Showing papers in "Arthritis & Rheumatism in 1974"
TL;DR: Results show the efficacy of the proposed criteria for early diagnosed patients, and support the inclusion of high titer antinuclear antibody (ANA) in the SLE criteria.
Abstract: Preliminary criteria for the classification of systemic lupus erythematosus (SLE) were applied to patients with early diagnosed SLE and rheumatoid arthritis (RA) who are participants in a prospective community study of arthritis of recent onset. Sensitivity of the criteria was 88%, and specificity against RA was 97.5%. Sensitivity increased to 92% without loss of specificity when high titer antinuclear antibody (ANA) was used as an alternative criteria manifestation to LE cells. These results show the efficacy of the proposed criteria for early diagnosed patients, and support the inclusion of high titer ANA in the SLE criteria.
376 citations
TL;DR: A soluble cytoplasmic RNA protein antigen (La) is described, which precipitates with sera of patients with systemic lupus erythematosus and a small number of patients who lack antinuclear factors but who have various connective tissue symptoms.
Abstract: A soluble cytoplasmic RNA protein antigen (La) is described, which precipitates with sera of patients with systemic lupus erythematosus and a small number of patients who lack antinuclear factors but who have various connective tissue symptoms. Antibodies to the cytoplasmic RNA protein are almost invariably (8 of 9 cases) accompanied by antibodies to a non-nucleic acid cytoplasmic antigen, Ro. Description of this antigen enlarges the spectrum of nucleic acid antigens reactive with the sera of patients with systemic lupus erythematosus.
275 citations
TL;DR: Infection rate and the number of disseminated infections were found to increase in lupus patients with increasing doses of corticosteroids and decreasing renal function, suggesting that the observed high infection rate in SLE cannot be attributed to steroid therapy and renal disease alone.
Abstract: Twenty-three patients with systemic lupus erythematosus (SLE), 20 with rheumatoid arthritis (RA), and 11 with the nephrotic syndrome (NPS) were selected for study of factors affecting the incidence of infection in these diseases. The overall infection rate (infections per 100 hospital days) in patients with SLE was significantly higher than it was in patients with RA or NPS. Infection rate and the number of disseminated infections were found to increase in lupus patients with increasing doses of corticosteroids and decreasing renal function. Lupus patients with normal renal function on no or low-dose corticosteroid therapy had an infection rate significantly higher than the infection rate of the control patient groups. This study suggests that the observed high infection rate in SLE cannot be attributed to steroid therapy and renal disease alone.
261 citations
TL;DR: The histocompatibility antigen HL-A 27 was identified in 43 of 49 patients with yersinia arthritis and in 36 of 40 patients with Reiter's disease, compared with 3 of 20 patients withYersinia infection without arthritis and 14% of the normal Finnish population.
Abstract: The histocompatibility antigen HL-A 27 was identified in 43 of 49 patients with yersinia arthritis and in 36 of 40 patients with Reiter's disease, compared with 3 of 20 patients with yersinia infection without arthritis and 14% of the normal Finnish population. HL-A 2 occurred in patients with reactive arthritis in the same high frequency as did HL-A 27, but this antigen is present in 55% of Finns. HL-A 27 negative patients usually had a mild or somewhat atypical disease.
236 citations
TL;DR: Eight of 70 patients with systemic lupus erythematosus followed for a median interval of 6 years and 8 months, developed malignancies, including a case of reticulum-cell sarcoma, multiple myeloma, Bowen's carcinoma of the skin and five carcinomas of the cervix.
Abstract: Eight of 70 patients with systemic lupus erythematosus (SLE) followed for a median interval of 6 years and 8 months, developed malignancies. These included a case of reticulum-cell sarcoma, multiple myeloma, Bowen's carcinoma of the skin and five carcinomas of the cervix. Six of the patients had been treated with corticosteroids, in 2 cases in association with azathioprine. An increased incidence of malignancy may be present in SLE and this possibility should be explored further.
132 citations
TL;DR: The presence of ANA should prove useful in identifying patients with JRA at risk for chronic iridocyclitis and juvenile rheumatoid arthritis and negative tests for ANA in patients with childhood-onset arthritis were found to be associated with acute iridocytesitis and subsequent ankylosing spondylitis.
