bluuebunny/crossref_metadata_2025 huggingface dataset:
A double‐blind placebo‐controlled study of auranofin in patients with psoriatic arthritis
Authors: Carette Simon , Calin Andrei , McCafferty Jim P. , Wallin Bruce A.
Published: February 2007

Two hundred thirty‐eight patients with psoriatic arthritis were entered into a 6‐month, multicenter, double‐blind trial comparing auranofin and placebo. Polyarthritis (>5 tender joints) was present in 90% of the patients, and 94% were seronegative. Auranofin treatment was statistically superior to placebo treatment, according to physician's global assessment and functional scores. A trend in favor of auranofin treatment was seen for each of the other disease parameters studied. Psoriasis worsened in 6 auranofin‐treated patients and in 3 placebo‐treated patients. The incidence and nature of other side effects were similar to those observed in similar trials of patients with rheumatoid arthritis. Our observations suggest that the use of auranofin in the treatment of psoriatic arthritis is safe, although its therapeutic advantage over treatment with nonsteroidal antiinflammatory drugs alone is modest.
Protective effects of corticosteroids on cartilage lesions and osteophyte formation in the pond‐nuki dog model of osteoarthritis
Authors: Pelletier Jean‐Pierre , Martel‐Pelletier Johanne
Published: February 2007

The in vivo effects of corticosteroids on osteoarthritic (OA) lesions were examined in 12 dogs in which the anterior cruciate ligament had been sectioned. Six were treated with oral prednisone and 6 were treated with intraarticular (IA) injections of triamcinolone hexacetonide (TH), at surgery and 4 weeks later. Twelve other operated dogs received no treatment. All dogs were killed 8 weeks postsurgery. Four of 15 normal control dogs received IA TH injections. Operated untreated dogs developed significant cartilage lesions on the femoral condyles and tibial plateaus with prominent osteophytes. Operated dogs treated orally or with IA injections had a significant reduction in osteophyte size. Cartilage erosions on femoral condyles were observed in 25% of the untreated dogs, 8% of the dogs receiving oral prednisone, and none of the dogs receiving IA TH. In both groups of treated dogs, the size of the tibial plateau lesions was significantly reduced compared with the operated untreated dogs. Histologically, corticosteroids significantly reduced the severity of OA structural changes of the cartilage on both medial and lateral femoral condyles and tibial plateaus in operated animals, with the exception of the lateral plateaus of those treated orally. In electron microscopy studies, we found no evidence of increased cell degeneration or death associated with steroids. IA corticosteroids had no deleterious effects on normal articular cartilage. These results indicate that glucocorticoids administered orally or intraarticularly are effective against the development of OA lesions in this model.
Correlation of anti‐Ro antibody with photosensitivity rash in systemic lupus erythematosus patients
Authors: Mond Chaim B. , Peterson Margaret G. E. , Rothfield Naomi F.
Published: February 2007

We studied 131 patients with systemic lupus erythematosus (SLE) to determine the relationship between the presence of anti‐Ro antibody in these patients and specific manifestations of SLE. There was a significant correlation between anti‐Ro and photosensitivity rash in SLE patients, regardless of the type of rash. No significant association was found between anti‐Ro and other SLE criteria or between anti‐Ro and demographic variables.
Reduced numbers of complement receptor type 1 on erythrocytes are associated with increased levels of anticardiolipin antibodies. Findings in patients with systemic lupus erythematosus and the antiphospholipid syndrome
Authors: Hammond Anthony , Rudge Andrew C. , Loizou Sozos , Bowcock Stella J. , Walport Mark J.
Published: February 2007

In several diseases, including systemic lupus erythematosus (SLE) and autoimmune hemolytic anemias, the numbers of complement receptor type 1 (CR1) expressed on erythrocytes of patients are reduced. In patients with SLE, anticardiolipin antibodies (aCL) have been associated with positive results on direct antiglobulin tests. Because of these findings, we investigated whether the reduced expression of erythrocyte CR1 in 61 patients (53 with SLE and 8 with the antiphospholipid syndrome) might be associated with the presence of aCL. A negative correlation was observed between aCL levels and mean numbers of CR1 (rs = −0.43, P = 0.001), and a positive correlation was observed between aCL levels and the levels of erythrocyte C4d and C3d (rs = 0.33 and 0.41, P = 0.01 and 0.001, respectively), but no correlation of aCL levels with serum C4 levels was found. When the results were further analyzed according to the IgG or IgM class of aCL, levels of antibodies of both classes were negatively correlated with CR1 numbers, but only IgM aCL levels were correlated with erythrocyte C4d and C3d numbers. The levels of anti‐double‐stranded DNA antibodies showed no correlation with erythrocyte CR1, C4d, or C3d numbers but were negatively correlated with serum C4 levels (rs = −0.43, P = 0.002). These data suggest that aCL, or a closely related antibody specificity, may bind to erythrocytes and may be directly involved in the mechanism for reduction of erythrocyte CR1 expression in SLE patients.
Canine serum keratan sulfate and hyaluronate concentrations. Relationship to age and osteoarthritis
Authors: Leipold Harry R. , Goldberg Ronald L. , Lust George
Published: February 2007

