bluuebunny/crossref_metadata_2025 huggingface dataset:
Low density neutrophils in patients with systemic lupus erythematosus, rheumatoid arthritis, and acute rheumatic fever
Authors: Hacbarth Elisa , Kajdacsy‐Balla Andre
Published: February 2007

Ficoll‐Hypaque density gradient preparations of peripheral blood mononuclear cells from patients with systemic lupus erythematosus, rheumatoid arthritis, and acute rheumatic fever were highly “contaminated” with low buoyant density neutrophils. Plasma from these patients could induce an in vitro decrease of buoyancy in neutrophils with normal buoyant density. Similar change could be induced by complement‐activated sera and aggregated gamma globulin. These data suggest that activated neutrophils are a common finding in the peripheral blood of these patients and may influence the interpretation of any studies with these cells. Functional studies of lymphocytes separated by Ficoll‐Hypaque gradients should also take into account the higher degree of impurity of the cell preparations in patients with rheumatic diseases.
A staphylococcal proteoglycan‐releasing factor
Authors: Smith R. Lane , Schurman David J.
Published: February 2007

We report the effect of staphylococci on induction of proteoglycan release from cartilage in organ culture and document the presence of a staphylococcal proteoglycan‐releasing factor in the bacterial growth medium. Staphylococci cocultured with cartilage increased release of proteoglycan 3‐4‐fold within 48 hours. Viable cartilage was essential for maximum loss of proteoglycan. Killed bacteria had no effect on proteoglycan release. Four Staphylococcus aureus strains yielded growth media preparations active in proteoglycan release. Analysis of the proteoglycan subunits released from cartilage showed only limited degradation, and glycosaminoglycan chain length was not significantly altered.
Successful treatment of autoimmunity in mrl/1 mice with ls‐2616, a new immunomodulator
Authors: Tarkowski A. , Gunnarsson K. , Nilsson L.‐Å. , Lindholm L. , Stålhandske T.
Published: February 2007

Autoimmune MRL/1 mice were treated with a recently developed substance with immunomodulating properties, LS‐2616. Treatment was initiated at the age of 8 weeks, before the onset of clinically apparent disease, and at 16 weeks of age, after development of established lupus disease. Beneficial therapeutic effects were obtained, even when LS‐2616 was administered at the lowest dose tested (1 mg/mouse/week) to 16‐week‐old mice. The effects of LS‐2616 on longevity, as well as on development of lymphadenopathy, splenomegaly, glomerulonephritis, and vasculitis, were pronounced and were comparable with those of cyclophosphamide. The results obtained suggest a potential role for LS‐2616 in the treatment of autoimmune disease in humans.
Female sex hormones suppress development of collagen‐induced arthritis in mice
Authors: Holmdahl Rikard , Jansson Liselott , Andersson Mikael
Published: February 2007

We have previously reported that male DBA/1 mice are more susceptible to collagen‐induced arthritis than are females. Here we report that oophorectomy makes female mice as susceptible to collagen arthritis as are normal males. Induction of collagen‐induced arthritis in mice is a T cell‐dependent process. The role of female sex hormones in modulating T cell‐dependent autoimmune diseases is discussed.
Basement membrane thickening of postcapillary venules and capillaries in rheumatoid synovium
Authors: Matsubara Tsukasa , Ziff Morris , Smith Ashbel
Published: February 2007

Pathologic changes in the basement membrane (BM) of postcapillary venules (PCV) and capillaries in rheumatoid arthritis (RA) synovium were studied by immunoelectron microscopy, using a monoclonal antibody against human type IV collagen, C(IV)22, and by electron microscopic morphometric analysis. The sublining region of RA synovium was classified into lymphocyte‐rich areas, transitional areas, and interstitial areas, according to their pattern of cellular infiltration. In lymphocyte‐rich areas, the BM of the PCV and capillaries were minimally thickened; disruption of the lamina densa was seldom seen. Transitional areas, which contained macrophages, lymphocytes, and plasma cells, had numerous PCV and capillaries. The BM was markedly thickened and partially multilamellated, and there were many disruptions in the lamina densa. The BM contained degenerated endothelial cells and cell debris. On immunostaining of this BM with monoclonal antibody C(IV)22, type IV collagen stained heavily, mainly in the disrupted lamina densa; this indicates that the thickening was, at least in part, the result of an increase in BM collagen. In uninfiltrated interstitial areas, BM were moderately thickened and multilamellated, and showed few disruptions of the lamina densa; there were similar increases in type IV collagen, but cell debris was seldom observed. Measurement of the BM width, the ratio of BM width to vessel diameter, and the fraction of vascular cross‐sectional area occupied by BM demonstrated that the thickness of the BM of both PCV and capillaries was greatest in transitional areas and was smallest in lymphocyte‐rich areas (P <0.01). Since macrophages and macrophage‐derived factors have been found to promote synthesis of BM collagen type IV, and since transitional and interstitial areas are rich in macrophages and histiocytes, respectively, it is suggested that these mononuclear cells and the factors secreted by them play a significant role in the thickening of the BM of PCV and capillaries in RA synovitis.
The assessment of pain in rheumatoid arthritis
Authors: Anderson Karen O. , Bradley Laurence A. , McDaniel Lisa K. , Young Larry D. , Turner Robert A. , Agudelo Carlos A. , Keefe Francis J. , Pisko Edward J. , Miller Snyder R. , Semble Elliott L.
Published: February 2007