Abstract: Positive tests for antinuclear antibodies (ANA) were found in 51 of 58 (88%) patients with chronic iridocyclitis and juvenile rheumatoid arthritis (Still's disease). Antinuclear antibodies were predominantly of the IgG class of immunoglobulins and were generally present in liters of 1:50 (six ANA units) or more. They were unassociated with disease activity, severity or duration, age of patient at onset or testing, or sex. Neither other autoantibodies nor antibodies reactive with DNA or RNA were associated. In 8 patients tested early in disease, ANA were found prior to the onset of iridocyclitis. The presence of ANA should prove useful in identifying patients with JRA at risk for chronic iridocyclitis. In contrast, negative tests for ANA in patients with childhood-onset arthritis and iridocyclitis were found to be associated with acute iridocyclitis and subsequent ankylosing spondylitis.
129 citations
TL;DR: Studies in human palaeopathology, while revealing unmistakable examples of ankylosing spondylitis dating back to prehistoric times, have as yet failed to provide convincing evidence of the existence of rheumatoid arthritis prior to Sydenham's description.
Abstract: The antiquity of rheumatoid arthritis, first clearly set off as an entity by Landre-Beauvais in 1800, is of more than historic interest. If the disease is actually of relatively recent origin, an environmental cause becomes likely. It is reasonably certain that it was identified by Sydenham in 1676. But studies in human palaeopathology, while revealing unmistakable examples of ankylosing spondylitis dating back to prehistoric times, have as yet failed to provide convincing evidence of the existence of rheumatoid arthritis prior to Sydenham's description.
126 citations
TL;DR: Sera from 38 patients with systemic lupus erythematosus, known from previous determinations to contain antibodies to native DNA, were studied using a modification of the Farr technique, with 14C-DNA as ligand, suggesting that qualitative differences in anti-DNA activity may be as important as quantitative ones.
Abstract: Sera from 38 patients with systemic lupus erythematosus, known from previous determinations to contain antibodies to native DNA (deoxyribonucleic acid), were studied using a modification of the Farr technique, with 14C-DNA as ligand. The sera fell into three groups with regard to antibodies to DNA: a) precipitating, b) nonprecipitating, and c) a mixture of both. Eighteen of these sera were studied further and titrated to obtain measures of their antigen binding capacity and estimates of avidity for DNA. Patients with lupus nephritis had either precipitating antibodies to DNA, or a mixture of precipitating and nonprecipitating, whereas those patients without nephritis had only nonprecipitating, antibodies to DNA. Furthermore the avidity for DNA was greatest in sera from patients with nephritis. The antigen binding capacity of sera from patients with and without lupus nephritis was similar, suggesting that qualitative differences in anti-DNA activity may be as important as quantitative ones.
116 citations
TL;DR: The findings reported suggest that immune complexes containing IgG RF and possibly low-molecular weight IgM may be involved in the pathogenesis of rheumatoid vasculitis.
Abstract: The occurrence of IgG rheumatoid factor (IgG RF) and low molecular weight IgM (7S IgM) has been studied in the sera of rheumatoid patients with and without vasculitis. IgG RF was found in 67% of patients with vasculitis and in only 9% of patients without vasculitis. 7S IgM was found in 80% of patients with rheumatoid vasculitis and only 18% of patients without vasculitis. Both IgG RF and 7S IgM occurred simultaneously in 60% of patients with vasculitis and 6% of patients without vasculitis. Techniques for demonstrating IgG RF and 7S IgM in serum are described. The findings reported suggest that immune complexes containing IgG RF and possibly low-molecular weight IgM may be involved in the pathogenesis of rheumatoid vasculitis.
114 citations
TL;DR: The serum urate-lowering effect of probenecid was used to monitor compliance in a placebo-controlled study of prophylactic colchicine therapy for intercritical gout, confirming the effectiveness of pro phytactic col chicine in this situation.
