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N Rothfield

Publications and source records attributed to N Rothfield.

At least 19 recordsLinked to original sources
PubMed2001

History of affective disorder and the temporal trajectory of fatigue in rheumatoid arthritis.

This study examines whether the general level and rate of change of fatigue over time is different for those rheumatoid arthritis (RA) patients with and those without a history of affective disorder (AD). Four hundred fifteen RA patients from a national panel had yearly telephone interviews to obtain fatigue and distress reports, and a one-time semistructured assessment of the history of depression and generalized anxiety disorder Growth-curve analysis was used to capture variations in initial fatigue levels and changes in fatigue over 7 years for those with and without a history. RA patients with a history of major AD reported levels of fatigue that were 10% higher than those without a history in the 1st year of the study. Their fatigue reports remained elevated over 7 years. Further analysis showed that the effects of a history of AD on fatigue are fully mediated through current distress, although those with a history had a significantly smaller distress-fatigue slope. Thus, a history of AD leaves RA patients at risk for a 7-year trajectory of fatigue that is consistently higher than that of patients without a history. The elevation in fatigue reports is, at least in part, a function of enduring levels of distress.

Anxiety Disorders↗
PubMed2001

Factors associated with low bone mineral density in female patients with systemic lupus erythematosus.

OBJECTIVE: To study risk factors for low bone mineral density (BMD, g/cm) in patients with systemic lupus erythematosus (SLE). METHODS: Ninety-two consecutive patients with SLE followed by rheumatology faculty between 1997 and 1999 completed a questionnaire regarding lifestyle during the clinic visit, a chart review was performed, and data were collected for the time of the first dual energy x-ray absorptiometry (DXA) examination. Univariate and multivariate statistical analyses were used to assess relationships between various risk factors and BMD. RESULTS: Ninety-eight percent of patients had received prednisone, 51% were postmenopausal (9 of whom received hormone replacement therapy), 68% had received hydroxychloroquine, and 15% were osteoporotic. The following factors were found to be significantly related to lower BMD by univariate analysis: Caucasian race, older age at diagnosis, higher age at the time of the first DXA, longer disease duration, higher cumulative corticosteroid dose, higher SLE Damage Index score, and postmenopausal status. In the multivariate analysis only the following factors were significant: Caucasian race, increased number of pregnancies, postmenopausal status, higher SLE Damage Index, and higher cumulative corticosteroid dose. An unexpected finding was that taking hydroxychloroquine was the only factor associated with higher BMD of the hip and spine in the univariate analysis, and it remained predictive of higher BMD of the hip and spine in the multivariate analysis. CONCLUSION: Hydroxychloroquine appears to protect against low BMD in corticosteroid treated patients with SLE.

Absorptiometry, Photon↗
PubMed2000

Recombinant human relaxin in the treatment of scleroderma. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Relaxin is a pregnancy-related hormone that has tissue remodeling and antifibrotic effects. Systemic sclerosis (scleroderma) is characterized by fibrosis of the skin, vasculature, and internal organs. OBJECTIVE: To assess the efficacy, safety, and dose-response effect of recombinant human relaxin in patients with scleroderma. DESIGN: Multicenter, parallel-group, randomized, double-blind, placebo-controlled trial. SETTING: Academic referral centers. PATIENTS: 68 patients who had had stable, diffuse scleroderma (moderate to severe) for less than 5 years. INTERVENTION: Recombinant human relaxin, 25 or 100 microg/kg of body weight per day, or placebo administered by continuous subcutaneous infusion over 24 weeks. MEASUREMENTS: Modified Rodnan skin score was the primary efficacy measure. Secondary measurements were pulmonary function, the Health Assessment Questionnaire, and other measures of scleroderma that reflected fibrosis. RESULTS: Patients who received 25 microg/kg of recombinant human relaxin per day had significantly lower skin scores than those who received placebo (mean change, -3.6 at 4 weeks [P = 0.021], -7.5 at 12 weeks [P < 0.001], and -8.7 at 24 weeks [P = 0.040]). Similar trends were noted in other outcome measures, including forced vital capacity, measures of oral aperture and hand extension, functional status, and global assessment. Patients who received 100 microg/kg of relaxin per day did not differ from those who received placebo. Drug-related adverse events included menometrorrhagia, reversible anemia, and complications of the subcutaneous drug administration system (site irritation and local infection). CONCLUSIONS: Twenty-four weeks of recombinant human relaxin, 25 microg/kg per day, is associated with reduced skin thickening, improved mobility, and improved function in patients with moderate to severe diffuse scleroderma.