It is difficult to objectively measure pain in rheumatoid arthritis (RA). A behavioral observation method for the assessment of RA pain has been developed. In this study, videotapes were made of 53 RA patients while they performed standardized maneuvers. Trained raters viewed the videotapes and recorded the frequencies of 7 pain behaviors. Clinical and laboratory measures of rheumatoid disease activity also were recorded for each patient. Rheumatology fellows viewed 20 randomly chosen video recordings of the patients and made global estimates of the intensity and unpleasantness of pain. Significant positive correlations were found between total pain behavior scores and measures of disease activity. The fellows' estimates of the intensity and unpleasantness of the patients' pain also were significantly and positively correlated with the total pain behavior scores. The behavioral observation method may be useful in the assessment of RA pain and may be included as an objective outcome measure in clinical trials with RA patients.
Intrauterine therapy for presumptive fetal myocarditis with acquired heart block due to systemic lupus erythematosus
Authors: Buyon Jill P. , Swersky Steven H. , Fox Harold E. , Bierman Frederick Z. , Winchester Robert J.
Published: February 2007

An experimental therapeutic regimen for congenital lupus erythematosus, which consists of treating the mother with high doses of dexamethasone and performing plasmapheresis (3 times per week), was developed. This regimen was administered to a woman whose pregnancy was complicated by the abrupt onset of fetal pericarditis, myocarditis, and complete heart block in the twenty‐fourth week of gestation. The effectiveness of plasmapheresis was evidenced by a decrease in the very high titer of SS‐B (La) antibodies in the mother. After 5 weeks of therapy, the cardiac disease was ameliorated. The infant tolerated delivery at week 31, and the heart block has persisted. The rationale for this therapy for fetal disease is discussed, with emphasis on 2 goals: 1) to diminish the quantity of maternal antibody that is transmitted to the fetus, and 2) to suppress the manifestations of fetal carditis with the use of glucocorticoids that are not inactivated by the placenta. Tentative recommendations for more intensive prenatal monitoring of maternal and fetal status for those at risk are outlined.
A common anti‐dna idiotype in sera of patients with active pulmonary tuberculosis
Authors: Sela O. , El‐Roeiy A. , Isenberg D. A. , Kennedy R. C. , Colaco C. B. , Pinkhas J. , Shoenfeld Y.
Published: February 2007

The sera of 57 patients with active, untreated pulmonary tuberculosis were examined for the presence of a common anti‐DNA idiotype, 16/6. Thirty‐four of the 57 sera (60%) had an increased level of the idiotype, as measured by enzyme‐linked immunosorbent assay using a specific rabbit anti‐16/6 serum. Of 28 matched control sera, only 1 (4%) was found to be positive for the idiotype. The sera of patients with tuberculosis also showed increased activity against a variety of antigens with which lupus autoantibodies are known to cross‐react (e.g., single‐stranded DNA, double‐stranded DNA, polynucleotides, and cardiolipin). A correlation was observed between serum IgG and IgM levels and the 16/6 idiotype levels.
Hla antigens in whipple's disease
Authors: Dobbins Iii William O. ,
Published: February 2007

The prevalence of HLA–A and B antigen loci in patients with Whipple's disease was determined from data obtained in a review of the literature and from personal communications. Data on the HLA–A and B locus typing of 30 patients were available (with the exception that 1 of the patients was not typed for the HLA–B locus), and for an additional 18 patients, HLA–B27 data were available. Of the 47 patients typed for B27, 13 (28%) were B27 positive. Twelve of the 48 patients had sacroiliitis, and 2 (17%) of them were B27 positive. These data suggest that Whipple's disease may be associated with HLA–B27, even in the absence of concomitant sacroiliitis.
Mast cell numbers in rheumatoid synovial tissues
Authors: Malone Daniel G. , Wilder Ronald L. , Saavedra‐Delgado Ana Maria , Metcalfe Dean D.
Published: February 2007

Synovial biopsy specimens from 20 patients with rheumatoid arthritis were subjected to quantitative analysis for several parameters of inflammation and for enumeration of synovial tissue mast cells. Strong positive correlations were found between numbers of mast cells per cubic millimeter of synovial tissue and the following synovial tissue parameters: inflammatory index (a quantification of lymphocytic infiltration), Leu‐3a grade (T helper/inducer lymphocytes), Leu‐1 grade (T lymphocyte), and plasma cell grade. A strong negative correlation was found between the synovial mast cell count and the extent of sublining layer fibrin deposition. Correlations between synovial mast cell count and Leu‐2a grade, ratio of Leu‐3a grade:Leu‐2a grade, OKM1 grade, HLA–DR grade, and lining layer thickness grade did not reach statistical significance. In addition, we obtained synovial specimens from 6 of the patients both before and after long‐term therapy with oral methotrexate and from 3 of the patients before, and 1 week after, an intraarticular injection of steroid. The 3 patients who had an intraarticular steroid injection showed a 67–96% decrease in the number of synovial tissue mast cells; there was no significant change in the number of synovial mast cells in the tissues of the 6 patients who received oral methotrexate. These observations are the first documentation of a quantitative relationship between the number of mast cells and the number and phenotypic profile of infiltrating lymphocytes in an inflamed tissue, which in this case, is human synovium. Our findings suggest that mast cells are involved in the pathologic interactions in rheumatoid arthritis and might play a role in the early phases of exacerbations of disease activity.
Lack of association between hla–dr2 and clinical response to methotrexate in patients with rheumatoid arthritis
Authors: Alarcóan Graciela S. , Billingsley Lynn M. , Clegg Daniel O. , Hardin Joe G. , Klippel John , Luggen Michael E. , Polisson Richard P. , Singer Joyce Z. , Szydlo Lillian , Willkens Robert F. , Acton Ronald T. , Barger Bruce O. , Dahl Stephen L. , Koopman William J.
Published: February 2007