Abstract: The serum urate-lowering effect of probenecid was used to monitor compliance in a placebo-controlled study of prophylactic colchicine therapy for intercritical gout. Although all patients included in the analysis had satisfactory control of hyperuricemia, 20 patients receiving 1.5 mg of colchicine daily averaged 2.3 attacks of acute gout per year of therapy, compared to 18 placebo-treated patients who averaged 6 attacks per year (P < 0.05), confirming the effectiveness of prophylactic colchicine in this situation.
113 citations
TL;DR: Although cyclophosphamide led to somewhat greater improvement than did azathioprine, additional long-term data will be necessary to establish the role of either drug in the routine management of lupus glomerulonephritis.
Abstract: Thirty-eight patients with lupus glomerulonephritis entered a 10-week in-hospital trial of immunosuppressive therapy. They were permitted prednisone ≤ 0.5 mg/kg/day for extrarenal manifestations and were randomly assigned to receive, in addition, cyclophosphamide or azathioprine or placebo. Renal function, urine sediment, proteinuria, anti-DNA, C3, and symptoms were assessed before and after therapy. This represents the first double-blind controlled comparison of two immunosuppressive drugs commonly used in nonmalignant diseases. Cyclophosphamide was significantly superior to both azathioprine and placebo for all six measures together and for the three renal measures alone. Cyclophosphamide was significantly better than placebo with regard to proteinuria, urinary RBC, and serum C3. Azathioprine was not significantly better than placebo in any individual measure. Although cyclophosphamide led to somewhat greater improvement than did azathioprine, additional long-term data will be necessary to establish the role of either drug in the routine management of lupus glomerulonephritis.
TL;DR: Evidence is presented to support the hypothesis that loss of suppressor function may play an important pathogenetic role in the development of autoimmunity.
Abstract: Recent studies support the concept of thymic regulatory or suppressor function. Such regulatory function appears to be present in the first month of life in NZB and NZB/W mice, but is rapidly lost with age. Evidence is presented to support the hypothesis that loss of suppressor function may play an important pathogenetic role in the development of autoimmunity.
TL;DR: Four pairs of first-degree relatives with polymyalgia rheumatica, giant cell arteritis, or both have been encountered among approximately 250 patients, two of which were mother-daughter combinations, the first such cases to be reported.
Abstract: Four pairs of first-degree relatives with polymyalgia rheumatica, giant cell arteritis, or both have been encountered among approximately 250 such patients Two of these pairs were mother-daughter combinations, the first such cases to be reported Chance alone is unlikely to account for this association The possible roles of environmental, genetic, and immunologic factors are considered
TL;DR: The findings presented suggest that both cellular and humoral immune responses occur in the rheumatoid synovium, and the interaction of T- and B-lymphocytes with liberation of lymphokines, which attract and immobilize macrophages and stimulate B-LYmphocytes to antibody synthesis.
Abstract: In the rheumatoid synovial membrane, small lymphocytes leave the blood by migrating mainly through the endothelial cells of the postcapillary venule. Extravascularly they form perivascular collections composed predominantly of small lymphocytes. A large fraction of these cells undergoes transition to form perivascular collections that consist mainly of plasma cells, indicating that they were initially B-lymphocytes. The small lymphocytes also migrate into the perivascular region where a mixture of cells is found—ie, small lymphocytes, undifferentiated blast cells, plasmablasts, plasma cells, and macrophages all in significant numbers. The presence of these cell types in close contact suggests the interaction of T- and B-lymphocytes with liberation of lymphokines, which attract and immobilize macrophages and stimulate B-lymphocytes to antibody synthesis. The findings presented suggest that both cellular and humoral immune responses occur in the rheumatoid synovium.
TL;DR: In extending an initial 6-month study to 3 years, treatment of patients with lupus nephritis by a combination of prednisone and azathioprine did not control the systemic or renal manifestations any better than did treatment withprednisone alone.
Abstract: In extending an initial 6-month study to 3 years, treatment of patients with lupus nephritis by a combination of prednisone and azathioprine did not control the systemic or renal manifestations any better than did treatment with prednisone alone. There were no differences in major renal disease flares between the two treatment groups. The incidence and duration of systemic, nonrenal flares were greater in the combined treatment group but did not increase after treatment with azathioprine was discontinued.