Elevated serum levels of keratan sulfate (KS) and hyaluronate (HA) in patients with osteoarthritis (OA) have been reported. We measured KS and HA in dogs to determine if there was an elevation of these serum glycosaminoglycans in a canine model of OA. A single intraarticular injection of 1 mg of chymopapain into a shoulder joint increased serum KS by tenfold, and HA by less than twofold, in 24 hours. Serum KS and HA levels were 3–5‐fold higher in dogs younger than 2 months of age than in older dogs. Serum KS and HA concentrations and synovial fluid KS concentrations were unrelated to spontaneous cartilage degeneration in 1‐year‐old dogs. Higher KS levels in synovial fluid correlated with higher KS levels in serum (r = 0.54, P < 0.025). The mean KS concentration in sera of older dogs (>3 years old) with OA was 37% higher than that in disease‐free controls, but the difference between the groups was not statistically significant. Thus, elevated levels of serum KS and HA do not appear to have clinical significance in this model of OA.
Subacute cutaneous lupus erythematosus during puva therapy for psoriasis: Case report and review of the literature
Authors: Dowdy Marcia J. , Nigra Thomas P. , Barth Werner F.
Published: February 2007

Lesions typical of subacute cutaneous lupus erythematosus developed in an elderly woman after 6 months of PUVA (8‐methoxypsoralen and longwave ultraviolet light) therapy for psoriasis. Pancytopenia, antibodies to double‐stranded DNA, and hypocomplementemia developed concurrently with the appearance of the cutaneous lesions. With discontinuation of photochemotherapy, the cutaneous lesions disappeared and the pancytopenia improved.
Microheterogeneity of alpha1‐acid glycoprotein in the detection of intercurrent infection in patients with rheumatoid arthritis
Authors: Pawlowski Tomasz , Mackiewicz Stefan H. , Mackiewicz Andrzej
Published: February 2007

We evaluated the clinical usefulness of determinations of α1 ‐acid glycoprotein (AGP) microheterogeneity in distinguishing patients who have active rheumatoid arthritis (RA) from those who have RA and an intercurrent infection. AGP microheterogeneity was studied by affinity electrophoresis with concanavalin A as the ligand, and the results were expressed as reactivity coefficients (RC). Significant differences were found between the mean RC ( ±SD) in healthy individuals (1.27 ± 0.16) and the mean RC in RA patients with intercurrent infection (1.74 ± 0.90), as well as with the mean RC in RA patients with grades III and IV disease activity (0.92 ± 0.18 and 0.81 ± 0.25, respectively). Moreover, an additional microheterogeneous form of AGP, similar to that observed in non‐RA patients with infections, was noted in RA patients with infections (sensitivity 100%, specificity 100%). The results show that an increase in AGP reactivity with concanavalin A is a sensitive indicator of intercurrent infection in patients with RA.
Genetic studies of Ro (SS‐A) and La (SS‐B) autoantibodies in families with systemic lupus erythematosus and primary sjögren's syndrome
Authors: Arnett Frank C. , Hamilton Robert G. , Reveille John D. , Bias Wilma B. , Harley John B. , Reichlin Morris
Published: February 2007

Using enzyme‐linked immunosorbent assays, autoantibodies to Ro (SS‐A) were detected in the sera of 21% of the first‐degree relatives and 11% of the second‐degree relatives of anti‐Ro–positive probands with systemic lupus erythematosus (SLE) or primary Sjögren's syndrome, as compared with 3% of normal control subjects (P = 0.003 and P = 0.09, respectively). In a parallel study, anti‐Ro occurred in 28% of the first‐degree relatives of unselected members of families of SLE patients, regardless of the proband's serologic status, compared with 6% of the relatives from normal healthy families. Antibodies to La and to Sm/nuclear RNP were infrequent. Anti‐Ro occurred in 41% of the relatives considered to have a dominant, non–HLA‐linked “autoimmune trait” by virtue of having any autoimmune disorder and/or serologic abnormality (antinuclear antibodies, anti–single‐stranded DNA, or biologic false‐positive VDRL test result), as compared with only 2% of the healthy, seronegative relatives without the trait (P = 0.009). Moreover, HLA–DR2 and/or DR3 occurred in 90% of anti‐Ro–positive subjects, regardless of their clinical status. These results demonstrate that the Ro autoantibody response occurs frequently in relatives of patients with SLE and is genetically mediated by both major histocompatibility complex and non–major histocompatibility complex effects.
Increased proto‐oncogene expression in peripheral blood T lymphocytes from patients with systemic sclerosis
Authors: Kahan Alice , Gerfaux Jacqueline , Kahan André , Joret Anne‐Marie , Menkès Charles J. , Amor Bernard
Published: February 2007

The expression of c‐myc, c‐myb, and c‐ras protooncogenes, determined using RNA hybridization techniques (slot‐blot), was significantly increased in peripheral blood T lymphocytes, but not in B cells, from 17 patients with systemic sclerosis with diffuse scleroderma, compared with the expression in normal control subjects. The magnitude of expression of c‐myc and c‐myb tended to be higher in patients with early, active disease. These results demonstrate an in vivo activation of T cells from systemic sclerosis patients, which may play an important role in the pathogenesis of the disease.
Aerobic fitness in patients with fibrositis. A controlled study of respiratory gas exchange and 133xenon clearance from exercising muscle
Authors: Bennett Robert M. , Clark Sharon R. , Goldberg Linn , Nelson Donna , Bonafede R. Peter , Porter John , Specht David
Published: February 2007

