bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the efficacy and safety of oral tiludronate in paget's disease of bone
Authors: Reginster J. Y. , Colson F. , Morlock G. , Combe B. , Ethgen D. , Geusens P. 
Published: February 2007

AbstractObjective. To assess the optimal dosage of oral tiludronate in Paget's disease of bone.Methods. We studied 149 patients with Paget's disease, in a double‐blind, randomized, placebo‐controlled trial. Patients were randomly assigned to 1 of 5 therapeutic groups: a daily dose of 100 mg, 200 mg, 400 mg, or 800 mg of oral tiludronate, or a placebo. Treatment was for 3 months, followed by 3 months of placebo‐controlled followup. Serum alkaline phosphatase activity (SAP) and fasting urinary excretion of hydroxyproline/creatinine (OH/Cr) were measured monthly, as were biochemical parameters reflecting renal, hepatic, and hematologic functions. Analgesic efficacy was self‐evaluated from a visual analog scale and a global pain index.Results. Statistical analysis revealed that beginning at a dosage of 200 mg/day, there was a direct dose‐dependent effect on the reduction of SAP and OH/Cr levels. Reduction of SAP levels was clinically significant at a dosage of 400 mg (44.9 ± 4.2% reduction at 90 days and 49.2 ± 4.5% at 180 days, mean ± SEM) and at 800 mg (53.4 ± 5% at 90 days and 59.3 ± 4.6% at 180 days). There was a significant reduction in pain in all groups, including the group taking placebo. In only those taking 800 mg/day of tiludronate was there a significant frequency of complete resolution of pain (versus placebo). Aside from mild gastrointestinal disturbances, as experienced with other oral bisphosphonates, clinical tolerance of all 5 regimens was good. Exhaustive biochemical investigations failed to reveal significant toxicity of tiludronate up to the 800‐mg daily dose investigated.Conclusion. Because of its significantly better antiresorptive effects and greater analgesic properties (compared with lower dosages), combined with the excellent clinical and biochemical tolerance, the 800‐mg daily dose of tiludronate appears to be optimal for the treatment of Paget's disease of bone.
Vasculitic neuropathy mimicking guillain‐barré syndrome
Authors: Suggs S. P. , Thomas T. D. , Joy J. L. , Lopez‐Mendez A. , Oh S. J. 
Published: February 2007

AbstractVasculitic neuropathy classically manifests as a subacute mononeuritis multiplex or polyneuropathy. Patients with a Guillain‐Barré syndrome (GBS)–like presentation are usually not considered to have an underlying vasculitis. We describe 2 patients with rapidly progressive areflexic paralysis that was initially diagnosed as GBS, in whom vasculitic neuropathy was found histologically.
Selection of T cell receptor Vβ elements by HLA‐DR determinants predisposing to Rheumatoid Arthritis
Authors: Weyand Cornelia M. , Oppitz Ulrich , Hicok Kevin , Goronzy Jörg J. 
Published: February 2007

AbstractObjective. Rheumatoid arthritis (RA) is genetically linked to a sequence motif encoding for the middle portion of the α‐helical loop, which is adjacent to the antigen‐binding groove of the HLA‐DR molecule. The disease‐associated element might be involved in binding the antigen or in interacting with the T cell receptor (TCR). To investigate the contribution of the disease‐associated element in T cell recognition events, we studied structural requirements in the interaction of T cell clones with HLA‐DR determinants.Methods. T cell clones restricted to disease‐associated HLA‐DR determinants were established by allogeneic stimulation of HLA–DRB1*0401+ or *0401–responders with HLA–DRB1*0404/8+ stimulators. Allele‐specific primer sets were used to identify the Vβ gene segment expressed by individual clones. Sequence analysis was applied to study the diversity of the TCR β‐chain junctional regions.Results. The repertoire of TCR Vβ elements was strongly biased toward the usage of Vβ6. HLA–DRB1*0401+ and *0401– donors preferentially recruited Vβ6+ T cells to recognize the disease‐associated HLA–DR determinant. Sequence data revealed that the Vβ6.6/7 and Vβ6.8/9 subtypes of the Vβ6 multigene family were overrepresented. The TCR β chains were characterized by a high degree of junctional diversity, supporting the view that a multitude of peptide–DR complexes were recognized and that the preferential use of Vβ6 was dictated by the TCR β chain–DRβ1 chain contact.Conclusion. T cells reactive with the disease‐associated HLA–DR structure are nonrandomly selected. The HLA‐DR component predisposing to RA might define molecular requirements that restrict the TCR–HLA interaction. Thus, the phenomenon of HLA association in RA might reflect a genetic control of T cell recognition, through the selection of the TCR repertoire.
Evidence for the presence of androgen receptors in the synovial tissue of rheumatoid arthritis patients and healthy controls
Authors: Cutolo Maurizio , Accardo Silvano , Villaggio Barbara , Clerico Paolo , Indiveri Francesco , Carruba Giuseppe , Fecarotta Emanuela , Castagnetta Luigi 
Published: February 2007

