bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐2 diphtheria fusion protein (dab486il‐2) in refractory rheumatoid arthritis a double‐blind, placebo‐controlled trial with open‐label extension
Authors: Moreland Larry W. , Sewell K. Lea , Trentham David E. , Bucy R. Pat , Sullivan William F. , Schrohenloher Ralph E. , Shmerling Robert H. , Parker Karen C. , Swartz William G. , Woodworth Thasia G. , Koopman William J. 
Published: February 2007

AbstractObjective. This pilot phase II, double‐blind, placebo‐controlled trial of 1 month duration, with a 2–3‐month open‐label extension, evaluated the safety, tolerability, biologic effects, and efficacy of interleukin‐2 diphtheria fusion protein (DAB486IL‐2) in refractory rheumatoid arthritis (RA).Methods. Forty‐five RA patients were enrolled in the trial, and were randomized, after a 3–4‐week diseasemodifying antirheumatic drug washout, to receive a daily intravenous dose of either DAB486‐IL‐2 or placebo (saline) for 5 days. A blinded, third‐party observer evaluated arthritis activity. Clinical response was defined as ≥25% improvement in swollen and tender joints and ≥25% improvement in at least 2 of 6 additional parameters. The double‐blind phase was 4 weeks; placebo patients could cross over to receive open‐label treatment for a maximum of 3 monthly DAB486IL‐2 cycles.Results. In the double‐blind phase, 4 of 22 patients (18%) in the treated group and none in the placebo group (P = 0.05) met the criteria for clinical response. During the open‐label treatment phase, 11 of 36 patients (31%) and 11 of 33 patients (33%) had a clinical response after completing 2 and 3 courses of DAB486IL‐2, respectively. Adverse events included transient fever/chills (45%), nause/vomiting (50%), elevated (≥13x normal) transaminases (55%), and increased joint pain (45%). Twelve patients (8 placebo, 4 DAB486IL‐2) did not complete 3 treatment cycles. No apparent differences were noted in CD4+ CD25+ cells of responders versus nonresponders, or of DAB486IL‐2‐treated versus placebo‐treated patients.Conclusion. Clinical responses were noted in patients treated with DAB486IL‐2 (18%) compared with placebo (0%) in the double‐blind phase. In the open‐label phase, 33% of patients completing 3 monthly DAB486IL‐2 cycles had improvement in arthritis activity. Further studies of IL‐2 diphtheria fusion proteins are warranted to elucidate factors that may predict clinical response and define mechanism(s) of action.
Longitudinal study of hand bone densitometry in rheumatoid arthritis
Authors: Deodhar Atul A. , Brabyn J. , Jones Peter W. , Davis Martin J. , Woolf Anthony D. 
Published: February 2007

AbstractObjective. To measure hand bone mineral content (BMC) by dual x‐ray absorptiometry and to seek clinical correlates in patients with rheumatoid arthritis (RA), in a prospective, longitudinal study.Methods. Eighty‐one patients with non–steroidtreated RA were assessed at baseline and at month 12, for hand BMC and for disease activity and severity. Hand BMC in patients was compared with that in a control group of 95 normal volunteers, and rate of loss was compared with that in 37 controls.Results. At the initial assessment, male and female patients with RA had lower hand BMC than controls, after correction for age, height, and weight (mean reduction 7.5% in men [P = 0.003] and 7.8% in women [P = 0.01]). After 1 year, there was a further loss of hand BMC in patients (median loss 3.25% in men [P = 0.001] and 1.46% in women [P = 0.05]), but normal controls did not have significant changes in their hand BMC. In patients with disease duration of <2 years at study entry, the parameters of disease activity improved over 1 year, but they lost significant amounts of hand BMC. Hand BMC loss correlated with baseline C‐reactive protein levels. In those with RA of >2 years duration at entry, the Health Assessment Questionnaire scores and Larsen scores had worsened after 1 year, but there was no significant loss of hand BMC.Conclusion. Patients with RA had low hand BMC compared with normal controls, even within 2 years of disease onset. The rate of loss was highest in patients with early disease and correlated with measures of initial disease activity. This loss continued despite clinical improvement.
Sleep electroencephalography and the clinical response to amitriptyline in patients with fibromyalgia
Authors: Carette Simon , Oakson Gerald , Guimont Chantal , Steriade Mircea 
Published: February 2007