Adolescent↗
PubMed1997

Reference sera for antinuclear antibodies. II. Further definition of antibody specificities in international antinuclear antibody reference sera by immunofluorescence and western blotting.

OBJECTIVE: To define the fine specificity of the 10 reference sera used for determination of antinuclear antibodies (ANA) and ANA subsets which are available from the Arthritis Foundation (AF) and from the Centers for Disease Control and Prevention (CDC). METHODS: AF/CDC sera were assessed by experienced laboratory staff, using indirect immunofluorescence and Western blotting. RESULTS: The original assignment of fluorescence patterns to 4 reference sera was confirmed, and the fluorescence intensities were determined using reference fluorescent beads. On Western blots, sera AF/CDC2 (anti-SS-B/La) and AF/CDC7 (anti-SS-A/Ro) did not detect Ro antigens, sera AF/CDC9 and AF/CDC10 appeared to be monospecific anti-Scl-70 and anti-Jo-1 sera, respectively, serum AF/CDC4 (anti-U1 small nuclear RNP) recognized the 70-kd band, and serum AF/CDC5 recognized the Sm antigen with its multiple bands. Semiquantitative analyses revealed that AF/CDC5, AF/CDC2, and AF/CDC10 were strongly reactive sera, whereas AF/CDC4 and AF/CDC9 were much weaker and should be used at lower dilutions on Western blots. CONCLUSION: The AF/CDC ANA reference sera, originally described as reference reagents for indirect immunofluorescence and double immunodiffusion techniques, are also useful for Western blotting. The data presented herein further support the use of these sera for reference purposes.

Antibodies, Antinuclear↗
PubMed1997

Analysis of IgG subclasses of human antitopoisomerase I autoantibodies suggests chronic B cell stimulation.

Antitopoisomerase I autoantibodies are highly specific of scleroderma and are mainly IgG. The present study was designed to evaluate the prevalence of each IgG antitopoisomerase I subclass. An ELISA for the detection of IgG antitopoisomerase I subclasses was standardized and used to study the antibodies from 49 antitopoisomerase I-positive patients identified from a total of 541 patients. Correlations and multivariate analysis were performed to determine the frequency of associations between the IgG antitopoisomerase I subclasses. All IgG antitopoisomerase I subclasses were found. Twelve patients (24.5%) had all four IgG antitopoisomerase I subclasses, 13 (26.5%) had three, 16 (32.7%) had two, and 7 (14.3%) had only one antitopoisomerase I subclass. The presence of all four IgG antitopoisomerase I subclasses suggests that this specific B-cell is the target of multiple activation pathways which indicate that there is a complex T-cell-cytokine-driven process. Together with the absence of other autoantibodies in these sera, our results support the concept of a multiple but highly selected and chronic B-cell activation in scleroderma patients with antitopoisomerase I.

Adult↗
PubMed1996

Localization of histidyl-tRNA synthetase (Jo-1) in human laryngeal epithelial carcinoma cell line (HEp-2 cells).

