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2.
Arthritis Rheum ; 39(12): 2021-7, 1996 Dec.
Article in English | MEDLINE | ID: mdl-8961907

ABSTRACT

OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective in the treatment of reactive arthritis (ReA) that has been unresponsive to nonsteroidal antiinflammatory drug (NSAID) therapy. METHODS: One hundred thirty-four patients with ReA who had failed to respond to NSAIDs were recruited from 19 clinics, randomized (double-blind) to receive either SSZ or placebo, and followed up for 36 weeks. The definition of treatment response was based on joint pain/tenderness and swelling scores and physician and patient global assessments. RESULTS: Longitudinal analysis revealed improvement in the patients taking SSZ compared with those taking placebo, which appeared at 4 weeks and continued through the trial (P = 0.02). At the end of treatment, response rates were 62.3% for SSZ treatment compared with 47.7% for placebo treatment. The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints. CONCLUSION: SSZ at a dosage of 2,000 mg/day is well tolerated and effective in patients with chronically active ReA.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Arthritis, Reactive/drug therapy , Placebos/therapeutic use , Sulfasalazine/therapeutic use , Adult , Anti-Inflammatory Agents/adverse effects , Female , Humans , Longitudinal Studies , Male , Middle Aged , Patient Compliance , Prohibitins , Sulfasalazine/adverse effects , Treatment Outcome , Treatment Refusal
3.
J Clin Rheumatol ; 2(2): 117, 1996 Apr.
Article in English | MEDLINE | ID: mdl-19078041
4.
Mol Immunol ; 32(16): 1259-69, 1995 Nov.
Article in English | MEDLINE | ID: mdl-8559150

ABSTRACT

The isolation and characterization of two human serum proteins, RHP and N-RHP, are described. N-RHP appears to be the normal counterpart of RHP which is found at elevated levels in sera of patients with rheumatoid arthritis [Rosano et al. (1988b) Inflammation 12, 351 - 360]. Although both proteins crossreact with anti-Factor H and have identical N-terminal amino acid sequences, they differ from Factor H in pI, solubility at low ionic strength, and in glycosylation. RHP differs from Factor H and N-RHP in antigenicity in the rabbit, in effect on the C1q-anti-C1q precipitin reaction, and in ability to disaggregate C1, the first component of the complement system. Removal of RHP, N-RHP and Factor H from binding to C1q is a prerequesite for separation of RHP and N-RHP from Factor H by anion exchange chromatography and isoelectric focusing. The finding of uniquely demonstrable RHP activity (enhancement of C1q-anti-C1q precipitin activity) in unfractionated sera from patients with rheumatoid arthritis, but not in normal sera, suggests that RHP is not an artefact of Factor H produced during isolation.


Subject(s)
Blood Proteins/immunology , Complement Factor H/immunology , Complement System Proteins/immunology , Amino Acids/analysis , Animals , Blood Proteins/chemistry , Blood Proteins/metabolism , Complement Activating Enzymes/immunology , Complement Activating Enzymes/metabolism , Complement Factor H/chemistry , Complement Factor H/metabolism , Complement System Proteins/metabolism , Epitopes/immunology , Humans , Rabbits
5.
Arthritis Rheum ; 38(8): 1107-14, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7639807

ABSTRACT

OBJECTIVE: To determine the following: 1) whether dietary supplementation with fish oil will allow the discontinuation of nonsteroidal antiinflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA); 2) the clinical efficacy of high-dose dietary omega 3 fatty acid fish oil supplementation in RA patients; and 3) the effect of fish oil supplements on the production of multiple cytokines in this population. METHODS: Sixty-six RA patients entered a double-blind, placebo-controlled, prospective study of fish oil supplementation while taking diclofenac (75 mg twice a day). Patients took either 130 mg/kg/day of omega 3 fatty acids or 9 capsules/day of corn oil. Placebo diclofenac was substituted at week 18 or 22, and fish oil supplements were continued for 8 weeks (to week 26 or 30). Serum levels of interleukin-1 beta (IL-1 beta), IL-2, IL-6, and IL-8 and tumor necrosis factor alpha were measured by enzyme-linked immunosorbent assay at baseline and during the study. RESULTS: In the group taking fish oil, there were significant decreases from baseline in the mean (+/- SEM) number of tender joints (5.3 +/- 0.835; P < 0.0001), duration of morning stiffness (-67.7 +/- 23.3 minutes; P = 0.008), physician's and patient's evaluation of global arthritis activity (-0.33 +/- 0.13; P = 0.017 and -0.38 +/- 0.17; P = 0.036, respectively), and physician's evaluation of pain (-0.38 +/- 0.12; P = 0.004). In patients taking corn oil, no clinical parameters improved from baseline. The decrease in the number of tender joints remained significant 8 weeks after discontinuing diclofenac in patients taking fish oil (-7.8 +/- 2.6; P = 0.011) and the decrease in the number of tender joints at this time was significant compared with that in patients receiving corn oil (P = 0.043). IL-1 beta decreased significantly from baseline through weeks 18 and 22 in patients consuming fish oil (-7.7 +/- 3.1; P = 0.026). CONCLUSION: Patients taking dietary supplements of fish oil exhibit improvements in clinical parameters of disease activity from baseline, including the number of tender joints, and these improvements are associated with significant decreases in levels of IL-1 beta from baseline. Some patients who take fish oil are able to discontinue NSAIDs without experiencing a disease flare.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Rheumatoid/diet therapy , Fish Oils/administration & dosage , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , Cytokines/biosynthesis , Cytokines/immunology , Data Interpretation, Statistical , Diclofenac/therapeutic use , Drug Administration Schedule , Fatty Acids, Omega-3/immunology , Fatty Acids, Omega-3/therapeutic use , Female , Fish Oils/immunology , Humans , Male , Middle Aged , Placebos , Time Factors
6.
8.
Inflammation ; 12(4): 351-60, 1988 Aug.
Article in English | MEDLINE | ID: mdl-3262584