AbstractObjective. To study the presence of androgen receptors in the synovial tissue of male and female patients with rheumatoid arthritis (RA) and matched healthy controls.Methods. Both site I (high affinity, low binding capacity) and site II (reduced affinity, higher binding capacity) androgen receptors were investigated in soluble and nuclear fractions of homogenized synovial samples, using the dextran‐coated charcoal method. The finding of pure, high‐affinity site I receptors in both fractions was considered indicative of androgen receptor positivity. In order to determine what type of synovial cell was positive for androgen receptors, cryosections of synovial tissues were immunostained with a specific monoclonal anti‐androgen receptor antibody (MAb), using both immunofluorescence and immunoperoxidase techniques. Double immunostaining with this MAb and specific MAb directed toward different macrophage/granulocyte antigens was also performed.Results. Remarkable differences were found between male and female controls: Most males were positive for androgen receptors, and most females were negative. The femtomolar content of androgen receptor in the nuclear fraction was fairly constant, but the soluble fraction showed a higher femtomolar concentration in female RA patients than in controls of either sex, as well as in male RA patients compared with female RA patients. The androgen receptor‐positive cells in both RA and control synovial cryosections were found by immunostaining to be macrophage‐like synoviocytes, and were also found to be HLA‐DR positive.Conclusions. The immunosuppressive action exerted by androgens might, at least in part, be mediated through their interaction with macrophage‐like synoviocytes functioning as antigen‐processing and antigen‐presenting cells in rheumatoid synovia.
Assessment of disease activity and impending flare in patients with systemic lupus erythematosus. Comparison of the use of complement split products and conventional measurements of complement
Authors: Buyon Jill P. , Tamerius John , Belmont H. Michael , Abramson Steven B. 
Published: February 2007

AbstractObjective. To determine whether increased levels of the complement split products generated in the activation of the alternative or classical pathway accompany more severe disease activity in patients with systemic lupus erythematosus (SLE) and whether these measurements are useful in predicting flares of disease.Methods. Levels of Ba, Bb, SC5b‐9, and C4d were measured in 380 plasma samples obtained from 86 SLE patients who were prospectively followed up for 15 months.Results. In the 20 patients who had inactive disease at the initiation of the study, the mean values of all of the complement split products at entry were within the normal range. In the 47 patients with stable or moderate disease activity, levels of Ba were significantly increased, while the mean values for Bb, SC5b‐9, and C4d did not differ significantly from those in patients with inactive disease. The mean entry value of each analyte was highest in the group of 19 patients who had the most severe disease activity at initial evaluation. Traditional measurements of complement, i.e., C3, C4, and CH50, followed similar trends, but did not discriminate between the 3 groups of patients as well as did measurements of the split products. Analysis of the disease course in the patients with inactive or stable/moderate disease revealed that an elevated level of C4d had the most sensitivity with regard to subsequent flare, while an elevated Bb level had the highest specificity and the greatest predictive value.Conclusion. These data suggest that elevated levels of complement split products, particularly products of alternative and terminal pathway activation, more accurately reflect disease activity than do conventional measurements of complement in SLE and may be useful in the prediction of impending disease flares.
Neuropathologic findings in multi‐infarct dementia associated with anticardiolipin antibody. Evidence for endothelial injury as the primary event
Authors: Westerman Eric M. , Miles Janet M. , Backonja Miroslav , Sundstrom Walter R. 
Published: February 2007

AbstractObjective. There are few reports describing histopathologic changes associated with the antiphospholipid antibody syndrome. We describe a patient with multi‐infarct dementia and antiphospholipid antibody syndrome, in whom a brain biopsy was performed.Methods. Biopsy material from the left frontal cortex, including meninges, cortex, and underlying subcortical white matter, was investigated. Microscopic examination and special staining were performed.Results. Microscopic examination showed lumenal occlusion by thrombi, and marked endothelial hyperplasia of small meningeal and cortical arterioles.Conclusion. These findings suggest that the pathogenesis of this cerebral vasculopathy is noninflammatory and is associated with reactive endothelial hyperplasia and thrombosis of small arterioles.
Presence of small proteoglycan fragments in normal and arthritic human cartilage
Authors: Witsch‐Prehm Petra , Miehlke Rolf , Kresse Hans 
Published: February 2007

