bluuebunny/crossref_metadata_2025 huggingface dataset:
Salicylate hepatotoxicity in patients with juvenile rheumatoid arthritis
Authors: Rich Robert R , Johnson John S
Published: February 2007

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.
Immunologically induced acute synovitis in rabbits studies of immune complexes in synovial fluid
Authors: Roger Hollister J , Liang George C , Mannik Mart
Published: February 2007

Large antigen‐antibody complexes that are selectively removed from circulation were not selectively removed when injected into the knees of a normal rabbit. The subsequent selective removal of the complexes depended on the influx of neutrophils. Nevertheless, macrophages of the normal synovial lining were able to phagocytize some immune complexes. When antigen and antibodies were administered separately by intravenous or intraarticular routes, little or no soluble complexes were found in synovial fluid, and most of the antigen‐antibody union was thought to occur in the synovial tissue.
Experimental bedsonial arthritis
Authors: Edwards Smith D , James Paul G , Schachter Julius , Engleman Ephraim P , Meyer Karl F
Published: February 2007

A bedsonia isolated from the joint of a patient with Reiter's syndrome produced arthritis when injected into the knees of Macaca mulatta or New Zealand white rabbits. The monkeys developed an acute self‐limited arthritis that resolved within 11 to 49 days. Symptoms were limited to the injected joints. Reinoculation of the same joints produced a similar arthritis, indicating that repeated exposure neither enhances nor diminishes clinical response. Repeated intraurethral inoculation produced urethritis in 1 macaque, and the organism was recovered from the urethra. Infected rabbits developed a chronic arthritis. Bedsonial infection and disease in the rabbit were disseminated from joint to eye and from joint to selected viscera. Viable multiplying organisms were essential to produce arthritis, and treatment with tetracycline before agent inoculation prevented disease. Bedsonial organisms other than those recovered from Reiter's syndrome also caused arthritis when injected into the knees of monkeys or rabbits.
Immune response of patients with rheumatoid arthritis during cyclophosphamide treatment
Authors: Curtis John E , Sharp John T , Lidsky Martin D , Hersh Evan M
Published: February 2007

The immune response was studied in 21 patients with rheumatoid arthritis. Eleven had been randomly assigned to receive cyclophosphamide, 50 to 75 mg/day, and 10 to receive a placebo. Immunologic responsiveness was assessed by delayed hypersensitivity skin testing, immunoglobulin levels, in vitro lymphocyte blastogenesis and the primary immune response. All patients had elevated levels of IgG, normal or low IgA and IgM. Delayed hypersensitivity and in vitro lymphocyte blastogenic responses after immunization with the primary antigens Keyhole limpet hemocyanin and the amino acid copolymer (GLAT) were normal. Keyhole limpet hemocyanin and GLAT hemagglutinin titers were lower than normal due to decreased IgG and IgM formation. Treatment for 8 weeks with cyclophosphamide, 50 to 75 mg/day, did not alter the clinical status of the patients and had no detectable effect on their immune reactivity.
Detection of circulating dna by counterimmunoelectrophoresis (cie)
Authors: Davis Gene L , Davis Iv John S
Published: February 2007

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.
Comparison of therapeutic and immunosuppressive effects of azathioprine, prednisolone and combined therapy in nzp/nzw mice
Authors: Hahn Bevra H , Bagby Mary K , Hamilton Tom R , Osterland C Kirk
Published: February 2007

Since NZB/NZW mice develop an immune nephritis similar to that of systemic lupus erythematosus in man, a study was designed in these mice to compare the clinical and immunologic effects of three immunosuppressive drug regimens. For 72 weeks, groups of 20 mice received daily oral therapy with a) no drugs, b) azathioprine, c) prednisolone or d) combined azathioprine‐prednisolone. The combined regimen was superior to either drug used alone in preventing deaths from renal disease. Prednisolone alone also prolonged life significantly, but not as effectively as combination therapy. Azathioprine alone was not effective. All drugs suppressed the antibody response to an exogenous antigen (Vi polysaccharide) equally well. None of the drug regimens prevented the appearance of proteinuria, antinuclear antibodies, Coombs' antibody, or γ‐globulin deposits in glomeruli. However, the ability of a therapeutic regimen to suppress antibodies to native DNA correlated well with its ability to suppress renal disease. No malignancies were found among 73 animals autopsied, but significant hepatic damage occurred in the groups receiving prednisolone. Thus, combined therapy was superior to either drug used alone, and the immunosuppressive effect of greatest clinical importance seemed to be the ability to prevent formation of anti‐DNA antibodies.
Hydralazine urinary metabolites in systemic lupus erythematosus
Authors: Litwin Allen , Adams Louis E , Hess Evelyn V , Mcmanus Joseph , Zimmer Hans
Published: February 2007

