bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of psychosocial adjustment in systemic sclerosis
Authors: Moser Debra K. , Clements Philip J. , Brecht Mary‐Lynn , Weiner Steven R.
Published: February 2007

Objective.To determine predictors of psychosocial adjustment in patients with systemic sclerosis (SSc).

Methods.We surveyed 94 patients with SSc. Age, sex, education level, marital status, work status, income, support group attendance, length of time since diagnosis, functional status, social support, illness‐related uncertainty, and hardiness were examined as potential predictors of psychosocial adjustment. The reliability and validity of the instruments used to measure these variables have been established.

Results.Only education level, functional ability, illness‐related uncertainty, hardiness, and social support were predictive of psychosocial adjustment. Education level and functional ability explained 14% of the variance in psychosocial adjustment, while illness‐related uncertainty, hardiness, and social support increased the explained variance to 38%.

Conclusion.Although patients with relatively poorer psychosocial adjustment to illness have lower formal education levels and more functional disability, the majority of the explained variance in psychosocial adjustment is ascribable to illness‐related uncertainty, low level of hardiness, and less satisfaction with social support.
Autoantigenic epitopes on dna topoisomerase i
Authors: Kuwana Masataka , Kaburaki Junichi , Mimori Tsuneyo , Tojo Takeshi , Homma Mitsuo
Published: February 2007

Objective. To elucidate the clinical and immunogenetic associations with reactivity to autoantigenic epitopes on DNA topoisomerase I (topo I) recognized by sera from patients with systemic sclerosis (SSc).

Methods. Autoantigenic epitopes on topo I were identified by screening an epitope library constructed from topo I complementary DNA restriction fragments using autoimmune anti–topo I–positive sera as a probe. Epitope reactivities of sera from 43 anti–topo I–positive SSc patients were surveyed by immunoblotting, and associations with clinical symptoms and HLA–DR types were examined.

Results. Four different epitope regions were identified on the topo I molecule. Immunoreactivity to the region encompassing amino acid residues 658–700, termed ER4, was found to be associated with diffuse cutaneous SSc, progressive pulmonary interstitial fibrosis, and poor prognosis for 15‐year survival. SSc patients with ER4 reactivity frequently displayed the DR2/DRw52 phenotype.

Conclusion. Molecular analysis of precise antigenic epitopes on topo I is helpful in classifying clinical subsets of SSc.
Modulation of human t cell responses by nitric oxide and its derivative, s‐nitrosoglutathione
Authors: Merryman Parvin F. , Clancy Robert M. , He Xiao Yuen , Abramson Steven B.
Published: February 2007

Objective. To examine the effects of nitric oxide (NO) and its more stable derivative, S‐nitrosoglutathione (SNO‐GSH), on the response of activated T lymphocytes.

Methods. The effects of NO and SNO‐GSH on DNA synthesis, interleukin‐2 (IL‐2) production, IL‐2 receptor expression, and cGMP accumulation were determined in phytohemagglutinin–activated peripheral blood mononuclear cells (PBMC) and spleen T cells.

Results. Nitric oxide (half‐life [T1/2] < 15 seconds) did not inhibit T cell proliferation. However, the derivative SNO‐GSH (25 μM) (T1/2 >2 hours) inhibited DNA synthesis by a mean ± SD of 65 ± 19.6% (P < 0.001) in PBMC and 75 ± 15% (P < 0.001) in spleen cells. Macrophage depletion of PBMC did not abrogate the inhibition. SNO‐GSH had no effect on IL‐2 production or IL‐2 receptor expression. NO (25 μM) increased the cGMP content of PBMC (0.65 ± 0.15 pmoles/106 cells; P < 0.04), as did SNO‐GSH (25 μM) in both PBMC (3.8 ± 1; P < 0.001) and spleen T cells (5.2 ± 1.2; P < 0.001). Methylene blue and hemoglobin, which are NO inhibitors, inhibited SNO‐GSH–induced cGMP accumulation (P < 0.001).

Conclusion. SNO‐GSH inhibits T cell DNA synthesis independently of IL‐2 production and in association with cGMP accumulation via a NO‐dependent mechanism. We suggest that NO and its S‐nitrosothiol derivatives may act as endogenous inhibitors of T cell–mediated inflammation.
Detection of human t lymphotropic virus type i tax gene in salivary gland epithelium from two patients with sjögren's syndrome
Authors: Mariette Xavier , Agbalika Felix , Daniel Marie‐ThéRèSe , Bisson Michel , Lagrange Philippe , Brouet Jean‐Claude , Morinet Frédéric
Published: February 2007

Objective. To investigate whether human T lymphotropic virus type I (HTLV‐I) could be involved in the pathogenesis of Sjögren's syndrome (SS).

Methods. Labial salivary gland (LSG) biopsy specimens from 9 patients with SS (4 with primary SS and 5 with SS secondary to rheumatoid arthritis) and 9 controls were studied for the presence of the tax gene of HTLV‐I using in situ hybridization, and for the presence of tax, gag, pol, and env genes of HTLV‐I using the polymerase chain reaction (PCR). Testing for antibodies to HTLV‐I and examination of lymphocytes on blood smears were performed to determine whether systemic viral infection was present.

Results. Using in situ hybridization and PCR, we detected the tax gene, but not the gag, pol, or env genes, of HTLV‐I in LSG sections from 2 of 9 patients with SS and from none of the control subjects. Tax DNA was present mostly in nuclei of epithelial cells, but also in some lymphoid cells. Serum of the 2 affected patients did not contain antibodies to HTLV‐I. In 1 patient, examination of blood smears revealed rare convoluted lymphocytes, sometimes with the appearance of “flower cells,” as observed in the blood of HTLV‐I–infected patients.

