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Showing papers in "Arthritis & Rheumatism in 1973"


Journal ArticleDOI
TL;DR: The fingers of 75 patients with connective tissue disorders were examined by “wide-field” capillary microscopy and 3 distinct groups were recognized among these patients: increased visibility of nailfold subpapillary plexus in rheumatoid arthritis, massive capillary dilatation in scleroderma-dermatomyositis, and focal loss of capillaries in systemic lupus erythematosus.
Abstract: The fingers of 75 patients with connective tissue disorders were examined by “wide-field” capillary microscopy Four diagnostic groups were included in this study: rheumatoid arthritis—28, scleroderma—22, dermatomyositis—8, and systemic lupus erythematosus—17On the basis of different patterns of elementary microvascular abnormalities and their distribution, 3 distinct groups were recognized among these patients: 1) increased visibility of nailfold subpapillary plexus in rheumatoid arthritis, 2) massive capillary dilatation in scleroderma-dermatomyositis, and 3) focal loss of capillaries and prominence of subpapillary vessels with “punched-out” lesions in systemic lupus erythematosus

308 citations


Journal ArticleDOI
TL;DR: Degenerative lesions characterized by osteochondrophyte spur formation and cartilage degeneration were induced by partial meniscectomy in the rabbit knee and may be useful in studies of osteoarthritis pathogenesis, pathology and treatment.
Abstract: Degenerative lesions characterized by osteochondrophyte spur formation and cartilage degeneration were induced by partial meniscectomy in the rabbit knee. Cartilage degenerative lesions included ulceration, fissure and cyst formation, and diminished concentration of matrix proteinpolysaccharide. Proliferation of chondrocytes represented efforts at repair. Osteophytes increased in size with time. Changes resembled certain components of degenerative joint disease. The partial meniscectorny animal may be useful in studies of osteoarthritis pathogenesis, pathology and treatment.

236 citations


Journal ArticleDOI
TL;DR: The gold-treated patients showed slight, but definite, improvement in all parameters measured, although only the change in sedimentation rate was statistically significant, although the number of patients treated was too small to allow definite conclusions.
Abstract: Sixty-eight patients with definite or classic rheumatoid arthritis were enrolled in a double-blind, controlled study of gold salt therapy. The initial phase compared weekly injections of gold thiomalate to placebo. One-third of the gold group were withdrawn from the trial because of toxicity and one-fourth of the controls because of no benefit. The gold-treated patients showed slight, but definite, improvement in all parameters measured, although only the change in sedimentation rate was statistically significant. In Phase 2, designed to ascertain the effects of maintenance therapy, the gold group showed no increase in the number of involved joints, improved their grip strength and had a fall in erythrocyte sedimentation rate. Over the same period the placebo group deteriorated in all these parameters. The number of patients treated, however, was too small to allow definite conclusions.

209 citations


Journal ArticleDOI
TL;DR: A sensitive, simple and rapid assay for these antibodies based on the observation that 3H-labeled nDNA passes through Millipore filters while3H-nDNA complexed with specific antibody is retained is described.
Abstract: Serum levels of antibody to native DNA (nDNA) in patients with systemic lupus erythematosus (SLE) correlate with disease activity. We describe a sensitive, simple and rapid assay for these antibodies based on the observation that 3H-labeled nDNA passes through Millipore filters while 3H-nDNA complexed with specific antibody is retained. The simplicity and rapidity of this assay should allow general utilization of serum anti-nDNA antibody determinations for monitoring disease activity in patients with SLE.

159 citations


Journal ArticleDOI
TL;DR: T-cell specificity of lymphoctotoxic antibodies in SLE is suggested, with marked decreased reactivity of the SLE sera with CLL lymphocytes and marked increased reactivity with fetal thymic cells as compared to controls.
Abstract: Lymphocytotoxic antibody activity of dera from 23 patients with systemiclupus erythematosus (SLE) was compared using three different sets of lymphocytes-peripheral blood lymphocytes from 20 normal controls, perpheral blood lymphocytes from 10 patients with chronic lymphocytic leudemia (CLL) and thymic [thymus-derived (T)] cells of 5 human fetuses. A marked decreased reactivity of the SLE sera with CLL lymphocytes and marked increased reactivity with fetal thymic cells as compared to controls was found. These data suggest T-cell specificity of lymphoctotoxic antibodies in SLE.