AbstractObjective. To determine the prevalence and clinical correlations of an anomaly consisting of electroencephalographic (EEG) waves within the alpha frequency band during non–rapid eye movement (NREM) sleep in patients with fibromyalgia, and to evaluate the alpha NREM sleep anomaly as a predictor of response to amitriptyline.Methods. Twenty‐two patients with fibromyalgia were studied in a 2‐month, double‐blind, crossover trial of amitriptyline (25 mg/day) versus placebo. Nocturnal EEGs were conducted on 2 consecutive nights at baseline and at the end of each 2‐month treatment period.Results. Six patients (27%) had a clinical response to amitriptyline, while none responded to placebo (P = 0.02). Treatment with amitriptyline or placebo did not result in any changes in the alpha ratings during NREM sleep. Only 8 patients (36%) exhibited the alpha NREM sleep anomaly at baseline. Those patients reported more sleep difficulty, but otherwise were clinically indistinguishable from those without this EEG sleep anomaly. Lower baseline alpha NREM sleep ratings were seen in responders to amitriptyline than in nonresponders, but these differences did not reach statistical significance.Conclusion. The alpha NREM sleep anomaly is present in only a small proportion of patients with fibromyalgia. It does not correlate with disease severity nor is it affected by treatment with amitriptyline. A larger sample size will be needed to adequately assess the value of this sleep anomaly in predicting the response to amitriptyline.
A longitudinal study of functional disability in a national cohort of patients with polymyositis/dermatomyositis
Authors: Clarke Ann E. , Bloch Daniel A. , Medsger Thomas A. , Oddis Chester V. 
Published: February 2007

AbstractObjective. To analyze changes in functional status and the factors contributing to disability in a national inception cohort of 257 patients with polymyositis/dermatomyositis (PM/DM).Methods. Data were gathered from patients' self‐reports on questionnaires: one concerning disease‐ and treatment‐related complications, and the other concerning disability, as reflected by a disability index (DI) derived from the Health Assessment Questionnaire (HAQ).Results. Based on certain characteristics that differentiated disability patterns, 3 groups of patients were identified. Group 1 patients (n = 153) were ≥60 years old and never had avascular necrosis (AVN) or a vertebral compression fracture (CF), Group 2 patients were >60 and never had AVN or a vertebral CF, and Group 3 patients reported AVN or a vertebral CF irrespective of age. As measured by the HAQ DI, disability increased very gradually over time in Group 1 patients and more rapidly in Group 2 and Group 3 patients. The increase in disability in patients experiencing AVN was greater than that in patients with similar pre‐AVN disease characteristics who did not develop AVN (P = 0.003).Conclusion. In this prospective study of disease course and iatrogenic factors related to functional disability in PM/DM, the HAQ DI increased with disease duration. Corticosteroid‐related morbidity, as reflected by the development of AVN or CF, significantly contributed to patient‐reported functional disability.
Nonsteroidal antiinflammatory drug‐induced gastroduodenal injury in children
Authors: Dowd James E. , Cimaz Rolando , Fink Chester W. 
Published: February 2007

AbstractObjective. To determine the incidence of abdominal pain and gastroduodenal injury in children with arthritis taking nonsteroidal antiinflammatory drugs (NSAIDs).Methods. A retrospective review of the records of all children (570 patients) receiving followup care in an academic rheumatology clinic between 1991 and 1993 was performed.Results. There were 344 patients who used NSAIDs during the study period. Abdominal pain was recorded in 27.9% of patients taking NSAIDs and 14.6% of patients not taking NSAIDs. Abdominal pain in 47 patients (49%) taking NSAIDs and 14 patients (42%) not taking NSAIDs was evaluated radiographically and/or endoscopically. Among those patients evaluated, gastric or duodenal injury was found in 16 (34.0%) who were taking NSAIDs and 1 (7.1%) who were not. This represented a relative risk for gastroduodenal injury of 4.8 for patients taking NSAIDs (P = 0.09). The incidence of injury did not change when analyses were controlled for prednisone or slow‐acting antirheumatic drug use. None of the children were hospitalized or died as a result of gastroduodenal injury during the 3‐year period.Conclusion. We conclude that NSAID use in children with arthritis frequently leads to gastroduodenal injury, with an estimated incidence and relative risk that are comparable to the rates found in adults with arthritis taking NSAIDs, but that hospitalization or death as a result of this injury is uncommon.
Number of children as a risk factor for low back pain in men and women
Authors: Silman Alan J. , Ferry Susan , Papageorgiou Ann C. , Jayson MALCOLM I. V. , Croft Peter R. 
Published: February 2007