Conclusion. None of the known endogenous retroviral sequences is homologous to the tax gene. Thus, we suggest that HTLV‐I (or another related retrovirus) can infect salivary epithelium. Transactivation properties of the tax protein could be implicated in the pathogenesis of SS. Alternatively, viral infection could cause de novo expression of HLA–DR antigens and favor the presentation of antigens by epithelial cells, leading, in some genetically predetermined subjects, to lymphoid infiltration of the gland.
A longitudinal study of subchondral plate and trabecular bone in cruciate‐deficient dogs with osteoarthritis followed up for 54 months
Authors: Dedrick D. K. , Goldstein S. A. , Brandt K. D. , O'Connor B. L. , Goulet R. W. , Albrecht M.
Published: February 2007

Objective. To evaluate the sequence of changes in articular cartilage, trabecular bone, and subchondral plate in dogs with osteoarthritis (OA), 3 months, 18 months, and 54 months after anterior cruciate ligament transection (ACLT).

Methods. Specimens of the medial tibial plateau were analyzed with microscopic computed tomography (micro‐CT) at a resolution of 60 μm, and biochemical and morphologic changes in the femoral articular cartilage were assessed.

Results. At 3 months and 18 months after ACLT, the articular cartilage in the unstable knee showed histologic changes typical of early OA and increased water content and uronic acid concentration; by 54 months, full‐thickness ulceration had developed. Micro‐CT analysis showed a loss of trabecular bone in the unstable knee, compared with the contralateral knee, at all time points. At both 18 and 54 months, the differences in trabecular thickness and surface‐to‐volume ratio were greater than at 3 months. Although the mean subchondral plate thickness, especially in the medial aspect of the medial tibial plateau, was greater in the OA knee than in the contralateral knee 18 months and 54 months after ACLT, these differences were not statistically significant; however, the difference was significantly greater at 54 months than at 3 months.

Conclusion. Thickening of the subchondral bone is not required for the development of cartilage changes of OA in this model. The bony changes that develop after ACLT, however, could result in abnormal transmission of stress to the overlying cartilage and thereby contribute to the progression of cartilage degeneration.
Calcific tendinitis in the proximal thigh
Authors: Hodge Jacqueline C. , Schneider Robert , Freiberger Robert H. , Magid Steven K.
Published: February 2007

Calcific tendinitis of the proximal thigh is a benign entity that may cause significant pain. It must be distinguished from chronic or malignant disorders, such as arthritis, infection, and soft tissue/cortical neoplasms. Although it may be self‐limited, some patients will benefit from medical intervention. In such cases, we recommend computed tomography–guided percutaneous steroid injection. Herein we describe the clinical and radiographic features of calcific tendinitis of the proximal thigh in 5 patients.
“Chronic lyme disease” as the incorrect diagnosis in patients with fibromyalgia
Authors: Hsu Vivien M. , Patella Sondra J. , Sigal Leonard H.
Published: February 2007

Objective. To evaluate a large number of patients referred with persistent symptoms thought to represent chronic Lyme disease.

Methods. We retrospectively reviewed the charts of nearly 800 patients referred with persisting nonspecific musculoskeletal and/or neurologic symptoms thought to represent chronic Lyme disease.

Results. Seventy‐seven patients were found to have fibromyalgia, not ongoing Lyme disease, as the explanation of their chronic symptoms. Many had received multiple courses of antibiotic therapy for symptoms of fibromyalgia mistakenly attributed to chronic Lyme disease. No patient reported permanent and/or total resolution of fibromyalgia symptoms following antibiotic therapy. Appropriate therapy for fibromyalgia in those who remained compliant, however, was often effective in improving some if not all of the chronic symptoms.

Conclusion. Fibromyalgia is a treatable and potentially curable disorder, and should be considered in the evaluation of patients with “refractory Lyme disease.”
Sulfasalazine in early rheumatoid arthritis. A 48‐week double‐blind, prospective, placebo‐controlled study
Authors: Hannonen Pekka , Möttönen Timo , Hakola Mikko , Oka Martti
Published: February 2007

Objective.To investigate the efficacy and tolerability of sulfasalazine (SSZ) in the treatment of early rheumatoid arthritis (RA).

Methods.Eighty patients (symptomatic disease < 12 months) were randomly assigned to treatment with SSZ or placebo for 48 weeks. Clinical, laboratory, and scintigraphic data were used to determine the effects of treatment.

Results.SSZ was superior to placebo in reducing the laboratory features of inflammation, the clinical parameters of disease activity, as well as the scintigraphic activity in the joints. Furthermore, fewer erosive changes developed in the joints of patients receiving active treatment, but the difference between treatment groups did not reach statistical significance.

Conclusion.SSZ is effective in the treatment of RA, and its onset of action is rapid. The results support the view that SSZ retards the development of joint erosions. However, like other conventional disease‐modifying antirheumatic drugs, its remission‐inducing ability is insufficient.
The effect of rheumatoid arthritis and steroid therapy on bone density in postmenopausal women
Authors: Hall Gerard M. , Spector Tim D. , Jane Griffin A. , S. M. Jawad Ali , Hall Margaret L. , Doyle David V.
Published: February 2007

Objective. To assess bone mineral density (BMD) in postmenopausal women with rheumatoid arthritis (RA) and the relative effects of disease activity, disability, and past and current use of corticosteroids.

Methods. One hundred ninety‐five postmenopausal patients with RA were compared with 597 postmenopausal control subjects. Bone density was measured at the lumbar spine and the proximal femur using dual x‐ray absorptiometry. Patients were divided into 3 groups according to corticosteroid use, i.e., never users (61%), current users (21%), and ex‐users (18%).