AbstractObjective. To characterize the small proteoglycans decorin and biglycan in normal human patellar cartilage and in cartilage from individuals with chronic polyarthritis.Methods. Cartilage extracts were chromatographed on DEAE‐Trisacryl and further separated by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis before and after enzymatic degradation of the glycosaminoglycan chains. Decorin and biglycan were visualized after Western blotting, using core protein‐specific polyclonal and monoclonal antibodies.Results. Core protein fragments of both proteoglycans were observed even in normal cartilage. In the case of decorin they amounted to up to 15% of the immunoreactive material, and up to 5% of the core protein was glycosaminoglycan free. The quantity of decorin core protein was reduced in arthritic cartilage, but the core protein fragments represented up to 45% of the immunoreactive material. Different zones of cartilage differed in their content of the fragments. Evidence for an increased proportion of biglycan fragments was not obtained.Conclusion. Chronic polyarthritis leads to increased degradation of small proteoglycans. A considerable proportion of decorin fragments is retained in the tissue. These alterations may have a negative influence on the mechanical stability of tissue.
Effect of intraarticular glycosaminoglycan polysulfate treatment on patellofemoral pain syndrome. A prospective, randomized double‐blind trial comparing glycosaminoglycan polysulfate with placebo and quadriceps muscle exercises
Authors: Kannus Pekka , Natri Antero , Niittymäki Seppo , Järvinen Markku 
Published: February 2007

AbstractObjective. To compare the effects of intraarticular (IA) injections of glycosaminoglycan polysulfate (GAGPS) plus basic conservative treatment with the effects of placebo injections plus conservative treatment and with the effects of conservative treatment alone in patients with chronic patellofemoral pain syndrome (PFPS).Methods. We treated 53 patients who presented with chronic PFPS in 1 knee, according to 1 of the 3 protocols, in a prospective, randomized, double‐blind study. Basic conservative treatment consisted of a 6‐week program of quadriceps muscle exercise, elimination of symptom‐producing activities, and oral doses of nonsteroidal antiinflammatory drugs. Physiologic saline served as placebo for injection. During the 6‐week treatment period, 5 injections were given 1 week apart. Along with measurements of quadriceps strength, standardized subjective, functional, and clinical assessments were performed at presentation, after 6 weeks of treatment, and after 6 months.Results. Results at 6 months indicated that IA injections of GAGPS or saline did not result in significant improvement beyond the good results achieved by the basic conservative treatment alone. More than two‐thirds of the patients in each group experienced complete recovery.Conclusion. Neither the GAGPS injections nor the physiologic saline injections are more effective than conservative therapy in the treatment of chronic PFPS. Restoration of normal quadriceps muscle function to the affected knee seems to be crucial in treating PFPS.
Appendicular and vertebral bone mass in ankylosing spondylitis. A comparison of plain radiographs with single‐ and dual‐photon absorptiometry and with quantitative computed tomography
Authors: Devogelaer Jean‐Pierre , Maldague Baudouin , Malghem Jacques , De Deuxchaisnes Charles Nagant 
Published: February 2007

AbstractObjective. We assessed the prevalence, severity, and anatomic distribution of ankylosing spondylitis (AS)‐related osteopenia (OP).Methods. We studied 70 patients (60 males, 10 premenopausal females) with AS (according to the New York criteria) to determine the frequency of OP. Bone mass was measured by plain radiographs of the spine, by single‐photon absorptiometry (SPA) of the distal and midshaft of the radius on the nondominant side, by dual‐photon absorptiometry (DPA) of the lumbar spine (L2‐L4), and by quantitative computed tomography (QCT) of the lumbar spine.Results. SPA values for the radius mass were normal in males and in females, both at the distal and midshaft sites. In contrast, spine radiographs showed diminished density of the vertebral bodies in 69% of the males and 50% of the premenopausal females. Two male patients had had a vertebral compression fracture, and one female patient had had two. DPA values for the spine mass were significantly diminished in the male patients compared with the controls, but not in the female patients. Males with less severe AS also had the largest reduction in lumbar bone mineral content. In patients with more severe disease, lumbar bone mineral content was not statistically different from that in controls. QCT of the lumbar spine performed in 10 patients disclosed low density of the trabecular bone of the vertebral bodies, more so in those with more severe AS and syndesmophyte formation and/or apophyseal joint fusion, which contrasts with the normal values on DPA in these patients.Conclusion. Male patients with AS have axial osteopenia. In those who have very severe AS with new bone formation, DPA demonstrates normal values as a result of two opposite trends: central osteopenia (as assessed from QCT) and peripheral new‐bone formation, which transforms vertebral bodies into long bones. This could modify the mechanical resistance of the spine and account for the propensity for anteroposterior transvertebral and transdiscal fractures after trauma in AS.
Signal transduction in Sjögren's syndrome T cells. Abnormalities associated with a newly described human A‐type retrovirus
Authors: Flescher Eliezer , Dauphinée Michael J. , Fossum Donna , Ledbetter Jeffrey , Talal Norman 
Published: February 2007