TL;DR: Both putatively native(n) commercial calf thymus DNA and 14C labeled human KB DNA contained significant amounts of denatured DNA (dDNA) as determined by methylated albumin-kieselguhr chromatography, sufficient to cause confusion regarding the antigenic specificity of anti-DNA antibody when unfractionated DNA was used in either the counterimmunoelectrophoresis or the Farr assays for anti- DNA antibody.
Abstract: Both putatively native(n) commercial calf thymus DNA and 14C labeled human KB DNA contained significant amounts of denatured DNA (dDNA) as determined by methylated albumin-kieselguhr chromatography. The proportion of dDNA in these preparations was sufficient to cause confusion regarding the antigenic specificity of anti-DNA antibody when unfractionated DNA was used in either the counterimmunoelectrophoresis or the Farr assays for anti-DNA antibody. Serum from patients with systemic lupus erythematosus contained both anti-nDNA and anti-dDNA antibodies. About 50% of patients with symptomatic procainamide-induced lupus (PLE) exhibited anti-dDNA; none had anti-nDNA. Procainamide treated patients with a positive ANF who did not have symptomatic PLE had neither anti-dDNA nor anti-nDNA.
TL;DR: Comparison was made of HL-A phenotypes in 122 patients with systemic lupus erythematosus and 1289 ethnically matched controls and no significant association was present between any HL- A antigen and clinical or laboratory manifestations of the disease.
Abstract: Comparison was made of HL-A phenotypes in 122 patients with systemic lupus erythematosus (SLE) and 1289 ethnically matched controls. The only significant association was between the HL-A antigen HL-A5 and the presence of SLE in Black Americans. A similar trend in 40 Caucasian patients did not reach a level of statistical significance. No significant association was present between any HL-A antigen and clinical or laboratory manifestations of the disease. Lymphocytotoxic antibodies were present in 36% of the patients and correlated with the presence of low total hemolytic complement and leukopenia.
TL;DR: The findings suggest that the probable interstitial or intracellular mechanism(s) of action of gold on the inflammatory process are not dependent upon serum gold concentrations and raise the possibility that whole blood radiogold disappearance curves would provide a means of selecting those patients who will derive maximum therapeutic benefit from chrysotherapy.
Abstract: The relationships between serum stable gold (197Au) concentration and serum and whole blood radioactive gold (195Au) disappearance curves to clinical course and gold excretion are analyzed in this prospective clinical-metabolic study of 18 patients with active rheumatoid arthritis (RA). Patients received a standard course of Myochrysine (197Au aurothiomalate), were given 195Au labeled aurothiomalate to monitor current dose dynamics, and clinically evaluated at regular intervals. Stable and radiogold concentrations in blood were measured serially on an outpatient basis and during periods of hospitalization using neutron activation anallysis and standard radiometric techniques. Serum concentrations of both isotopes failed to correlate with clinical course and toxicity. Serum radiogold disappearance curves were similar in patients who received radioactive gold on two or more occasions, despite changes in clinical course. Whole blood radiogold disappearance curves however were significantly different in most and least improved patients. These findings, and others reported herein, suggest that a) the probable interstitial or intracellular mechanism(s) of action of gold on the inflammatory process are not dependent upon serum gold concentrations and b) they raise the possibility that whole blood radiogold disappearance curves would provide a means of selecting those patients who will derive maximum therapeutic benefit from chrysotherapy.
TL;DR: It was concluded that immunosuppression was induced by decreasing the absolute numbers of normal T- and B-cells rather than by a selective effect on either one.
Abstract: T- and B-lymphocytes were enumerated in 46 normal subjects, and in 30 patients with rheumatoid arthritis and 4 with psoriatic arthritis by the following cell markers: spontaneous sheep red blood cell rosettes (early and late), complement-receptor and aggregated gamma globulin receptor lymphocytes. The results of these studies were compared to those from 6 patients with rheumatoid arthritis and 7 with psoriatic arthritis on varying doses of azathioprine. The proportions of T and B cells in all groups were essentially similar. Neither was there any change in the density gradient distribution and response to stimulation by phytohemagglutinin stimulation. Because azathioprine led to lymphopenia in these patients, it was concluded that immunosuppression was induced by decreasing the absolute numbers of normal T- and B-cells rather than by a selective effect on either one. In contrast some patients with systemic lupus erythematosus on azathioprine had a lower proportion of T-cells than normal. This was probably independent of the effect of azathioprine.