Urinary metabolites of hydralazine were studied using a paper chromatographic technic. The major urinary metabolite detected in both normal subjects and patients with systemic lupus erythematosus was 3‐methyltriazolo [3,4‐a] phthalazine. Differences were not detected between the two groups.
Report of the familial occurrence of systemic lupus erythematosus in male siblings
Authors: Spector David A , Jampol Lee M , Hayslett John P
Published: February 2007

The occurrence of systemic lupus erythematosus (SLE) is reported in 2 pairs of male siblings. Since the occurrence of idopathic SLE is uncommon in the male, these cases provide additional support to the hypothesis that genetic factors play an important role in pathogenesis. Of additional interest in these patients was the varied clinical manifestations of disease between brothers, suggesting that additional factors govern the clinical expression of this disorder.
A Controlled Trial of Gold Salt Therapy in Rheumatoid Arthritis
Authors: Mainland  , Sutcliffe M. I. , O'brien W. M. , Healey L. A. , Mikkeisen W. M. , Wallace S. L.
Published: February 2007

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.
Experimentally Induced Degenerative Joint Lesions Following Partial Meniscectomy in the Rabbit
Authors: Moskowitz Roland W. , Davis Wirt , Sammarco James , Martens Mark , Baker Jack , Mayor Michael , Burstein A. H. , Frankel V. H.
Published: February 2007

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.
Virologic Studies on Rheumatoid Arthritis
Authors: Wilkes R. Michael , Simsarian James P. , Hopps Hope E. , Roth Henry , Decker John L. , Aptekar Robert G. , Meyer Harry M.
Published: February 2007

A search for viral agents associated with rheumatoid arthritis was made using cell lines derived from 64 joint fluids and 41 tissue biopsies (including 29 synovia, 10 rheumatoid nodules, and 2 rheumatoid cartilage). Virus recovery was attempted using a variety of techniques including cell fusion. No viruses were isolated nor were significant patterns of antiviral antibodies found in sera from patients with arthritis. Using seven different viruses, including rubella and Newcastle disease virus, the viral susceptibility of cell lines derived from rheumatoid and nonrheumatoid patients was compared; there was no evidence of significant differences.
Electron Microscopic Studies of Lymphoid Cells in the Rheumatoid Synovial Membrane
Authors: Kobayashi Ikuo , Ziff Morris
Published: February 2007

The sublining layer of the rheumatoid synovium has been examined in the electron microscope. In this layer lymphocytes appeared to leave the blood by passing through the endothelial cytoplasm of venules and veins to form dense perivascular accumulations rich in either lymphocytes, plasma cells or both. Undifferentiated blast cells and plasmablasts were also observed in these collections. The finding of predominantly lymphocytic accumulations around some vessels and predominantly plasma‐cellrich accumulations in a similar distribution around others suggested that most of the lymphocytes were plasma cell precursors or B lymphocytes.
Rapid, Simple Detection of Trace Amounts of Synovial Fluid
Authors: Goldenberg Don L. , Brandt Kenneth D. , Cohen Alan S.
Published: February 2007

Two rapid, simple methods for demonstrating trace amounts of synovial fluid are compared. Both a) mucin formation and b) metachromatic staining are capable of detecting as little as 0.5 μl of synovial fluid and, hence, will be useful whenever the ability to identify small amounts of synovial fluid with certainty is of clinical importance.
Experimental skin lesions in mice resembling systemic lupus erythematosus
Authors: Natali P. G. , Tan E. M.
Published: February 2007

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.
Patterns of finger capillary abnormalities in connective tissue disease by “wide‐field” microscopy
Authors: Maricq Hildegard Rand , Carwile LeRoy E.
Published: February 2007

