bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonsteroidal antiinflammatory drugs in rheumatoid arthritis and osteoarthritis. Support for the concept of “responders” and “nonresponders”
Authors: Walker Judith S. , Sheather‐Reid Rachel B. , Carmody John J. , Day Richard O. , Vial Janet H. 
Published: February 2007

AbstractObjective. A range of functional, biochemical, and psychological indicators was used to test the concept of “responders”/“nonresponders” and to seek predictors of response to 2 nonsteroidal antiinflammatory drugs in 9 patients with rheumatoid arthritis (RA) and 11 with osteoarthritis (OA).Methods. In a balanced, randomized, doubleblind, latin‐square study design that involved four 4‐ week treatment periods, patients received ketoprofen or piroxicam (each for 2 of the 4 periods). Clinical and laboratory responses (pain, tenderness, swelling, patient and physician global assessments, acute‐phase protein levels, and disability) were assessed in the last 2 weeks of each period. Responders were those who showed >30% improvement in at least 5 of 7 measures of disease activity. Mood was also assessed.Results. At baseline, variables were higher in RA than in OA patients. The drugs produced clear improvements in patients' visual analog scale scores, physicians' overall assessments, and patients' responses to the McGill Pain Questionnaire, as well as plasma prostaglandin concentrations. In patients with either RA or OA, responders could be distinguished from nonresponders; about one‐third of patients were unambiguous responders. In RA, there were responder nonresponder differences in lymphocyte counts, erythrocyte sedimentation rate (ESR), and levels of tumor necrosis factor α, but no differences were seen in OA patients. However, caution in interpretation of the data is necessary because of the small number of patients. Responders had improved mood scores compared with nonresponders in both disease groups. Baseline ESR and white blood cell counts were correlated with responder status in RA patients.Conclusion. This study provides support for the responder/nonresponder concept. It also indicates that in RA, pretreatment ESR and lymphocyte counts are possibly useful indicators of therapeutic response.
Predictors of total body bone mineral density in non‐corticosteroid‐treated prepubertal children with juvenile rheumatoid arthritis
Authors: Henderson Carol J. , Specker Bonny L. , Sierra Rosa I. , Wilmott Robert W. , Lovell Daniel J. , Cawkwell Gail Dunkel , Campaigne Barbara N. 
Published: February 2007

AbstractObjective. To determine the extent of significant osteopenia in prepubertal patients with juvenile rheumatoid arthritis (JRA) not treated with corticosteroids and to identify variables that are highly related to bone mineralization in this population.Methods. In a cross‐sectional study, 48 JRA patients and 25 healthy control subjects ages 4.6–11.0 years were evaluated. Total body bone mineral density (TB BMD) was determined by Hologic dual energy x‐ray absorptiometry. All patients were prepubertal (Tanner stage I or II) and had never taken corticosteroids. For comparison, JRA patients were divided into “low” TB BMD (Z score ⩽−1) or “normal” TB BMD (Z score >‐1).Results. The overall mean ± SD TB BMD scores did not differ between the JRA subjects (0.75 ± 0.06 gm/cm2) and controls (0.73 ± 0.07 gm/cm2; P > 0.30). However, 29.2% of the JRA patients had low TB BMD, whereas only 16% would be expected to have low TB BMD based on the standard normal distribution (goodness of fit X2 = 4.84, P = 0.01). The mean Z score for the JRA patients with low TB BMD was ‐1.43, and for those with normal TB BMD, it was 0.32. The JRA subjects with low TB BMD were significantly younger, had more active articular disease, greater physical function limitation, higher erythrocyte sedimentation rate, higher joint count severity score, lower body mass index, lower lean body mass, less participation in organized sports, and more protein and vitamin D in their diet compared with JRA patients with normal TB BMD (all P < 0.05). Using logistic regression, a model including age at JRA onset, Juvenile Arthritis Functional Assessment Report (JAFAR) score, triceps skinfold percentiles, percentage US recommended daily allowance for dietary magnesium intake, and serum 1,25‐dihydroxyvitamin D levels was able to accurately segregate 79.6% of the JRA subjects into either the low or normal TB BMD groups (X2 = 20.5, P = 0.001).Conclusion. This study demonstrated that in a mildly to moderately ill prepubertal JRA population that had never been exposed to corticosteroids, almost 30% had significantly low TB BMD. The patients with low TB BMD had more active and severe articular disease and greater physical function limitation. Disease‐related parameters in JRA appear to exert a negative effect on bone mineralization even in prepubertal children, which can be demonstrated despite the exclusion of corticosteroid‐treated patients.
Development of validated disease activity and damage indices for the juvenile idiopathic inflammatory myopathies. I. Physician, parent, and patient global assessments
Authors: Rider Lisa G. , Miller Frederick W. , Feldman Brian M. , Perez Maria D. , Rennebohm Robert M. , Lindsley Carol B. , Zemel Lawrence S. , Wallace Carol A. , Ballinger Susan H. , Bowyer Suzanne L. , Reed Ann M. , Passo Murray H. , Katona Ildy M. , Lachenbruch Peter A. 
Published: February 2007