Recent studies have indicated an association between the HLA–DR2 phenotype and substantial response to methotrexate in patients with rheumatoid arthritis (RA). To further resolve this issue, we analyzed this relationship. Our data, obtained from a multicenter, double‐blind study of rigorously assessed patients with RA, demonstrated that neither HLA–DR2 nor any other HLA–DR specificity is significantly associated with a substantial clinical response to methotrexate in patients with RA.
Low plasma androgens in women with systemic lupus erythematosus
Authors: Lahita Robert G. , Bradlow H. Leon , Ginzler Ellen , Pang Songya , New Maria
Published: February 2007

The high ratio of women with systemic lupus erythematosus (SLE) has remained unexplained, despite the recent description of metabolic abnormalities of estrogen and androgen metabolism. Alterations of steroid metabolism in patients with SLE could be important in the pathogenesis of this disease, since it has been reported that gonadal steroids modulate the immune system. Moreover, research with inbred lupus mice has shown that estrogens have adverse effects on the disease in both sexes, whereas androgen therapy or oophorectomy is protective in females. Recently, the finding of elevated testosterone oxidation at C‐17 in females with SLE suggested that plasma androgen levels in males and females with SLE should be examined more closely. We studied the varying degrees of clinical activity, with regard to plasma levels of 4 significant androgens: testosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate in a series of 5 male and 42 female SLE patients. Decreased levels of all androgens were observed in women with SLE. The lowest levels of plasma androgens were found in female patients who had active disease, as determined by laboratory and clinical assessment. These data support the fact that specific abnormalities of androgen metabolism in the female are associated with SLE, and may contribute in some way to morbidity and mortality. More importantly, these data may have implications for future therapeutic regimens based on male hormone replacement.
Modulation of prostaglandin E2 synthesis in rabbit synoviocytes
Authors: Rothenberg Ralph J.
Published: February 2007

Prostaglandin E2 (PGE2) production by rabbit synoviocytes was markedly stimulated by hydroxyapatite only after a 60‐minute delay. Release of 3H‐arachidonic acid (C20:4) and 3H‐PGE2 from cells with phospholipids that were prelabeled with 3H‐C20:4 did not occur in parallel. At 240 minutes, phospholipase activity in sonicated cell suspensions had increased only 38%, while cyclooxygenase activity had doubled (109%). This doubling, as well as the production of synoviocyte PGE2, was prevented by inhibiting the synthesis of protein. Cyclooxygenase is an inducible enzyme, and as such, it is a rate‐controlling step in PGE2 production.
Low‐dose methotrexate compared with azathioprine in the treatment of rheumatoid arthritis. a twenty‐four—week controlled clinical trial
Authors: Hamdy H. , McKendry R. J. R. , Mierins E. , Liver J. A.
Published: February 2007

Forty‐two patients with definite or classic rheumatoid arthritis entered a prospective 24‐week, double‐blind, parallel clinical trial, followed by an 18‐month open phase. All subjects had active synovitis that was unresponsive to nonsteroidal antiinflammatory medications and conventional slow‐acting antirheumatic drugs. Initial treatment with azathioprine (AZA), 100 mg/day, or methotrexate (MTX), 10 mg/week, orally, was adjusted at predefined intervals. Both treatment groups showed statistically significant improvement at week 24, compared with baseline status, in all 9 clinical outcome variables. There were no apparent statistically significant differences in these outcome variables between the 2 treatment groups. There was a trend toward a more marked and rapid improvement in the MTX‐treated group. Radiologic evidence of progression of joint damage was similar in both treatment groups at 24 and 52 weeks. Four of the 42 patients (2 receiving MTX and 2 receiving AZA) discontinued the study because of side effects, and 1 MTX‐treated patient withdrew because of personal reasons. Outcome measures at week 52 (open phase) were not statistically different from those at week 24. Twenty‐three patients were still taking the medication at week 104. We found that AZA and MTX were similarly effective in the treatment of rheumatoid arthritis, and that this beneficial effect was maintained for up to 2 years in most patients.
An immunoassay differentiating sera with antibodies to sm alone, antibodies to sm/RNP complex, and antibodies to RNP alone
Authors: Tsay Gregory J. , Chan Edward K. L. , Peebles Carol L. , Pollard K. Michael , Tan Eng M.
Published: February 2007

Combined DEAE‐Sephacel and hydroxyapatite chromatography resulted in a separation of free Sm antigen from the Sm/RNP complex in rabbit thymus extracts. In Western blots, the free Sm preparation contained an immunoreactive 14‐kd (D) protein, whereas the Sm/RNP complex contained, in addition to the 14‐kd protein, a 68‐kd—reactive protein and its putative degradation fragments. Ethidium bromide staining of these preparations separated by agarose gel electrophoresis showed that the Sm/RNP preparation contained RNA, but the free Sm preparation did not. These preparations were used as antigens in an enzyme‐linked immunosorbent assay (ELISA). Sera characterized as anti‐Sm only, anti‐Sm/RNP, and anti‐RNP only were assayed. A quotient (Q) was derived from the ELISA optical density obtained with Sm/RNP as antigen divided by the optical density obtained with free Sm as antigen. Q values <4.0 characterized sera with anti‐Sm only, values of 4.0–12.0 were observed in sera with anti‐Sm plus anti‐RNP, and values >12.0 in sera with anti‐RNP only. Sera with antibodies to other nuclear antigens were not reactive in this system. It has traditionally been difficult to identify sera with anti‐RNP when this is present simultaneously with, and in lower concentration than, anti‐Sm. With this method, such sera can be identified by their Q value, which falls in an intermediate region between a lower Q for anti‐Sm and a higher Q for anti‐RNP.
Human recombinant interleukin‐1β stimulates glycosaminoglycan production in human synovial fibroblast cultures
Authors: Yaron Ilana , Meyer Frank A. , Dayer Jean‐Michel , Yaron Michael
Published: February 2007