AbstractObjective. To estimate the influence of the number of liveborn children on the risk of low back pain.Methods. The study design was a cross‐sectional population‐based survey. The 4,501 respondents to a postal survey were asked to provide data on the occurrence of low back pain and on any children they had. Data on some potential confounding variables were also obtained.Results. There was an increased risk of low back pain in those who were married compared with those who were unmarried, among both men (odds ratio 1.7) and women (odds ratio 1.6). Among married individuals, there was a linear trend of increasing risk with increasing numbers of children.Conclusion. The risk of low back pain is related more to childrearing than to childbearing, although this effect might be partially mediated by unknown confounders associated with increasing family size.
Emergence of oligoclonal t cell populations following therapeutic t cell depletion in rheumatoid arthritis
Authors: Jendro Michael C. , Ganten Tom , Matteson Eric L. , Weyand Cornelia M. , Goronzy JÖRg J. 
Published: February 2007

AbstractObjective. To examine the compartment of CD4+ T cells in patients with rheumatoid arthritis (RA) who have developed persistent lymphopenia following antibody‐mediated T cell depletion and to investigate why T cell depletion is of limited therapeutic efficacy.Methods. Circulating T lymphocytes from 10 patients with seropositive RA treated with the monoclonal antibody (MAb) CAMPATH‐1H were longitudinally monitored by fluorescence‐activated cell sorter analysis with MAb. To assess the molecular diversity of repopulating T cells, random samples of T cell clones from the peripheral blood of 3 patients were analyzed by sequencing the T cell receptor (TCR) β chains. At the time of recurring disease, the synovial tissue was examined by immunohistochemistry, and the repertoires of peripheral and synovial tissue T cells were compared by TCR β‐chain sequencing and by semiquantitative hybridization with oligonucleotides specific for the V–D–Jβ junctional region of selected clones.Results. The reconstitution of the peripheral T cell compartment was very slow. A mean CD4+ T cell count of 105/μl was reached 34 weeks following MAb treatment. After treatment, the percentage of CD4+ T cells with the CD45RO+ phenotype was significantly increased (P = 0.001), indicating the expansion of antigen‐primed memory T cells. TCR β‐chain sequences revealed a marked restriction in the diversity of repopulating T cells with the emergence of dominant clonotypes. Despite the low counts of peripheral CD4+ T cells, the synovial tissue was infiltrated by CD4+ T cells to a similar extent as that in RA patients not treated with MAb. Selected clonotypes that had emerged in the peripheral blood compartment dominated the repertoire of tissue‐infiltrating T cells in the synovium.Conclusion. In patients with RA, T cell depletion induces a long‐term imbalance in T cell homeostasis. Clonal proliferation of CD4+ T cells severely restricts the diversity of available T cell specificities and results in the emergence of dominant clonotypes, which accumulate in the synovial tissue despite peripheral lymphopenia.
Hematologic and cytofluorographic analysis of patients with feltyapos;s syndrome a hypothesis that a discrete event leads to large granular lymphocyte expansions in this condition
Authors: Bowman S. J. , Corrigall V. , Panayi G. S. , Lanchbury J. S. 
Published: February 2007

AbstractObjective. To compare hematologic and cyto‐fluorographic features in Feltyapos;s syndrome (FS) patients with and without the large granular lymphocyte (LGL) syndrome.Methods. Peripheral blood cells from FS patients and from 2 control groups (rheumatoid arthritis [RA] patients and subjects without symptoms of a rheumatic disease) were analyzed by hematologic and cytofluorographic techniques. A separate assessment of disease activity was performed.Results. FS patients had reduced lymphocyte and platelet counts, with a parallel reduction in lymphocyte subsets examined. CD4 counts were reduced in all FS patients, including those with the LGL syndrome. Disease activity was lower in FS patients than in RA control patients. Treatment was similar in all patient groups. No direct association was seen between LGL numbers and duration of RA or neutrophil counts in RA groups.Conclusion. Hematologic abnormalities in FS extend beyond neutropenia. Although similarities were seen between FS patients and FS patients with the LGL syndrome (e.g., CD4 lymphopenia), evidence for a gradation from FS to the LGL syndrome was not seen, thus favoring the hypothesis that a “transforming event” is required.
Heterogeneity in the expression of ro and la antigens in human skin
Authors: Niimi Yayoi , Ioannides Demetris , Buyon Jill , Bystryn Jean‐Claude 
Published: February 2007