TL;DR: The presence of binding in immunochemically pure IgG and the pattern of inhibition by native and denatured DNA support the thesis that DNA binding of normal, non-SLE, and SLE sera is antibody and similar in kind although not in degree.
Abstract: Modifications of the Farr ammonium sulfate precipitation assay for DNA antibodies have increased sensitivity and led to the detection of DNA binding in the sera of healthy subjects and subjects with rheumatic disease other than systemic lupus erythematosus (SLE). The presence of binding in immunochemically pure IgG and the pattern of inhibition by native and denatured DNA support the thesis that DNA binding of normal, non-SLE, and SLE sera is antibody and similar in kind although not in degree. The presence of antibodies to DNA in normal and non-SLE sera may limit the qualitative role of these antibodies in SLE and render DNA antibodies similar to antiglobulin and other antinuclear antibodies in rheumatic disease.
TL;DR: In this paper, a chronic synovitis developed characterized by synovial effusion, hyperplasia of the lining layer and infiltration of the sublining layer with histiocytes and fibroblasts.
Abstract: Arthritis was produced in the rabbit by intraarticular injection of a preparation of mediators of cellular immunity (lymphokines) obtained from KLH-sensitized lymphocytes. Following three injections, a chronic synovitis developed characterized by synovial effusion, hyperplasia of the lining layer and infiltration of the sublining layer with histiocytes and fibroblasts. These findings indicate that mediators of cellular immunity may produce a chronic synovitis when injected into the normal joint. They also demonstrate a mechanism whereby the cellular immune response may produce synovial inflammation.
TL;DR: This study suggests that the inital deposition of calcium pyrophosphate crystals is in the interstitium of the cartilage, the smallest deposits lie in a yet unidentified dense material that may be glycosaminoglycan.
Abstract: Cartilage has been studied from 12 patients with different degrees of chondrocalcinosis. Degenerative changes and patches of decreased saphranin 0 staining were present even in areas without calcium deposits. Alkaline phosphatase was identified only in the basal layer and was slightly decreased. By electron microscopy mildly involved cartilage showed small diameter isolated crystals lying in a finely granular material. Similar granular material, staining dark with ruthenium red, was present around the crystalline deposits of the knee menisci. No intracellular crystals were seen and no relationship between crystals and the matrix vesicles was observed. This study suggests that the inital deposition of calcium pyrophosphate crystals is in the interstitium of the cartilage. The smallest deposits lie in a yet unidentified dense material that may be glycosaminoglycan.
TL;DR: Various antirheumatic drugs were tested in a newly described model of cartilage degradation-induced by the nonphagocytic release of neutral protease from viable human leukocytes in the presence of aggregated human IgG, suggesting that the activity of compounds in the model system described might predict their effect in vivo in rheumatoid arthritis.
Abstract: Various antirheumatic drugs were tested in a newly described model of cartilage degradation-induced by the nonphagocytic release of neutral protease from viable human leukocytes in the presence of aggregated human IgG. Steroidal and nonsteroidal antiinflammatory drugs inhibited the enzyme release process but not neutral protease activity, whereas gold and chloroquine inhibited the enzyme activity without affecting the release process. Several other drugs, known not to have antiinflammatory activity, were inactive. Neutral protease appears to be preformed in neutrophils and not induced by de novo synthesis during phagocytosis. The concentrations at which the antirheumatic drugs were active in vitro correlated with blood levels usually achieved in man. It is suggested that the activity of compounds in the model system described might predict their effect in vivo in rheumatoid arthritis.
TL;DR: It is suggested that eosinophilia may be the most common side effect of gold therapy and provides a useful guide for monitoring patients receiving gold salts.