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—17.On 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.
Interactions of aspirin with nonsteroidal antiinflammatory drugs in man
Authors: Rubin Alan , Rodda Bruce E. , Warrick Patricia , Gruber Charles M. , Ridolfo Anthony S.
Published: February 2007

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.
Prevalence of rheumatoid arthritis in alaskan eskimos
Authors: Palmer Beasley R. , Retailliau Henry , Healey L. A.
Published: February 2007

A rheumatoid arthritis prevalence survey was conducted in eight Alaskan Eskimo villages during the summer of 1970. Eleven cases of definite rheumatoid arthritis were found among 1443 Eskimos over 14 years of age. The frequency of 1.0% among adult females and 0.5% among adult males is almost identical with the National Health Examination Survey prevalence estimate for the general United States.
Familial aggregation of polymyalgia rheumatica and giant cell arteritis
Authors: Liang George C. , Simkin Peter A. , Hunder Gene G. , Wilske Kenneth R. , Healey L. A.
Published: February 2007

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.
Lymphocyte characteristics in rheumatic patients and the effect of azathioprine therapy
Authors: Yu David T. , Clements Philip J. , Peter James B. , Levy Joshua , Paulus Harold E. , Barnett Eugene V.
Published: February 2007

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.
Copper‐catalyzed thermal aggregation of human gamma‐globulin inhibition by histidine, gold thiomalate, and penicillamine
Authors: Gerber Donald A.
Published: February 2007

Gold thiomalate (40 μM), penicillamine (40 μM), and histidine (20 μM) inhibit the copper‐catalyzed (20 μM) thermal aggregation of human gamma globulin (0.8 mg/ml). At these concentrations, inhibition of gamma globulin aggregation was 87%, 96%, and 99% complete. This effect may be related to the reported suppressive effect of these agents in rheumatoid arthritis and adds support to the hypothesis that the hypohistidinemia of rheumatoid arthritis participates in the pathogenesis of the disease.
Anti‐DNA antibody in procainmide‐induced lupus erythematosus. Determination using DNA fractionated by methylated albumin‐kieselguhr chromatography
Authors: Winfield John B. , Davis John S.
Published: February 2007

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.
Effect of single oral doses of benzbromarone on serum and urinary uric acid
Authors: Jain Adesh K. , Ryan Jerome R. , McMahon F. Gilbert , Noveck Robert J.
Published: February 2007

The effects of various single oral doses of micronized benzbromarone on serum and urinary uric acid and urinary oxypurines were studied in 5 healthy volunteers and in 5 patients with gout. There was an effective, unequivocal, and dose‐related reduction in serum uric acid levels in both groups. The simultaneous increased excretion of urinary uric acid but not of oxypurines suggests the mechanism of effect is uricosuria. The prolonged duration of action up to 48 hours after dosing is advantageous as the drug need be taken only once a day. The data presented favor a protracted trial of benzbromarone in patients with gout and hyperuricemia.
Pharmacodynamics of 197Au and 195Au labeled aurothiomalate in blood. Correlation with course of rheumatoid arthritis, gold toxicity and gold excretion
Authors: Gottlieb Norman L. , Smith Patricia M. , Smith Edward M.
Published: February 2007

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.
Compensated polarized light microscopy using cellophane adhesive tape
Authors: Fagan Terrence J. , Lidsky Martin D.
Published: February 2007

Compensated polarized light microscopy is a useful diagnostic tool whose basis is poorly understood by the clinician. The elementary physics of compensated polarized light are reviewed. A simple method of converting the ordinary light microscope into a compensated polarized light microscope, using cellophane adhesive tape and polarizing sunglass, is described.
Relation of cellular infiltration of rheumatoid synovial membrane to its immune response
Authors: Ziff Morris
Published: February 2007

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.
Selective depletion of Ig‐bearing lymphocytes by cyclophosphamide in rheumatoid arthritis and systemic lupus erythematosu guidelines for dosage
Authors: Horwitz David A.
Published: February 2007

