bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term prospective trial of low‐dose methotrexate in rheumatoid arthritis
Authors: Weinblatt Michael E. , Trentham David E. , Fraser Patricia A. , Holdsworth Donald E. , Falchuk Kenneth R. , Weissman Barbara N. , Coblyn Jonathan S.
Published: February 2007

Twenty‐six patients with severe rheumatoid arthritis who had completed a randomized crossover trial of methotrexate elected to continue to receive the drug in a long‐term prospective study. At 36 months, 16 patients remained in the study. Over this period of time, significant improvement was noted in the number of painful and swollen joints, physician and patient global assessments, erythrocyte sedimentation rate, and prednisone dose. Adverse reactions occurred in 16 patients (62%), including nausea, alopecia, headache, stomatitis, herpes zoster, and diarrhea. Mild leukopenia (3 patients), thrombocytopenia (3 patients), and elevated transaminase levels (8 patients) resolved with temporary drug discontinuation. No patient withdrew due to drug toxicity. Liver biopsy specimens in 17 patients after 24 months of treatment showed no evidence of fibrosis or cirrhosis. A significant increase in the percentage of T3 and T4 blood cells and increases in lymphocyte proliferation to concanavalin A and purified protein derivative of tuberculin were found after 2 years of therapy. Our findings indicate that methotrexate has remained effective over 36 months of therapy, with acceptable toxicity levels and no evidence of systemic immunosuppression.
Tenderness in 75 anatomic sites. distinguishing fibromyalgia patients from controls
Authors: Simms Robert W. , Goldenberg Don L. , Felson David T. , Mason John H.
Published: February 2007

We studied tenderness at 75 unilateral anatomic locations in 10 fibromyalgia patients and 10 normal control subjects to determine which sites best identified patients with fibromyalgia. Using a dolorimeter, the mean amount of pressure required to elicit tenderness was significantly lower in patients than in controls at 19 sites (P < 0.001). Of the previously proposed tender points, only 2 were included in those 19 best discriminating points. Fifteen of the 19 best discriminating points were clustered in regions around the anterior shoulder, anterior chest, posterior scapula, and medial knee. The 19 sites that we have identified best separate patients with fibromyalgia from controls, although the discriminating power of these sites in other chronic pain syndromes will require further study. Examination of specific regions may be more useful clinically than the exact anatomic sites within these regions.
Stability of normal joint findings in persistent classic rheumatoid arthritis
Authors: Roberts W. Neal , Daltroy Lawren H. , Anderson Ronald J.
Published: February 2007

We reviewed the records of 44 patients, retrospectively selected because they had had persistently active rheumatoid arthritis for more than 5 years (mean ± SD followup 9.8 ± 2.6 years) and because they met the American Rheumatism Association criteria for classic disease, to determine the change in extent of the anatomic distribution of joint involvement over time. The positive predictive value of a lack of inflammation in a joint during the first year for the lack of involvement over the ensuing 4 years was 87%. Thirty‐eight of the 43 joints that required replacement were inflamed in the first year of disease.
The american rheumatism association 1987 revised criteria for the classification of rheumatoid arthritis
Authors: Arnett Frank C. , Edworthy Steven M. , Bloch Daniel A. , Mcshane Dennis J. , Fries James F. , Cooper Norman S. , Healey Louis A. , Kaplan Stephen R. , Liang Matthew H. , Luthra Harvinder S. , Medsger Thomas A. , Mitchell Donald M. , Neustadt David H. , Pinals Robert S. , Schaller Jane G. , Sharp John T. , Wilder Ronald L. , Hunder Gene G.
Published: February 2007

The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non‐RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a “classification tree” schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91–94% sensitivity and 89% specificity for RA when compared with non‐RA rheumatic disease control subjects.
Lupus pregnancy. a prospective study of placental changes
Authors: Hanly John G. , Gladman Dafna D. , Rose Toby H. , Laskin Carl A. , Urowitz Murray B.
Published: February 2007

Eleven patients with systemic lupus erythematosus (SLE) were monitored prospectively during pregnancy. Clinical and serologic features of disease activity were recorded, and after delivery, a careful search for pathologic changes in the placenta was carried out. Seven patients delivered live infants, and 4 patients had unsuccessful pregnancies, with fetal loss occurring between 12 and 27 weeks of gestation. One of these 4 patients had active SLE at delivery, and all had circulating lupus anticoagulant and thrombocytopenia. Other serologic abnormalities, including anticardiolipin and anti‐Ro antibodies, were not associated with fetal loss. The overall placental size was reduced in SLE patients compared with that in healthy controls and in diabetic controls. A variety of pathologic changes were noted, including placental infarction, intraplacental hematoma, deposition of immunoglobulin and complement, and thickening of the trophoblast basement membrane. The reduction in placental size appeared to enhance the clinical significance of these pathologic changes.
Synovial fluid inorganic pyrophosphate concentration and nucleotide pyrophosphohydrolase activity in basic calcium phosphate deposition arthropathy and milwaukee shoulder syndrome
Authors: Rachow John W. , Ryan Lawrence M. , Mccarty Daniel J. , Halverson Paul C.
Published: February 2007

Synovial fluid (SF) inorganic pyrophosphate (PPi) concentration is elevated in calcium pyrophosphate dihydrate (CPPD) crystal deposition arthropathy. Since CPPD and basic calcium phosphate (BCP) crystals often are present in the same joints, we determined [PPi] and activity of the PPi‐generating enzyme, nucleotide pyrophosphohydrolase (NPPH), in SF from the joints of patients with various arthropathies, including those with BCP crystals. We found elevated SF [PPi] in joints with BCP crystals, as well as in joints with CPPD crystals. The presence of BCP crystals in synovial fluids was also predictive of elevated NPPH activity.
The relationship of socioeconomic status to subsequent health status in systemic lupus erythematosus
Authors: Esdaile John M. , Sampalis John S. , Lacaille Diane , Danoff Deborah
Published: February 2007