AbstractObjective. To determine the reliability, content validity, and responsiveness of physician global assessments of disease activity and damage in the juvenile idiopathic inflammatory myopathies (IIM), and to investigate concordance among physician, parent, and patient global ratings.Methods. Sixteen pediatric rheumatologists rated 10 juvenile IIM paper patient cases for global disease activity and damage, and assessed the importance of 51 clinical and laboratory parameters in formulating their global assessments. Then, 117 juvenile IIM patients were enrolled in a protocol to examine the relationship between Likert and visual analog scale global assessments, their sensitivity to change, and the comparability of physician, parent, and patient global ratings.Results. Pediatric rheumatologists demonstrated excellent interrater reliability in their global assessments of juvenile IIM disease activity and damage (97.7% and 94.7% agreement among raters, respectively), and agreed on a core set of clinical parameters in formulating their judgments. Likert scale ratings correlated with those on a visual analog scale, and both were comparable in responsiveness (standardized response means −0.56 for disease activity, 0.02 [Likert] and 0.14 [visual analog] for damage, measured over 8 months). Parent global ratings of disease activity correlated with physician assessments, but were not colinear (Spearman's correlation [r] = 0.41−0.45). Patient global disease activity assessments correlated with those done by parents (r = 0.57−0.84) and physicians (r = 0.37−0.63), but demonstrated less responsiveness (standardized response means −0.21 and −0.12, respectively, over 8 months).Conclusion. Physician global assessments of juvenile IIM disease activity and damage demonstrated high interrater reliability and were shown to be comprehensive measures. Both physician and parent disease activity assessments should be considered valuable as quantitative measures for evaluating therapeutic responses in juvenile IIM patients.
Mediastinal mass and hilar adenopathy. Rare thoracic manifestations of wegener's granulomatosis
Authors: George Teresa M. , Cash Joseph M. , Farver Carol , van Dyke Carolyn W. , Hoffman Gary S. , Sneller Michael , Derus Charles L. 
Published: February 2007