Aerobic fitness was evaluated in 25 women with fibrositis, by having them exercise to volitional exhaustion on an electronically braked cycle ergometer. Compared with published standards, >80% of the fibrositis patients were not physically fit, as assessed by maximal oxygen uptake. Compared with matched sedentary controls, fibrositis patients accurately perceived their level of exertion in relation to oxygen consumption and attained a similar level of lactic acidosis, as assessed by their respiratory quotient and ventilatory threshold. Exercising muscle blood flow was estimated by 133xenon clearance in a subgroup of 16 fibrositis patients and compared with that in 16 matched sedentary controls; the fibrositis patients exhibited reduced 133xenon clearance. These results indicate a need to include aerobic fitness as a matched variable in future controlled studies of fibrositis and suggest that the “detraining phenomenon” may be of relevance to the etiopathogenesis of the disease.
Nuclear imaging and clinical features of childhood reflex neurovascular dystrophy: Comparison with adults
Authors: Goldsmith Donald P. , Vivino Frederick B. , Eichenfield Andrew H. , Athreya Balu H. , Heyman Sydney
Published: February 2007

Reflex neurovascular dystrophy (RND) is less common in children than in adults, and differences in onset, clinical course, response to treatment, and degree of disability suggest a different pathogenesis. We have assessed the usefulness of nuclear imaging in 15 children with RND who were evaluated from March 1983 to September 1985. Abnormal findings on 3‐phase bone scans were observed in 14 children, with diffusely decreased bone uptake at the symptomatic site being the most common observation. This contrasts sharply with previous reports of diffusely increased uptake in most adults with RND.
Effects of salicylate on chondrocytes from osteoarthritic and contralateral knees of dogs with unilateral anterior cruciate ligament transection
Authors: Slowman‐Kovacs Sally D. , Albrecht Marjorie E. , Brandt Kenneth D.
Published: February 2007

Salicylates suppress net glycosaminoglycan synthesis in articular cartilage. The inhibitory effect is greater in osteoarthritic (OA) cartilage than in normal cartilage. Whether the isolated OA chondrocyte is inherently more susceptible to the effects of salicylate on glycosaminoglycan metabolism has not been determined. The results of this study show that, after isolation from the extracellular matrix, normal and OA chondrocytes in suspension culture are similarly susceptible to the metabolic effects of salicylate. However, chondrocytes from the contralateral knees of dogs with unilateral OA were notably resistant to the effects of salicylate.
Hepatic infarction in a patient with the lupus anticoagulant
Authors: Mor F. , Beigel Y. , Inbal A. , Goren M. , Wysenbeek A. J.
Published: February 2007

We describe a 31‐year‐old patient with missed abortion, thrombocytopenia, and clinical, laboratory, and radiologic evidence of hepatic infarction. On evaluation, she was found to have the lupus anticoagulant. The association between enhanced thrombosis and the lupus anticoagulant is discussed, and previously reported thrombotic complications are described. The etiology, clinical course, and radiologic features of liver infarction are summarized, and the importance of recognizing and treating this form of hypercoagulability is stressed. To our knowledge, this is the first description of liver infarction associated with the lupus anticoagulant.
A simplified twenty‐eight–joint quantitative articular index in rheumatoid arthritis
Authors: Fuchs Howard A. , Brooks Raye H. , Callahan Leigh F. , Pincus Theodore
Published: February 2007

We describe a joint index that includes only 28 joints: 10 proximal interphalangeal joints of the fingers, 10 metacarpophalangeal joints, and the wrists, elbows, shoulders, and knees. These joints are evaluated for swelling, tenderness, and limited motion, with the findings scored as abnormal or normal. The 28‐joint index is considerably easier to use than traditional methods, and appears to yield as much information in terms of correlation with other measures of clinical status, including hand radiograph scores, American Rheumatism Association functional class, grip strength, walking time, and activities of daily living questionnaire scores (r = 0.25–0.53, P < 0.001). Simplified joint counts might facilitate acquisition of quantitative articular data in research and clinical rheumatologic settings.
Decreased expression of interleukin‐2 binding molecules (p70/75) in T cells from patients with systemic lupus erythematosus
Authors: Tanaka Toshio , Saiki Osamu , Negoro Shigeru , Igarashi Tsuyoshi , Kuritani Taro , Hara Hideki , Suemura Masaki , Kishimoto Susumu
Published: February 2007

Using radiolabeled interleukin‐2 (IL‐2), affinity cross‐linking and binding assays revealed that the expression of intermediate‐affinity IL‐2 binding molecules (p70/75) on freshly prepared T cells from patients with systemic lupus erythematosus (SLE) was significantly decreased in comparison with that in normal subjects. The proliferative response of T cells to high doses of IL‐2 was also reduced in patients with SLE. The decreased expression of p70/75 reflects the hyporespon‐siveness to IL‐2 of T cells in patients with SLE.
Treatment of the anemia of rheumatoid arthritis with recombinant human erythropoietin: Clinical and in vitro studies
Authors: Means Robert T. , Olsen Nancy J. , Krantz Sanford B. , Dessypris Emmanuel N. , Graber Stanley E. , Stone William J. , O'Neil Vicki L. , Pincus Theodore
Published: February 2007

Two anemic patients with rheumatoid arthritis were treated with recombinant human erythropoietin (EPO) for 5 months. Both patients showed significant increases in hematocrit, red cell volumes, and marrow erythroid and megakaryocyte progenitor cells. No significant toxic effects from EPO were observed. These data indicate that EPO may be effective in overcoming the pathogenetic factors that limit erythropoiesis in rheumatoid arthritis.
Pregnancy does not cause systemic lupus erythematosus to worsen
Authors: Lockshin Michael D.
Published: February 2007