We examined the relationship of socioeconomic status to health status, as determined by the Arthritis Impact Measurement Scales, in 78 systemic lupus ery‐thematosus patients who had been entered into a prospective study. After controlling for age, disease duration, and disease severity, a significant relationship between socioeconomic status and outcome was not demonstrated. All study subjects had health insurance for medical services. The results have potential implications for health care policy.
Tibialis posterior tendon rupture: a cause of rheumatoid flat foot
Authors: Downey Daniel J. , Simkin Peter A. , Mack Laurence A. , Richardson Michael L. , Kilcoyne Ray F. , Hansen Sigvard T.
Published: February 2007

Flat foot, a major cause of foot pain and disability, may result from rupture of the tibialis posterior tendon. We describe 2 patients with rheumatoid arthritis who developed flat feet secondary to surgically confirmed tendon rupture, and we discuss the anatomy and diagnosis of this condition. In the second patient, we also present the results of tendon imaging with both magnetic resonance and ultrasound.
Spinal cord compression by epidural lipomatosis in juvenile rheumatoid arthritis
Authors: Arroyo Ivonne L. , Barron Karyl S. , Brewer Earl J.
Published: February 2007

Two cases of spinal cord compression secondary to steroid‐induced epidural lipomatosis in systemic juvenile rheumatoid arthritis (JRA) patients are reported. This complication of prolonged corticosteroid therapy has not been described previously in children with JRA. Epidural lipomatosis should be considered in the differential diagnosis of JRA patients receiving high‐dose and/or prolonged corticosteroid therapy who present with neurologic signs and symptoms referable to the spinal cord.
Team versus non‐team outpatient care in rheumatoid arthritis
Authors: Ahlmen Monica , Sullivan Marianne , Bjelle Anders
Published: February 2007

In a rheumatology department, 2 randomized groups of female outpatients with rheumatoid arthritis were studied prospectively for 1 year. The outcome of multidisciplinary team care (T group, 31 patients) was compared with that of regular outpatient clinic care (NT group, 28 patients). Pharmacologic treatment and orthopedic specialist consultations were similar in both groups, but use of paramedical care was higher in the T group. Outcome measures of disease activity, specific joint function, and self‐rated physical discomfort disclosed no significant differences between the 2 groups. Mental well‐being increased in the T group. Overall health, measured by the Sickness Impact Profile, improved significantly only in the T group. This improvement was also significant compared with the NT group.
Spirochetal antigens and lymphoid cell surface markers in lyme synovitis
Authors: Steere Allen C. , Duray Paul H. , Butcher Eugene C.
Published: February 2007

Using monoclonal antibodies to spirochetal antigens and lymphoid cell surface markers, we examined the synovial lesions of 12 patients with Lyme disease, and compared them with rheumatoid synovium and tonsillar lymphoid tissue. The synovial lesions of Lyme disease patients and rheumatoid arthritis patients were similar and often consisted of the elements found in normal organized lymphoid tissue. In both diseases, T cells, predominantly of the helper/inducer subset, were distributed diffusely in subsynovial lining areas, often with nodular aggregates of tightly intermixed T and B cells. IgD‐bearing B cells were scattered within the aggregates, and a few follicular dendritic cells and activated germinal center B cells were sometimes present. Outside the aggregates, many plasma cells, high endothelial venules, scattered macrophages, and a few dendritic macrophages were found. HLA–DR and DQ expression was intense throughout the lesions. In 6 of the 12 patients with Lyme arthritis, but in none of those with rheumatoid arthritis, a few spirochetes and globular antigen deposits were seen in and around blood vessels in areas of lymphocytic infiltration. Thus, in Lyme arthritis, a small number of spirochetes are probably the antigenic stimulus for chronic synovial inflammation.
Effects of warming up on reliability of anthropometric techniques in ankylosing spondylitis
Authors: Neal Roberts W. , Liang Matthew H. , Pallozzi Lorna M. , Daltroy Lawren H.
Published: February 2007

To determine the effect of warm‐up on anthropometric measures, 10 patients with ankylosing spondylitis and 10 normal control subjects were measured over a 1‐hour period by one therapist. A series of 4 measures–a modified Schober's test, finger‐to‐floor with the subject standing on a 23‐cm stool, chest expansion, and cervical rotation using an arthrodial protractor—were repeated completely 4 times. Subjects exercised between each series (except between the third and fourth series). Intra‐rater reliability was determined by comparing measurement 3 with measurement 4, and the warm‐up effect was determined by comparing measurement 1 with measurement 3. The Schober's test and chest expansion are stable measures and are not affected by warm‐up. However, the finger‐to‐floor and cervical rotation exercises require warm‐up to ensure stable values for clinical or research followup of spondylitis.
A long‐term prospective study of the use of methotrexate in rheumatoid arthritis
Authors: Kremer Joel M. , Lee Joong K.
Published: February 2007