AbstractObjective. To assess the frequency and characteristics of hilar and mediastinal involvement in patients with Wegener's granulomatosis (WG).Methods. A patient with WG presented with the unusual finding of a mediastinal mass, prompting a comprehensive review of 302 patient records from 2 WG registries to obtain evidence of hilar adenopathy or mediastinal masses. Clinic progress notes and findings of chest imaging studies (routine imaging and computed tomography) were reviewed for the presence of hilar lymphadenopathy, mediastinal masses, or mediastinal lymphadenopathy. All radiographs and surgical pathology specimens from these lesions were reviewed.Results. Six examples of mediastinal or hilar involvement (2.0%) were identified among 302 patients with WG. Three of these 6 patients had mediastinal masses. One patient with a mediastinal mass also had mediastinal lymphadenopathy. Two of the patients with mediastinal masses had lung parenchymal lesions. The remaining 3 patients had enlarged hilar lymph nodes in addition to pulmonary parenchymal lesions. All of the patients were treated with corticosteroids and cytotoxic drugs. Followup information was available on all patients. Two patients died. In the remaining 4 patients, the mediastinal mass or hilar lymphadenopathy decreased in size or resolved after 2 months of immunosuppressive therapy.Conclusion. In the past, hilar adenopathy and/or mediastinal mass have been considered unlikely features of WG, and their presence has prompted consideration of an alternative diagnosis. Although this caution remains valuable, the present retrospective review of data from 2 large WG registries illustrates that such findings may rarely be a part of the spectrum of WG chest disease. Because these findings are uncommon, they necessitate consideration of a primary or concurrent infection or malignancy in the diagnostic evaluation.
Anticardiolipin IgG subclasses association of IgG2 with arterial and/or venous thrombosis
Authors: Sammaritano Lisa R. , Ng Sonia , Sobel Rachel , Salmon Jane E. , Lo Siu Kong , Simantov Ronit , Silverstein Roy , Furie Richard , Kaell Alan 
Published: February 2007

AbstractObjective. To determine whether the presence of anticardiolipin antibodies (aCL) of a specific IgG subclass is associated with clinical complications of the antiphospholipid antibody syndrome (APS) and whether polymorphisms of Fc receptors for IgG (FcγR) with differential binding preferences contribute to an increased risk of thrombotic complications.Methods. In 60 patients with IgG aCL, we assessed clinical complications of the APS, measured the level of antibody activity, and determined the IgG subclass distribution of aCL by a modified enzymelinked immunosorbent assay (ELISA) with murine antihuman IgG subclass monoclonal antibodies. Selective IgG subclass adsorption studies were performed to determine the relative contribution of specific IgG subclasses to overall aCL activity. Fcγ receptor IIA (FcγRIIA) genotypes of aCL patients with thrombosis and of non‐systemic lupus erythematosus controls were determined by polymerase chain reaction amplification of genomic DNA and allele‐specific probes.Results. IgG2 aCL, detected in 75% of the patients, was the major subclass of aCL. Selective adsorption studies demonstrated that IgG2, in contrast to IgG1, was the predominant subclass responsible for aCL reactivity. IgG2 aCL was the only subclass associated with clinical complications, specifically, arterial and/or venous thrombosis (P < 0.04). The presence of FcγRIIA‐H131, a receptor expressed on platelets, monocytes, and endothelial cells and the only human FcγR which efficiently recognizes IgG2, was associated with thrombosis in aCL patients. Among 45 high‐titer (>40 GPL [IgG phospholipid] units) aCL patients with thrombosis, 40% were homozygous for FcγRIIA‐H131, compared with 25% of disease‐free controls (P = 0.042).Conclusion. While all 4 IgG subclasses are found in autoimmune aCL, only the presence of IgG2 is significantly associated with thrombotic complications. Reactivity in aCL ELISA is largely due to the presence of IgG2 in high‐titer patients. The presence of IgG2 aCL, particularly in association with FcγRIIA‐H131, may be a useful clinical predictor of increased thrombotic risk in patients with autoimmune IgG aCL. Allelic variants of FcγRIIA with distinct capacities to interact with IgG subclasses provide a mechanism for genetic susceptibility to an autoantibody‐induced prothrombotic state.
Localization of hepatitis C virus in cutaneous vasculitic lesions in patients with type II cryoglobulinemia
Authors: Agnello Vincent , Ábel György 
Published: February 2007