Human recombinant interleukin‐1β (rIL‐1β) stimulated glycosaminoglycan (GAG) production in human synovial fibroblast cultures. A dose‐dependent increase in GAG production was found, to a maximum of 500%. Increase was detected at doses as low as 1 pg/ml of rIL‐1β, reached a maximum at 10‐100 pg/ml, and was apparent 10 hours after addition of rIL‐1β. Stimulation of GAG was always accompanied by increased accumulation of prostaglandin E (PGE) in culture media and by increased collagenase production in approximately one‐half the experiments. Indomethacin (5 m̈/ml) completely inhibited PGE stimulation by rIL‐1β, but only partially inhibited that of GAG overproduction and had no effect on collagenase production. Hydrocortisone (2 m̈/ml) inhibited stimulation of all 3 parameters. Stimulation of hyaluronate in synovial cultures prevailed over that of sulfated GAG, which occurred to à lesser extent. Our results support earlier suggestions that interleukin‐1 is a major active mononuclear cell factor that is capable of inducing profound changes in connective tissue cell function.
Passive transfer studies with type II collagen antibody in b10.D2/old and new line and C57b1/6 normal and beige (chediak‐higashi) strains: evidence of important roles for C5 and multiple inflammatory cell types in the development of erosive arthritis
Authors: Watson W. C. , Brown P. S. , Pitcock J. A. , Townes A. S.
Published: February 2007

C5‐normal B10.D2/new line mice were susceptible to passively transferred arthritis from purified type II collagen antibody, and in vitro studies demonstrated that, when bound to cartilage, this antibody readily activated complement C5 to C5a. C5‐deficient B10.D2/old line mice failed to develop passively transferred arthritis, despite the deposition of antibody and C3 along the cartilage surface. C57B1/6 mice were susceptible to passively transferred arthritis, which was characterized in histopathologic studies as an erosive synovitis involving multiple inflammatory cell types. In contrast, neither clinical nor histologic evidence of arthritis was observed in C57B1/6 mice with the beige mutation (Chediak‐Higashi syndrome).
The immunologic detection and characterization of cartilage proteoglycan degradation products in synovial fluids of patients with arthritis
Authors: Witter James , Roughley Peter J. , Webber Carolyn , Roberts Nancy , Keystone Edward , Poole A. Robin
Published: February 2007

Antibodies were used in radioimmunoassays with gel chromatography to detect the hyaluronic acid‐binding region, core protein, and keratan sulfate of human cartilage protoeglycan in the synovial fluids of patients with rheumatoid arthritis, juvenile rheumatoid arthritis, and osteoarthritis. All fluids contained proteoglycan that was mainly included on Sepharose CL‐4B; this result indicates cleavage of proteoglycan (which is normally excluded). The hyaluronic acid‐binding region was the smallest and most commonly detected fragment. It was relatively free of keratan sulfate and core protein, and it could sometimes bind to hyaluronic acid. Other larger fragments containing core protein and/or keratan sulfate were detected in every fluid.
Bradykinin, a new potential mediator of inflammation‐induced bone resorption
Authors: Lerner Ulf H. , Jones Ian L. , Gustafson Gunnar T.
Published: February 2007

The effect of bradykinin and desArg9‐bradykinin on bone was studied in cultures of calvarial bones taken from 6–7‐day‐old mice. Bradykinin, at and above a 3‐nM concentration, caused a dose‐dependent stimulation of bone mineral mobilization and matrix degradation. Bradykinin‐stimulated resorption was inhibited by calcitonin, an increased concentration of phosphate in the culture medium, hydrocortisone, dexamethasone, indomethacin, meclofenamic acid, naproxen, and 5,8,11,14‐eicosatetraenoic acid. The results suggest that bradykinin stimulates osteoclast‐mediated bone resorption by a process that is dependent on endogenous prostaglandin production. The stimulatory effect of bradykinin, but not of parathyroid hormone and prostaglandin E2, was potentiated by the angiotensin‐converting enzyme inhibitor, BPP5a. Treatment with carboxypeptidase B did not affect the capacity of the peptide to stimulated 45Ca release. DesArg9‐bradykinin (1 m̈mole/liter) stimulated 45Ca release to the same degree as did bradykinin. Bradykinin (3 m̈M) did not affect the degradation of cartilage proteoglycans, as assessed by the release of 35S‐sulfate from prelabeled calf articular cartilage in organ culture. These findings suggest that generation of bradykinin in inflammatory lesions of rheumatoid arthritis and periodontitis may contribute to the bone resorptive process seen in the joints and alveolar bone; however, bradykinin does not directly activate chondrocytes into a catabolic state.
Plasma hydroxychloroquine concentrations and efficacy in rheumatoid arthritis
Authors: Miller Donald R. , Fiechtner Justus J. , Carpenter James R. , Brown Richard R. , Stroshane Ronald M. , Stecher Vera J.
Published: February 2007