To evaluate risk for exacerbation of systemic lupus erythematosus (SLE) during pregnancy, we pro‐spectively evaluated 80 pregnant women with SLE for manifestations of disease activity. Fifty‐three of these women were not taking prednisone at the time of conception. Disease activity was scored in 4 ways: global assessment, prednisone therapy, cumulative number of organ systems with abnormalities, and display of abnormalities of each organ system. No patient received prophylactic therapy to prevent disease exacerbation. Thrombocytopenia, proteinuria, and hypocomplementemia were the most common abnormalities and were usually attributable to the pregnancy complications of preeclampsia and anticardiolipin antibody syndrome rather than to SLE. If all possible abnormalities were attributed to SLE, disease exacerbation occurred in <25% of all patients; if only SLE‐specific abnormalities were counted, disease exacerbation occurred in <13%. Worsening of SLE is uncommon in pregnancy, and prophylactic prednisone therapy is unnecessary.
Methotrexate in rheumatoid arthritis. Toxic effects as the major factor in limiting long‐term treatment
Authors: Alarcóan Graciela S. , Tracy Irene C. , Blackburn Warren D.
Published: February 2007

In an effort to understand the prognostic features that may influence the probability of a patient's continuing to take methotrexate (MTX) over time, we studied 152 rheumatoid arthritis patients treated with MTX between 1981 and 1986. The overall probability of continuing to take MTX was 71.2% at 1 year, 55.5% at 3 years, 50% at 5 years, and 49% at 6 years. By univariate analysis, patients who started MTX therapy later in the study, American blacks, younger patients, those with less severe disease, and those with less frequent or less severe toxic events appeared to have a better probability of continuing the drug therapy. When these parameters were evaluated by multivariate analysis, only the time when MTX was started and the occurrence of toxic effects independently influenced the probability of continuing MTX. Thus, by current practice standards, toxic effects emerge as the main reason for MTX discontinuation.
Cross‐reactive antiidiotypic antibodies against human rheumatoid factors from patients with juvenile rheumatoid arthritis
Authors: Moore Terry L. , Osborn Thomas G. , Dorner Robert W.
Published: February 2007

We prepared antiidiotypic (anti‐Id) antibody to 2 polyclonal IgM rheumatoid factors (IgM‐RF) and 2 polyclonal “hidden” IgM‐RF. The anti‐Id antibodies were isolated by chromatography on Sepharose 4B, to which was bound rabbit anti‐human IgG Fc fragments. F(ab′)2 fragments from the anti‐Id antibodies were generated by pepsin digestion and isolated by gel filtration. The anti‐Id antibodies directed against RF from 4 patients with juvenile rheumatoid arthritis (JRA) were tested by an inhibition hemolytic assay for crossreactivity with IgM‐RF from 4 adult patients with rheumatoid arthritis, 6 patients with JRA, and 13 JRA patients with hidden RF. The 4 anti‐Id antibodies had variable cross‐reactivity with the isolated adult RA RF, JRA RF, and JRA hidden RF. Similar results were obtained by a direct‐binding enzyme‐linked immunosorbent assay for the anti‐Id antibodies. The broad pattern of cross‐reactivity was apparently unrelated to a particular amino acid sequence, but was associated with the antigen‐binding site of IgM‐RF. These results suggest the possibility that the anti‐Id antibodies prepared against isolated RF obtained from JRA patients bear the “internal image” of antigen; that is, the Fc region of human IgG. These anti‐Id antibodies may be generated in JRA patients and may possess specific immunomodulatory properties.
Plasma dna in systemic lupus erythematosus. Characterization of cloned base sequences
Authors: Li Jin Zhau , Steinman Charles R.
Published: February 2007

Little is known about plasma DNA in patients with systemic lupus erythematosus (SLE). Previous studies have suggested that it may, in fact, not be derived from the random nucleolysis that might be expected to accompany cell death, which might have been the simplest explanation of its origin. To extend the results of other studies, plasma DNA, obtained from a subgroup of SLE patients who had large amounts of immunoprecipitable plasma DNA, was cloned into a plasmid vector, and the nucleotide base sequences were studied by nucleic acid hybridization. One possible explanation for the anomalous renaturation kinetics of plasma DNA in SLE—namely, that it contained non‐human genomic base sequences—was rendered untenable by the fact that 51 consecutive DNA clones from 2 SLE patients were each shown to contain human genomic DNA sequences. Plasma DNA from SLE patients also differed from human genomic control DNA in that those sequences derived from the highly repetitive fraction of human DNA were specifically enriched in one such sequence, Alu, which constituted 55% of the repeat sequences in the plasma DNA clones as compared with 13% in control DNA clones. There was a decrease in the frequency of non‐Alu repeat sequences (9% for plasma DNA compared with 23% in control DNA). These differences were statistically significant, and they indicate that SLE plasma DNA contains a nonrandom selection of human genomic base sequences. Several explanations for these findings are considered.
The effect of tumor necrosis factor α and γ‐interferon on the resorption of human articular cartilage and on the production of prostaglandin e and of caseinase activity by human articular chondrocytes
Authors: Bunning Rowena A. D. , Russell R. Graham G.
Published: February 2007