147 citations


Journal ArticleDOI
TL;DR: The hypothesis favored here is that, possibly secondary to altered glutamate catabolism, glutamine apparently is overutilized for urate overproduction by the liver, underutilization for reduced renal ammonia formation, and the kidneys, modulating urinary uric acid excretion, sustain the hyperuricemia.
Abstract: Advances in management of acute gouty arthritis, tophaceous gout and uric acid nephrolithiasis are briefly reviewed. With respect to pathogenesis, specific enzyme abnormalities have been demonstrated in rare monogenic cases but the presumptive polygenic and multifactorial pathogenesis in most cases of primary gout remains uncertain. The hypothesis favored here is that, possibly secondary to altered glutamate catabolism, glutamine apparently is overutilized for urate overproduction by the liver, underutilized for reduced renal ammonia formation. The kidneys, modulating urinary uric acid excretion, sustain the hyperuricemia.

108 citations


Journal ArticleDOI
TL;DR: Using counterimmunoelectrophoresis, DNA was found in plasma in a variety of illnesses which are delineated in this study and is at least ten times more sensitive than simple immunodiffusion in the detection of DNA.
Abstract: Using counterimmunoelectrophoresis, DNA may be detected at concentrations as low as 1.5 μ/ml in plasma and 0.2 μg/ml in serum. Serum, however, was not suitable for this study because DNA was sporadically released into serum during the clotting process. Counterimmunoelectrophoresis is at least ten times more sensitive than simple immunodiffusion in the detection of DNA. DNA was found in plasma in a variety of illnesses which are delineated in this study.

107 citations



Journal ArticleDOI
TL;DR: Salicylates were administered to 6 patients with juvenile rheumatoid arthritis in doses sufficient to produce a serum salicylate level in excess of 25 mg/100 ml and all 6 patients developed elevations of serum glutamic oxaloacetic transaminase and serum glutamate pyruvic transaminases.
Abstract: Salicylates were administered to 6 patients with juvenile rheumatoid arthritis in doses sufficient to produce a serum salicylate level in excess of 25 mg/100 ml All 6 patients developed elevations of serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase In addition, 4 patients had other evidence of hepatic dysfunction Abnormalities were dose-related and were reversible upon lowering the salicylate dose Liver biopsies performed in 2 patients revealed a mononuclear cell infiltrate of portal triads in both and scattered single cell necrosis in the parenchyma in 1 case

102 citations


Journal ArticleDOI
TL;DR: A new microassay method with precision of ±5% was developed to quantitate pyrophosphate in synovial fluid and plasma with starting volumes of 0.5 ml, finding a highly significant elevation in some patients with osteoarthritis and gouty arthritis and in subjects with pseudogout.
Abstract: A new microassay method with precision of ±5% was developed to quantitate pyrophosphate in synovial fluid and plasma with starting volumes of 0.5 ml. A highly significant elevation of synovial fluid pyrophosphate concentration was found in some patients with osteoarthritis and gouty arthritis in addition to the well-established elevation in synovial fluid of subjects with pseudogout. No gradient of pyrophosphate between plasma and synovial fluid of patients with rheumatoid arthritis or in normal subjects was detectable. Studies of various parameters reflecting inflammation failed to show a correlation with the concentration of pyrophosphate in patients with pseudogout.

100 citations



Journal ArticleDOI
TL;DR: MLC suppression appeared to be localized to IgG serum fractions separated by DEAE chromatography, and showed a strong correlation with presence of lymphocytotoxic antibody in individual sera.
Abstract: Sera and IgG fractions from normal subjects as well as patients with rheumatoid arthritis and systemic lupus erythematosus were added to mixed leukocyte reactions (MLC) in an attempt to study the effects on cell-to-cell interactions in such systems. Seven and seven-tenths percent of 52 RA sera and 26% of 27 SLE sera showed suppression of MLC reactivity. MLC suppression appeared to be localized to IgG serum fractions separated by DEAE chromatography. This suppressive effect showed a strong correlation with presence of lymphocytotoxic antibody in individual sera.