Results. Compared with controls, the never users had no difference in BMD at the lumbar spine, but a 6.9% reduction at the femur (95% confidence interval [95% CI] 3.4–10.3%). In current users (mean daily prednisolone dosage 6.9 mg), BMD was reduced by 6.5% at the spine (95% CI 0–13.0%) and by 7.4% at the hip (95% CI 1.2–13.6%) compared with never users, after adjustment for age, weight, duration of menopause, and functional disability. Mean BMD was similar in the ex‐user and never user groups. Results were confirmed in 54 patients who had whole‐body BMD measurements. There were inverse correlations between BMD and Health Assessment Questionnaire scores (femoral BMD r = –0.23, P < 0.01; whole‐body BMD r = –0.40, P < 0.01) and between BMD and cumulative steroid dose (femoral BMD r = –0.32, P < 0.01; whole‐body BMD r = –0.72, P < 0.01).

Conclusion. Osteoporosis in postmenopausal women with RA is more evident at the hip than the spine, and the most important determinants of bone loss are disability and cumulative corticosteroid dose. Low‐dose steroids cannot be used with complacency, but recovery after discontinuation of use may be possible.
Up‐regulation by tumor necrosis factor α of intercellular adhesion molecule 1 expression and function in synovial fibroblasts and its inhibition by glucocorticoids
Authors: Bsc Philippe Tessier, , Audette Marie , Bsc Paola Cattaruzzi, , Mccoll Shaun R.
Published: February 2007

Objective. To examine the regulation of the intercellular adhesion molecule 1 (ICAM‐1) gene in cultured human synovial fibroblasts in response to tumor necrosis factor α (TNFα), and investigate its modulation by the synthetic glucocorticoid, dexamethasone.

Methods. Cell surface expression of ICAM‐1 was determined by flow cytometry, enzyme immunoassay, and immunoprecipitation. ICAM‐1 messenger RNA (mRNA) levels were monitored by Northern blot. ICAM‐1 function was determined by measuring the adhesion of monocytes to synovial fibroblasts.

Results. ICAM‐1 expression on unstimulated cells was weak but was rapidly enhanced in both a time‐ and dose‐dependent manner following exposure to TNFα. Treatment of the cells with TNFα also resulted in both a time‐ and dose‐dependent increase in steady‐state ICAM‐1 mRNA levels, as determined by Northern blot. The increased expression of ICAM‐1 was inhibited by cycloheximide and actinomycin D. Cultured synovial fibroblasts from patients with rheumatoid and nonrheumatoid arthropathies responded similarly to TNFα. Adhesion studies demonstrated that ICAM‐1 is involved in the adherence of peripheral blood monocytes to TNFα‐activated synovial fibroblasts. In addition, dexamethasone inhibited TNFα‐induced surface expression of ICAM‐1, accumulation of ICAM‐1 mRNA, and adhesion of monocytes to TNFα‐activated synovial fibroblasts.

Conclusion. These combined results provide further evidence of an important role of ICAM‐1 in inflammatory synovitis, as well as a potentially novel site of antiinflammatory action of glucocorticoids.
Differential in vivo expression of collagenase messenger RNA in synovium and cartilage. Quantitative comparison with stromelysin messenger rna levels in human rheumatoid arthritis and osteoarthritis patients and in two animal models of acute inflammatory arthritis
Authors: Wolfe Ms Gloria C. , , Macnaul Bs Karen L. , , Buechel Frederick F. , Mcdonnell Joseph , Hoerrner Bs Lori A. , , Lark Michael W. , Moore Vernon L. , Hutchinson Nancy I.
Published: February 2007

Objective. To compare quantitatively the in vivo expression of collagenase messenger RNA (mRNA) and stromelysin mRNA in the joint tissues of human osteoarthritis (OA) and rheumatoid arthritis (RA) patients and in two animal models of acute inflammatory arthritis.

Methods. In vivo levels of metalloproteinase mRNA and protein were determined by quantitative Northern hybridization and by enzyme‐linked immunosorbent assay, respectively.

Results. In synovium, mean levels of collagenase mRNA were similar to those of stromelysin mRNA; however, in cartilage, mean levels of collagenase mRNA were significantly lower. The ratios of collagenase mRNA to stromelysin mRNA levels in RA and OA cartilage reflected similar ratios of collagenase protein to stromelysin protein levels in synovial fluid.

Conclusion. The regulation of collagenase mRNA expression in cartilage is distinct from that of stromelysin, suggesting distinct roles for these two metalloproteinases in normal and abnormal physiologic functioning of cartilage.
A distinctive autoantibody profile in black female patients with lupus nephritis
Authors: Mccarty G. A. , Harley J. B. , Reichlin M.
Published: February 2007

Objective. Lupus nephritis has often been associated with anti‐DNA, but, based on the findings in eluate studies, it appears that other antigen–antibody reactions, such as those involving anti–Ro/SS‐A, antinuclear RNP (anti‐nRNP), and/or anti‐Sm, may also contribute to the pathogenesis of nephritis. In the present investigation, we identified and further studied a distinctive precipitin profile present in black women with nephritis.

Methods. Longitudinal clinical and serologic studies of a cohort of university‐based systemic lupus erythematosus (SLE) patients (n = 120) were carried out over an 8‐year period.

Results. A subset of 20 black female patients was identified, of whom 8 had lupus nephritis (group I) and 12 did not (group II). Group I was characterized by a distinct precipitin profile consisting of anti–Ro/SS‐A, anti‐Sm, and anti‐nRNP, but no anti–La/SS‐B. SLE disease duration at presentation was significantly shorter in group I than in group II (mean 1.94 years versus 5.21 years; P = 0.02). The distinctive precipitin profile of anti–Ro/SS‐A, anti‐Sm, and anti‐nRNP occurred exclusively in group I patients (6 of 8, versus 0 of 12 in group II; P < 0.001). In white lupus nephritis patients, this precipitin profile was not seen.