The present study was designed to determine the subcellular localization of histidyl-tRNA synthetase (Jo-1) in human laryngeal epithelial carcinoma cell line (HEp-2 cells). Indirect immunofluorescence using commercial HEp-2 cells with human serum and human-affinity-purified anti-Jo-1 antibodies was performed using confocal microscopy. Anti-histidyl-tRNA-synthetase-positive sera showed distinct nuclear and cytoplasmic granular staining in HEp-2 cells. Affinity purified anti-Jo-1 produced an identical pattern to the whole serum, whereas the serum fraction that did not bind to the affinity column was negative by immunofluorescence on HEp-2 cells. Two commercial human anti-Jo-1-positive control sera and seven anti-Jo-1-positive sera from patients with myositis reproduced the nuclear and cytoplasmic granular pattern. We conclude that Jo-1 is present in cytoplasm and in intact nuclei from HEp-2 cells. The presence of tRNA synthetases in intact nuclei suggests that they have an unsuspected function in the nucleus.

Cell Nucleus↗
PubMed1995

Hypergammaglobulinemic purpura in systemic autoimmune rheumatic diseases: predictive value of anti-Ro(SSA) and anti-La(SSB) antibodies and treatment with indomethacin and hydroxychloroquine.

OBJECTIVE: To define the clinical manifestations, autoantibody associations, optimal treatment, and prognosis of hypergammaglobulinemic purpura associated with systemic autoimmune rheumatic diseases. METHODS: Of 303 consecutive patients with systemic autoimmune rheumatic diseases evaluated over 5 years, 17 French Canadian patients with hypergammaglobulinemic purpura with systemic lupus erythematosus (SLE) (n = 12) or another systemic autoimmune rheumatic disease (n = 5) were identified and followed prospectively. Mild secondary Sjörgren's syndrome developed in 9 (53%) patients. RESULTS: Sixteen (94.1%) patients were women. Attacks of hypergammaglobulinemic purpura occurred in the pretibial (76.5%) or perimalleolar (70.5%) areas or the dorsal aspect of the feet (52.9%). Triggering factors included walking, prolonged standing, and alcohol intake. The mean duration of attacks was 6.1 days. Systemic manifestations consistent with a flare of the underlying systemic autoimmune rheumatic diseases accompanied hypergammaglobulinemic purpura attacks in 15 (88%) patients. Arthralgias (n = 13, 86.6%), arthritis (n = 9, 69.2%), and periarthritis were characterstically localized adjacent to the purpura. Anti-Ro antibodies were expressed in all (100%) patients with hypergammaglobulinemic purpura with SLE, but in only 11 (28.9%) of 38 consecutive patients with SLE without hypergammaglobulinemic purpura (P < 0.000001, odds ratio 84, 95% confidence interval 4.6, 1525). The positive predictive values for hypergammaglobulinemic purpura in SLE were: anti-Ro plus anti-La 73%, anti-La 57%, and anti-Ro 52%. The negative predictive value of anti-Ro was 100%. Although 11 (92%) patients with SLE with anti-Ro expressed anti-52 kDa Ro [4 (36.3%) of whom also expressed anti-60 kDa Ro], this frequency was not greater than in anti-Ro positive patients with SLE without hypergammaglobulinemic purpura. The effects of indomethacin or hydroxychloroquine were assessed over 6 months in 8 patients with recurrent incapacitating hypergammaglobulinemic purpura. Complete (n = 4) or partial (n = 4) remission of hypergammaglobulinemic purpura occurred. In 5 additional patients with severe hypergammaglobulinemic purpura, attacks stopped with prednisone 25 to 60 mg daily. The mean duration of hypergammaglobulinemic purpura followup was 5.4 years (range 1-6 years). At last followup, hypergammaglobulinemic purpura had resolved in 11 (64.7%) patients despite persistently abnormal serology. CONCLUSION: In the absence of anti-Ro antibodies, a presumptive diagnosis of hypergammaglobulinemic purpura secondary to SLE should be questioned. Prednisone should be used only in severe hypergammaglobulinemic purpura. Indomethacin and hydroxychloroquine are of value in the treatment of milder hypergammaglobulinemic purpura.

Adult↗
PubMed1994

Anticentromere autoantibodies. Evaluation of an ELISA using recombinant fusion protein CENP-B as antigen.