Plasma levels of hydroxychloroquine (HCQ) and its metabolites were measured, by high performance liquid chromatography, in 37 rheumatoid arthritis patients who could be clearly distinguished as responders (n = 28) or nonresponders (n = 9) to HCQ, 400 mg/day. Efficacy in both groups was determined by the patients' erythrocyte sedimentation rates, joint counts, morning stiffness, global assessments, concurrent drug therapies, and grip strength. The response rate was 76%. Responders had a mean HCQ level of 213 ng/ml, versus 306 in nonresponders (P < 0.05). The mean level of HCQ plus total metabolites in responders was 363 ng/ml, versus 554 in nonresponders (P < 0.01). We conclude that monitoring plasma HCQ levels is unlikely to be helpful in individualizing effective drug dosage.
Quantitative pain assessment for routine care of rheumatoid arthritis patients, using a pain scale based on activities of daily living and a visual analog pain scale
Authors: Callahan Leigh F. , Brooks Raye H. , Summey Jane A. , Pincus Theodore
Published: February 2007

Pain was assessed quantitatively as a component of routine visits of 385 outpatients with rheumatoid arthritis, using a pain scale based on activities of daily living (ADL) and a visual analog scale. The ADL pain scale met psychometric criteria for validity and reliability. Scores on the 2 pain scales were correlated significantly with one another and with other measures of disease status, including joint count, grip strength, walking time, button test, morning stiffness, erythrocyte sedimentation rate, global self‐assessment, ADL difficulty, and ADL dissatisfaction scales. Correlations of ADL pain scale scores with other measures were higher than were correlations of visual analog scale scores with other measures, in both unadjusted and adjusted analyses. Significantly more patients completed the ADL pain scale without assistance than the number of those who completed the visual analog pain scale. The ADL pain scale was more sensitive to problems in ADL than were the ADL scales for difficulty and dissatisfaction. The ADL and visual analog pain scales appear to provide useful data for quantitative assessment of pain in the routine care of rheumatoid arthritis patients.
Hydroxyapatite deposition in osteoarthritic articular cartilage of the proximal femoral head
Authors: Ohira Takashi , Ishikawa Koichiro
Published: February 2007

Hydroxyapatite crystal deposition in the articular cartilage of the proximal femoral head was examined by using light and electron microscopy and electron probe microanalysis. The hydroxyapatite deposition was significantly more frequent in patients with osteoarthritis (40.7%, 22 of 54) than in control subjects (6.0%, 3 of 50) (P < 0.001). Initial deposition of needle‐like crystals was always seen on or within the electron‐dense, amorphous material around the degenerating hypertrophic chondrocytes. Matrix vesicles were rarely seen in the calcifying areas.
Autoantigenic histone epitopes: a comparison between procainamide‐ and hydralazine‐induced lupus
Authors: Craft Joe E. , Radding Jeffrey A. , Harding Matthew W. , Bernstein Robert M. , Hardin John A.
Published: February 2007

Using the technique of immunoblotting, we assessed the ability of sera from 19 patients with drug‐induced lupus to bind individual histones and specific histone fragments. The pattern of histone epitopes bound by sera from 9 patients with procainamide‐induced lupus was very similar to that described previously in spontaneous systemic lupus erythematosus. In contrast, sera from 10 patients with hydralazine‐induced lupus bound a broader array of individual histones and recognized a different set of histone epitopes. We conclude that these 2 drugs induce antihistone antibodies through somewhat different mechanisms, which possibly involve differences in their ability to structurally alter chromatin.
Determinants of axial bone loss in rheumatoid arthritis
Authors: Sambrook Philip N. , Eisman John A. , Champion G. David , Yeates Michael G. , Pocock Nicholas A. , Eberl Stefan
Published: February 2007

To assess mechanisms that cause generalized osteoporosis in rheumatoid arthritis (RA), we measured bone mineral density (BMD) by dual photon absorptiometry in the lumbar spine and femoral neck of 111 patients with RA. BMD was significantly reduced at both sites in these patients. Physical activity correlated significantly with BMD in patients with RA, and was found, by multiple regression analysis, to be a significant predictor of femoral bone density in female patients. Multiparity exerted a protective effect on lumbar bone density. Prednisolone (mean dosage 8 mg/day) was not associated with significantly increased bone loss in women, whereas higher dosages in men (mean 10.3 mg/day) were associated with increased lumbar bone loss. Reduced physical activity leading to a form of disuse osteoporosis appears to be an important factor in axial bone loss in RA.
Weight bearing controls glycosaminoglycan concentration and articualr cartilage thickness in the knee joints of young beagle dogs
Authors: Kiviranta Ilkka , Jurvelin Jukka , Tammi Markku , SääMäunen Anna‐Marja , Helminen Heikki J.
Published: February 2007

Casting of the right knee (stifle) joints of young beagle dogs for 11 weeks caused up to 48% reduction in the glycosaminoglycan (GAG) concentration of the uncalcified articular cartilage, as assessed by a new microspectrophotometric method. The GAGs were depleted mainly in the superficial zone of the cartilage. Although the thickness of the uncalcified cartilage was not decreased, the calcified cartilage under the tidemark was thinned by 6–25% at the femoral condyles. The increased weight‐bearing in the limb opposite the one in the splint caused uncalcified cartilage thickness to be augmented by 19% and GAG concentration by 25–35% in the intermediate, deep, and calcified zones of the summits of the femoral condyles; the changes were smaller in other, less loaded parts of the joint. It is concluded that in young dogs, increased weight‐bearing augments local proteoglycan content of the articular cartilage matrix, while unloading reduces it.
Frozen shoulder in hyperthyroidism
Authors: Wohlgethan Jeffrey R.
Published: February 2007