In cultured human articular chondrocytes, addition of tumor necrosis factor α (TNFα1) stimulated caseinase activity over the range of 10−11M to 10−7M and stimulated prostaglandin E (PGE) production over the range of 10−10M to 10−7M. Maximal stimulation was observed at 10−8M TNFα for both activities. Gamma‐interferon (γ‐IFN) had a variable effect on PGE production and no significant effect on caseinase activity in articular chondrocyte cultures over a concentration range of 0.1–1,000 units/ml. Co‐incubation of TNFα with γ‐IFN enhanced PGE production and decreased caseinase activity. Concentrations as low as 1 unit/ml of γ‐IFN had significant effects on TNF‐stimulated production of PGE and on caseinase activity. Resorption of human articular cartilage was stimulated by TNFα (10−7M) and was inhibited by γ‐IFN (1,000 units/ml). It is possible that cartilage breakdown in vivo may be modulated by such interactions between cytokines.
Rheumatic syndromes and β2‐microglobulin amyloidosis in patients receiving long‐term peritoneal dialysis
Authors: Cornéalis F. , Bardin T. , Faller B. , Verger C. , Allouache M. , Raymond P. , Rottembourg J. , Tourlière D. , Benhamou C. , Noel L. H. , Kuntz D.
Published: February 2007

We studied 56 patients who had been receiving peritoneal dialysis for >3 years, to investigate the prevalence of rheumatic diseases suggestive of β2‐microglobulin (β2m) amyloid deposition. Eight patients were found to have carpal tunnel syndrome, 16 had chronic shoulder pain, 8 had subchondral bone cysts, and 13 had destructive arthropathies. Amyloid reacting with anti‐β2 m was demonstrated in the hip synovium of 1 patient. Serum β2m levels were elevated in all patients. These data suggest that peritoneal dialysis, like hemodialysis, may lead to the development of an arthropathy associated with β2m accumulation and β2m amyloid deposition.
Double‐blind trial of recombinant γ‐interferon versus placebo in the treatment of rheumatoid arthritis
Authors: Cannon Grant W. , Pincus Seth H. , Emkey Ronald D. , Denes Alex , Cohen Selwyn A. , Wolfe Frederick , Anthony Saway P. , Jaffer Adrian M. , Weaver Arthur L. , Cogen Lewis , Schindler John D.
Published: February 2007

One hundred five patients were enrolled in a 12‐week, randomized, prospective, double‐blind, placebo‐controlled trial of recombinant human γ‐interferon (rHuγ‐IFN) for the treatment of rheumatoid arthritis. Fifty‐four patients received rHuγ‐IFN and 51 received placebo. Forty‐two patients in each group completed the 12‐week trial. Some clinical improvement occurred in both groups of patients. Although the improvement with rHuγ‐IFN was greater than that with placebo, the differences were generally not statistically significant.
Prevalence of scleroderma spectrum disorders in the general population of south carolina
Authors: Maricq Hildegard R. , Weinrich Martin C. , Keil Julian E. , Smith Edwin A. , Harper Frank E. , Nussbaum Alan I. , Carwile Leroy E. , McGregor Andrew R. , Diat Francoise , Rosal Erick J.
Published: February 2007

The prevalence of scleroderma spectrum disorders (including systemic sclerosis [SSc] meeting the American Rheumatism Association criteria and the less typical disorders meeting only our study criteria) was determined in a random sample of 6,998 subjects from the general population of South Carolina. The results suggest that the prevalence of these disorders may range from 67 to 265 per 100,000, which is 4.9 to 19.2 times higher than previously reported for definite SSc. The ratio of nondefinite cases to definite cases of SSc (those meeting American Rheumatism Association criteria) was 2.5. Most of the nondefinite cases were unrecognized prior to our study, which suggests the need for improved early diagnosis of scleroderma spectrum disorders. Brief histories of the 7 patients with scleroderma spectrum disorders whose cases formed the basis for our calculation of prevalence rates are included in this report.
Pristane‐induced arthritis. the immunologic and genetic features of an experimental murine model of autoimmune disease
Authors: Wooley Paul H. , Seibold James R. , Whalen Janey D. , Chapdelaine Joan M.
Published: February 2007

Pristane was injected intraperitoneally into mice of several strains, inducing an inflammatory seropositive arthritis in susceptible strains. The evolving histologic features included synovial hyperplasia, periostitis, and progressive marginal erosions. Multiple serologic immune abnormalities, including rheumatoid factor and anticollagen antibodies, also developed. Genetic analysis indicated that the major histocompatibility complex (H‐2), C5 hemolytic complement (Hc), Newcastle disease virus‐induced interferon (IF‐1), and athymic (nu/nu) loci were involved in regulating susceptibility to pristane‐induced arthritis. This experimental murine disease may provide a novel model of rheumatoid arthritis.
Altered metabolism of poly(adp‐ribose) in the peripheral blood lymphocytes of patients with systemic lupus erythematosus
Authors: Sibley John T. , Haug Brenda L. , Lee Jeremy S.
Published: February 2007

A method was developed to measure poly(ADP‐ribose) metabolism in peripheral blood lymphocytes. The technique involved the isolation of lymphocytes on Ficoll gradients, followed by lysis with 5M NaCl. The synthesis and degradation of poly(ADP‐ribose) in this crude lysate, measured by the incorporation of 3H‐labeled NAD into acid‐precipitable counts, was compared in 18 patients with systemic lupus erythematosus (SLE), 10 patients with rheumatoid arthritis, and in 10 control patients without rheumatoid arthritis. Patients with SLE showed a 70% decrease in poly(ADP‐ribose) synthesis (P < 0.001); this decreased synthesis persisted even with the addition of histones or DNase. We present possible explanations of the role of poly(ADP‐ribose) in SLE.
Cytokines in chronic inflammatory arthritis. III. Rheumatoid arthritis monocytes are not unusually sensitive to γ‐interferon, but have defective γ‐interferon–mediated HLA–DQ and HLA–DR induction
Authors: Bergroth Ville , Zvaifler Nathan J. , Firestein Gary S.
Published: February 2007