AbstractObjective. To investigate the role of hepatitis C virus (HCV) in the pathogenesis of the cutaneous vasculitis in patients with type II cryoglobulinemia.Methods. Using in situ hybridization detection of HCV, we studied 6 test patients and various control subjects. Serum HCV was quantitated, cryoglobulins were analyzed by column chromatography at 37°C, and lowdensity lipoprotein (LDL) receptors on keratinocytes were detected using LDL labeled with fluorescent dye.Results. In the cutaneous vasculitic lesions from test patients, but not control subjects, the HCV virion was found in association with IgM and IgG. HCV alone was detected in some vessel walls, and in skin and ductal epithelium and vascular endothelium in inflamed, but not normal, skin. Cryoglobulins showed HCV, monomeric IgM, and monomeric IgG, with little or no immune complexes. The extent of the lesions correlated with levels of viremia. Up‐regulation of LDL receptors on keratinocytes was detected in inflamed, but not normal, skin.Conclusion. HCV was present in the cutaneous vasculitic lesions, most likely in complexes with IgM and IgG formed in situ. These findings and the correlation of the severity of the rash with the level of viremia suggest that HCV plays a major role in the pathogenesis of cutaneous vasculitis in these patients and strengthens the rationale for antiviral drug therapy. The presence of HCV in keratinocytes and ductal epithelial and vascular endothelial cells may be the in vivo manifestation of endocytosis of HCV by the LDL receptors that has recently been demonstrated in vitro. The upregulation of LDL receptors on keratinocytes in inflamed skin is consistent with this postulation.
Effects of inflammation and treatment on bone turnover and bone mass in polymyalgia rheumatica
Authors: Dolan A. L. , Moniz C. , Li F. , Mackintosh C. , Todd P. , Dasgupta B. , Corrigall V. , Panayi G. S. 
Published: February 2007

AbstractObjective. Polymyalgia rheumatica (PMR) has an abrupt onset of inflammatory symptoms, making it a useful model for studying the effects of inflammation in bone. PMR requires corticosteroid treatment, which may itself have a detrimental effect on bone. This study used serially measured biochemical markers of bone turnover and bone density to address the relative contributions of systemic inflammation and corticosteroid therapy to bone loss.Methods. Fifty untreated patients with PMR were randomized to receive oral prednisolone or intramuscular methylprednisolone. Biochemical bone markers (pyridinoline [PYR], deoxypyridinoline [DPYR], procollagen type I carboxy‐terminal peptide [PICP]) and bone mineral density (BMD) were measured at baseline and at 6, 12, and 24 months.Results. The median disease duration at presentation was 12 weeks (range 5–32 weeks). Levels of urinary crosslinks were increased in patients with untreated PMR compared with controls (PYR 74.9 ± 30.0 nmole/mmole creatinine, DPYR 14.6 ± 6.4 nmoles/mmole creatinine [mean ± SD]; P = 0.0001); the PICP level was normal (115.0 ± 39.0 μg/liter). With treatment, the crosslinks levels fell and PICP levels rose within 6 months (P = 0.01). Bone resorption (PYR) correlated with untreated disease activity (erythrocyte sedimentation rate [ESR]) (r = 0.5, P = 0.003) and with interleukin‐6 levels (r = 0.48, P = 0.05). There was a significant reduction in BMD of both the hip and the spine after 12 months of treatment (P = 0.0002), with no difference between treatment groups. As the steroid dosage was reduced, bone mass improved. Initial ESR influenced the percent change in BMD at 1 year (r = 0.35, P = 0.05), while cumulative steroid dose, mean ESR, and type of steroid used did not.Conclusion. Inflammation in PMR increases bone resorption and appears to have a more detrimental effect on bone than does low‐dose corticosteroid. If corticosteroids can be tapered and discontinued, bone loss in PMR can be a transient phenomenon.
Induction of interleukin‐1 and subsequent tissue factor expression by anti‐proteinase 3 antibodies in human umbilical vein endothelial cells
Authors: de Bandt Michel , Ollivier Véronique , Babin‐Chevaye Catherine , Khechaï Fouzi , de Prost Dominique , Hakim Jacques , Pasquier Catherine , Meyer Olivier 
Published: February 2007