Conclusion. While the mechanism responsible for the relationship of this distinctive serologic profile to the development of nephritis in black female lupus patients remains to be determined, its presence may be used as a marker for severe and progressive renal disease.
Low levels of total cholesterol, high‐density lipoprotein, and apolipoprotein a1 in association with anticardiolipin antibodies in patients with systemic lupus erythematosus
Authors: Lahita R. G. , Rivkin E. , Cavanagh Ms I. , , Romano P.
Published: February 2007

Objective. To determine if there is an association between low levels of high‐density lipoprotein cholesterol (HDL), apolipoprotein A1 (Apo A1), total cholesterol, and anticardiolipin antibody (aCL) in patients with systemic lupus erythematosus (SLE) who are not taking corticosteroids.

Methods. We studied 75 outpatients with documented SLE who were attending our hospital clinics: 57 were aCL positive and 18 were aCL negative. Both IgG and IgM aCL levels were determined by enzyme‐linked immunosorbent assay. Lipid fractions (total cholesterol, HDL, low‐density lipoprotein, very–low‐density lipoprotein, and triglycerides) were determined by standard enzymatic techniques. Apo A1 and Apo B levels were determined by nephelometry.

Results. Patients with SLE who were IgG aCL + had low levels of serum cholesterol (mean ± SD 173.6 ± 34.6 mg/dl) and HDL (43.9 ± 16.3 mg/dl) compared with aCL– SLE patients, normal donors, and patients with other diseases. Apo A1 levels were also low in the aCL + group (95.5 ± 50.9 mg/dl) compared with the aCL– group (152.7 ± 32.6 mg/dl). There was no association of total cholesterol level or aCL titer with clinical activity.

Conclusion. These data indicate that in SLE patients, there is an association between antibody against the phospholipid cardiolipin and low levels of cholesterol, HDL, and Apo A1.
IDENTIFICATION OF A UNIVERSAL B CELL EPITOPE ON DNA TOPOISOMERASE I, AN AUTOANTIGEN ASSOCIATED WITH SCLERODERMA
Authors: Kato Tomohiro , Yamamoto Kazuhiko , Takeuchi Hajime , Okubo Mitsuo , Hara Eiji , Nakada Susumu , Oda Kinichiro , Ito Koji , Nishioka Kusuki
Published: February 2007

Objective. To investigate the distribution of B cell autoepitopes of human DNA topoisomerase I (topo I), an autoantigen associated with scleroderma.

Methods. A complementary DNA clone, T1B, was used to produce recombinant proteins of topo I as β‐galactosidase fusion proteins. Immunoreactivity to these fusion proteins was then tested in 35 anti–topo I–positive sera from patients with scleroderma, by immunoblotting, enzyme‐linked immunosorbent assay, and double immunodiffusion.

Results. One epitope was found to be universally recognized by all sera tested. Thirty‐two of the samples recognized multiple antigenic regions, but sera from the remaining 3 patients recognized only this universal epitope, and in longitudinal studies of 1 of these 3 patients, the serum recognized only this epitope for more than 2 years, even though multiple, potent, antigenic regions were found on topo I.

Conclusion. Recognition of multiple epitopes in most patients suggests that the topo I molecule itself would drive the autoimmunity on topo I. However, antigen‐driven autoimmunity could not explain the production of the monoreactive anti–topo I antibody seen in the 3 patients. We thus hypothesize that there is a process whereby recognition of the universal epitope by cross‐reaction develops into antigen‐driven autoimmunity.
Phosphocitrate prevents disease progression in murine progressive ankylosis
Authors: Krug Hollis E. , Mahowald Maren L. , Halverson Paul B. , Sallis John D. , Cheung Herman S.
Published: February 2007

Objective. Mice with progressive ankylosis, a spontaneous arthropathy, were treated with phosphocitrate (PC) in vivo to determine the effect of PC on disease progression.

Methods. Two groups of mice with progressive ankylosis (matched for age, weight, and sex) were treated parenterally for 6 weeks with either PC or saline vehicle.

Results. Clinically, histologically, and microradiographically, there were significant differences in disease progression and severity in the PC‐treated and the saline‐treated mice.

Conclusion. PC appears to inhibit disease progression in murine progressive ankylosis.
Persistence of borrelia burgdorferi in ligamentous tissue from a patient with chronic lyme borreliosis
Authors: Häupl Thomas , Hahn Gabriele , Rittig Michael , Krause Andreas , Schoerner Christoph , Schönherr Ulrich , Kalden Joachim R. , Burmester Gerd R.
Published: February 2007

Objective. To document the persistence of Borrelia burgdorferi in ligamentous tissue samples obtained from a woman with chronic Lyme borreliosis.

Methods. Spirochetes were isolated from samples of ligamentous tissue, and the spirochetes were characterized antigenetically and by molecular biology techniques. The ligamentous tissue was examined by electron microscopy. Humoral and cellular immune responses were analyzed.

Results. Choroiditis was the first recognized manifestation of Lyme disease in this patient. Despite antibiotic therapy, there was progression to a chronic stage, with multisystem manifestations. The initially significant immune system activation was followed by a loss of the specific humoral immune response and a decrease in the cellular immune response to B burgdorferi over the course of the disease. “Trigger finger” developed, and a portion of the flexor retinaculum obtained at surgery was cultured. Viable spirochetes were identified. Ultramorphologically, the spirochetes were situated between collagen fibers and along fibroblasts, some of which were deeply invaginated by these organisms. The cultured bacteria were identified as B burgdorferi by reactions with specific immune sera and monoclonal antibodies, and by polymerase chain reaction amplification and Southern blot hybridization techniques.