AbstractObjective. To determine whether there are variations in the expression of Ro and La antigens in human skin.Methods. Levels of expression of Ro and/or La antigens in 26 specimens of normal human skin (11 sun‐exposed, 15 sun‐protected) were measured by indirect immunofluorescence with monospecific antisera.Results. Levels of expression of both antigens varied by more than 2,000‐fold in the skin of different individuals. There usually was a correlation between the levels of expression of Ro and La antigens in the same skin specimen. There was no correlation found between the levels of Ro or La antigen expression and sun exposure, nor was there a correlation found between levels of antigen expression and location of the skin on the body.Conclusion. There is a marked heterogeneity in the expression of both Ro and La antigens in the skin of different individuals. The present study findings suggest that the levels of expression of these antigens may play a role in the propensity of some individuals to develop anti‐Ro or anti‐La antibodies and/or skin lesions associated with the presence of these antibodies.
Effects of tenidap on canine experimental osteoarthritis i. morphologic and metalloprotease analysis
Authors: Fernandes Julio C. , Martel‐Pelletier Johanne , Otterness Ivan G. , Lopez‐Anaya Arturo , Mineau François , Tardif Ginette , Pelletier Jean‐Pierre 
Published: February 2007

AbstractObjective. To examine the effects of tenidap and diclofenac on osteoarthritic lesions and metalloprotease activity in experimental osteoarthritis (OA).Methods. The anterior cruciate ligament of the right stifle joint of 25 mongrel dogs was sectioned by a stab wound. Seven dogs received no treatment, 6 were treated with oral omeprazole (20 mg/day), another 6 were treated with diclofenac (0.25 mg/kg/twice daily) plus omeprazole (20 mg/day), and 6 received oral tenidap (3 mg/kg/twice daily) plus omeprazole (20 mg/day). The dogs received medication for 8 weeks; all dogs were killed at the end of this period. Eight normal dogs were used as controls. Lesions were evaluated macroscopically for the incidence and size of osteophytes and the area and grade of cartilage erosions on the condyles and plateaus, along with histologic evaluation of the severity of the cartilage lesions and synovial inflammation. Stromelysin and collagenase activities and the collagenase messenger RNA (mRNA) level were measured in cartilage and synovial membrane.Results. Compared with the untreated or omeprazole‐treated OA groups, the dogs treated with tenidap exhibited significant reduction in the incidence (P < 0.001) and size (P < 0.0001) of osteophytes. Tenidap also significantly decreased the size and grade of cartilage macroscopic lesions, as well as the histologic severity of cartilage lesions on both condyles and plateaus. The histologic severity of synovial inflammatory reaction was also significantly reduced (P < 0.003) in the tenidap group. Tenidap markedly decreased stromelysin and collagenase activity in both cartilage (stromelysin P < 0.003; collagenase P < 0.01) and synovial membrane (stromelysin P < 0.003; collagenase P < 0.005). Moreover, tenidap also decreased the collagenase mRNA level in cartilage (P < 0.005) and synovial membrane (P < 0.002). Diclofenac slightly reduced the incidence and size of osteophytes and cartilage lesions, but these changes were not statistically significant. Diclofenac had no effect on the severity of synovial inflammation, metalloprotease activity, or collagenase expression.Conclusion. This study showed that tenidap had a more potent anti‐osteoarthritic effect than diclofenac in this model. The effect of the drug in suppressing metalloprotease synthesis, a process known to play a major role in the pathophysiology of osteoarthritic lesions, may explain its mechanism of action.
Signal transduction through chondrocyte integrin receptors induces matrix metalloproteinase synthesis and synergizes with interleukin‐1
Authors: Arner E. C. , Tortorella M. D. 
Published: February 2007