Journal ArticleDOI
TL;DR: In immunized irradiated mice, immunofluorescent studies showed fixation of mouse Ig and complement in the form of finely stippled and large lumpy deposits in the dermal—epidermal areas and in nuclei of epidermal cells that lend support to the immune complex theory of pathogenesis of SLE skin lesions.
Abstract: An experimental model in mice was investigated to test the hypothesis that the immunohistochemical findings in skin lesions of human systemic lupus erythematosus (SLE) might be due to circulating antibody reacting with nuclear antigens. Mice were immunized with ultraviolet (UV)-irradiated DNA to produce high titers of circulating antibody to a DNA photoproduct, thymine dimer. These immunized mice were then whole-body irradiated with UV, a procedure which caused thymine dimer formation in DNA of skin cells and subsequent release of thymine dimers extracellularly during spontaneous repair of the photochemically damaged DNA. In immunized irradiated mice, immunofluorescent studies showed fixation of mouse Ig and complement in the form of finely stippled and large lumpy deposits in the dermal—epidermal areas and in nuclei of epidermal cells. These findings were morphologically quite similar to those seen in human SLE skin lesions. These immunohistochemical lesions in mice were not observed in mice receiving only immunization or only irradiation. These and other data lend support to the immune complex theory of pathogenesis of SLE skin lesions.

Journal ArticleDOI
TL;DR: Two sets of experiments suggest that pharmacologic doses of prostaglandins are anti-inflammatory in acute and chronic models, and that the effect is not mediated entirely by stimulation of the pituitary and/or adrenal glands.
Abstract: Prostaglandin E1 (PGE1) suppressed acute carrageenan-induced inflammation and chronic joint inflammation characteristic of adjuvant disease in the rat. Placement of PGE1 into subcutaneous air blebs at the time of carrageenan injection retarded movement of polymorphonuclear leukocytes into the focus of inflammation and produced a concentration-dependent reduction in exudate β-glucuronidase and lactate dehydrogenase activities, an effect also observed in adrenalectomized rats. PGE2 also significantly reduced enzyme activities released into inflammatory exudates. Ultrastructural studies indicated that carrageenan was ingested by invading polymorphs and enclosed within phagocytic vacuoles, the membranes of which subsequently ruptured. More lysosomes remained intact after carrageenan uptake in bleb leukocytes from PGE1-treated than from control rats and there was no loss of phagosomal membrane integrity in cells from treated rats. Treatment of adrenalectomized rats with PGE1 (300 μg twice daily) prevented adjuvant-induced systemic arthritis, reduced the acute inflammatory reaction at the site of adjuvant injection, and reduced the number of circulating small lymphocytes. Together, these two sets of experiments suggest that pharmacologic doses of prostaglandins are anti-inflammatory in acute and chronic models, and that the effect is not mediated entirely by stimulation of the pituitary and/or adrenal glands.

Journal ArticleDOI
TL;DR: The findings in this cell culture system are at variance with other published evidence that hypoxia is a major histogenetic force favoring chondrogenic expression.
Abstract: Radiosulfate incorporation, DNA synthesis, and glycoiysis by rabbit articular chondrocytes and skin fibrocytes in monolayer culture were compared under different concentrations of oxygen (19, 6.8, 1.3, and 0.6%). Cell for cell, chondrocytes under each condition had higher levels of radiosulfate incorporation and glycolysis than did fibrocytes. Growth of the fibrocytes was reduced approximately 20% when the oxygen concentration was reduced to 6.8%, but that of chondrocytes was unaffected. A progressive Pasteur effect was observed with both cell types. Radiosulfate incorporation was reduced at low oxygen concentrations. The findings in this cell culture system are thus at variance with other published evidence that hypoxia is a major histogenetic force favoring chondrogenic expression.



Journal ArticleDOI
TL;DR: The findings support the postulate that immune injury underlies the neurologic manifestations of SLE and that hemolytic C4 was unstable in CSF stored at -45°C.
Abstract: Of 35 patients with systemic lupus erythematosus (SLE) studied for up to 18 months, 6 had acute neurologic disease and 3 had acute psychiatric syndromes attributed to SLE during which the mean hemolytic titer of the fourth component of complement in the cerebrospinal fluid (CSF C4) did not differ significantly from the mean of 50 titers in control SLE patients. However, in 4 patients serial determinations disclosed a depression of titer at the time of acute central nervous system involvement (P < 0.01). Hemolytic C4 was unstable in CSF stored at -45°C. Two decay patterns were noted in SLE patients; titers fell more rapidly in patients with more active lupus (P < 0.001). The findings support the postulate that immune injury underlies the neurologic manifestations of SLE.