Cyclophosphamide was given to 11 patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in doses regulated by monitoring effects on small lymphocytes. Total leukocyte counts, the numbers of immunoglobulin‐positive and Ig‐negative small lymphocytes by immunofluorescence and the proliferative response of lymphocytes to phytohemagglutinin (PHA) were measured. The number of both Ig‐positive and Ig‐negative small lymphocytes decreased following cyclophosphamide. When dosage was reduced to maintenance levels, the Ig‐positive cells remained less than 75% of baseline values, whereas the Ig‐negative lymphocytes returned toward the baseline. During this time PHA values were normal or increased. On maintenance therapy, objective evidence of improvement was observed in 10 patients. These studies suggested a selective depletion of B‐lymphocytes by cyclophosphamide and that a reduction of other leukocytes is not necessary for a favorable clinical response. Adverse side effects were rare. Direct quantitation of B‐lymphocytes may be helpful in regulating clinically effective individual doses of cyclophosphamide in a manner that is relatively safe.
Chromosome abnormalities from cyclophosphamide therapy in rheumatoid arthritis and progressive systemic sclerosis (scleroderma)
Authors: Tolchin Sanford F. , Winkelstein Alan , Rodnan Gerald P. , Pan Sylvia F. , Nankin Howard R.
Published: February 2007

In patients with rheumatoid arthritis and scleroderma, the frequency of major chromosome abnormalities was appreciably increased by prolonged therapy with cyclophosphamide. Metaphases from 8 patients with rheumatoid arthritis, receiving this cytotoxic drug (0.5–2.0 mg/kg/day), showed a significantly greater frequency in hypodiploidy and chromosome type breaks than a comparable control series. In addition, 5 patients with scleroderma were studied before and after the administration of cyclophosphamide and a significant increase in the number of cytogenetic aberrations was observed during therapy.
Malignancy in a series of 70 patients with systemic lupus erythematosus
Authors: Canoso Juan J. , Cohen Alan S.
Published: February 2007

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.
Technetium counting in rheumatoid arthritis evaluation in the small joints of the hand
Authors: Sturrock R. D. , Nicholson Rosemary , Wojtulewski J. A.
Published: February 2007

An apparatus is described for external directional technetium counting of the proximal interphalangeal joints of the hand. In 11 normal and 14 rheumatoid subjects a significantly higher count rate was reached in the rheumatoid group (t = 3.79 P < 0.005). There was a good correlation between the rate of uptake and total count rate of technetium over an inflamed joint and this was taken to demonstrate the importance of the effect of vascularity on technetium kinetics. Clinical improvement following gold and penicillamine therapy was reflected in a fall in count rates which closely paralleled a reduction in ring sizes.
The role of xanthine oxidase in hyperuricemic states
Authors: Marcolongo Roberto , Marinello Enrico , Pompucci Giuseppe , Pagani Roberto
Published: February 2007

The behavior of xanthine oxidase in the jejunal mucosa of patients with gout and in the liver of normal subjects during secondary drug‐induced hyperuricemia was studied. Xanthine oxidase activity was not increased significantly in the jejunal mucosa of patients with gout, whereas an RNA, hypoxanthine, EA‐TDA, or fructose load in normal subjects caused liver xanthine oxidase levels to rise to values that were two‐ to fourfold higher than those for the control group. The results indicated that previously reported increases in liver xanthine oxidase levels in patients with gout, who were overexcretors, were neither primary nor genetically determined but were related to increased production of the enzyme.
Incidence of myocardial infarction in patients with rheumatoid arthritis
Authors: Davis Richard F. , Engleman Edgar G.
Published: February 2007

At autopsy, 62 patients with rheumatoid arthritis (RA) showed significantly lower morbidity (P < 0.001) and mortality (P < 0.02) from myocardial infarction than 62 matched control patients, but there were no significant differences in frequency of cerebral infarction or pulmonary embolism. Coronary artery atherosclerosis occurred as frequently in the patients with RA as in the control population, suggesting that there may be a decreased tendency toward thrombosis in the rheumatoid group. Therapy with aspirin and the consequent inhibition of platelet aggregation may explain this observation.
Further observations on the treatment of lupus nephritis with prednisone and combined prednisone and azathioprine
Authors: Donadio James V. , Holley Keith E. , Wagoner Richard D. , Ferguson Richard H. , McDuffie Frederic C.
Published: February 2007