AbstractObjective. To study the effects of a novel A‐type retrovirus, detected in cocultures of lip biopsy specimens from Sjögren's syndrome (SS) patients and a human T cell line, on the infected T cells.Methods. Interleukin‐2 (IL‐2) and IL‐6 secretion were measured by bioassay and enzyme‐linked immunosorbent assay, respectively, in the infected and noninfected cell lines. Surface antigen expression was determined by flow cytometry, using monoclonal antibodies. Protein kinase C (PKC) activity was measured using an enzyme assay kit, and calcium mobilization was assessed with a fluorescent probe.Results. Infected cells expressed less CD4 and IL‐6 receptor, but more HLA‐DR, compared with noninfected cells. Infected cells also produced less IL‐2 and displayed reduced PKC activation and calcium mobilization. A similar defect in calcium mobilization was detected in T cells from SS patients.Conclusion. These data suggest a possible involvement of the newly described retrovirus in T cell abnormalities.
Quantitative immunohistologic criteria are superior to the lymphocytic focus score criterion for the diagnosis of Sjögren's syndrome
Authors: Bodeutsch C. , De Wilde P. C. M. , Kater L. , Van Houwelingen J. C. , Van Den Hoogen F. H. J. , Kruize A. A. , Hené R. J. , Van De Putte L. B. A. , Vooijs G. P. 
Published: February 2007

AbstractObjective.The aim of the present study was to evaluate the diagnostic value of quantitative immunohistologic criteria for Sjögren's syndrome (SS) in labial salivary gland biopsies.Methods.Quantitative immunohistologic examination was performed on labial salivary gland biopsy samples from 80 healthy controls, 32 patients with primary SS, 14 patients with secondary SS, 5 with “probable” SS, 36 with keratoconjunctivitis sicca (KCS) with a lymphocytic focus score <1 on the lip biopsy, and 18 with rheumatoid arthritis (RA) without clinical evidence of SS.Results.This is the first study to show that immunohistologic criteria for SS, based on the percentages of IgA‐containing and IgG‐containing plasma cells, are able to 1) confirm the diagnosis of SS in labial salivary glands of KCS patients in the absence of grade IV lymphocytic adenitis; and 2) distinguish between a grade IV focal lymphocytic adenitis in the labial salivary glands of SS patients and of RA patients without SS.Conclusion.Quantitative immunohistologic criteria were shown to be much more sensitive and disease specific than the widely accepted grade IV lymphocytic adenitis criterion, which corresponds to a lymphocytic focus score >1, and these criteria should be included in the international diagnostic criteria for Sjögren's syndrome.
Elevated serum levels of soluble interleukin‐2 receptor in patients with Wegener's granulomatosis. Association with disease activity
Authors: Schmitt Wilhelm H. , Heesen Christoph , Csernok Elena , Rautmann Annegret , Gross Wolfgang L. 
Published: February 2007

AbstractObjective. To investigate whether soluble interleukin‐2 receptor (sIL‐2R), a marker of T cell activation, could be a useful marker of disease activity in Wegener's granulomatosis (WG).Methods. Soluble IL‐2R levels were determined by enzyme‐linked immunosorbent assay. WG disease activity in 102 patients was assessed according to clinical features and levels of classic antineutrophil cytoplasmic antibody (c‐ANCA) and C‐reactive protein (CRP).Results. Soluble IL‐2R levels were higher in patients with generalized and active disease than in those with limited and inactive disease. In 25 patients with complete clinical remission, sIL‐2R levels were significantly elevated, although levels of CRP and c‐ANCA were normal. Eight of these 25 patients had disease relapses within 6 months. Levels of sIL‐2R were significantly higher in patients who had relapses than in those who did not. Patients with clinically active WG but low c‐ANCA or CRP levels had elevated levels of sIL‐2R.Conclusion. Levels of sIL‐2R correlate with disease activity in patients with WG, and may indicate imminent relapse.
Tryptophan metabolism via the kynurenine pathway in patients with the eosinophilia–Myalgia syndrome
Authors: Silver Richard M. , McKinley Kevin , Smith Edwin A. , Quearry Bonnie , Harati Yadollah , Sternberg Esther M. , Heyes Melvyn P. 
Published: February 2007