Journal ArticleDOI
TL;DR: Both intracellular mobilization and extracellular release of granular enzymes by phagocytizing leukocytes are inhibited by colchicine and cortisol, and Salicylate, contrary to suggestions based on studies with isolated lysosomes from liver, did not show these effects.
Abstract: Granular (lysosomal) enzymes are released from phagocytizing human leukocytes and are believed to be important in the tissue damage of acute inflammation Antiinflammatory drugs such as colchicine, cortisol, and salicylate have been reported to “stabilize” isolated lysosomes or to inhibit degranulation within cells These drugs, by altering mobilization of granular enzymes within cells, might be expected to affect the release of these enzymes outside of cells Human blood leukocytes, isolated by dextran sedimentation, were incubated in autologous serum-buffer media, with or without colchicine (25 × 10−5M), cortisol (5 × 10−4M), Na salicylate (22 × 10−3M), or acetylsalicylic acid (10−3M), for 30 minutes, 375° C, and then with or without heat-killed staphylococci Both cellular and extracellular activities of granular enzymes (lysozyme, acid phosphatase, cathepsin) were measured Both intracellular mobilization and extracellular release of granular enzymes by phagocytizing leukocytes are inhibited by colchicine and cortisol Salicylate, contrary to suggestions based on studies with isolated lysosomes from liver, did not show these effects These results may account in part for antiinflammatory effects of colchicine and cortisol, but not of salicylate

Journal ArticleDOI
TL;DR: In this paper, the effects of salicylates on fenoprofen and indomethacin were evaluated in comparative clinical trials of nonsteroidal antiinflammatory agents.
Abstract: Healthy volunteers ingested fenoprofen and indomethacin, each alone or combined with aspirin. Concentrations in plasma of both fenoprofen and indomethacin were reduced significantly when administered with aspirin. Reduction of fenoprofen concentrations depended on the aspirin dosage and occurred whether fenoprofen was administered orally or intravenously. Fenoprofen did not affect plasma concentrations of salicylates. These results emphasize the need to assess carefully the effects of salicylates in comparative clinical trials of nonsteroidal antiinflammatory agents.

Journal ArticleDOI
TL;DR: A 52-year-old male developed subcutaneous nodules and polyarthritis in association with an acinar cell carcinoma of the pancreas and did not respond to aspirin, phenylbutazone, indomethacin or corticosteroid therapy.
Abstract: A 52-year-old male developed subcutaneous nodules and polyarthritis in association with an acinar cell carcinoma of the pancreas. The arthritis did not respond to aspirin, phenylbutazone, indomethacin or corticosteroid therapy. Typical changes of pancreatic enzyme-induced injuries in the subcutaneous nodules and around the joints were found at autopsy.

Journal ArticleDOI
TL;DR: Cell-mediated immunity in rheumatoid arthritis was assessed by skin testing with 5 common antigens in 84 patients, dinitrochlorobenzene application in 13, and in Vitro phytohemagglutinin stimulation of buffy coat cells in 39, revealing two populations of RA patients.
Abstract: Cell-mediated immunity in rheumatoid arthritis (RA) was assessed by skin testing with 5 common antigens in 84 patients, dinitrochlorobenzene (DNCB) application in 13, and in Vitro phytohemagglutinin (PHA) stimulation of buffy coat cells in 39.Routine skin-test reactions were recorded as the largest diameter of induration present at 48 hours. Controls included normal subjects, family members of patients with rheumatic disorders, and patients with unrelated illnesses. Results revealed two populations of RA patients. Forty-two percent were completely anergic to the 5 antigens and 14% gave a history of herpes zoster. The remainder showed reactivity similar to that seen in patient controls. Most RA subjects demonstrated normal or only minimally diminished PHA responses. The RA patients had normal inflammatory responses to the initial DNCB application, but immune reactions to this agent paralleled skin-test reactivity to the other antigens. The anergic individuals could be separated from the reactive population primarily by the increased duration of disease activity but not by medication taken or the degree of disease activity when tested.