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.
Prophylactic colchicine therapy of intercritical gout. A placebo‐controlled study of probenecid‐treated patients
Authors: Paulus Harold E. , Schlosstein Lee H. , Godfrey Robert G. , Klinenberg James R. , Bluestone Rodney
Published: February 2007

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.
The articular cartilage in familial chondrocalcinosis. Light and electron microscopic study
Authors: Reginato Antonio J. , Schumacher H. Ralph , Martinez Virginia A.
Published: February 2007

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.
Septic arthritis due to nonencapsulated cryptococcus neoformans with coexisting sarcoidosis
Authors: Levinson D. J. , Silcox D. C. , Rippon J. W. , Thomsen S.
Published: February 2007

A patient with septic arthritis of the knee due to a nonencapsulated strain of Cryptococcus neoformans neoformans is reported. Predisposing factors included repeated trauma and sarcoidosis. Serologic tests and pathologic examination were consistent with the mutant strains recovered from infected tissue. The organism was eradicated by combined synovectomy and chemotherapy with amphotericin B and 5‐fluorocytosine. The significance of capsular material is discussed. To our knowledge this is the first reported example of human infection caused by a nonencapsulated C neoformans.
Nature of cold‐reactive antibodies to lymphocyte surface determinants in systemic lupus erythematosus
Authors: Winfield John B. , Winchester Robert J. , Wernet Peter , Fu Shu Man , Kunkel Henry G.
Published: February 2007

Antilymphocyte antibodies in serum from patients with systemic lupus erythematosus (SLE), as detected by microcytotoxicity and indirect immunofluorescence, were predominantly cold reactive and of the IgM class. These IgM antibodies were most active at 4°C. IgG antibodies were infrequent, and were only minimally lymphocytotoxic. Most sera were cytotoxic for autologous lymphocytes and were equally reactive with normal and SLE lymphocytes, as well as with B‐ and T‐cell preparations. Separate T‐ and B‐cell specificities, which appeared not to be related to HL‐A determinants, were identified by differential absorption experiments. The functional significance of these antilymphocyte antibodies is discussed.
Azathioprine in rheumatoid arthritis
Authors: Hunter Thomas , Urowitz Murray B. , Gordon Duncan A. , Smythe Hugh A. , Ogryzlo Metro A.
Published: February 2007

In 1973 we reported the beneficial effects of azathioprine in a double blind, cross‐over study in 17 patients with classic rheumatoid arthritis. During subsequent follow‐up over a mean period of 40 months, 4 patients had discontinued therapy because of poor therapeutic response and 1 because of nausea. Eleven of the 12 patients still taking azathioprine had maintained their initial beneficial response or showed further improvement. Adverse side effects during the follow‐up period were minor. They included nausea in 1 patient and leukopenia with thrombocytopenia in another. An increased incidence of chromosomal abormalities was detected in those patients still receiving azathioprine.
Long‐term maintenance therapy with azathioprine in systemic lupus erythematosus
Authors: Ginzler Ellen , Sharon Ezra , Diamond Herbert , Kaplan David
Published: February 2007

One hundred ten patients with systemic lupus erythematosus (SLE) were classified into two groups, patients with central nervous system (CNS) or severe renal disease (usually associated with a poor prognosis) and patients without these manifestations, to define criteria for azathioprine therapy. Fifty‐four of 68 patients with a poor prognosis received azathioprine. Azathioprine‐treated patients showed improved longterm survival (72% vs 29%, P <.005) and fewer hospitalizations (0.24/patient‐years vs 0.89/patient‐years, P <.d001). Azathioprine therapy in 19 of 42 patients with a good prognosis was associated with fewer hospitalizations (.02/patient‐years vs.17/patient‐years, P <.05), but no decrease in maintenance prednisone requirement. Progression from a good to a poor prognosis was less frequent (1 of 20 vs 11 of 34, P <.05) among azathioprine‐treated patients. Toxicity of azathioprine was minimal. Azathioprine therapy is indicated in patients with CNS or severe renal disease, and in patients whose prognosis was good with frequent hospitalizations or a maintenance prednisone requirement greater than 15 mg/day.
Immunoglobulin deposits in skin in systemic lupus erythematosus
Authors: Wierzchowiecki M. O. , Quismorio F. P. , Friou G. J.
Published: February 2007