OBJECTIVE: To evaluate an enzyme-linked immunosorbent assay (ELISA) for anticentromere autoantibodies (ACA). METHODS: Sera from 611 patients with scleroderma, CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), Raynaud's disease, and connective tissue disease control patients were studied by ELISA using the fusion protein CENP-B, by immunofluorescence on dividing HEp-2 cells, and by immunoblotting on chromosomes and CENP-B. RESULTS: Compared with immunofluorescence, the CENP-B ELISA sensitivity was 94% and the specificity was 93%. In 19.7% of the cases, there was a probability of a false-positive result and in 1.9%, a probability of a false-negative result, yielding positive and negative predictive values of 0.80 and 0.98, respectively. CONCLUSION: The CENP-B ELISA is a sensitive and specific assay for ACA.

Antibodies↗
PubMed1994

Autoantibodies in scleroderma and tightskin mice.

There is much evidence to suggest that scleroderma in human patients is caused by a fundamental defect in the immune system. In tightskin mice, the scleroderma syndrome is associated with autoimmunity, particularly autoantibodies interacting with scleroderma target antigens.

Animals↗
PubMed1993

A simple severity of disease index for systemic lupus erythematosus.

Although indices of activity for systemic lupus erythematosus have been developed and validated, a disease staging system requires the measurement of severity as well. We have constructed such a scale, the Lupus Severity of Disease Index (Lupus SDI). Accepted clinical, pathologic and physiologic classification schemes were employed to validate this index at two separate research institutions. The Lupus SDI allows homogenization of patient populations for the purposes of research and, possibly, for case mix adjustment.

Adolescent↗
PubMed1992

Autoantibodies in patients with primary pulmonary hypertension: association with anti-Ku.

PURPOSE: Patients with primary pulmonary hypertension (PPH) frequently have Raynaud's phenomenon, serum antinuclear antibodies (ANAs), and/or pulmonary vascular lesions similar to those seen in certain connective tissue diseases, especially scleroderma. A number of relatively disease-specific autoantibodies have been described in connective tissue diseases but have not been studied in patients with PPH. Therefore, sera from PPH patients were studied for a variety of autoantibodies, seeking a possible link between this pulmonary disorder and connective tissue diseases. PATIENTS AND METHODS: Sera from 31 patients with PPH and 24 with secondary pulmonary hypertension (SPH) were studied for the following autoantibodies: anti-centromere (indirect immunofluorescence of Hep-2 cells), anti-CENP-B by immunoblotting and enzyme immunoassay (EIA) using cloned CENP-B fusion protein, anti-topoisomerase I (Scl-70), anti-Ku using immunoblotting of affinity purified antigens, anti-cardiolipin using EIA, and anti-Ro (SS-A), La (SS-B), Sm, nRNP, Jo-1, PM-Scl, and Mi-2 by counter-current immunoelectrophoresis. RESULTS: Anti-Ku antibodies were found in 23% of patients with PPH, 4% with SPH, and none of 24 normal controls (PPH versus SPH, p = 0.06: PPH versus controls, p = 0.01). Antibodies to CENP-B were found in one patient each with PPH and SPH, anti-topoisomerase I in one with SPH, and anti-Ro (SS-A) and La (SS-B) in one with PPH. Overall, 12 patients (39%) with PPH had Raynaud's phenomenon or positive ANA results, with 9 (29%) having more specific autoantibodies associated with connective tissue diseases. CONCLUSIONS: These results further suggest a link between at least a subgroup of patients with PPH and autoimmune connective tissue diseases, with anti-Ku antibodies being a possible new serologic marker.

Adult↗
PubMed1988

Efficacy of antimalarials in systemic lupus erythematosus.