ABSTRACT

RHP is a recently described serum protein which inhibits a number of physiologic functions of C1q unbound to C1r2 x C1s2. In this report we show that sera from patients with rheumatoid arthritis contained elevated levels of RHP and of unbound C1q. Sera from patients with systemic lupus erythematosus contained normal levels of RHP and were characterized by deficits of C1q required to form C1 from existing levels of C1r and C1s.


Subject(s)
Arthritis, Rheumatoid/blood , Blood Proteins/analysis , Complement Activating Enzymes/analysis , Complement C1 Inactivator Proteins/analysis , Complement C1/analysis , Lupus Erythematosus, Systemic/blood , Adult , Aged , Complement C1q , Female , Humans , Male , Middle Aged
10.
Complement ; 5(2): 57-64, 1988.
Article in English | MEDLINE | ID: mdl-3259913

ABSTRACT

We have previously shown that serum levels of C1q, unbound to C1r X C1s, are elevated in rheumatoid arthritis. We have also shown that RHP, a newly described serum protein which affects the C1q-anti C1q precipitin reaction, is also present at elevated levels in rheumatoid arthritis. We now show that RHP inhibits the hemolytic activity of C1q, disaggregates C1, and inhibits the ability of C1q bound to latex beads or to aggregated IgG to enhance the oxidative metabolism of neutrophils.


Subject(s)
Arthritis, Rheumatoid/blood , Blood Proteins/pharmacology , Complement Activating Enzymes/physiology , Complement C1 Inactivator Proteins , Complement C1/physiology , Adsorption , Arthritis, Rheumatoid/immunology , Calcium/metabolism , Complement C1/metabolism , Complement C1q , Hemolysis , Humans , Immunoelectrophoresis , Immunoglobulin G/metabolism , Luminescent Measurements , Microspheres , Neutrophils/metabolism , Oxygen/blood
12.
J Rheumatol ; 14(3): 435-8, 1987 Jun.
Article in English | MEDLINE | ID: mdl-3114483

ABSTRACT

Alveolar macrophages obtained by bronchoalveolar lavage (BAL) were evaluated by electron dispersive microanalysis (EDX) for the presence of elemental gold. EDX revealed gold in 90% (9/10) of patients with RA who were currently receiving chrysotherapy or who had discontinued chrysotherapy less than 24 months before BAL. All patients who had discontinued chrysotherapy more than 24 months before BAL (range: 3-14 years) were EDX negative (4/4), as were patients with RA who had never received gold therapy (5/5). Seven patients with RA (7/19) had clinical evidence of interstitial lung disease and 12 patients (12/19) had no interstitial lung disease. There was no correlation between chrysotherapy and the development of interstitial lung disease. These results demonstrate that gold is retained for prolonged periods in pulmonary tissue macrophages but do not identify any relationship between gold and chronic rheumatoid lung disease.


Subject(s)
Arthritis, Rheumatoid/metabolism , Gold/metabolism , Macrophages/metabolism , Pulmonary Alveoli/metabolism , Arthritis, Rheumatoid/drug therapy , Electron Probe Microanalysis , Gold Sodium Thiomalate/adverse effects , Gold Sodium Thiomalate/therapeutic use , Humans , Prospective Studies , Pulmonary Fibrosis/chemically induced
15.
Am Rev Respir Dis ; 133(3): 450-4, 1986 Mar.
Article in English | MEDLINE | ID: mdl-3485395