Immunoglobulin deposits in the dermal‐epidermal junction of clinically normal skin from patients with SLE were eluted by acid buffer. The eluates contained antinuclear and antibasement membrane antibody activities. The anti‐BM antibody reacted with skin and esophageal but not glomerular basement membrane. Enzymatic studies indicated that the antibody reacted with carbohydrate moeities in the basement membrane. The anti‐BM antibody was not present in corresponding sera of SLE patients.
Monozygotic twins discordant for systemic lupus erythematosus
Authors: Yocum Michael W. , Grossman Jay , Waterhouse Christine , Abraham George N. , May‐June Allyn G. , Condemi John J.
Published: February 2007

A pair of monozygotic twins discordant for systemic lupus erythematosus (SLE) were studied and no differences noted in their immune response to tetanus toxoid, keyhole lympet hemocyanin, DNCB, delayed sensitivity, or antibody titers to viruses. Both were noted to have biologically false positive serology at an early age, but only one twin developed SLE. The clinically unaffected twin underwent castration at an early age, suggesting that ovarian hormones May‐June play an important role in the development of SLE.
Cell‐mediated immunity in rheumatic diseases
Authors: Lockshin M. D. , Eisenhauer A. C. , Kohn R. , Weksler M. , Block S. , Mushlin S. B.
Published: February 2007

Lymphocyte responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen were tested in normal patients and in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), scleroderma (PSS), other connective tissue disease, and other illnesses. The relationship of lymphocyte response to diagnosis, therapy, and T‐ and B‐lymphocyte populations was analyzed. Additional studies included the determination of proliferative responses of various combinations of purified T and B lymphocytes cultured with plant mitogens. Lymphocytes from patients with RA and SLE incorporated significantly less thymidine in the presence of plant mitogens as compared to normal and comparably ill subjects. Treatment had no effect on mitogen response. Responses to all three mitogens correlated closely in patients with RA, SLE, or PSS; no correlation was noted between the response to mitogen of lymphocytes in culture and the number of T cell ultured.
Connective tissue response to immobility
Authors: Woo Savio L‐Y , Matthews John V. , Akeson Wayne H. , Amiel David , Richard Convery F.
Published: February 2007

The biomechanical changes in rabbit knee confracture were measured after 9 weeks of immobilization. These results were correlated with the biochemical composition of periarticular connective knee tissue of the same knees. The loss of total hexosamine correlates significantly with joint stiffness on an animal‐to‐animal basis. Total hexosamine also correlates with the energy required cyclicly to flex and to extend the experimental joints. Of the individual glycosaminoglycan fractions, only hyaluronic acid showed significant correlation with the biomechanical data. The possible mechanism of contracture formation was postulated based on these results.
Depressed synovial fluid levels of properdin and properdin factor b in patients with rheumatoid arthritis
Authors: Ruddy Shaun , Fearon Douglas T. , Austen K. Frank
Published: February 2007

Two proteins in the properdin system, properdin and factor B, and complement components C4 and C3 were measured by radial immunodiffusion in serums and synovial fluids from 21 patients with rheumatoid arthritis (RA) and positive tests for rheumatoid factor, 9 patients with seronegative RA, and 10 with degenerative joint disease. In addition to depressions of synovial fluid C4 which correlated with lowered C3 in seropositive RA, consistent with activation of the classic pathway, low synovial fluid levels of factor B and properdin in seropositive RA indicate intraarticular activation of the properdin pathway as well.
Antibody levels to parainfluenza, rubella, measles, and influenza a virus in children with polymyositis
Authors: Koch Milton , Brody Jacob A. , Nemo George J. , Sever John L.
Published: February 2007

The CF and HI antibody titers to rubella and measles viruses, the CF titers to influenza A, and the HI titers to parainfluenza 1, 2, and 3 were carried out on the sera of 20 patients with childhood polymyositis and their matched controls. The titers for measles, parainfluenza 1, and influenza A were slightly higher for patients than for controls. The control group had antibody titers to rubella and parainfluenza 2 and 3 higher than or similar to those of patients. Strong patterns or significant differences for a given virus or virus group were not encountered.
Aseptic meningitis in systemic lupus erythematosus
Authors: Canoso Juan J. , Cohen Alan S.
Published: February 2007

