52‐kd polypeptide component of the Ro particle. We found in this study that the immune response to the 60‐kd Ro antigen is heterogeneous. Some sera specifically recognize the native Ro antigen but fail to bind the corresponding denatured polypeptides. In addition, after immunodepletion using the denatured 60‐kd Ro polypeptide, all anti‐Ro‐positive sera tested still contained high titers of antibodies recognizing conformational determinants on the Ro antigen. The frequent immunodominance of anti‐Ro antibodies targeted to conformational determinants suggests that native autoantigens may directly drive the autoimmune response.
Shoulder disorders in the elderly: A community survey
Authors: Chard M. D. , Hazleman R. , Hazleman B. L. , King R. H. , Reiss B. B.
Published: February 2007

A community survey of identifiable symptomatic shoulder disorders in a sample of 644 elderly people over age 70 (318 male and 326 female) revealed a prevalence of 21%. Shoulder disorders were more common in women (25%, versus 17% in men). Approximately 70% of the cases of shoulder pain involved the rotator cuff. Fewer than 40% of the subjects sought medical attention for these symptoms. Increased medical awareness is needed, since the elderly often do not volunteer information about such symptoms.
The latex test revisited. Rheumatoid factor testing in 8,287 rheumatic disease patients
Authors: Wolfe Frederick , Cathey Mary Ann , Roberts F. Kay
Published: February 2007

Rheumatoid factor (RF) testing by latex fixation in 8,287 outpatients yielded a sensitivity of 81.6% and 78.0% at titers of 1:20 and 1:80, respectively, and a specificity against noninflammatory rheumatic disorders (NIRD) of 96.6% and 97.9% and against NIRD plus inflammatory disorders of 95.2% and 96.8%, respectively. The predictive value of a positive test result at the clinic prevalence rate for rheumatoid arthritis (RA) (16.4%) was approximately 80%, and was 70% at 10% prevalence and 10% at 1% prevalence. No associations of RF with age or sex were found in non‐RA patients. RF titers increased minimally with age in RA patients and were higher in men than in women. This study suggests that latex testing is far more specific than has been believed and that the titer is not spuriously increased with age.
Long‐term colchicine treatment in children with familial mediterranean fever
Authors: Zemer Deborah , Livneh Avi , Danon Yehuda L. , Pras Mordechai , Sohar Ezra
Published: February 2007

Three hundred fifty children (younger than age 16) who had familial Mediterranean fever (FMF) were given continuous prophylactic treatment with colchicine (1–2 mg/day) for 6–13 years. Complete remission of febrile attacks was achieved in 64% of the patients, and partial remission in 31%. Protracted attacks of arthritis virtually disappeared. None of the children developed amyloidosis while on the colchicine regimen. Side effects of colchicine were insignificant, and did not prompt permanent discontinuation of treatment in any of the children. Their growth, development, and subsequent fertility were normal. The efficacy of long‐term colchicine treatment of children with FMF makes early diagnosis life saving.
In Situ Hybridization Studies of Stromelysin and Collagenase Messenger RNA Expression in Rheumatoid Synovium
Authors: Gravallese Ellen M. , Darling Jama M. , Ladd Amy L. , Katz Jeffrey N. , Glimcher Laurie H.
Published: February 2007

Destructive joint changes in rheumatoid arthritis (RA) are thought to be mediated in part by the neutral proteinases collagenase and stromelysin. Collagenase messenger RNA (mRNA) has been previously localized to the synovial lining layer. In this study, synovial tissue from 8 patients with RA and 2 patients with osteoarthritis was examined for proteinase production by in situ hybridization. Stromelysin mRNA localized predominantly to the synovial lining layer cells. In serial sections, collagenase mRNA was shown to be localized to the same tissue areas as those producing stromelysin mRNA, and grain counts revealed a direct correlation between production of stromelysin mRNA and production of collagenase mRNA. All patients with RA were producing collagenase and stromelysin mRNA in detectable amounts. One of 2 osteoarthritis patients was producing these metalloproteinases, but in levels below those found in the RA patients. These data support the identity of the synovial lining cells as the major synovial cells producing collagenase and stromelysin in RA and provide new evidence for the coordinate production of collagenase and stromelysin in RA in vivo.
Human Synovial Mast Cell Involvement in Rheumatoid Arthritis and Osteoarthritis. Relationship to Disease Type, Clinical Activity, and Antirheumatic Therapy
Authors: Bridges Alan J. , Malone Daniel G. , Jicinsky Judy , Chen Marcus , Ory Peter , Engber William , Graziano Frank M.
Published: February 2007