AbstractObjective. To study the role of signal transduction via integrin receptors in the production of metalloproteinase by rabbit articular chondrocytes.Methods. Confluent, primary rabbit articular chondrocytes (RAC) were incubated for 72 hours in the presence of interleukin‐1 (IL‐1), Arg‐Gly‐Asp (RGD) peptide, or a combination of IL‐1 and RGD peptide. Media were analyzed for stromelysin enzymatic activity using a 3H‐labeled transferrin substrate, and for stromelysin and collagenase protein by Western analysis. Gelatinase activity was analyzed by gelatin zymography. IL‐1 receptor antagonist (IL‐1Ra) protein was used to determine the involvement of IL‐1 in mediating the effects of RGD peptide, and fluorescence‐activated cell sorter analysis (FACS) was used to examine the effect of IL‐1 on chondrocyte integrin subunit expression.Results. RGD peptides induced chondrocyte synthesis of stromelysin, collagenase, and 92‐kd gelatinase B, and increased synthesis of the constitutively expressed 72‐kd gelatinase A. Further studies focusing on stromelysin demonstrated that this up‐regulation was concentration dependent and that RGD peptides synergized with IL‐1 in inducing stromelysin synthesis. RGD‐induced stromelysin production was inhibited by the IL‐1Ra in a concentration‐dependent manner, indicating that induction by RGD requires binding of IL‐1 to its receptor. FACS analysis of RAC showed that IL‐1 stimulation increased the expression of β1 and αv integrin subunits on the chondrocyte surface.Conclusion. Our data demonstrate that signal transduction through chondrocyte integrin receptors up‐regulates metalloproteinase expression and that this is likely mediated through induction of IL‐1. They also suggest that the binding of adhesion molecules to their chondrocyte integrin receptors reduces the amount of IL‐1 required to induce stromelysin synthesis. Up‐regulation of chondrocyte integrin expression by IL‐1 may play a role in the synergistic effects seen with a combination of IL‐1 and RGD peptides. Since elevated levels of both IL‐1 and adhesion molecules are present in rheumatoid arthritis and osteoarthritis synovial fluid, our data suggest that this interaction may be important in mediating the cartilage destruction accompanying these diseases.
Tuberculous and foreign‐body granulomatous reactions involving a total knee prosthesis
Authors: Lusk Rodney H. , Wienke Eugene C. , Milligan Thomas W. , Albus Thomas E. 
Published: February 2007

AbstractThis case report describes loosening of a right knee prosthesis and represents the first report of the simultaneous occurrence of 2 granulomatous processes involving a prosthetic joint. Microscopic examination of the tissue revealed areas of foreign‐body granulomas and areas of necrotizing granulomas and caseation. Acid‐fast bacilli cultures were positive for Mycobacterium tuberculosis. The pathophysiology of implant loosening following an inflammatory reaction to components of prosthetic materials is discussed. Also discussed is the occurrence of infectious complications and rarity of tuberculous infections associated with prosthetic implants.
Glomerulonephritis associated with complete deficiency of the fourth component of complement response to intravenous immunoglobulin
Authors: Welch Thomas R. , McAdams A. James , Beischel Linda S. 
Published: February 2007

AbstractA 15‐year‐old girl with complete C4 deficiency and a lupus‐like disorder developed evidence of nephritis after 4 years of followup. Renal biopsy demonstrated an immune complex glomerulonephritis, with deposits in the capillary loops, the paramesangium, and the mesangial matrix. Renal function was normal. The patient was treated with monthly infusions of intravenous immunoglobulin for 6 months. The treatment was well tolerated, and resulted in resolution of the rash and hematuria. Followup biopsy showed less proliferation and fewer loop deposits. In light of the serious risk of infections that is associated with complement deficiency, approaches to glomerulonephritis that do not include immunosuppression should be considered.
Hydatid disease an unusual cause of chronic monarthritis
Authors: Campoy E. , Rodriguez‐moreno J. , Del Blanco J. , Narvaez J. , Clavaguera T. , Roig‐escofet D. 
Published: February 2007

AbstractWe describe a patient with granulomatous synovitis secondary to osseus hydatid disease that manifested with chronic monarthritis, eosinophilia, and urticaria.
Special article the economic cost and social and psychological impact of musculoskeletal conditions
Authors: Yelin Edward , Callahan Leigh F. ,   THE NATIONAL ARTHRITIS DATA WORK GROUP
Published: February 2007

AbstractObjective. To provide an indication of the economic, social, and psychological impact of musculoskeletal conditions in the United States.Methods. Review of the literature combined with estimates of data concerning health care utilization and acute and chronic disability due to musculoskeletal conditions, from the 1990–1992 National Health Interview Survey.Results. The cost of musculoskeletal conditions was $149.4 billion in 1992, of which 48% was due to direct medical care costs and the remainder was due to indirect costs resulting from wage losses. This amount translates to ˜2.5% of the Gross National Product, a sharp rise since the prior studies, even if part of the increase is an artifact of improved accounting methods. Each year, persons with musculoskeletal conditions make 315 million physician visits, have more than 8 million hospital admissions, and experience ˜1.5 billion days of restricted activity. Approximately 42% of persons with musculoskeletal conditions–more than 17 million in all–are limited in their activities.Conclusion. The economic and social costs of musculoskeletal conditions are substantial. These conditions are responsible for a sizable amount of health care use and disability, and they significantly affect the psychological status of the individuals with the conditions as well as their families.