Three patients with aseptic meningitis were subsequently diagnosed as having lupus erythematosus. One patient had a single meningitic episode, another had chronic meningitis, and the third two acute episodes 5 years apart. All 3 patients developed further neuropsychiatric manifestations of SLE, leading to death in 1. Aseptic meningitis appears to be an early manifestation of SLE and may herald more serious brain damage. No new cases of aseptic meningitis occurred in this series after initiation of therapy for SLE. In contrast, bacterial meningitis did occur as a late complication of the disease.
Freeze‐etch study of collagen
Authors: Belton John C. , Michaeli Dov , Fudenberg H. Hugh
Published: February 2007

The freeze‐fracture technique was used to study the fine structure of native collagen from rat tendon and lung. The collagen filaments were organized into a spiraled lamellar substructure within each fibril. Small particles, representing the broken ends of the collagen filaments, were found in nearly straight rows when the lamellae were broken tranversely. Filamentous connections were shown which span the interfibrillar matrix and unite all of the fibrils into a reticular network. The fibrils were coated with material that was greatly hydrated in vivo. Sublimation occurred more rapidly from some portions of the coating substance than from others, resulting in a banding pattern with a 610 Å repeat distance.
Changes in the lipids of human articular cartilage with age
Authors: Bonner Walter M. , Jonsson Haldor , Malanos Cynthia , Bryant Max
Published: February 2007

Histochemical and chemical studies demonstrated a significant increase in the lipids of articular cartilage with advancing age. Triglycerides, cholesterol, and phospholipids were identified chemically and were shown by comparative staining procedures to be present in intracellular and extracellular lipids. The distribution and the composition of the extracellular lipids were interpreted as indicating that the extracellular lipids are of cellular origin. Glycolipids were extracted from cartilage of all ages and were shown to account for a portion of the increase in total lipid with age. Glycolipids extracted from aged cartilage were partially characterized. Cerebrosides, sulfatides, and gangliosides were detected. Glycolipids were estimated to comprise from 5 to 10% of the total lipid of articular cartilage. Arachidonic acid concentrations increased markedly with age in the surface of cartilage but were present in trace amounts in deep cartilage, demonstrating clear‐cut differences in the levels as well as the location of this fatty acid precursor of the prostaglandins (PGE2 and PGF2α).
Mechanism of action of colchicine
Authors: Chang Yi‐Han
Published: February 2007

Colchicine suppresses the development of carrageenan‐induced edema in the rat with a minimum effective oral dose of 6.0 mg/kg. The slope of the dose‐response regression line for colchicine differs significantly from that of indomethacin and phenylbutazone. Based on the dosages required to achieve a 50% suppression of this inflammation, colchicine is 0.6 and 1.5 times as potent as indomethacin and phenylbutazone, respectively. In the reversed passive Arthus reaction in the rat, the suppressive activity of colchicine is at least 50 times that of indomethacin and 100 times that of phenylbutazone. The possible significance of these results with regard to the unique effectiveness of colchicine in the treatment of gout is discussed.
Wegener' granulomatosis
Authors: Reza Michael J. , Dornfeld Leslie , Goldberg Leonard S. , Bluestone Rodney , Pearson Carl M.
Published: February 2007

Ten patients with Wegener' granulomatosis were treated with cyclophosphamide and followed for periods up to 7 years. In all cases cyclophosphamide induced complete remissions. The mean duration of remission (to date) was 38 months. Six patients have been in remission for a mean of 46 months after cyclophosphamide was discontinued; 2 have been disease‐free for 7 years. Of the 10 patients treated, only 1 relapsed and she responded to a second course of cyclophosphamide. These results indicate that cyclophosphamide is the drug of choice in Wegener' granulomatosis. The long‐term effectiveness of this drug suggests that it may induce permanent remissions in certain patients with Wegener' granulomatosis.
Antibodies to dna in patients with rheumatoid arthritis and juvenile rheumatoid arthritis
Authors: Bell Carolyn , Talal Norman , Schur Peter H.
Published: February 2007