A patient who presented with bilateral frozen shoulders and unrecognized hyperthyroidism is described. Both frozen shoulder and the related shoulder–hand syndrome may occur in this setting. These poorly understood rheumatic conditions often are complications of stroke, spinal cord injury, or diabetes. Dysfunction of the autonomic nervous system is thought to be of pathogenic importance. It is postulated that the close resemblance of hyperthyroidism to activation of the sympathetic nervous system may underlie its association with frozen shoulder and shoulder–hand syndrome.
Randomized, double‐blind, placebo‐controlled study of the treatment of the painful shoulder
Authors: Petri Michelle , Dobrow Robert , Neiman Richard , Whiting‐O'keefe Quinn , Seaman William E.
Published: February 2007

The effect of triamcinolone subacromial bursa injection versus naproxen therapy was compared in a randomized, double‐blind, placebo‐controlled study of 100 patients who had painful shoulders. Outcome was compared using degree of active abduction, pain, limitation of function, and a clinical index that combined equally weighted measures of all of these. In a time‐adjusted analysis, triamcinolone was superior to placebo in all clinical variables. Naproxen was superior to placebo in all variables except pain. Triamcinolone was superior to naproxen in the relief of pain (P = 0.04) and the clinical index (P = 0.04). Multiple linear regression analysis showed that naproxen and triamcinolone treatment accounted for only 16% of the variation in outcome, compared with 44% accounted for by the clinical index prior to treatment. Thus, patients with a poor pretreatment clinical index (those with the most room for improvement) were least likely to improve. We conclude that both triamcinolone (P = 0.00005) and naproxen (P = 0.02) are superior to placebo in the treatment of the painful shoulder.
Elevated plasma C3 anaphylatoxin levels in rheumatoid arthritis patients
Authors: Moxley George , Ruddy Shaun
Published: February 2007

Because synovial fluid levels of the C3 anaphylatoxins, C3a and C3a desArg, are more than 7 times higher in patients with rheumatoid arthritis (RA) than in patients with degenerative joint disease or traumatic arthritis, we conducted a prospective study of plasma levels of C3 and C5 anaphylatoxins in 11 RA patients. The mean level of C3 anaphylatoxin in 37 RA plasma specimens was twice as high as that in samples obtained from 9 normal volunteers (272.9 ± 106.1 ng/ml versus 133.9 plusmn; 19.4 ng/ml) (P<0.05). We found that the joint index and the disease activity index were correlated with the plasma C3 anaphylatoxin level, and that the correlation values were similar to those for serum C‐reactive protein level and for the Westergren erythrocyte sedimentation rate. In correlations of the joint index and disease activity index with combinations of laboratory test results, the plasma C3a level, the serum C‐reactive protein level, and the erythrocyte sedimentation rate, we found that almost any pair of laboratory tests correlated more strongly than did any one test.
Prevalence of thyroid disease and abnormal thyroid function test results in patients with systemic lupus erythematosus
Authors: Miller Frederick W. , Moore Gerald F. , Weintraub Bruce D. , Steinberg Alfred D.
Published: February 2007

Although thyroid disease has been associated with other autoimmune conditions, it is not well recognized in systemic lupus erythematosus (SLE) patients. We found that in 332 SLE patients hospitalized during a 5‐year period, the overall prevalence of diagnosed thyroid disease (7.5%) was similar to that in other female populations, but the prevalence of diagnosed hypothyroidism (6.6%) was unexpectedly high. There was also a high frequency of abnormal thyroid function test results in 175 SLE patients without diagnosed thyroid disease who underwent laboratory screening. More than 45% of these patients had elevated levels of thyroid‐stimulating hormone, 34% had low T3 determinations, and 18% had high antimicrosomal antibody titers. When patients were categorized into “functional groups,” some showed evidence of the “euthyroid sick syndrome” (15%), but many more had laboratory test results suggestive of true (5%) or incipient (39%) primary hypothyroidism. We conclude that abnormal thyroid function test results are common in patients with SLE and that hypothyroidism, especially, should be considered when evaluating symptoms and signs in SLE patients.
The effect of indication on hypersensitivity reactions associated with zomepirac sodium and other nonsteroidal antiinflammatory drugs
Authors: Strom Brian L. , Carson Jeffrey L. , Morse M.Lee , West M. Lee , Soper Keith A.
Published: February 2007

A large, computerized database derived from Medicaid claims was used to evaluate the risk of allergy and/or anaphylaxis associated with the use of nonsteroidal antiinflammatory drugs (NSAIDs) as a class and the risk associated with the use of zomepirac relative to other NSAIDs. We compared 51,797 patients exposed to NSAIDs with 35,634 age‐ and sex‐matched patients who had not been exposed. As a class, NSAIDs were associated with an adjusted relative risk (95% confidence interval) of hypersensitivity reactions of 2.0 (1.3–2.9). The increased risk was accentuated in those with a diagnosis compatible with acute pain (3.6 [2.2–5.9]) and absent in those without such a diagnosis (1.1 [0.6–1.9]). Comparison of those exposed to zomepirac with those exposed to other NSAIDs resulted in an age‐adjusted relative risk of 2.0 (1.1–4.7). Stratification by the probable indication for NSAID use again suggested that the risk may be explained by the use of the NSAIDs for different indications. We concluded that NSAIDs are associated with an increased risk of allergy and/or anaphylaxis, and the use of zomepirac appears to be associated with an increased risk compared with the use of other NSAIDs. However, that increased risk may be a function of the primary indication for the drug or, more likely, the regimen associated with that indication, rather than an intrinsic property of the drug.
Synthesis of arachidonate oxidation products by synovial joint tissues during the development of chronic erosive arthritis
Authors: Henderson B. , Higgs G. A.
Published: February 2007