Twenty‐five patients have completed a mean of 53 months of treatment with methotrexate (MTX) as part of a prospective study of the long‐term safety and efficacy of the drug. Since the times of the last report (at a mean of 29 months), the mean dosage of MTX has increased from 12.4 mg/week to 14.6 mg/week, whereas the mean prednisone dosage has decreased from a baseline of 7.1 mg/day to 1.9 mg/day. A significant improvement from baseline in all clinical parameters tested was maintained, and response to therapy did not vary significantly between the assessment at 29 months and that at 53 months. Toxic reactions were as common during months 30–53 as during the first 29 months of the study, with patterns of toxic reactions remaining consistent within each patient. Radiologic evidence of disease progression was not seen before 24 months of MTX treatment, but after this time, it was observed in some patients. We conclude that many clinical features of long‐term MTX therapy are distinctly different from what might have been expected after the short‐term trials.
Effects of fasting on disease activity, neutrophil function, fatty acid composition, and leukotriene biosynthesis in patients with rheumatoid arthritis
Authors: Hafström Ingiäld , Ringertz Bo , Gyllenhammar Hans , Palmblad Jan , Harms‐Ringdahl Mats
Published: February 2007

Fourteen patients with rheumatoid arthritis (RA) were studied before, during, and after a 1‐week total fast. Disease activity decreased, as did the neutrophil release of lysozyme induced by the ionophore A23187. The ability of zymosan‐activated RA patient serum to aggregate control neutrophils was reduced, together with serum concentrations of C3. The relative contents of arachidonic acid and eicosapentaenoic acid were increased in serum, platelets, and neutrophils, whereas levels of linoleic acid and linolenic acid were unchanged. Fasting also reduced the release of leukotriene B4 from neutrophils. We thus conclude that a reduced ability to generate cytotaxins, reduced release of enzyme, and reduced leukotriene formation from RA neutrophils, together with an altered fatty acid composition of membrane phospholipids, may be mechanisms for the decrease of inflammatory symptoms that results from fasting.
The use of methotrexate in steroid‐resistant systemic lupus erythematosus
Authors: Rothenberg R. J. , Graziano F. M. , Grandone J. T. , Goldberg J. W. , Bjarnason D. F. , Finesilver A. G.
Published: February 2007

Although the use of methotrexate (MTX) is gaining acceptance in the treatment of several connective tissue diseases, there is little evidence of its therapeutic value in systemic lupus erythematosus (SLE). We examined the response to MTX in patients with steroid‐resistant SLE in an open, unblinded study. Of 10 SLE patients treated with MTX (7.5 mg/weekly), 7 showed improvement. The other 3 stopped therapy because of lack of response or because of side effects. Improvements were noted within 3 months in responding patients. These promising observations suggest that controlled studies of MTX for the treatment of SLE are justified.
Antineurofilament antibody evaluation in neuropsychiatric systemic lupus erythematosus
Authors: Robbins Mark L. , Kornguth Steven E. , Bell Carolyn L. , Kalinke Tom , England Douglas , Turski Patrick , Graziano Frank M.
Published: February 2007

We used Western blot analysis to examine the occurrence and titer of antibody to cytoskeletal neurofilament protein antigens in patients with neuropsychiatric manifestations of systemic lupus erythematosus (SLE) and in controls. Twenty‐two patients with neuropsychiatric SLE (NPSLE) had an increased incidence of antineurofilament antibody (ANFA) compared with 34 patients with SLE without neuropsychiatric symptoms, 78 patients with other disease processes, and 22 healthy controls. ANFA were found to be directed against the 205,000‐ and 160,000‐dalton proteins of the neurofilament triplet. Patients with a diffuse NPSLE clinical presentation had the greatest frequency of serum ANFA (7 of 12, 58%) compared with all other groups examined. Magnetic resonance imaging and serum anticardiolipin antibody testing were also performed in selected patients with NPSLE. Patients with a focal clinical presentation of NPSLE, positive magnetic resonance imaging findings, and negative serum ANFA had significantly elevated levels of anticardiolipin antibody.
B cells expressing cd5 are increased in sjögren's syndrome
Authors: Dauphinée Michael , Tovar Zair , Talal Norman
Published: February 2007

In this investigation of B cells expressing the CD5 (Leu‐1) cell surface marker, we found increased numbers of these cells in 13 of 19 patients with primary Sjögren's syndrome (SS) (68%), as well as in the rheumatoid arthritis patients. The percentage of B cells that demonstrated increased expression of CD5 was 46% in SS patients, 47% in rheumatoid arthritis patients, 24% in systemic lupus erythematosus patients, and 26% in normal subjects. Over a 2‐year period, CD5 expression on B cells was a stable finding in several patients, except for 2 who required either steroid therapy or combined chemotherapy and irradiation for malignant lymphoma. Both of these patients had clinical remissions and their levels of CD5+ B cells returned to normal. The first patient had a clinical picture of SS/systemic lupus erythematosus overlap, associated with polyclonal B cell activation and decreased production of interleukin‐2 in response to stimulation with phytohemagglutinin. These cellular immune abnormalities returned to normal after the institution of corticosteroids. Our observations suggest a relationship between the CD5+ B cell abnormality and disease activity. The results are discussed in relation to immunoregulatory properties of CD5+ B cells in autoimmune mice and the characteristic predisposition to malignant lymphoma among SS patients.
Dose‐dependent induction of anti–native dna antibodies in cats by propylthiouracil
Authors: Aucoin David P. , Rubin Robert L. , Peterson Mark E. , Reidenberg Marcus M. , Drayer Dennis E. , Hurvitz Arthur I. , Lahita Robert G.
Published: February 2007