AbstractObjective. To investigate the metabolism of L‐tryptophan (LT) via the kynurenine pathway in patients with the eosinophilia–myalgia syndrome (EMS).Methods. Measurement of LT, L‐kynurenine, and quinolinic acid in plasma and cerebrospinal fluid (CSF) from subjects with EMS, from asymptomatic users of LT, and from normal subjects.Results. Plasma LT concentrations were lower in untreated EMS patients (n = 5) than in corticosteroid‐treated EMS patients (n = 5; P < 0.05) and in asymptomatic users of LT (n = 5; P < 0.05). Untreated EMS patients, who had discontinued LT weeks to months prior to study, had significantly higher plasma levels of L‐kynurenine and quinolinic acid than did corticosteroid‐treated EMS patients (P < 0.05), normal subjects (P < 0.02), and asymptomatic users of LT (P < 0.05). EMS patients also had significantly elevated levels of L‐kynurenine (P < 0.05) and quinolinic acid (P < 0.001) in CSF compared with normal subjects. After a 1‐gm oral dose of LT, untreated EMS patients (n = 4) showed lower peak levels of LT and accentuated synthesis of L‐kynurenine and quinolinic acid, compared with these values in corticosteroid‐treated EMS patients (n = 2), who responded like normal subjects (n = 5).Conclusion. These data demonstrate that during the active phase of EMS, LT metabolism via the kynurenine pathway was accentuated, probably secondary to induction of the enzyme indoleamine‐2,3‐dioxygenase. Ingestion of large amounts of LT (median daily dose 1.5 gm) resulted in high concentrations of kynurenine‐pathway metabolites in blood and extrahepatic tissues, which was accentuated in EMS patients and which may have played a significant role in the pathogenesis of the disease.
Fecundity before disease onset in women with rheumatoid arthritis
Authors: Lee Nelson J. , Koepsell Thomas D. , Dugowson Carin E. , Voigt Lynda F. , Daling Janet R. , Hansen John A. 
Published: February 2007

AbstractObjective. To examine fecundity prior to disease onset in women with rheumatoid arthritis (RA).Methods. Two hundred fifty‐nine RA patients with an opportunity for pregnancy were compared with 1,258 control women as part of a prospective case‐control study of recent‐onset RA in women.Results. A 12‐month or longer interval to pregnancy was found in 42% of RA cases compared with 34% of controls (odds ratio = 1.44, 95% confidence interval 1.10, 1.91). This difference was not accounted for by an older age when attempting to become pregnant among the RA cases compared with the controls. The result was unrelated to rheumatoid factor or HLA‐DR4 status.Conclusion. Women with RA were found to have decreased fecundity prior to disease onset, compared with control women.
HLA–DR4 subtypes in new zealand polynesians. predominance of dw13 in the healthy population and association of dw15 with rheumatoid arthritis
Authors: Tan Paul L. J. , Farmiloe Sarah , Roberts Maurice , Geursen Arie , Skinner Margot A. 
Published: February 2007

AbstractObjective. To analyze HLA–DR4 alleles in New Zealand Polynesians with rheumatoid arthritis (RA).Methods. Thirty Polynesians and 30 Caucasians with RA, as well as 65 Polynesian and 60 Caucasian healthy blood donors, were DR4 subtyped using the polymerase chain reaction and sequence‐specific oligonucleotide probes.Results.The frequency of DR4 (DRB1*04) was increased in both Polynesian (P <0.001) and Caucasian (P <0.005) RA patients compared with race‐matched controls. Dw4 (DRB1*0401) was detected in 15 of 30 Caucasian patients but only 2 of 30 Polynesian patients (P <0.001). In Polynesians, RA was associated with Dw15 (DRB1*0405), which was present in 11 of 30 patients and 3 of 65 controls (P < 0.001). Dw13 (DRB1*0403) was the most frequent DR4 allele in healthy Polynesians, but was not significantly associated with RA.Conclusion. The predominance of the Dw13 subtype in Polynesians may explain in part the low prevalence of RA in this population. The association of Dw15 with RA in Polynesians supports the hypothesis that the third hypervariable region of DRβ determines susceptibility to RA.