An animal model, antigen‐induced arthritis in the rabbit, was used to investigate the synthesis of arachidonic acid oxidation products (eicosanoids) by tissues of the knee joints during the initiation and early phase of this developing chronic destructive lesion. High concentrations of immunoreactive prostaglandin E2 and immunoreactive leukotriene B4 were found to be present in the synovial fluid in the early lesion. These levels rapidly declined, as did the ablity of the infiltrating cells of the arthritic joint fluids to synthesize leukotriene B4. Articular cartilage and synovial lining were maintained for 24 hours in nonproliferative organ culture, and the synthesis of eicosanoids was measured by assay of the culture fluids. The synovial lining was the major source of eicosanoids. Synthesis of prostaglandin E2, prostacyclin, thromboxane A2, and leukotriene B4 by the arthritic synovial lining was low during the first few days, but reached maximal values between day 5 and day 15 of disease duration. Maximal eicosanoid production occurred around the time that damage to articular cartilage and bone has been reported to occur, though it is not certain that these two events are linked. It was demonstrated that, in chronic lesions, the arthritic synovial lining was still producing elevated levels of eicosanoids compared with levels in the control tissue.
In vivo capillary microscopy findings and ophthalmoscopy findings in scleroderma
Authors: Ranft Juergen , Lammersen Teresa , Heidrich Heinz
Published: February 2007

We used in vivo capillary microscopy to examine the nailfold capillaries of 19 patients with scleroderma (18 women and 1 man; average age 56.6), and compared these findings with those obtained using an ophthalmoscope. The ophthalmoscope revealed hemorrhages in 68% of the patients, a reduction in the number of capillaries in 79%, avascular areas in 79%, and dilated capillaries in 84%. The findings from ophthalmoscopy showed a correlation of approximately 80% with those from capillary microscopy. Since the diagnosis of scleroderma can be confirmed with this instrument, we suggest that it be used when microscopy equipment is not available.
Development of selective igm deficiency in systemic lupus erythematosus patients with disease of long duration
Authors: Saiki Osamu , Saeki Yukihiko , Tanaka Toshio , Doi Satoru , Hara Hideki , Negoro Shigeru , Igarashi Tsuyoshi , Kishimoto Susumu
Published: February 2007

Statistical analysis of serum immunoglobulin levels in 54 systemic lupus erythematosus (SLE) patients showed a decrease in serum IgM (normal 77 ± 26 mg/dl; P < 0.001) that was closely related to disease duration. The longer the duration of SLE, the more striking the decrease in serum levels of IgM (r = −0.74, P<0.01). Selective IgM deficiency (<47 mg/dl) occurred in SLE patients whose disease was clinically inactive or less active.
Circulating hyaluronic acid levels vary with physical activity in healthy subjects and in rheumatoid arthritis patients. relationship to synovitis mass and morning stiffness
Authors: Engströum‐Laurent, Anna , Hällgren Roger
Published: February 2007

We evaluated the possible influence of physical activity on serum levels of hyaluronic acid (HA), plasma levels of elastase, and serum levels of procollagen III peptide. In 15 healthy individuals, HA increased from 26 ± 9 m̈g/liter (mean ± SD) before arising from a night'S sleep to 54 ± 24 m̈g/liter 1 hour after arising and performance of normal morning activities (P < 0.001). HA in 14 patients who had inflammatory arthritis increased from 124 ± 104 m̈g/liter to 402 ± 232 m̈g/liter under the same conditions (P < 0.001). The elevation due to physical activity was significantly (P < 0.001) higher in patients with rheumatoid arthritis (RA) than that found in controls. A slight increase of HA in the afternoon was also observed in healthy subjects who performed heavy exercise, but a marked increase was seen in RA patients who performed moderate exercise. In another group of 24 RA patients, a more standardized blood sampling was performed before arising and during normal morning activities. An increase in HA was significantly (P < 0.001) correlated to the synovitis mass, estimated by the Ritchie articular index. Maximum increases of HA were seen 30 and 60 minutes after arising; thereafter, levels decreased to those measured at rest. During the morning activities, procollagen III peptide remained stable, while plasma elastase tended to increase. It is proposed that HA, produced in the joint tissue structures and accumulated at rest, is carried by the lymph vessels to the general circulation during physical activity. In RA, the more pronounced HA outflow is probably due to enhanced synthesis, and thus accumulation, of HA in the inflamed joint tissue. This may be a cause of morning stiffness, because HA that has excessively accumulated in the joint tissue could immobilize water and mechanically hinder joint movements. This hypothesis was supported by the observed relationship between the transient increase of HA and duration of morning stiffness.
Folate status of rheumatoid arthritis patients receiving long‐term, low‐dose methotrexate therapy
Authors: Morgan Sarah L. , Baggott Joseph E. , Altz‐Smith Mary
Published: February 2007