No recent study has been published on the efficacy of antimalarial drugs in the treatment of systemic lupus erythematosus (SLE). However, antimalarial drug therapy was reported in several early studies to control SLE more effectively than corticosteroids alone and to permit lower doses of steroids to be used. To confirm these findings, we conducted a retrospective study of 43 SLE patients who had been taking antimalarials but in whom such therapy had been discontinued after two to 13 years due to the development of macular changes. Each patient served as his own control by the matching of each year during which antimalarial drugs were taken with one year without antimalarial medication. There was a total of 76 matched years for the 43 patients. Overall, no significant correlation was shown between antimalarial drug therapy and the presence or absence of general symptoms (fever, fatigue, weight loss); skin, cardiac, pulmonary, or central nervous system manifestations, arthritis, or other symptoms or signs that were measured. Although antimalarials reduced the required dosage of corticosteroids significantly (p less than 0.05), the amount of reduction was not considered clinically meaningful. Treatment with antimalarial drugs significantly reduced the number of disease flare-ups (p less than 0.05). There were also significant differences between the years with and without chloroquine therapy 500 mg per day (the only regimen for which adequate data were available for analysis) in terms of general symptoms and skin manifestations (p less than 0.05). A prospective, double-blind study of large numbers of patients would be important to confirm the findings of this retrospective study--and the observations of many rheumatologists that antimalarials are helpful in the treatment of SLE.

Adolescent↗
PubMed1987

Detection of anticentromere antibodies using cloned autoantigen CENP-B.

A solid-phase enzyme-linked immunosorbent assay has been established using a cloned fusion protein, CtermCENP-B [beta-gal], as antigen. The fusion protein carries the major epitope of CENP-B, the major centromeric autoantigen. The enzyme-linked immunosorbent assay was more sensitive than immunofluorescence techniques in detecting anticentromere antibodies in patients with scleroderma or Raynaud's disease, and was weakly positive in 3% of normal controls and in 3% of 70 patients with other connective tissue diseases.

Adult↗
PubMed1986

Three human chromosomal autoantigens are recognized by sera from patients with anti-centromere antibodies.

We have identified 39 individuals with anti-centromere antibodies (ACA) in our patient population, all of whom have Raynaud's syndrome or disease. We have used sera from the ACA-positive patients and from 123 controls (22 normal individuals and 101 additional patients with either Raynaud's disease or Raynaud's syndrome plus an associated connective tissue disease) to screen the proteins of highly purified human (HeLa) mitotic chromosomes by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting. Three antigens were recognized by the sera from the ACA-positive patients. These were centromere protein (CENP)-B (80,000 mol wt--recognized by all ACA-positive sera), CENP-A (17,000 mol wt--recognized by 38 of 39 ACA-positive sera), and CENP-C (140,000 mol wt--recognized by 37 of 39 ACA-positive sera). None of these antigens were recognized by any of the 123 control sera, although binding was occasionally seen to other chromosomal antigens. Therefore the ACA response is highly uniform in our patient population. Antibody to CENP-B shows a 100% correlation with anti-centromere staining by indirect immunofluorescence.

Adult↗
PubMed1985

Anticytoskeletal autoantibodies in the connective tissue diseases.

The sera of 103 patients with connective tissue diseases were studied for the presence of anticytoskeletal antibodies by using an indirect immunofluorescence method. PTK2 cells fixed with paraformaldehyde and digitonin were used as substrate. Antibodies to intermediate filaments were detected in sera of 85.7% of polymyositis/dermatomyositis (PM/DM), 62.8% of systemic sclerosis, 54.5% of rheumatoid arthritis, and 37.5% of systemic lupus erythematosus patients, and in 42.5% of normal sera. High titers of these antibodies, which were IgM, were present in 30% of patients' and 5% of normal sera. Antibodies to microfilaments were present in 11.6% of patients' sera and absent in all control sera. These antibodies were IgM or IgG. The switch from an IgM to an IgG antibody was observed in 1 patient. An IgG antibody to the spindle poles and midbody of mitotic cells was present in the serum of 1 patient with the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). Antibodies to intermediate filaments and to microfilaments occur commonly in the connective tissue diseases, particularly in PM/DM, and are not detected with substrates or fixation methods used in routine antinuclear antibody testing.

Antibodies↗