Conclusion. To our knowledge, this is the first report of the isolation of B burgdorferi from ligamentous tissue. This suggests that tendon tissues serve as a specific site of spirochete residence in human hosts.
Bronchiolitis obliterans organizing pneumonia associated with essential mixed cryoglobulinemia
Authors: Zackrison Leila H. , Katz Paul
Published: February 2007

Bronchiolitis obliterans organizing pneumonia (BOOP) is an uncommon and underrecognized pathologic finding observed in a variety of syndromes including connective tissue diseases. Although lung involvement in essential mixed cryoglobulinemia (EMC) has been reported, there are no previous reports of BOOP in EMC. We report herein a case of longstanding EMC associated with interstitial and cavitary lung disease histologically consistent with BOOP. A theory of a possible etiologic basis for the development of BOOP in patients with connective tissue diseases is discussed.
Bone mineral density and knee osteoarthritis in elderly men and women. the framingham study
Authors: Hannan Marian T. , Anderson Jennifer J. , Zhang Yuqing , Levy Daniel , Felson David T.
Published: February 2007

Objective. To examine the possible inverse relationship between osteoporosis and osteoarthritis (OA) by evaluating the association between bone mineral density (BMD) and knee OA in the Framingham Study cohort.

Methods. Of the 1,154 Framingham Study cohort subjects in whom BMD measurements were obtained at biennial examination 20, 932 (81%) had had knee OA assessed during the Framingham Knee OA Study 4 years earlier. BMD of the proximal femur and radius was measured by densitometry. Knee OA was assessed from a weight‐bearing anteroposterior radiograph and graded on a scale of 0 (no OA) to 4 (severe OA). Osteophytes and joint space narrowing were also evaluated separately. Linear regression was used to test the association of BMD with knee OA, with osteophytes, and with joint space narrowing, after adjustment for age, body mass index, and mean number of cigarettes smoked per day.

Results. The subjects included 572 women and 360 men with an age range of 63–91 years (mean 71 years). Of these, 351 had no OA, 269 had grade 1 OA, 170 had grade 2 OA, 93 had grade 3 OA, and 49 had grade 4 OA. Mean femoral BMD at the 3 proximal femur sites was 5–9% higher in men and women with either grade 1, grade 2, or grade 3 knee OA, compared with those with no knee OA (P < 0.0001). Mean femoral BMD in those with grade 4 OA was not higher than in those with no OA. Radius BMD was not associated with knee OA in subjects of either sex. Women with osteophytes had higher BMD compared with women with no osteophytes. Mean BMD did not differ across levels of joint space narrowing.

Conclusion. We conclude that, among women, femoral BMD is higher in those with osteophytosis of the knee, and BMD is not necessarily associated with joint space narrowing.
Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor α
Authors: Elliott Michael J. , Maini Ravinder N. , Feldmann Marc , Long‐Fox Alice , Charles Peter , Katsikis Peter , Brennan Fionula M. , Walker Jean , Bijl Hanny , Ghrayeb John , Woody James N.
Published: February 2007

Objective. To evaluate the safety and efficacy of a chimeric monoclonal antibody to tumor necrosis factor α (TNFα) in the treatment of patients with rheumatoid arthritis (RA).

Methods. Twenty patients with active RA were treated with 20 mg/kg of anti‐TNFα in an open phase I/II trial lasting 8 weeks.

Results. The treatment was well tolerated, with no serious adverse events. Significant improvements were seen in the Ritchie Articular Index, which fell from a median of 28 at study entry to a median of 6 by week 6 (P < 0.001), the swollen joint count, which fell from 18 to 5 (P < 0.001) over the same period, and in the other major clinical assessments. Serum C‐reactive protein levels fell from a median of 39.5 mg/liter at study entry to 8 mg/liter at week 6 (P < 0.001), and significant decreases were also seen in serum amyloid A and interleukin‐6 levels.

Conclusion. Treatment with anti‐TNFα was safe and well tolerated and resulted in significant clinical and laboratory improvements. These preliminary results support the hypothesis that TNFα is an important regulator in RA, and suggest that it may be a useful new therapeutic target in this disease.
The effect of long‐term methotrexate therapy on hepatic fibrosis in rheumatoid arthritis
Authors: Bjorkman David J. , Boschert Mark , Tolman Keith G. , Clegg Daniel O. , Ward John R.
Published: February 2007

Objective. To evaluate the progression of hepatic fibrosis in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX).

Methods. Fifteen patients receiving MTX for RA were prospectively studied by electron microscopic analysis of biopsy specimens.

Results. Five of the 15 patients had evidence of increased hepatic collagen after 2 years of MTX therapy.

Conclusion. Hepatic fibrosis may progress in a subgroup of RA patients treated with MTX.
Inhibition of cartilage proteoglycan release by a specific inactivator of cathepsin b and an inhibitor of matrix metalloproteinases. evidence for two converging pathways of chondrocyte‐mediated proteoglycan degradation
Authors: Buttle David J. , Handley Christopher J. , Ilic Mirna Z. , Saklatvala Jeremy , Murata Mitsuo , Barrett Alan J.
Published: February 2007

Objective. To investigate mechanisms of cartilage matrix destruction by a study of the effects of a specific inactivator of cathepsin B and an inhibitor of several matrix metalloproteinases (MMP) on cartilage proteoglycan release.

Methods. Cartilage explants were treated with either recombinant human interleukin‐1α (rHuIL‐1α) or retinoic acid in the presence or absence of the inhibitors, and proteoglycan release was quantitated. Tests for nonspecific effects of the inhibitors included reversibility, rates of protein synthesis and glycolysis, and effects on other rHuIL‐1α–mediated events.

Results. The cathepsin B inactivator inhibited rHuIL‐1α–stimulated proteoglycan release at nanomolar concentrations, but failed to significantly inhibit retinoic acid–stimulated proteoglycan release. An inhibitor of MMP was inhibitory to both rHuIL‐1α–stimulated release and retinoic acid–stimulated release.