Mast cells were isolated by enzymatic digestion of synovium obtained from 48 patients with rheumatoid arthritis (RA) and 42 patients with osteoarthritis (OA). A significantly lower percentage of stainable synovial mast cells was obtained by tissue digestion from patients with clinically active RA compared with those with less active disease. The 54 patients treated with nonsteroidal antiinflammatory drugs had a significantly lower percentage of stainable synovial mast cells in cell suspension than did the other 36 patients. When anti‐IgE antibody was used as a secretagogue in vitro, significantly greater histamine release was observed from synovial mast cells of RA patients compared with OA patients. Greater histamine release in response to anti‐IgE was observed in the RA patients with more clinically active disease and those who were treated with prednisone, compared with RA patients without these features. Synovial mast cells of RA patients treated with a disease‐modifying antirheumatic drug had a significantly lower mean histamine content than did cells from patients not receiving such treatment. Our data suggest that there are differences between synovial mast cells from tissues of patients with RA and OA and suggest that synovial mast cells may be activated in clinically active RA. In addition, the data indicate an effect of systemic anti‐rheumatic therapy on mast cells isolated from synovium of patients with arthritis.
Expression and Function of Surface Antigens on Scleroderma Fibroblasts
Authors: Abraham D. , Lupoli S. , McWhirter A. , Plater‐Zyberk C. , Piela T. H. , Korn J. H. , Olsen Irwin , Black C.
Published: February 2007

Dermal fibroblasts from patients with systemic sclerosis (SSc) bound a much greater number of T lymphocytes than did normal dermal fibroblasts. Monoclonal antibodies (MAb) against classes I and II antigens of the major histocompatibility complex (MHC) and their receptors, CD8 and CD4, had no effect on T cell interaction with SSc and normal cells, while MAb against lymphocyte function–associated antigen type 3 (LFA‐3) and CD2 both strongly inhibited lymphocyte attachment. MAb against intercellular adhesion molecule type 1 (ICAM‐1) and LFA‐1 also prevented binding of T lymphocytes, but had a more marked effect on adhesion to SSc fibroblasts than to normal fibroblasts; they also completely abolished the increased binding to fibroblasts treated with interleukin‐1α, tumor necrosis factor α, and interferon‐γ. No difference was found in the proportion of normal and SSc fibroblasts that expressed MHC classes I and II and LFA‐3, but more SSc cells expressed ICAM‐1, and at a higher level, than did normal fibroblasts. These results show that cultured SSc cells have elevated binding to T lymphocytes, which possibly results from expansion of a subset of fibroblasts that produces high levels of ICAM‐1.
Effects of Body Weight Restriction on the Development and Progression of Spontaneous Osteoarthritis in Guinea Pigs
Authors: Bendele Alison M. , Hulman James F.
Published: February 2007

Hartley albino guinea pigs develop spontaneous osteoarthritis (OA) of the knee joint. A study was done to determine the importance of body weight in the pathogenesis of this disease. Two groups of 20 male guinea pigs each were maintained on the same diets. The control group was allowed ad libitum feed consumption and the other group was restricted to 30–35 gm of feed per day. Ten animals from each group were killed at 9 months of age to evaluate histologic features of the knee joints. The severity of the OA lesions was reduced by 40%, in conjunction with a 28% decrease in body weight, in the diet‐restricted group. The remaining animals were killed at 18 months of age. Those in the diet‐restricted group had a 56% reduction in severity of lesions, with a 29% decrease in body weight. These results indicate that body mass in guinea pigs, as in humans, is an important predisposing factor for the development of spontaneous OA of the knee.
The European Spondylarthropathy Study Group Preliminary Criteria for the Classification of Spondylarthropathy
Authors: Dougados Maxime , Linden Sjef Van Der , Juhlin Roger , Huitfeldt Bernhard , Amor Bernard , Calin Andrei , Cats Arnold , Dijkmans Ben , Olivieri Ignazio , Pasero Giampiero , Veys Eric , Zeidler Henning
Published: February 2007

Classification criteria for most of the disorders belonging to the spondylarthropathy group already exist. However, the spectrum of spondylarthropathy is wider than the sum of these disorders suggests. Sero‐negative oligoarthritis, dactylitis or polyarthritis of the lower extremities, heel pain due to enthesitis, and other undifferentiated cases of spondylarthropathy have been ignored in epidemiologic studies because of the inadequacy of existing criteria. In order to define classification criteria that also encompass patients with undifferentiated spondylarthropathy, we studied 403 patients with all forms of spondylarthropathy and 674 control patients with other rheumatic diseases. The diagnoses were based on the local clinical expert's opinion. The 403 patients included 168 with ankylosing spondylitis, 68 with psoriatic arthritis, 41 with reactive arthritis, 17 with inflammatory bowel disease and arthritis, and 109 with unclassified spondylarthropathy. Based on statiscal analysis and clinical reasoning, we propose the following classification criteria for spondylarthropathy inflammatory spinal pain or synovitis (asymmetric or predominantly in the lower limbs), together with at least 1 of the following: positive family history, psoriasis inflammatory bowel disease, urethritis, or acute diarrhea, alternating buttock pain, enthesopathy, or sacroiliitis as determined from radiography of the pelvic region. These criteria resulted in a sensitivity of 87% and a specificity of 87%. The proposed classification criteria are easy to apply in clinical practice and performed well in all 7 participating centers. However, we regard them as preliminary until they have been further evaluated in other settings.