Antibodies to double‐stranded DNA (DSDNA) were found in 18 patients with RA, in 5 patients with JRA, and in 5 patients with undiagnosed connective tissue disease. Five patients had clinical features consistent with both RA and SLE, 11 with only RA, and 5 with only JRA. Based on these observations, the presence of serum anti‐DSDNA antibodies should not be used as a sole criterion in the diagnosis of SLE.
Relapsing polychondritis
Authors: Shaul Stephen R. , Schumacher H. Ralph
Published: February 2007

Light microscopic and for the first time electron microscopic (EM) studies of involved elastic ear cartilage in a patient with relapsing polychondritis confirm the superficial location of the inflammatory reaction. EM studies of deep cartilage were identical to those on controls except for a rare necrotic cell. Superficial cartilage showed a finely granular electron‐dense material. This material, which may be protein, possibly of enzyme or immunoglobulin origin, also surrounded some elastic fibrils. Findings of predominantly superficial changes and the multisystem disease in the present patient and in many others suggest that the cartilage destruction is part of a systemic inflammatory disease.
Electron microscopic observations of immunoreactive cells in the rheumatoid synovial membrane
Authors: Ishikawa Hitoshi , Ziff Morris
Published: February 2007

The perivascular infiltrates of the rheumatoid synovium were examined in the electron microscope. Lymphocyte‐rich, plasma cell‐rich, and transitional areas were observed. The transitional areas contained lymphocytes, plasma cells, blast cells, macrophages, and fibroblasts. Although lymphoblasts were frequent, the blast cells were predominantly plasmablasts. Marked degeneration of fibroblasts in the vicinity of lymphoblasts suggested the liberation of a lymphotoxin by the lymphoblasts. There was close contact between blast cells and macrophages and between macrophages and lymphocytes. The close association of lymphoblasts, plasmablasts, and macrophages in the transitional areas suggests that these are sites of T‐ and B‐cell interaction in the rheumatoid synovial immune response.
Experimental hemarthrosis in the knee of the mature canine
Authors: Convery F. Richard , Woo Savio L‐Y , Akeson Wayne H. , Amiel David , Malcom Lawrence L.
Published: February 2007

The knee joints of 14 skeletally mature mongrel dogs were subjected to a continuous hemarthrosis. Minimal morphologic changes of the articular cartilage did not occur until after 16 weeks. As early as 4 weeks, biochemical analyses showed a significant decrease in glycosaminoglycans (GAG) that became progressively more severe with time, whereas total collagen was not significantly altered until after 12 and 16 weeks. Bioengineering measurements of the experimental cartilage surfaces showed that the tissue becomes more deformable as well as less resistive to shear than the control at 8 weeks. These differences increased as the duration of hemarthrosis increased.
Absent factor II in systemic lupus erythematosus. Immunologic studies and response to corticosteroid therapy
Authors: Natelson Ethan A. , Cyprus Gerald S. , Hettig Robert A.
Published: February 2007

This report describes a patient with active systemic lupus erythematosus (SLE) who evidenced severe bleeding consequent to a profound and isolated reduction in plasma factor II (prothrombin) activity. Absence of the factor is documented by immunologic means and its return after corticosteroid therapy is demonstrated. The authors recommend inclusion of this acquired coagulopathy among other more traditional diagnostic manifestations of SLE.
Dermatoglyphic study of systemic lupus erythematosus
Authors: Dubois Robert W. , Weiner John M. , Dubois Edmund L.
Published: February 2007

Dermatoglyphic patterns were analyzed from two races of patients with SLE: a Mexican‐American series of 27 females with SLE and 28 matched controls, and a Caucasian series of 28 females with SLE and 26 matched controls. Eighty‐five measurements and 23 indices were analyzed. From these data, eleven parameters were statistically significant, four separating the Mexican‐American SLE group from their controls and seven separating the Caucasian SLE group from their controls (P values < 0.002 to < 0.05). Only two parameters were significantly different between the two normal series, but nine parameters differentiated the Mexican‐American SLE from the Caucasian SLE groups. A multiple linear discriminant function was computed using the most significant parameters. A misclassification rate of 25–30% was observed between patients and matched controls. Dermatoglyphic patterns have been shown to be genetically controlled. These data suggest a genetic abnormality associated with SLE.