Conclusion. Cathepsin B is implicated in rHuIL‐1α–stimulated loss of cartilage proteoglycan. Its lack of involvement in retinoic acid–stimulated proteoglycan release suggests the existence of at least 2 pathways of cartilage proteoglycan breakdown, which may converge at the activation of a matrix prometalloproteinase.
Loss of trabecular bone mineral density in systemic lupus erythematosus
Authors: Kalla Asgar Ali , Fataar Abdul Basier , Jessop Susan Jane , Bewerunge Linda
Published: February 2007

Objective. To evaluate trabecular bone mineral density (BMD) in young ambulatory female patients with systemic lupus erythematosus (SLE).

Methods. Bone mineral density (gm/cm2) at the lumbar vertebrae (L1–L4) and at the left femur (neck, trochanter, intertrochanter, and Ward's triangle) was measured by dual x‐ray absorptiometry in 46 SLE patients (mean age 31 years, mean disease duration 76 months) and in 108 healthy female controls (mean age 32 years). Twenty‐two of the SLE patients were receiving corticosteroids (CS) at the time of the study.

Results. Lumbar BMD in the SLE patients was less severely reduced than was BMD at the femoral sites, but the SLE group was closer to the lumbar fracture threshold of 0.812 gm/cm2 than was the control group (P = 0.0009). There were no significant differences between the SLE patients currently being treated with corticosteroids and those who were not (P > 0.3). BMD at Ward's triangle and at the femoral neck was not significantly reduced in the SLE patients. Total femoral BMD had a sensitivity of 76% and specificity of 62% in differentiating the SLE group from the controls. The positive predictive value was 61% and the negative predictive value was 89%. The prevalence of osteopenia in the SLE patients was 25%.

Conclusion. SLE causes significant trabecular bone loss, which is not due to corticosteroid therapy.
Sjögren's syndrome presenting as hypokalemic periodic paralysis
Authors: Dowd James E. , Lipsky Peter E.
Published: February 2007

We describe a 21‐year‐old Hispanic woman who presented with hypokalemic paralysis as the initial manifestation of Sjögren's syndrome (SS). Our review of the English literature revealed 12 previously reported cases of SS and renal tubular acidosis (RTA). Paralysis often preceded the sicca complex in those patients. Renal function in the patients with hypokalemic paralysis was reduced compared with that in patients who had primary SS and RTA but no history of hypokalemic paralysis (P < 0.002). Hypokalemic periodic paralysis is a rare manifestation of SS. It is seen more often in patients with primary SS, may precede the classic sicca complex, and may serve as a clinical marker for more severe renal disease in patients who have primary SS and RTA.
Systemic lupus erythematosus in a rhesus macaque
Authors: Anderson Scott T. , Klein Edwin C.
Published: February 2007

We describe the clinical course and histopathologic findings in a rhesus macaque (Macaca mulatta) which developed a systemic inflammatory disorder resembling systemic lupus erythematosus (SLE). The manifestations of the SLE included antinuclear antibody, hemolytic anemia, membranoproliferative glomerulonephritis, and arthritis. To our knowledge, spontaneously occurring SLE has not previously been described in nonhuman primates.
Idiopathic inflammatory myopathy of the antisynthetase (jo‐1) type associated with noncaseating granulomas
Authors: Moder Kevin G. , Gaffey Thomas A. , Matteson Eric L.
Published: February 2007

The idiopathic inflammatory myopathies are a heterogeneous group of syndromes that share the finding of chronic muscle inflammation. Recently, serologic subtyping of autoantibodies found in patients with these syndromes has been used to identify distinct clinical entities. We describe a 36‐year‐old woman who, based on the findings of polymyositis documented by both electromyography and muscle biopsy, features of Raynaud's phenomenon, symmetric polyarthritis, “mechanic's hands,” and Jo‐1 antibody positivity, was considered to have the antisynthetase subset of idiopathic inflammatory myopathy. In addition, the patient had granulomatous synovitis, and noncaseating granulomas were found in a breast nodule. This is the first published report of granuloma formation in the antisynthetase syndrome.
Comparison of Amitriptyline, Cyclobenzaprine, and Placebo in the Treatment of Fibromyalgia
Authors: Carette Simon , Bell Mary J. , Reynolds W. John , Haraoui Boulos , Mccain Glenn A. , Bykerk Vivian P. , Edworthy Steven M. , Baron Murray , Koehler Barry E. , Fam Adel G. , Bellamy Nicholas , Guimont Chantal
Published: February 2007

Objective. To compare the relative efficacy and tolerability of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia, and to identify predictors of response to amitriptyline and cyclobenzaprine.

Methods, Two hundred eight patients who fulfilled the American College of Rheumatology criteria for the classification of fibromyalgia were entered into a 6‐month prospective, double‐blind, multicenter trial and were randomized to 1 of 3 treatment groups: amitriptyline, cyclobenzaprine, or placebo.

Results. After 1 month, 21%, 12%, and 0% of the amitriptyline, cyclobenzaprine, and placebo patients, respectively, had significant clinical improvement (amitriptyline versus placebo P = 0.002, cyclobenzaprine versus placebo P = 0.02, amitriptyline versus cyclobenzaprine P not significant). These percentages increased to 36%, 33%, and 19%, respectively, at the 6‐month assessment (P not significant). The nature and frequency of side effects reported by patients treated with amitriptyline and those reported by patients treated with cyclobenzaprine were similar. A normal Minnesota Multiphasic Personality Inventory (MMPI) profile at baseline was predictive of clinical improvement at the 1‐month evaluation (odds ratio 3.3, 95% confidence interval 1.2—9.0). However, neither the MMPI profile nor any of the demographic, clinical, or functional parameters evaluated at baseline predicted long‐term response.