Macrophages present in the synovium and synovial fluid of patients with rheumatoid arthritis (RA) express large amounts of HLA–DR molecules on their surface, despite low levels of γ‐interferon (γ‐IFN) in the joint. To determine whether this apparent paradox is the result of increased sensitivity to γ‐IFN in RA, we compared concentrations of γ‐IFN that induced HLA–DR and DQ on peripheral blood monocytes of RA patients and normal donors, using fluorescence‐activated cell sorter analysis. Among normal donors, highly variable sensitivity to γ‐IFN was observed. Higher amounts of γ‐IFN were required to induce class II major histocompatibility complex molecules on RA monocytes versus normal monocytes. The maximum amount of HLA–DR that could be induced on RA and normal monocytes was similar; however, peak levels of HLA–DQ were significantly less in RA. Monocytes from patients with other forms of chronic inflammatory arthritis had intermediate HLA–DQ expression after γ‐IFN treatment. These data suggest that an increased sensitivity to γ‐IFN in RA does not account for the high level of HLA–DR expression in the joint. Also, a defect in HLA–DQ and HLA–DR induction by γ‐IFN was observed.
Involvement of nonarticular cartilage, as demonstrated by release of a cartilage‐specific protein, in rheumatoid arthritis
Authors: Saxne Tore , Heinegård Dick
Published: February 2007

Analysis of human cartilage extracts by radio‐immunoassay showed that the noncollagenous 148‐kd cartilage matrix protein was present in extracts of tracheal cartilage but was undetectable in normal or arthritic joint cartilage, corroborating previous results with bovine cartilage samples. Concentrations of the protein in the circulation, as studied by radioimmunoassay, were greatly elevated in patients with rheumatoid arthritis and polyarticular juvenile rheumatoid arthritis. In contrast, patients with reactive arthritis and oligoarticular juvenile rheumatoid arthritis, as well as rheumatoid arthritis patients treated with low‐dose glucocorticoids, had levels similar to those in healthy controls. The serum concentrations were not related to age. A patient with polychondritis and tracheal involvement had a high serum concentration of the protein, which decreased during plasma exchange and cyclo‐phosphamide treatment. Studies of the release of this cartilage matrix protein, which is present in nonarticular cartilage but not in articular cartilage, should aid in the understanding of the mechanisms of cartilage involvement in disease, and the protein may become a clinically useful marker.
Secretion of antibodies to types I and II collagen by synovial tissue cells in patients with rheumatoid arthritis
Authors: Tarkowski Andrej , Carlsten Hans , Herberts Peter , Klareskog Lars , Koopman William J.
Published: February 2007

Production of antibodies to IgG and to type I and type II collagen (CI and CII) was analyzed by enzyme‐linked immunospot assay in patients with rheumatoid arthritis (RA) and patients with other inflammatory or degenerative joint diseases. Anti‐CII–secreting cells, generally in high numbers, were found among mono‐nuclear cells eluted from inflamed synovial tissue in 12 of 13 patients with seropositive RA and 9 of 14 patients with seronegative RA or with undetermined serum rheumatoid factor levels. In contrast, no anti‐CII–producing B cells were present among synoviocytes from 4 patients with other joint diseases. In none of 7 RA sera did we find significant levels of anti‐CII. Synovial B cells secreting antibodies specific for CI were observed less frequently in patients with RA. These results indicate that measurement of serum antibody levels is not adequate to assess actual autoantibody production in rheumatoid joints and that local autoimmune reactions to CII are common in RA, which implies that collagen‐reactive T cells are present within the inflamed joints of RA patients. The possible role of a local collagen auto‐immunity in RA is discussed, particularly in relation to its putative role in rheumatoid factor production.
Which traditional measures should be used in rheumatoid arthritis clinical trials?
Authors: Anderson Jennifer J. , Felson David T. , Meenan Robert F. , James Williams H.
Published: February 2007

It is standard practice to use multiple outcome measures in rheumatoid arthritis (RA) clinical trials. Because of this, multiple testing is usually done, and there is confusion in the interpretation of the results. It is not clear which measures are the most sensitive to detecting improvement and which provide independent information. To address these questions, we conducted an analysis of pooled raw data from 3 placebo‐controlled RA trials: one of methotrexate, another of oral and injectable gold, and the third of low‐dose and high‐dose D‐penicillamine. The results show that the joint tenderness count, erythrocyte sedimentation rate, grip strength, and physician assessment of disease activity perform best in RA clinical trials and cover the domain of change measured by traditional outcome measures. Other clinical measures may provide little additional useful information for a standard therapeutic trial of up to 6 months duration, and some measures, such as the proximal interphalangeal joint circumference, hemoglobin level, and 50‐foot walking time, can be eliminated from such trials.
Reliability and validity of six systems for the clinical assessment of disease activity in systemic lupus erythematosus
Authors: Liang Matthew H. , Socher Steven A. , Larson Martin G. , Schur Peter H.
Published: February 2007