Abstract: Adverse clinical reactions (predominantly skin rashes) were seen in 14 of 50 patients receiving gold therapy for rheumatoid arthritis. In 11 of the 14 eosinophilia either accompanied or preceded the reaction. A further 9 patients who received gold developed eosinophilia alone. IgE levels were increased in 17 of the 20 patients with eosinophilia but were normal in 24 of 27 patients who received gold without apparent adverse effects. In only 1 patient on gold was a skin rash not accompanied by either eosinophilia or a raised IgE level. All eosinophil counts and IgE levels fell to normal after therapy was discontinued. It is suggested that eosinophilia may be the most common side effect of gold therapy and provides a useful guide for monitoring patients receiving gold salts. The strong association with raised IgE levels suggests that type 1 hypersensitivity may be the mechanism of these reactions.
TL;DR: None of the patients in the present series could be clearly categorized into either the bacteremic or septic joint syndromes of gonococcal arthritis.
Abstract: The clinical picture was analyzed in 31 patients with acute arthritis and proven gonococcal infection. Patients with positive blood cultures and those with positive synovial fluid cultures were mutually exclusive. However, these two groups were indistinguishable on the basis of mean duration of illness prior to initial examination, the number of joints involved or the magnitude of synovial fluid leukocytosis. Notably, features that have been particularly associated with gonococcemia—eg, chills, a migratory polyarticular prodrome and typical skin lesions, were present in most cases. Thus, on clinical grounds none of the patients in the present series could be clearly categorized into either the bacteremic or septic joint syndromes of gonococcal arthritis.
TL;DR: It is suggested that low synovial fluid oxygen tension is detrimental to articular cartilage glycosaminoglycan metabolism.
Abstract: Adult rabbit articular cartilage slice and plug explants were cultured in MEM/NCTC 109/fetal calf serum at 37°C in various oxygen tensions. In both the slice and plug explants, 35SO4 incorporation exhibited a broad tolerance to oxygen tensions varying from 5 (38 mm. Hg) to 60 (456 mm Hg) per cent. Significantly (P 0.01) less 35SO4 was incorporated in 1 (7.6 mm Hg) and 90% (684 mm Hg) oxygen than in 21% (160 mm Hg) oxygen. No histologic or autoradiographic differences, and only slight histochemical differences, were discernible after seven days culture in the various oxygen tensions. It is suggested that low synovial fluid oxygen tension is detrimental to articular cartilage glycosaminoglycan metabolism.
TL;DR: It is indicated that gold has little affinity for keratinous tissues, and that determination of gold content in these tissues is not helpful in differentiating gold-toxic from nontoxic patients.
Abstract: Serial hair and nail specimens were obtained from 18 patients with rheumatoid arthritis receiving chrysotherapy. Punch biopsies of skin lesions and normal-appearing skin from 4 other patients with gold dermatitis, and serial skin biopsies from 4 additional patients were obtained at intervals during chrysotherapy. Gold content was measured in these samples using neutron activation analysis. Small quantities of gold were found in hair (mean = 0.30 μg/g), nail (mean = 0.17 μg/g), and skin (mean = 0.03 μg/g) prior to chrysotherapy, with two- to fivefold increases after 3–12 months of treatment. Compared to those from patients who did not develop gold toxicity, gold concentrations in all three tissues were similar in patients who developed gold toxicity. Gold levels were identical in skin lesions and normal-appearing skin of patients with gold dermatitis. These findings indicate that gold has little affinity for keratinous tissues, and that determination of gold content in these tissues is not helpful in differentiating gold-toxic from nontoxic patients.
TL;DR: Life table analysis of 31 patients with biopsy proven diffuse proliferative glomerulonephritis due to Systemic Lupus Erythematosus reveals a 77.7% five-year survival.
Abstract: Life table analysis of 31 patients with biopsy proven diffuse proliferative glomerulonephritis due to Systemic Lupus Erythematosus reveals a 77.7% five-year survival. Patients with similar lesions have, in the past, had an approximate 20% five-year survival. The improved survival is attributed to the combined use of prednisone and chlorambucil and a panel of frequently repeated laboratory tests that provides a guide to the activity of the systemic disease.