The folate status of 29 healthy control subjects, 16 rheumatoid arthritis (RA) patients taking methotrexate (MTX), and 20 RA patients who were not being treated with MTX was estimated by an assay of the folate‐dependent enzymatic synthesis of serine from formate and glycine, which is termed the C1 index. Analysis of variance demonstrated that the specific activity of the enzyme system in lymphocytes was significantly lower in the MTX‐treated group, with an activity approximately one‐half that of the control and the non—MTX‐treated groups. Since the C1 index is one of the first biochemical parameters found to be different between MTX‐treated and non—MTX‐treated groups, alterations in folate‐mediated amino acid metabolism may be involved in the mechanism of response to MTX therapy. Use of the C1 index may assist in the development of protocols which preserve the efficacy of MTX therapy while minimizing toxicity.
Quantitative defect of CD4+2H4+ cells in systemic lupus erythematosus and sjögren'S syndrome
Authors: Sato Kazuto , Miyasaka Nobuyuki , Yamaoka Kunio , Okuda Masaharu , Yata Junichi , Nishioka Kusuki
Published: February 2007

Surface antigens of T lymphocytes in peripheral blood mononuclear cells from 19 patients with systemic lupus erythematosus (SLE), 14 patients with Sjögren'S syndrome (SS), and 14 healthy control subjects were studied by 2‐color analysis. The proportion of CD4+2H4+ cells, which correspond to a suppressor/inducer subset, was decreased significantly in both SLE and SS. In contrast, the percentage of CD4+4B4+ cells, which define a helper/inducer subset, showed no significant difference among the patient groups. These data suggest that quantitative defect of suppressor/inducer cells may play an important role in the immunoregulatory disturbance in SLE and SS.
Hypermobility: features and differential incidence between the sexes
Authors: Larsson Lars‐Goran , Baum John , Mudholkar Govind S.
Published: February 2007

Six hundred sixty individuals from a music school were studied to determine the frequency of incidence and the nature of their hypermobility. They were interviewed and examined for the 5 recognized features of hypermobility (laxity of the thumbs, fingers, elbows, spine, and knees). The incidence of hypermobility, according to the number of joints involved, followed an empiric geometric law. Approximately 27% of the individuals had 1 lax joint, whereas only 3% possessed all 5 features. Specific features were present at different frequencies in the 2 sexes. The ratio of the occurrence of 2 features in women compared with the occurrence in men was 2:1. Ratios for the occurrence of 3, 4, and 5 features were 4:1, 8:1, and 3:1, respectively. Thus, hypermobility was a predominantly female characteristic. Joint laxity declined with age, although not to a statistically significant degree. In men, the decline started when they were in their mid‐twenties; however, in women, joint laxity continued through the mid‐forties.
Characteristics of responders and nonresponders to slow‐acting antirheumatic drugs in juvenile rheumatoid arthritis
Authors: Giannini Edward H. , Brewer Earl J. , Kuzmina Nina , Alekseev Lev , Shokh Boris P.
Published: February 2007

A 12‐month double‐blind, parallel, randomized, placebo‐controlled multicenter trial of D‐penicillamine and hydroxychloroquine was conducted in 162 children with juvenile rheumatoid arthritis in the United States and in the Union of Soviet Socialist Republics. No statistically significant intergroup differences were detected in primary outcome variables. We investigated the possible existence of select subgroups of patients who have a higher likelihood of response to active drugs than to placebo. Using previously published criteria, each patient was classified as a responder or nonresponder, and their demographic and disease characteristics at baseline were compared. We were unable to identify a subgroup of individuals who were more likely to respond to D‐penicillamine or hydroxychloroquine than to placebo.
Antioxidant activity of synovial fluid, hyaluronic acid, and two subcomponents of hyaluronic acid. synovial fluid scavenging effect is enhanced in rheumatoid arthritis patients
Authors: Sato Hideki , Takahashi Terumi , Ide Hirotsugu , Fukushima Toshiyuki , Tabata Minoru , Sekine Fusao , Kobayashi Kazuo , Negishi Masao , Niwa Yukie
Published: February 2007

To test the scavenging of reactive oxygen species (ROS), we added synovial fluids from patients with rheumatoid arthritis (RA) and osteoarthritis, as well as hyaluronic acid (HA) and its 2 subcomponents, D‐glucuronic acid and N‐acetyl‐D‐glucosamine, to 2 ROS‐generating systems, activated neutrophils and xanthine‐xanthine oxidase. Synovial fluid from RA patients, HA, and D‐glucuronic acid markedly decreased the O2‐, H2O2, OH‐, and chemiluminescence measured in both systems. HA and synovial fluid, which are known to be susceptible to degradation by excessive ROS in RA patients, also seem to play an active role in protecting articular tissues from oxidative damage.
Identification of brain lesions in neuropsychiatric systemic lupus erythematosus by magnetic resonance scanning
Authors: Mccune W. Joseph , Macguire Anne , Aisen Alex , Gebarski Stephen
Published: February 2007

Cranial magnetic resonance imaging in 28 systemic lupus erythematosus patients who had experienced 30 acute neuropsychiatric events showed focal brain lesions in 16 of 30 events (53%) and low brain volume (atrophy) in 20 of 30 events (67%). Definite focal lesions were significantly more frequent in patients with clinically localized neurologic deficits (8 of 8, 100%), or seizures (5 of 6, 83%) than in patients without such localizing signs (3 of 16, 19%). Many of these lesions were occult on intravenous contrast‐enhanced x‐ray computed tomography. In 2 patients, lesions in gray matter resolved within 2 or 3 weeks, in association with clinical improvement. Magnetic resonance imaging is an important technique for detecting the extent of brain injury in cerebral lupus.