Six systems for defining and evaluating disease activity in patients with systemic lupus erythematosus (SLE) (the Ropes system, the National Institutes of Health [NIH] system, the New York Hospital for Special Surgery system, the British Isles Lupus Assessment Group [BILAG] scale, the University of Toronto SLE Disease Activity Index [SLE‐DAI], and the Systemic Lupus Activity Measure [SLAM]) were tested on 25 SLE patients who were selected to represent a range of disease activity. The patients were evaluated independently by 2 physicians on 2 occasions approximately 1 month apart. Differences between patients demonstrated the largest source of variation in scores, accounting for 56–84% of the total variance, depending on the instrument. Differences between physicians (i.e., error) showed the next largest variation, 11–28% of the total variance, and differences between visits made up 5–16% of the total. The BILAG, SLE‐DAI, and SLAM had the best inter‐visit and inter‐rater reliability. Convergent validity was shown by the strong correlations of scores among the different instruments (r = 0.81–0.97). All instruments correlated highly with the physicians' clinical impression of disease but less well with their evaluation of disease severity. The number of American Rheumatism Association criteria for SLE that were met by the patients correlated poorly with the physicians' global evaluation and with the scores of the instruments. The patients' self‐reported disease activity scores correlated highly with the physicians' assessments of disease activity (r = 0.85–0.91), and the mean values from self‐reports and from physicians' assessments were nearly equal. In contrast, severity scores correlated less well between self‐reports and physician assessments (r = 0.49–0.69), and mean self‐reported severity values were lower than the means from physicians. The BILAG, SLE‐DAI, and SLAM systems appear to have better psychometric properties than the others for clinical research.
HLA–Bw60 increases susceptibility to ankylosing spondylitis in HLA–B27+ patients
Authors: Robinson Wendy P. , Van Der Linden Sjef M. , Khan Muhammad A. , Rentsch Hans‐Ueli , Cats Arnold , Russell Anthony , Thomson Glenys
Published: February 2007

We examined the distribution of non‐B27 alleles of the HLA–B locus among B27+ patients with ankylosing spondylitis (AS), to detect any additional HLA–B locus allele(s) that may act in conjunction with B27 to increase susceptibility to AS. HLA–Bw60 (or B40 when the Bw60,61 split of B40 was not typed for) was shown to be increased among B27+ AS patients in each of 5 independent data sets. This increase was statistically significant in 4 of the 5 data sets studied, and the overall significance was P < 0.00001. Susceptibility to AS in B27+ individuals was further increased by a factor of ∼3 when Bw60 was also present. The distribution of HLA–A alleles on the B27‐bearing haplotypes in AS patients was not significantly different from that in normal controls. On the other hand, the distribution of HLA–A alleles on Bw60‐bearing haplotypes was significantly different from the distribution of A alleles on Bw60 haplotypes in the general population (P < 0.0005). Bw60 was not increased in B27‐ patients with AS. A dominant mode of inheritance generally fits AS; however, our sib pair analysis indicates that the B27, Bw60 disease subgroup follows a more recessive mode of inheritance.
Gait alterations in dogs after transection of the anterior cruciate ligament
Authors: O'connor Brian L. , Visco Denise M. , Heck David A. , Myers Stephen L. , Brandt Kenneth D.
Published: February 2007

We calculated mean peak vertical forces (MFz) of each limb of 9 adult mongrel dogs before and 2 weeks, 6 weeks, and 12 weeks after left anterior cruciate ligament transection (ACLT). Five additional dogs were studied before and 2 weeks and 6 weeks after sham ACLT. The gaits of 3 dogs that had undergone ACLT 2.5 years previously were also analyzed. Preoperatively, there were no differences in the MFz of the right and left hind limbs of the 9 dogs; we found that each limb exerted approximately 70% of the dog's static body weight on the force plate. Two weeks following ACLT, the MFz of the operated limbs decreased to 25% of the static body weight, while at 6 weeks and 12 weeks after surgery, the MFz generated by the operated limbs rose to about 32% and 37% of static body weight, respectively. No change was noted in the MFz of the contralateral hind limbs. In the 3 dogs that had undergone ACLT 2.5 years earlier, the MFz in the unstable stifle joint was 50% of static body weight. At both 2 weeks and 6 weeks after surgery, the MFz values for all 4 limbs of the animals subjected to sham ACLT were comparable with baseline values. These observations indicate that the osteoarthritic changes seen in the unstable limb are associated with decreased loading of that limb, without increased (compensatory) loading of the contralateral hind limb.
A new and highly sensitive immunohistologic diagnostic criterion for Sjögren's syndrome
Authors: De Wilde P. C. M. , Kater L. , Baak J. P. A. , Van Houwelingen J. C. , Hené R. J. , Slootweg P. J.
Published: February 2007

Immunohistologic investigation of the sublabial salivary glands of 65 surgical patients who were free of systemic disease (control) and 19 patients with Sjögren's syndrome resulted in a new diagnostic criterion for SS that was more disease‐specific than the widely used lymphocytic focus score criterion. Our bivariate classification criterion, which is based on the percentages of IgA‐ and IgG‐containing plasma cells, has a specificity of 95.4% and a sensitivity of 100%, while its overall percentage of misclassification is 3.6%. This immunohistologic diagnostic criterion results in a reduction of the percentage of false‐positive diagnoses from 9% to 4.6%.
A meta‐analysis of the clinical manifestations of older‐onset systemic lupus erythematosus
Authors: Ward Michael M. , Polisson Richard P.
Published: February 2007