Cats receiving propylthiouracil (PTU) develop antinuclear antibodies (ANA) and an immune‐mediated disease syndrome characterized by anorexia, lymphadenopathy, weight loss, and Coombs‐positive hemolytic anemia. Investigation of the ANA specificity indicated that the predominant ANA activity consisted of anti–native DNA (nDNA) antibodies. The formation of anti‐nDNA antibodies and immune‐mediated disease syndrome appeared to be dose‐dependent, even in cats in which a response had been induced on 4 prior occasions. These results supply further evidence that PTU‐induced autoimmunity is not the result of a simple drug allergy. Rather, it appears that PTU induces a lupus‐like syndrome, including the hallmark sign of systemic lupus erythematosus, anti‐nDNA antibodies.
Molecular heterogeneity of complement component c4‐null and 21‐hydroxylase genes in systemic lupus erythematosus
Authors: Goldstein Rose , Arnett Frank C. , Mclean Robert H. , Bias Wilma B. , Duvic Madeleine
Published: February 2007

C4A‐null alleles (C4A*Q0) and hereditary complete C4 deficiency (homozygous C4A*Q0, C4B*Q0) are associated with systemic lupus erythematosus (SLE). Using Southern blot analysis with C4 and 21‐hydroxylase (21‐OH) DNA probes, we studied SLE patients and normal control subjects with or without C4A*Q0, and 2 C4‐deficient SLE patients. A previously reported large C4A,21‐OHA gene deletion associated in normal subjects with the HLA—A1;B8;DR3;C4AQ0 haplotype was detected by the appearance of a new C4 Hind III 8.5‐kb fragment and disappearance of a 3.2‐kb 21‐OH Taq I fragment. In 3 SLE patients with homozygous C4A*Q0 and 15 with heterozygous C4A*Q0, this deletion pattern occurred almost exclusively in association with the HLA—B8;DR3;C4A*Q0 phenotype; the one exception was a black SLE patient. Other C4A*Q0‐bearing HLA phenotypes in white patients and black patients with SLE, and the 2 completely C4‐deficient SLE patients, had normal DNA hybridization to both C4 and 21‐OH probes. The genetic basis for C4‐null alleles in SLE is heterogeneous. A large C4A,21‐OHA deletion occurs mainly on the HLA—B8;DR3;C4AQ0 haplotype in SLE and controls. Other HLA haplotypes bearing C4A*Q0 have normal C4 and 21‐OH genes, as demonstrated by Southern blot analysis.
Trends in incidence and clinical presentation of temporal arteritis in olmsted county, minnesota, 1950–1985
Authors: Machado E. B. V. , Michet Clement J. , Ballard David J. , Hunder Gene G. , Beard C. Mary , Chu Chu‐Pin , O'Fallon W. Michael
Published: February 2007

Ninety‐four Olmsted County, Minnesota residents with temporal arteritis (TA) initially diagnosed between 1950 and 1985 (incidence cohort) were identified. The age‐ and sex‐adjusted incidence of TA per 100,000 population age 50 years or older was 17.0 (95% confidence interval [CI] 13.6–20.5), with a marked increase in incidence with age and a threefold greater incidence in women (23.4, 95% CI 18.2–28.7) than in men (7.4, 95% CI 3.7–11.0). The previously described secular increase in TA incidence in Olmsted County women continued from 1970 through 1985, while TA incidence in men declined in this latter time period. Although the frequency of classic clinical manifestations of TA declined over time, the percentage of patients undergoing biopsy who have positive specimens remained relatively constant (women 41%, men 26%). The incidence rate of temporal artery biopsy also increased for women during this period, but declined for men, suggesting that the differing trends in TA incidence by sex may be partially attributable to a detection bias. Future research in TA etiology and epidemiology should focus on possible causal factors linked to the differential TA incidence by sex.
Dyslipoproteinemia in pediatric systemic lupus erythematosus
Authors: Ilowite Norman T. , Samuel Paul , Ginzler Ellen , Jacobson Marc S.
Published: February 2007

Patients with systemic lupus erythematosus are at increased risk for premature atherosclerosis. We examined one possible etiologic factor, dyslipoproteinemia, both before and after corticosteroid therapy. We identified 2 distinct patterns of dyslipoproteinemia. One is attributable to active disease; the other is attributable, in part, to corticosteroid therapy. The dyslipoproteinemia of active disease consists of depressed high density lipoprotein cholesterol and apoprotein A‐I with elevated very low density lipoprotein cholesterol and triglyceride, while the dyslipoproteinemia after corticosteroid therapy consists of increased total cholesterol, very low density lipoprotein cholesterol, and triglyceride. The possible pathophysiologic mechanisms responsible for these patterns, as well as the possible roles in premature atherosclerosis seen in systemic lupus erythematosus patients, are discussed.
Phenothiazine‐induced systemic lupus erythematosus with superior vena cava syndrome: case report and review of the literature
Authors: Steen Virginia D. , Ramsey‐Goldman Rosalind
Published: February 2007

Phenothiazine‐induced lupus with circulating anticoagulant (CAC) has been reported infrequently, and is rarely associated with significant symptoms. We describe a patient who we suspect had perphenazine‐induced lupus erythematosus with CAC. She had recurrent episodes of venous thrombosis and ultimately developed superior vena cava syndrome. The relationships among phenothiazine‐induced lupus, CAC, and thrombosis are discussed.
Light and electron microscopic studies on the synovial membrane in reiter's syndrome.
Authors: Ralph H. Schumacher , Magge Sathish , Varghese Cherian P. , Sleckman Joseph , Rothfuss Susan , Clayburne Gilda , Sieck Marie
Published: February 2007