Conclusion. Our data confirm the short‐term efficacy of amitriptyline and cyclobenzaprine in a small percentage of patients with fibromyalgia. Long‐term efficacy could not be demonstrated because of a higher‐than‐expected placebo response. Predictors of response to these drugs could not be determined.
Objective and Subjective Sleep Disturbances in Patients with Rheumatoid Arthritis
Authors: Hirsch Marco , Carlander Bertrand , Vergé Monick , Tafti Mehdi , Anaya Juan‐Manuel , Billiard Michel , Sany Jacques
Published: February 2007

Objective. To assess objective and subjective evidence of sleep disturbances in patients with rheumatoid arthritis (RA) and to examine correlations between parameters of inflammatory activity and sleep pathology.

Methods. Nineteen RA patients and 19 age‐matched healthy control subjects underwent all‐night polysomnography on 2 consecutive nights. RA patients were also evaluated for daytime sleepiness by mean sleep latency test and responded to a self‐report questionnaire on their first night.

Results. Whereas normal sleep architecture is conserved in RA, we confirmed former findings of severe sleep fragmentation and an enhanced presence of primary sleep disorders. No correlation exists between RA activity and the sleep disorders. Subjective assessment was not consistent with the objective evidence of sleep disruption, unlike the findings in patients with fibrositis.

Conclusion. Sleep is severly disturbed in patients with RA, regardless of the inflammatory disease activity. the specificity of the sleep disorders assessed needs confirmation, as does specific sleep therapy for these patients.
Interleukin‐2 Receptor Levels in the Sera of Rheumatoid Arthritis Patients Treated with Methotrexate
Authors: Polisson Richard P. , Dooley Mary Anne , Dawson Deborah V. , Pisetsky David S.
Published: February 2007

Objective. To evaluate the association of the level of soluble serum interleukin‐2 receptor (sIL‐2R) with disease activity and response to therapy in patients with rheumatoid arthritis (RA).

Methods. The sIL‐2R levels of 148 patients with refractory RA were determined by enzyme‐linked immunosorbent assay. This parameter was correlated with other clinical observations obtained during a prospective, randomized, placebo‐controlled trial of methotrexate, sponsored by the Cooperative Systematic Studies of Rheumatic Diseases consortium. Using statistical modeling, the usefulness of sIL‐2R as a measure of disease activity and a predictor of outcome was evaluated.

Results. The mean sIL‐2R level in all RA patients was markedly elevated compared with that in normal control subjects, and decreased significantly during the trial. There was no correlation of the sIL‐2R level and the joint pain/tenderness count either at study entry or study end. There was a significant correlation of the sIL‐2R level and the erythrocyte sedimentation rate, both at study entry and study end. A multiple linear regression model showed that treatment with methotrexate, but not the sIL‐2R level or the change in sIL‐2R level, predicted a change in joint count. A stepwise multiple logistic regression model defined no significant predictive information for outcome for the level of sIL‐2R at study entry.

Conclusion. After controlling for the simultaneous effects of other important clinical variables, the level of sIL‐2R does not appear to predict the response to methotrexate in patients with refractory RA. Further analysis of cohorts of patients with earlier RA needs to be performed.
Increased Antiretroviral Antibody Reactivity in Sera from a Defined Population of Patients with Systemic Lupus Erythematosus
Authors: Blomberg Jonas , Nived Ola , Pipkorn RüDiger , Bengtsson Anders , Erlinge David , Sturfelt Gunnar
Published: February 2007

Objective. The implied role of retroviruses in the pathogenesis of murine systemic lupus erythematosus (SLE) led us to study antiretroviral antibodies in a population‐based SLE cohort.

Methods. Immunoassays using whole virus and synthetic peptides were performed on sera from 72 patients with SLE and 88 control subjects.

Results. Reactions with whole baboon endogenous virus occurred more frequently in patients with SLE, and correlated with the presence of anti‐RNP and anti‐Sm. Some retroviral env and gag peptides, several of which were similar to U1 small nuclear RNP, reacted more strongly in patients with SLE, and their presence was correlated with discoid rash, hematologic disorder, and other symptoms.

Conclusion. These results provide circumstantial evidence for involvement of retroviruses in the pathogenesis of human SLE; further studies should be carried out using other techniques for measurement of retroviral expression.
Abnormalities of Renal Physiology in Systemic Sclerosis
Authors: Clements Philip J. , Lachenbruch Peter A. , Furst Daniel E. , Maxwell Morton , Danovitch Gabriel , Paulus Harold E.
Published: February 2007

Objective. To evaluate the prognostic value of measurements of renal plasma flow and circulating vasoactive hormones in patients with systemic sclerosis (SSc).

Methods. Renal plasma flow (para‐aminohippurate [PAH] clearance) and levels of selected circulating hormones (plasma renin activity [PRA] and serum aldosterone and catecholamines) were assessed in 57 SSc patients under the following conditions: at rest, in response to cold, while in upright position, and in response to sodium depletion. Survival was assessed 10.7 years after testing (20 patients had died).

Results. Both unstimulated and stimulated PRA clearance rates were frequently elevated. Resting PAH clearances were usually abnormally low. PAH clearances and levels of aldosterone and catecholamines did not change during cold stimulation. Supine PRA levels following acute sodium depletion correlated with survival (P < 0.008).

Conclusion. The frequent finding of elevated PRA and reduced PAH values reflects clinically the high frequency of renovascular disease noted histopathologically in SSc. Isolated decreases in PAH and elevations in PRA, however, did not predict renal crisis. Changes in PAH clearances were not demonstrable during cold stimulation. An abnormally high supine PRA after sodium depletion correlated with improved survival.
Clinical and Prognostic Associations Based on Serum Antinuclear Antibodies in Japanese Patients with Systemic Sclerosis
Authors: Kuwana Masataka , Kaburaki Junichi , Okano Yutaka , Tojo Takeshi , Homma Mitsuo
Published: February 2007

Objective. To clarify the clinical features and prognosis of systemic sclerosis (SSc) based on serum antinuclear antibodies (ANA).