AbstractObjective. To assess the ability of anti‐proteinase 3 (anti‐PR3) classic antineutrophil cytoplasmic antibodies (cANCA) to stimulate endothelial expression of tissue factor (TF), which is the main initiator of the coagulation cascade that can lead to endothelial injury and thrombosis in patients with Wegener's granulomatosis.Methods. Human umbilical vein endothelial cells (HUVEC) were grown to confluence and stimulated with affinity‐purified anti‐PR3 antibodies, Igs from healthy subjects, and endotoxin (lipopolysaccharide) as positive control.Results. TF activity was generated in anti‐PR3‐ stimulated cells, as shown by a chromogenic test. This activity was inhibited by specific anti‐TF antibodies. TF messenger RNA (mRNA) was found in anti‐PR3‐ stimulated cells, as detected by reverse transcriptasepolymerase chain reaction, but not in cells stimulated with irrelevant human Igs or Igs from normal control sera. TF expression reached maximum levels 12 hours after exposure to the anti‐PR3 cANCA, and did not require complement. TF mRNA expression was inhibited by cycloheximide, suggesting a requirement for protein synthesis. When added to the incubation medium, interleukin‐1 (IL‐1) receptor antagonist inhibited the induced TF mRNA expression, suggesting that cANCA‐stimulated cells initiate IL‐1 synthesis. Moreover, cANCA induced IL‐lα mRNA before TF mRNA.Conclusion. This study showed that anti‐PR3 treatment of HUVEC induces sequential expression of IL‐lα mRNA and TF mRNA, as well as their corresponding proteins. Both proteins could have pathogenic roles in the vasculitic process, since TF is the main initiator of the coagulation cascade.
In vitro induction of proinflammatory cytokine secretion by juvenile rheumatoid arthritis synovial fluid immune complexes
Authors: Jarvis James N. , Wang Wenlian , Moore Heide T. , Zhao Lin , Xu Chengsu 
Published: February 2007

AbstractObjective. To characterize juvenile rheumatoid arthritis synovial fluid (SF) immune complexes and to examine their interaction with leukocytes.Methods. SF immunoglobulin‐containing fractions were prepared by sequential chromatography on protein A and Sephacryl 300. Fractions were subdivided according to molecular weight, characterized for immunoglobulin and complement content, and incubated with either promonocytic U937 cells or normal human peripheral blood mononuclear cells (PBMC).Results. High molecular weight SF immunoglobulin‐containing fractions stimulated the release of interleukin‐lβ (IL‐1β) from U937 cells. These same complexes stimulated tumor necrosis factor α (TNFα), IL‐lβ, IL‐6, IL‐8, and granulocytemacrophage colony‐stimulating factor (GM‐CSF) from PBMC. Lower molecular weight material was less efficient in inducing any of the cytokines. TNFα and IL‐1β were the earliest of the messenger RNAs examined to be induced by the high molecular weight complexes. However, the secretion of IL‐6, IL‐8, and GM‐CSF stimulated by the complexes was not completely dependent upon the secretion of IL‐1β. Addition of IL‐1 receptor antagonist to the cell cultures reduced GM‐CSF and IL‐6 production by 40% and IL‐8 production by 25% in PBMC.Conclusion. SF immunoglobulin fractions contain immune complexes that vary in size, composition, and phlogistic potential. High molecular weight complexes are capable of inducing a spectrum of proinflammatory cytokines, all of which have been implicated in the pathogenesis of rhematic disease.
Osteoarthritic Lesions. Involvement of three different collagenases
Authors: Shlopov Boris V. , Lie Wen‐Rong , Mainardi Carlo L. , Cole Ada A. , Chubinskaya Susan , Hasty Karen A. 
Published: February 2007