Studies by light microscopy on synovium obtained from 11 patients with Reiter's syndrome during the first month of an episode showed proliferation of synovial lining cells, polymorphonuclear neutrophils among the synovial lining cells, increased surface fibrin, and vascular congestion. Biopsy specimens taken later showed vascular congestion and still proliferated synovial lining cells, fewer polymorphonuclear neutrophils in some, and a tendency toward increased infiltration with lymphocytes and plasma cells. Electron microscopy of samples from 8 patients during the first month of disease activity showed occlusion of vessels by platelets in 4, and fibrin or dense granular material in the vessel walls in 4. Five of the patients with arthritis of less than 4 weeks duration had unidentified intracellular and extracellular particles; some of these were highly suggestive of Chlamydia. No such particles were noted in samples from patients with more chronic cases. Using an antibody to Chlamydia trachomatis and the peroxidase‐antiperoxidase technique, immunocytochemistry showed reaction product in synovial macrophages in 2 patients with arthritis of less than 4 weeks duration, but not in the 1 patient studied who had more chronic disease. These studies provide support for dramatic synovial vascular injury consistent with that caused by endotoxin and the presence of chlamydial antigen in synovial macrophages, at least in the early phases of synovitis.
Analysis of the histologic variation of synovitis in rheumatoid arthritis
Authors: Rooney Madeleine , Condell Deborah , Quinlan William , Daly Leslie , Whelan Alex , Feighery Conleth , Bresnihan Barry
Published: February 2007

One hundred forty‐five synovial biopsy specimens were obtained from 30 procedures performed on the knee joints of 29 patients with rheumatoid arthritis. All patients had clinically active rheumatoid arthritis and none had received slow‐acting disease‐modifying drugs or intraarticular corticosteroids. Scores were assigned to each biopsy specimen for each of 6 histologic features to quantify variation within each joint. In the majority of knee joint biopsies, there was considerable clustering of scores for all histologic features. Thus, on a scale of 0–10, 82% of the scores for synoviocyte hyperplasia were within 1 point of the median score for a given joint. Similarly, between 69% and 85% of the scores for the remaining features (fibrosis, vessel proliferation, perivascular infiltrates, focal aggregates, and diffuse infiltrates of lymphocytes) were within 1 point of the median values. Multiple biopsies were obtained at arthroscopy in 8 patients. Tissue was selected from areas of apparent maximal and minimal involvement, to enhance the likelihood of regional histologic variation. Of the scores for synoviocyte hyperplasia, 91% were within 1 point of the median values for a given joint, and of the scores for the remaining 5 features, 72–94% fell within 1 point of the median values. In addition, highly significant statistical correlations of the intensity of synovial lining layer hyperplasia, vessel proliferation, mononuclear cell infiltration, fibrosis, and clinical measurements of synovitis were observed.
Suppression of human fibroblast proliferation by d‐penicillamine and copper sulfate in vitro
Authors: Matsubara Tsukasa , Hirohata Kazushi
Published: February 2007

We examined the effect of D‐penicillamine (DP) and copper sulfate (CuSO4) on human fibroblast proliferation in vitro. DP plus CuSO4 inhibited both basal and interleukin‐1 (IL‐1)‐induced tritiated thymidine incorporation into fibroblasts in a dose‐ and time‐dependent manner. Significant inhibition was observed at the level of 60 μM in the presence of 4 μM CuSO4. At this range of concentrations, which is attained in serum and in tissues of treated patients, DP alone or CuSO4 alone did not affect fibroblast proliferation. Similar inhibition was observed with various thiols in the presence of copper, but not with disulfides such as DP disulfide or oxidized glutathione. Inhibition of fibroblast DNA synthesis induced by DP and CuSO4 was reversed by the simultaneous addition of catalase or horseradish peroxidase, but not by boiled catalase or superoxide dismutase. The inhibition by DP and CuSO4, therefore, may be attributable to hydrogen peroxide produced by these 2 agents. DP, in the presence of CuSO4, did not affect IL‐1 secretion from human peripheral mononuclear phagocytes. These observations indicate that hydrogen peroxide produced by DP plus CuSO4 inhibits IL‐1–induced fibroblast proliferation by directly affecting fibroblasts, without alteration of IL‐1 secretion from mononuclear phagocytes. Thus, DP may play a role in inhibiting the growth of rheumatoid pannus and excessive collagenation in scleroderma by direct inhibition of fibroblast proliferation.
Sex hormone status and osteoporosis in postmenopausal women with rheumatoid arthritis
Authors: Sambrook P. N. , Eisman J. A. , Champion G. D. , Pocock N. A.
Published: February 2007

Sex hormones have important effects on bone, especially in postmenopausal women. These hormones may be of particular significance in patients with rheumatoid arthritis (RA), who have a high frequency of osteoporosis. To examine this, we measured estrogen and androgen concentrations and bone mineral density (BMD) in 49 postmenopausal women with RA and 49 normal postmenopausal women. Compared with the controls, postmenopausal RA patients had significantly reduced levels of estrone (median 18 pmoles/liter versus 49; P < 0.001), dehydroepiandosterone sulfate (DHEAS) (median 0.3 μmoles/liter versus 2.0; P < 0.001), testosterone (median 0.6 nmoles/liter versus 0.95; P < 0.001), and femoral BMD (mean 0.72 gm/cm2 versus 0.80; P < 0.002). Prednisolone therapy in 22 patients (mean dosage 8 mg/day) was associated with reductions in estrone and testosterone levels; however, DHEAS and femoral BMD were also decreased in RA patients who were not receiving corticosteroids. Reduced DHEAS levels in postmenopausal women with RA may increase their risk of osteoporosis.
N‐acetylprocainamide is a less potent inducer of t cell autoreactivity than procainamide
Authors: Richardson Bruce , Cornacchia Elizabeth , Golbus Joseph , Maybaum Jonathan , Strahler John , Hanash Samir
Published: February 2007