Journal ArticleDOI
TL;DR: For patients whose primary organ involvement by scleroderma is renal and whose other lesions are relatively stable, hemodialysis and kidney transplantation may provide additional years of reasonably comfortable life.
Abstract: A merchant mariner had scleroderma with polyarthralgias and Raynaud's phenomenon for 15 years before the onset of rapidly progressive renal failure and severe hypertension. Intimal proliferation obliterated or greatly narrowed the lumina of renal arterioles. Initially, he tolerated periodic hemodialysis and efforts to reduce hypertension poorly but did better after bilateral nephrectomy. In the 18 months since successful kidney transplantation, arthralgias and Raynaud's phenomenon have disappeared and skin has become less tightly bound to underlying structures. Blood pressure remains normal. The grafted kidney shows no evidence of disease. For patients whose primary organ involvement by scleroderma is renal and whose other lesions are relatively stable, hemodialysis and kidney transplantation may provide additional years of reasonably comfortable life.


Journal ArticleDOI
TL;DR: Histopathologic studies of tibiotarsal joints from rats with adjuvant disease show complete suppression of arthritis in animals treated with prostaglandin E1 (PGE1) from time of adjUvant injection.
Abstract: Histopathologic studies of tibiotarsal joints from rats with adjuvant disease show complete suppression of arthritis in animals treated with prostaglandin E1 (PGE1) from time of adjuvant injection. Established synovitis is improved by PGE1 treatment and progression of arthritis and cartilage destruction is halted.

Journal ArticleDOI
TL;DR: A prospective electron microscopic study demonstrated tubuloreticular structures (TRS) in the buffy coat lymphocytes of 32 patients with connective tissue disease; there were some indications of greater disease activity in the TRS-positive group.
Abstract: A prospective electron microscopic study, incorporating blind controls, demonstrated tubuloreticular structures (TRS) in the buffy coat lymphocytes of 32 patients with connective tissue disease. From 1 to 8% of the lymphocyte sections were involved. The abnormal structures consisted of interwoven, electron-dense tubules (220 to 280 A diameter) which were located within the endoplasmic reticulum. Tubuloreticular structures were found in lymphocytes from 20 of 30 patients with systemic lupus erythematosus (SLE), 2 of 4 with discoid lupus erythematosus, 8 of 20 with other connective tissue disease and none of 22 control cases. Clinical evaluation of the patients with SLE disclosed no specific differences between those with TRS-positive or TRS-negative lymphocytes; there were some indications of greater disease activity in the TRS-positive group. The biologic nature of TRS is unknown, but they have been linked to virus infection under both clinical and experimental conditions.

Journal ArticleDOI
TL;DR: Identical twins with calcific periarthritis demonstrable at multiple sites first developed painful episodes of inflammation at age 22, which supports the possibility that the disease might be due to genetic inheritance of a metabolic defect.
Abstract: Identical twins with calcific periarthritis demonstrable at multiple sites first developed painful episodes of inflammation at age 22.The occurrence of this disorder in twins has not been reported previously. This observation, particularly if supported by additional cases with familial involvement, supports the possibility that the disease might be due to genetic inheritance of a metabolic defect.


Journal ArticleDOI
TL;DR: Serial studies in three patients treated with a stable dose of corticosteroids demonstrated similar binding and specificity over several years of disease.
Abstract: Antibodies binding reovirus RNA (3H-reovirus RNA) were demonstrated in 35 of 50 sera (70%) from patients with systemic lupus erythematosus (SLE) and in 22 of 29 sera (76%) from New Zealand hybrid mice (NZB/NZW F1) using a cellulose ester filter radioimmunoassay. By contrast, they were present in only 19% of 69 patients with Sjogren's syndrome, 14% of 21 patients with rheumatoid arthritis and 4% of 88 normal adult controls. This assay method will also measure antibodies to DNA and synthetic RNA and depends on entrapment of radioactive nucleic acid immune complexes on the filter. Serial studies in three patients treated with a stable dose of corticosteroids demonstrated similar binding and specificity over several years of disease.