ABSTRACT

Rheumatoid arthritis (RA), a systemic disorder of unknown cause, is associated with a variety of well-recognized pulmonary abnormalities including interstitial lung disease. To investigate possible pathogenic events in this disorder, we performed bronchoalveolar lavage (BAL) in 24 patients with classic or definite RA. Using radiographic and physiologic parameters as well as BAL cell differentials, 3 distinct groups emerged. Group I consisted of 9 patients with evidence of clinical interstitial lung involvement. Group II consisted of 5 patients without evidence of clinical interstitial lung disease (normal chest roentgenogram and functional testing) but who had abnormal BAL cellular differentials. The 10 remaining patients (Group III) had no evidence of clinical interstitial lung disease and had normal BAL cell differentials. Bronchoalveolar lavage in Group I had a significantly increased percentage of neutrophils (12.4 +/- 4.2; p less than 0.05) compared with Group II (2.4 +/- 0.8) and Group III (2.9 +/- 0.6). All patients in Group II had elevated BAL lymphocytes (24.4 +/- 6.4) compared with Group I (10.1 +/- 3.8; p greater than 0.05) and Group III (5.4 +/- 0.7; p less than 0.01). Both Groups I and II had detectable IgM in BAL (0.02 +/- 0.01 and 0.04 +/- 0.02 mg/mg of albumin, respectively), whereas Group III patients and normal control subjects did not (p less than 0.01). There was a marked reduction in BAL T-lymphocyte Leu 3/Leu 2A (helper/suppressor) cell ratios in Group I (0.92 +/- 0.02; p less than 0.05) compared with Group II (2.6 +/- 0.6) and Group III (1.6 +/- 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Arthritis, Rheumatoid/pathology , Body Fluids/analysis , Bronchi/pathology , Pulmonary Alveoli/pathology , Arthritis, Rheumatoid/immunology , Humans , Immunity, Cellular , Immunoglobulins/analysis , Leukocyte Count , Smoking , T-Lymphocytes/classification , Therapeutic Irrigation
16.
Biochem Biophys Res Commun ; 128(3): 1288-94, 1985 May 16.
Article in English | MEDLINE | ID: mdl-3873940

ABSTRACT

We have isolated and purified to apparent homogeneity a serum protein which appears to be a biological marker for active rheumatoid arthritis. The protein has been found in the sera in all 44 active rheumatoid arthritis patients thus far studied and is absent from, or present in undetected amounts, in sera from normal subjects or from patients with other arthritides. The protein has a molecular weight of 135,000 daltons, an isoelectric pH of 5.1-5.3, and it enhances the size of the C1q-anti C1q ring.


Subject(s)
Arthritis, Rheumatoid/blood , Blood Proteins/isolation & purification , Complement Activating Enzymes/immunology , Antibodies/immunology , Arthritis, Rheumatoid/immunology , Blood Proteins/immunology , Complement C1q , Humans , Isoelectric Point , Molecular Weight , Precipitins/immunology
17.
J Rheumatol ; 12(1): 182-3, 1985 Feb.
Article in English | MEDLINE | ID: mdl-3981508
19.
J Lab Clin Med ; 103(2): 313-21, 1984 Feb.
Article in English | MEDLINE | ID: mdl-6319517

ABSTRACT

Modifications of radial immunodiffusion and of hemolytic assays of C1q are described, which enable the results of these assays to be in agreement with those obtained by hydroxyproline assay. Using these assays, we show that C1q serum levels are significantly increased in rheumatoid arthritis (RA) and that the excess C1q levels in this disease are not accompanied by increased levels of C1r and C1s. Active RA is therefore characterized by increased levels of hemolytically active C1q that has a physiologically active stem region unbound to C1r and C1s.


Subject(s)
Arthritis, Rheumatoid/blood , Complement Activating Enzymes/blood , Complement C1q , Complement C1r , Complement C1s , Hemolytic Plaque Technique , Humans , Hydroxyproline , Immunodiffusion/methods
20.
J Rheumatol ; 6(6): 656-63, 1979.
Article in English | MEDLINE | ID: mdl-529249

ABSTRACT

Clq levels in sera of adult patients with rheumatoid arthritis (RA) were found to be significantly higher than corresponding levels of normal subjects (p less than 10(-3)) The increase in Clq observed in RA was not seen in systemic lupus erythematosus, chronic polyarticular gouty arthritis, ankylosing spondylitis, Paget's disease of bone, or Hodgkin's disease. Clq levels were determined both chemically (calculated) from the protein-bound hydroxyproline content of the euglobulin fraction) and by radial immunodiffusion. Although the estimates of Clq by these 2 methods did not agree, the increase of Clq in RA was found by the use of either method.


Subject(s)
Arthritis, Rheumatoid/blood , Hydroxyproline/blood , Adult , Complement C1/analysis , Female , Gout/blood , Hodgkin Disease/blood , Humans , Lupus Erythematosus, Systemic/blood , Male , Middle Aged , Osteitis Deformans/blood , Protein Binding , Serum Globulins/analysis , Spondylitis, Ankylosing/blood
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