We have reported that an inhibitor of DNA methylation, 5‐azacytidine, makes cloned, antigen‐specific CD4 + T cells autoreactive, and that procainamide and hydralazine mimic this effect. Those results suggested that procainamide and hydralazine may induce autoimmunity by inhibiting DNA methylation and causing T cell autoreactivity. We report now that N‐acetylprocainamide, a procainamide derivative that does not induce lupus, is also a DNA methylation inhibitor, but it is 100 times less potent than procainamide in inducing T cell autoreactivity.
Subacute cutaneous lupus erythematosus. clinical, serologic, immunogenetic, and therapeutic considerations in seventy‐two patients
Authors: Callen Jeffrey P. , Klein Jon
Published: February 2007

We studied 72 patients with subacute cutaneous lupus erythematosus (SCLE). Forty‐nine of the patients had been part of an earlier study. The cutaneous disease was primarily annular in 17 patients, papulosquamous in 48, and a combination in 7. Although the major feature of SCLE is nonscarring, non‐atrophy‐producing lesions, scarring discoid lesions were observed in 21 patients. Thirty‐six patients fulfilled criteria for systemic lupus erythematosus. Cytoplasmic antibodies were present in only 22 patients. However, in the group of 23 patients recently analyzed, 13 of 22 tested had anti–Ro (SS‐A) and/or anti–La (SS‐B). HLA–DR3 was present in 22 of 59 patients. Neither anti–Ro (SS‐A) nor HLA–DR3 correlated with any clinical finding. Fortyseven patients have had continued activity of their disease, but in most patients, the disease has been controlled with sunscreens, topical and intralesional corticosteroids, and oral hydroxychloroquine. A broad spectrum of systemic lupus erythematosus–associated phenomena can occur in patients with SCLE. The disease is frequently easily controlled, and may become quiescent. This subset of lupus patients is less distinctive than has been previously suggested.
Possible involvement of epstein‐barr virus in polyclonal b cell activation in sjögren's syndrome
Authors: Yamaoka Kunio , Miyasaka Nobuyuki , Yamamoto Kohtaro
Published: February 2007

We sought evidence of Epstein‐Barr virus (EBV) involvement in the mechanism of polyclonal B cell activation in 29 patients with Sjögren's syndrome (SS). Serum levels of anti‐viral capsid antigen antibodies of both the IgG and the IgM class were significantly elevated in these patients. Excretion of EBV from the oropharynx was frequently observed, as well. Spontaneously transformed B cell lines that produced a large amount of transforming EBV were established preferentially from SS patients. We also found that an EBV‐specific regulatory mechanism was impaired in these patients. Our findings thus provide evidence of the involvement of EBV in patients with SS.
A controlled study of the effects of a supervised cardiovascular fitness training program on the manifestations of primary fibromyalgia
Authors: Mccain Glenn A. , Bell David A. , Mai François M. , Halliday Paul D.
Published: February 2007

Forty‐two patients with primary fibromyalgia were randomized into a 20‐week program consisting of either cardiovascular fitness (CVR) training or simple flexibility exercises (FLEX) that did not lead to enhanced cardiovascular fitness. Patients were supervised by the same medical fitness instructors. Patients in neither group had contact with members of the other group, and were blinded as to the exercise taught to the alternative group. Groups met for 60 minutes 3 times each week. The compliance rate was 90%. Thirty‐eight patients completed the study (18 with CVR training and 20 with FLEX). Blind assessments (standardized in preliminary trials to achieve acceptable inter‐rater agreement) were performed by the same 2 examiners. After 20 weeks, patients receiving CVR training showed significantly improved cardiovascular fitness scores compared with those receiving FLEX training (t[35] = −4.22, P < 0.003). Logistic regression analysis showed clinically and statistically significant improvements in pain threshold scores, which were measured directly over fibrositic tender points, in patients undergoing CVR (t[35] = 2.21, P < 0.04). There was also a trend toward improvement in pain scores (visual analog scale) in the CVR group, but this did not reach statistical significance. There was no improvement in the percentage of body area affected by fibrositic symptoms or the number of nights per week or hours per night of disturbed sleep (self‐report inventories). However, compared with the FLEX group, the CVR‐trained patients improved significantly in both patient and physician global assessment scores. Because multidimensional symptom self‐report inventory scores were similar in CVR‐trained and FLEX‐trained groups before and after exercise, improvements in the CVR‐trained group were not the result of a reduction in psychological distress. Thus, a supervised cardiovascular fitness training program may provide some therapeutic benefit to selected patients with primary fibromyalgia syndrome.
Accelerated nodulosis and vasculitis during methotrexate therapy for rheumatoid arthritis
Authors: Segal Rafael , Caspi Dan , Tishler Moshe , Fishel Beno , Yaron Michael
Published: February 2007

Three women with classic rheumatoid arthritis, who were receiving weekly doses of methotrexate (MTX), developed accelerated subcutaneous nodulosis, despite good response to the drug. In 2 of the patients, the onset of nodulosis occurred within 3 months and 5 months, respectively, after starting MTX; in the third patient, it was observed only after 4 years of MTX therapy. In all 3 patients, the onset was unusually abrupt, with extensive distribution and remarkable nodule size. Additional manifestations of cutaneous vasculitis in 2 of the patients and Raynaud's phenomenon in the third appeared concomitantly with the nodulosis. Physicians prescribing MTX therapy for patients with rheumatoid arthritis should be aware of these potential complications.
Reversal of progressive necrotizing vasculitis with intravenous pulse cyclophosphamide and methylprednisolone
Authors: Fort John G. , Abruzzo John L.
Published: February 2007