AbstractObjective. To assess the presence of fibroblast collagenase (MMP‐1), neutrophil collagenase (MMP‐8), and collagenase 3 (MMP‐13) in osteoarthritic (OA) cartilage, with particular emphasis on areas of macroscopic cartilage erosion.Methods. Messenger RNA (mRNA) levels were assessed by reverse transcriptase‐polymerase chain reaction (RT‐PCR), in situ hybridization, and Northern blot analysis.Results. MMP‐1 and MMP‐13 were expressed at higher levels by OA chondrocytes than by normal chondrocytes. In addition, mRNA for MMP‐8 was present in OA cartilage but not normal cartilage by PCR and Northern blot analyses. Chondrocytes from areas surrounding the OA lesion expressed greater quantities of MMP‐1 and MMP‐13 compared with normal chondrocytes, suggesting local modulation by mechanical and inflammatory factors. Tumor necrosis factor α stimulated the expression of all 3 collagenases. Retinoic acid, an agent which induces autodigestion of cartilage in vitro, stimulated only the expression of MMP‐13.Conclusion. These findings suggest a key role of MMP‐13 and MMP‐8, as well as MMP‐1 in osteoarthritis.
Molecular diagnosis of ureaplasma urealyticum in an immunocompetent patient with destructive reactive polyarthritis
Authors: Vittecoq Olivier , Favre Sylvie , Daragon Alain , Biga Norman , Cambon‐Michot Chantal , Loët Xavier Le , Schaeverbeke Thierry , Bébéar Christiane 
Published: February 2007

AbstractPolymerase chain reaction (PCR) amplification, which is a useful method for detecting infectious agents in joints, has potential utility in the molecular diagnosis of venereal‐associated arthritis. Among pathogens detected by this technique, Ureaplasma urealyticum, which is primarily associated with reactive arthritis (ReA), is also implicated in septic arthritis in immunocompromised patients. We report here a case of destructive polyarthritis, initially suggestive of septic arthritis, in an immunocompetent patient whose PCR positivity for U urealyticum DNA in one joint, in conjunction with the disease outcome and histologic findings, led to the diagnosis of destructive ReA.
Modulation of synovial cell function by somatostatin in patients with rheumatoid arthritis
Authors: Takeba Yuko , Suzuki Noboru , Takeno Mitsuhiro , Asai Tomiaki , Tsuboi Seiji , Hoshino Takashi , Sakane Tsuyoshi , Takeba Yuko , Suzuki Noboru , Takeno Mitsuhiro , Hoshino Takashi , Sakane Tsuyoshi , Asai Tomiaki , Tsuboi Seiji 
Published: February 2007

AbstractObjective. To elucidate the role of neurologic, endocrine, and immune system interactions in the development of pathologic responses in patients with rheumatoid arthritis (RA), we studied somatostatin (SOM) production and somatostatin receptor (SOMR) expression in RA synovium and its function in patients with RA.Methods. The effects of SOM on proinflammatory cytokine (interleukin‐6 [IL‐6] and IL‐8) and collagenase production by RA synovial cells were estimated by enzyme‐linked immunosorbent assay, and their messenger RNA expression was assessed by reverse transcription‐polymerase chain reaction (RT‐PCR) using limiting dilutions of the complementary DNA. The expression of SOMR by RA synovial cells was also studied by RT‐PCR. Local production of SOM was estimated by RT‐PCR and immunohistochemical staining.Results. Physiologic concentrations (≈ 10−10M) of SOM inhibited proliferation of RA synovial cells. The production of proinflammatory cytokines and matrix metalloproteinases by RA synovial cells was also modulated by SOM. SOMR subtypes 1 and 2 were expressed on fibroblast‐like synovial cells, and the expression of SOMR‐2 was up‐regulated by proinflammatory cytokine treatment of the synovial cells from patients with RA. RA fibroblast‐like cells synthesized SOM by themselves, suggesting that SOM acts as an autocrine regulator of synovial cell function in patients with RA.Conclusion. SOM inhibited aberrant synovial cell function in patients with RA, suggesting possible clinical applications of this neuropeptide.