Methods. We studied 275 consecutive Japanese patients newly diagnosed as having SSc, who were first evaluated during the period 1971—1990. Eight SSc–related ANA were identified using indirect immunofluorescence, double immunodiffusion, or immunoprecipitation assays. Clinical and prognostic features were retrospectively analyzed in patient groups, categorized by their serum ANA.

Results. Cumulative survival rates at 10 years after diagnosis of SSc were 93% in patients with anticentromere antibodies (ACA), 72% in those with anti—U1 RNP, 66% in those with anti—DNA topoisomerase I (anti—topo I), and 30% in those with anti‐RNA polymerases I, II, and III (anti‐RNAP). Major organ involvement linked to cause of death included biliary cirrhosis in patients with ACA, isolated pulmonary arterial hypertension and cerebral hemorrhage in those with anti—U1 RNP, pulmonary interstitial fibrosis in those with anti—topo I, and cardiac and renal involvement in those with anti‐RNAP.

Conclusion. Determinations of serum ANA in SSc patients are useful in predicting organ involvement and long‐term outcome.
Chronicity of The Eosinophilia—Myalgia Syndrome
Authors: Kaufman Lee D.
Published: February 2007

Objective. To define the natural history and outcome of eosinophilia—myalgia syndrome (EMS) among a cohort of patients followed up at one center since the onset of their disease.

Methods. Fifty‐seven patients with well‐characterized EMS were evaluated prospectively at a university hospital for 21—64 months (mean 36 months).

Results. Eighty‐eight percent of the patients continue to have symptomatic disease with >3 clinical manifestations. Fatigue (91%), muscle cramping (75%), myalgia (70%), paresthesias with objectively demonstrated hypesthesias (62%), articular symptoms (54%), scleroderma‐like skin changes (44%), and proximal muscle weakness (40%) are the most common features of chronic EMS. New findings identified among this cohort include cognitive symptoms in 86% of the study group, tremor, and myoclonus.

Conclusion. The recognition of new manifestations in EMS and ongoing clinical disease in 88% of patients highlights the chronic nature of this disorder. Continued prospective followup of a large patient base is warranted to further define the natural history of this newly recognized illness.
Clinical Significance of Antibodies to Native or Denatured 60‐kd or 52‐kd Ro/SS‐A Proteins in Sjögren's Syndrome
Authors: Tsuzaka Kensei , Fujii Takao , Akizuki Masashi , Mimori Tsuneyo , Tojo Takeshi , Fujii Hirohumi , Tsukatani Yasushi , Kubo Atsushi , Homma Mitsuo
Published: February 2007

Objective. To evaluate the clinical significance of antibodies to native or denatured (anti‐n or anti‐d) 60‐or 52‐kd Ro/SS‐A proteins (60K or 52K) in Sjögren's syndrome (SS).

Methods. The presence of antibodies to denatured and native Ro/SS‐A proteins was determined by immunoblotting and immunoprecipitation, respectively. Salivary gland dysfunction was evaluated by salivary function scintigraphy.

Results. The incidence of anti—d‐60K without anti—d‐52K was lower among patients with systemic lupus erythematosus with SS (SLE/SS) and among those with primary SS, compared with patients who had SLE without SS, whereas anti—d‐52K without anti—d‐60K was more common in SLE/SS patients and primary SS patients than in SLE patients without SS. All of the patients with anti—Ro/SS‐A had anti—n‐60K. Serologic abnormalities and salivary gland dysfunction were associated with anti—n‐60K in SS, whereas Hashimoto's thyroiditis in SS was related to anti—d‐60K. anti—d‐52K was not associated with any extraglandular or glandular symptoms in SS.

Conclusion. The data indicate that anti—n‐60K, which appears to recognize conformational epitopes, is associated with clinical features of SS characterized by glandular dysfunction.
Antibodies to Hmg Proteins in Patients with Drug‐Induced Autoimmunity
Authors: Ayer Linda M. , Rubin Robert L. , Dixon Gordon H. , Fritzler Marvin J.
Published: February 2007

Objective. To determine the prevalence of auto‐antibodies to high‐mobility group (HMG) proteins in sera from patients with drug‐induced lupus (DIL).

Methods. Forty‐two patients who developed auto‐antibodies and/or lupus after treatment with procainamide or other drugs were tested for HMG autoantibodies by immunoblotting and enzyme‐linked immunosorbent assay (ELISA).

Results. Twenty‐eight of the 42 sera (67%) bound HMG‐14 and/or HMG‐17. In comparison, 9 of 42 (21%) bound HMG‐1 and/or HMG‐2. There was a good correlation between ELISA results and binding on immunoblots.

Conclusion. The high prevalence of antibodies to the nucleosomal core HMGs (HMG‐14 and HMG‐17) in DIL patients adds evidence implicating nucleosomes as immunogens in drug‐induced autoimmunity.
Elevations of Neutrophil Proteinase 3 in Serum of Patients with Wegener's Granulomatosis and Polyarteritis Nodosa
Authors: Henshaw Timothy J. , Malone Christine C. , Gabay Joelle E. , Williams Ralph C.
Published: February 2007

Objective. To determine serum levels of proteinase 3 (PR3) in normal subjects and patients with Wegener's granulomatosis (WG), polyarteritis nodosa (PAN), chronic renal failure, and systemic lupus erythematosus (SLE).

Methods. Serum levels of PR3 were measured by enzyme‐linked immunosorbent assay employing a monospecific rabbit polyclonal antibody against PR3.

Results. Quantifiable levels of PR3 were detected in all serum samples examined, including those of normal subjects. Marked elevations of serum PR3, which decreased with treatment, were found in patients with active WG. Patients with PAN, SLE, and chronic renal failure also showed elevated levels of PR3.

Conclusion. Quantitating serum PR3 may be useful in the management of patients with WG and other connective tissue diseases.