We describe a patient with polyarteritis nodosa who, despite therapy with daily doses of oral prednisone and cyclophosphamide, developed acute renal failure. Renal histopathologic examination demonstrated crescentic glomerulonephritis. Treatment with intravenous pulse cyclophosphamide and methylprednisolone resulted in clinical improvement and significant recovery of renal function.
Human autoantibody secreted by immortalized lymphocyte cell line against the 68k polypeptide of the u1 small nuclear ribonucleoprotein
Authors: Chen Jintao , Takeda Yoshihiko , Vanderslice W. Eric , Sharp Gordon C. , Pettersson Ingvar , Roséan Anders , Wigzell Hans , Wang Richard J.
Published: February 2007

Autoantibody of an immortalized human lymphocyte cell line, Su‐2E4, derived from peripheral lymphocytes of a patient with mixed connective tissue disease, showed specific binding of the 68K polypeptide of U1 small nuclear RNP (snRNP) and immunoprecipitation of U1 RNA. The reaction patterns of Su‐2E4 and a murine monoclonal anti‐(U1)snRNP line, 2.73, and results of a competition assay with the 2 antibodies suggest similar, but not necessarily identical, epitope recognition.
Sex hormone status of male patients with rheumatoid arthritis: evidence of low serum concentrations of testosterone at baseline and after human chorionic gonadotropin stimulation
Authors: Cutolo Maurizio , Balleari Enrico , Giusti Massimo , Monachesi Mario , Accardo Silvano
Published: February 2007

Serum concentrations of luteinizing hormone, follicle‐stimulating hormone, prolactin, 17 beta‐estradiol, testosterone, androstenedione, dehydrotestosterone, dehydroepiandrosterone sulfate, and cortisol were examined in 14 men with rheumatoid arthritis (RA) and in age‐matched osteoarthritis controls. Hypophyseal, adrenal, and testicular responses to stimulation with luteinizing hormone‐‐releasing hormone, adrenocorticotropin, and human chorionic gonadotropin, respectively, were evaluated in 8 RA patients and in 8 age‐matched healthy volunteers. Basal serum testosterone concentrations were significantly lower in male RA patients than in the osteoarthritis control subjects (P < 0.01). After human chorionic gonadotropin stimulation, serum concentrations of testosterone were also lower in the RA patients than in normal healthy controls (P < 0.05). These findings suggest that diminished testicular steroid biosynthesis might contribute to the serum testosterone deficiency observed in male RA patients.
Auto antibodies to intracellular proteins in human systemic lupus erythematosus are not due to random polyclonal b cell activation
Authors: Gharavi Azzudin E. , Chu Jia‐Li , Elkon Keith B.
Published: February 2007

Antibody binding to total protein extracted from a mammalian source (HeLa cells) and from a prokaryotic source (Escherichia coli) was compared in sera from patients with systemic lupus erythematosus (SLE) and sera from normal subjects. When the average numbers of peptides or proteins recognized by IgG antibodies were compared on immunoblots, SLE sera bound to a significantly greater number of proteins from the HeLa cell extract than did sera from normal individuals (P < 0.001). In contrast, SLE sera actually bound to fewer E coli proteins than did the sera obtained from normal controls, although the difference was not statistically significant. There was no correlation between the number of E coli proteins and HeLa proteins recognized by individual SLE sera, and there was no trend toward reactivity with a larger number of antigens in sera containing higher levels of IgG. IgG from SLE sera did not bind to 6 purified eukaryotic protein standards (selected solely on the basis of differences in size and charge) either in their denatured state or in their native state. These findings indicate that the high levels of IgG antibodies against selected eukaryotic intracellular proteins in patients with SLE cannot be explained by a random polyclonal B cell activation.
A 16/6 idiotype—positive anti‐DNA antibody is encoded by a conserved VH gene with no somatic mutation
Authors: Chen Pojen P. , Liu Ming‐Fei , Sinha Suman , Carson Dennis A.
Published: February 2007

Recently, the heavy chain of 16/6 idiotype—positive human anti‐DNA antibodies was found to be similar, but not identical, to the VH26 gene. We resequenced the VH26 gene and found that its coding sequence is actually identical to the complementary DNA sequence of the anti‐DNA antibodies previously described. Together with the previous data, our findings demonstrate that some human autoantibodies are encoded directly by immunoglobulin V region genes, and that these V region genes are remarkably conserved in populations.
Stimulation of interleukin‐1α and interleukin‐1β release from human monocytes by cyanogen bromide peptides of type ii collagen
Authors: Goto Makoto , Yoshinoya Sadayoshi , Miyamoto Terumasa , Sasano Minoru , Okamotoy Masahiro , Nishioka Kusuki , Terato Kuniaki , Nagai Yutaka
Published: February 2007

Pyrogen‐free cartilage fragments from patients with fracture, osteoarthritis, or rheumatoid arthritis were found to stimulate the production of interleukin‐1α—like and interleukin‐1β—like factor by peripheral blood mononuclear cells from healthy individuals and rheumatoid arthritis patients. The stimulatory cartilaginous component was type II collagen, and the major stimulatory determinant on type II collagen was found to be cyanogen bromide 11 peptide. These results suggest a possible pathogenic role of the intact cartilaginous component in interleukin‐1—mediated joint destruction.
The effects of scleroderma serum on human microvascular endothelial cells
Authors: Marks Rory M. , Czerniecki Maria , Andrews Brian S. , Penny Ronald
Published: February 2007