Systemic lupus erythematosus (SLE) with onset in later life has been reported to have a clinical presentation different from that in younger individuals; however, the disease manifestations typical of older‐onset SLE patients are known to vary widely among published studies. Meta‐analysis is a statistical process capable of quantitatively combining the results of these reports. This meta‐analysis examines the methodologic features of studies investigating age‐associated manifestations of SLE, and pools estimates of association between clinical features of SLE and age across these studies. Serositis, interstitial pulmonary disease, anti‐La antibodies, and Sjögren's syndrome were most strongly and consistently associated with older‐onset SLE, while alopecia, Raynaud's phenomenon, fever, lymphadenopathy, hypocomplementemia, and neuropsychiatric illness were present less frequently in this group. The extent to which information bias, selection bias, and uncontrolled confounding effects potentially influence these results is discussed. The available information in the literature does not describe the spectrum of clinical manifestations of SLE in the elderly sufficiently to allow its categorization as a distinct entity.
DNA analysis of HLA–DR and DQ genes in american blacks with systemic lupus erythematosus
Authors: Reveille John D. , Schrohenloher Ralph E. , Acton Ronald T. , Barger Bruce O.
Published: February 2007

We studied DNA polymorphisms of HLA–DR and DQ alleles in 63 American black patients with systemic lupus erythematosus (SLE). We found no HLA–DRβ, DQα, or DQβ restriction fragment length polymorphism (RFLP) or RFLP‐determined DR or DQ specificity associated with SLE in either the patients or in 57 control subjects. DRw52b was positively associated with renal involvement and negatively associated with anti–nuclear RNP antibodies. Antibodies to Ro (SS‐A) and La (SS‐B) were associated with DR3(DRw17), DQw2.3. Early‐onset SLE (≦20 years of age) was associated with DRw8, and the frequency of neuropsychiatric involvement correlated negatively with a 3.7‐kb Taq I DQα RFLP. This suggests a role for DR and DQ genes in the clinical and serologic expression of SLE in American blacks.
Inflammation of the deep infrapatellar bursa of the knee
Authors: Taylor Philip W.
Published: February 2007

Two cases of inflammation of the deep infrapatellar bursa of the knee are reported. The first represents the fifth case of infection of the deep infrapatellar bursa that has been reported, and the second represents the first report of gout in the deep infrapatellar bursa. The cases are discussed with emphasis on their importance in the evaluation of the painful knee.
Two types of antibodies inhibiting interleukin‐2 production by normal lymphocytes in patients with systemic lupus erythematosus
Authors: Miyagi Jun , Minato Nagahiro , Kano Shogo , Sumiya Morito , Kasahara Tadashi
Published: February 2007

Decreased interleukin‐2 (IL‐2) production by lymphocytes in vitro has previously been demonstrated in patients with systemic lupus erythematosus (SLE). In the present study, we examined whether inhibitory factors in SLE patient sera are involved in defective IL‐2 production. Our results indicate that purified IgG fractions of some SLE sera inhibit IL‐2 production at 2 distinct phases of the IL‐1‐dependent IL‐2 production system in vitro: first, by binding to adherent cells and probably inhibiting IL‐1 production by macrophages, similar to the action of anti–HLA–DR antibodies, and second, by binding to T cells and blocking the interaction of IL‐1 and T cells.
Factor B activation products in patients with systemic lupus erythematosus. A marker of severe disease activity
Authors: Kerr Leslie Dubin , Adelsberg Bernard R. , Schulman Paul , Spiera Harry
Published: February 2007

Complement activation patterns were determined in a group of 51 patients with systemic lupus erythematosus (SLE), and the clinical outcomes of these patients at 2 years were correlated with the complement activation patterns. Activation of the classical pathway was monitored by analysis of C4a desArg levels and total C4 levels, and activation of the alternative pathway was monitored by isoelectric focusing/immunofixation and quantitative analyses of Factor B. Activation of C3 (a general measure of complement activation) was determined by an enzyme‐linked immunosorbent assay for C3d and by quantitative analysis of C3. Patients were stratified into 3 groups: those with C4 but not C3 activation; those with C4 and C3 but not Factor B activation; and those with C4, C3, and Factor B activation. At the end of 2 years, there was a statistically significant difference in the morbidity and mortality rates of the third group of SLE patients compared with those in the other 2 groups. There was also a statistically significant association between the presence of Ba and cutaneous vasculitis. Unlike the patterns seen with in vitro–activated serum or with membrane‐activated plasma, the Bb activation fragment was not present in the activated plasma samples from the SLE patients. These data suggest that activation of the alternative complement pathway may be a marker for severe SLE and that the Bb fragment may be playing a role in the development of this more serious pathologic condition.
Maternal antibodies to Ro (SS‐A) are associated with both early onset of disease and male sex among children with systemic lupus erythematosus
Authors: Lehman THOMAS J. A. , Reichlin Morris , Santner Thomas J. , Silverman Earl , Petty Ross E. , Spencer Charles H. , Harley John B.
Published: February 2007

In this study of 71 children with systemic lupus erythematosus (SLE) and 188 of their first‐degree relatives, we demonstrated that the development of SLE in male children younger than age 18, and in all children younger than age 10 at the time of diagnosis, is strongly correlated with the presence of antibodies to Ro (SS‐A) in the mother's serum. When the relative antibody concentration was quantified, increased quantities of antibody to Ro (SS‐A) were also found in mothers of male probands and mothers of probands whose SLE was diagnosed before age 10. No similar association was found for the presence or amount of antibody to Ro (SS‐A) in other first‐degree relatives or for antibody to La (SS‐B) or nuclear RNP in any relative. The explanation for the association of maternal anti–Ro (SS‐A) antibodies and early diagnosis of SLE or male sex is not apparent. These findings extend the association of maternal antibodies to Ro (SS‐A) from transient “neonatal” SLE to SLE in childhood, and suggest that maternal antibodies to Ro (SS‐A) may be of fundamental importance in the pathogenesis of some cases of childhood SLE.