To investigate the vascular immunopathology of systemic sclerosis, we developed a model consisting of human microvascular endothelial cells, leukocytes, and serum. Sera from 19% of the patients studied mediated antibody‐dependent cellular cytotoxicity against endothelial cells. Some sera also mediated cytotoxicity against aortic endothelium and fibroblasts. K lymphocytes, the cells that mediate antibody‐dependent cellular cytotoxicity, were identified in the skin of some patients. The sera alone were not cytotoxic or growth inhibitory, and did not affect endothelial prostacyclin production.
A comparison of cyclobenzaprine and placebo in the management of fibrositis
Authors: Bennett Robert M. , Gatter Robert A. , Campbell Stephen M. , Andrews Ronald P. , Clark Sharon R. , Scarola Joseph A.
Published: February 2007

The efficacy of cyclobenzaprine (Flexeril), as compared with placebo, was tested in a 12‐week, double‐blind, controlled trial of 120 patients with fibrositis. Of the patients who received placebo, 52% dropped out due to lack of efficacy of the drug, compared with 16% of patients taking cyclobenzaprine. The dropout rate due to adverse reactions was similar in the 2 groups. Patients taking cyclobenzaprine experienced a significant decrease in the severity of pain and a significant increase in the quality of sleep. There was a trend toward improvement in the symptoms of fatigue, but morning stiffness was not alleviated. These improvements in symptoms were associated with a significant reduction in the total number of tender points and in muscle tightness. Our findings indicate that cyclobenzaprine is a useful adjunct in treating patients with the fibrositis syndrome.
Hla—dr antigens and anticardiolipin antibodies in northern italian systemic lupus erythematosus patients
Authors: Savi M. , Ferraccioli G. F. , Neri T. M. , Zanelli P. , Dall'Aglio P. P. , Tincani A. , Balestrieri G. , Carella G. , Cattaneo R.
Published: February 2007

Eighty systemic lupus erythematosus (SLE) patients attending 3 clinical centers were evaluated immunologically and immunogenetically. No HLA class I1 antigens were found to be significantly associated with SLE in these patients. A highly significant (P = 6.17 × 1o−7) association was observed between anticardiolipin antibodies and DR7. A lesser association (P < 0.025) was also observed between DR2 and/or DR3 and anti—Ro (SS‐A) antibodies. No relationship was found between any DR antigen and anti‐Sm/RNP, antidouble‐stranded DNA, or anti—La (SS‐B) antibodies.
The effect of folic acid supplementation on the toxicity of low‐dose methotrexate in patients with rheumatoid arthritis
Authors: Morgan Sarah L. , Baggott Joseph E. , Vaughn William H. , Young Peggy K. , Austin Janet V. , Krumdieck Carlos L. , Alarcon Graciela S.
Published: February 2007

Thirty‐two patients with rheumatoid arthritis completed a 24‐week, placebo‐controlled, double‐blind trial of folic acid (FA) supplementation during low‐dose methotrexate (MTX) therapy. Administration of the daily FA supplement significantly lowered toxicity scores without affecting efficacy, as measured by joint counts, joint indices, and patient and physician evaluation of disease activity. Fifteen patients experienced some sort of toxicity; 67% were in the placebo group, and 33% were in the FA supplement group. Four patients in the placebo group had toxicity levels serious enough to require discontinuation of the MTX, while no patients in the FA supplement group discontinued MTX because of toxicity. Low‐normal initial plasma and red blood cell folate levels were predictive of future toxicity with MTX therapy. We conclude that a daily supplement of 1 mg of FA during low‐dose MTX therapy (median dose 7.5 mg/week [16.4 μmoles]) is useful in lessening toxicity without altering efficacy during the first 6 months of treatment.
Subclinical renal dysfunction in rheumatoid arthritis
Authors: Boers Maarten , Dijkmans Ben A. C. , Breedveld Ferdinand C. , Camps Jan A. J. , Chang Peter C. , Brummelen Peter Van , Pauwels Ernest K. J. , Cats Arnold
Published: February 2007

We studied renal function in 35 patients with chronic, seropositive rheumatoid arthritis (RA), of whom 7 had vasculitis, 10 had hypergammaglobulinemia, and 18 had neither of these 2 conditions. Findings included a decreased glomerular filtration rate in 8 patients, (micro)proteinuria in 11, a defective urine concentration in 10, and increased urinary tubular enzyme levels in 15. These results indicate that subclinical renal dysfunction is common in patients with chronic, seropositive RA. In addition, vasculitis and hypergammaglobulinemia were not identified as risk factors for renal dysfunction in the RA patients studied.
Ligand‐dependent release of active neutrophil collagenase
Authors: Chatham W. Winn , Heck Louis W. , Blackburn Warren D.
Published: February 2007

The amount of active neutrophil (PMN) collagenase released extracellularly is dependent on the PMN‐activating ligand. Neutrophils stimulated with soluble ligands, including FMLP, platelet‐activating factor, or heat‐aggregated IgG, released very little active collagenase, in contrast to cells stimulated with opsonized zymosan or surface‐bound IgG. However, opsonized zymosan and surface‐bound IgG did not differ appreciably from soluble ligands in effecting PMN production of superoxide, release of the specific granule component lactoferrin, or total (latent plus active) collagenase release, which suggests that there is more efficient collagenase activation during PMN stimulation with surface‐bound ligands. These results suggest a role for surface (cartilage)‐bound IgG in the release and activation of human neutrophil collagenase in the joints of patients with rheumatoid arthritis.