bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary fish oil and olive oil supplementation in patients with Rheumatoid Arthritis clinical and immunologic effects
Authors: Kremer Joel M. , Lawrence David A. , Jubiz William , Digiacomo Ralph , Rynes Richard , Bartholomew Lee E. , Sherman Malcolm 
Published: February 2007

AbstractForty‐nine patients with active rheumatoid arthritis completed a 24‐week, prospective, double‐blind, randomized study of dietary supplementation with 2 different dosages of fish oil and 1 dosage of olive oil. Clinical evaluations were performed at baseline and every 6 weeks thereafter, and immunologic variables were measured at baseline and after 24 weeks of study. The 3 groups of patients were matched for age, sex, disease severity, and use of disease‐modifying antirheumatic drugs (DMARDs). Subjects continued receiving DMARDs and other background medications without change during the study. Twenty patients consumed daily dietary supplements of n3 fatty acids containing 27 mg/kg eicosapentaenoic acid (EPA) and 18 mg/kg docosahexaenoic acid (DHA) (low dose), 17 patients ingested 54 mg/kg EPA and 36 mg/kg DHA (high dose), and 12 patients ingested olive oil capsules containing 6.8 gm of oleic acid. Significant improvements from baseline in the number of tender joints were noted in the low‐dose group at week 24 (P = 0.05) and in the high‐dose group at weeks 18 (P = 0.04) and 24 (P = 0.02). Significant decreases from baseline in the number of swollen joints were noted in the low‐dose group at weeks 12 (P = 0.003), 18 (P = 0.002), and 24 (P = 0.001) and in the high‐dose group at weeks 12 (P = 0.0001), 18 (P = 0.008), and 24 (P = 0.02). A total of 5 of 45 clinical measures were significantly changed from baseline in the olive oil group, 8 of 45 in the low‐dose fish oil group, and 21 of 45 in the high‐dose fish oil group during the study (P = 0.0002). Neutrophil leukotriene B4 production decreased by 19% from baseline in the low‐dose fish oil group (P = 0.0003) and 20% in the high‐dose group (P = 0.03), while macrophage interleukin‐1 production decreased by 38.5% in the olive oil group (P not significant), 40.6% in the low‐dose group (P = 0.06), and 54.7% in the high‐dose group (P = 0.0005). Tritiated thymidine incorporation in peripheral blood mononuclear cells after stimulation with concanavalin A increased significantly in all 3 groups after 24 weeks, compared with baseline values. We conclude that the clinical benefits of dietary supplementation with omega‐3 fatty acids are more commonly observed in patients consuming higher dosages of fish oil for time intervals that are longer than those previously studied. Dietary supplementation with olive oil is also associated with certain changes in immune function, which require further investigation.
Noradrenergic and peptidergic nerves in the synovial membrane of the sprague‐dawley rat
Authors: Bjurholm A. , Kreicbergs A. , Ahmed M. , Schultzberg M. 
Published: February 2007

AbstractThis immunohistochemical study of nerves in the synovial tissue of Sprague‐Dawley rats demonstrated the occurrence of 4 neuropeptides and 2 enzymes that are involved in the synthesis of catecholamines. Substance P and calcitonin gene‐related peptide were colocalized in fibers that terminated as varicosal endings in the synoviocyte layer. Similarly, tyrosine hydroxylase and dopamine β‐hydroxylase, which reflect the presence of noradrenaline, were colocalized with neuropeptide Y. These fibers were predominantly found adjacent to and within blood vessel walls. Immunoreactivity to vasoactive intestinal polypeptide was seen in varicose nerve terminals in the synoviocyte layer. Many were localized in vessel walls. There is accumulating evidence of an involvement of substance P and noradrenaline in the pathogenesis of inflammatory joint disease and nociception. The role of these colocalized neuropeptides, namely, calcitonin gene‐related peptide and neuropeptide Y, in the pathophysiology of such conditions warrants further analysis.
Biliary elimination of low‐dose methotrexate in humans
Authors: Nuernberg Bernd , Koehnke Rachelle , Solsky Marilyn , Hoffman John , Furst Daniel E. 
Published: February 2007

AbstractWe studied the pharmacokinetics of methotrexate (MTX) in a 64‐year‐old man with rheumatoid arthritis. After 6 months of treatment, acute clinical complications arose, requiring emergency laparotomy and cholecystotomy. A biliary tube was inserted, and this allowed for direct analysis of the bile. The pharmacokinetics of 2 separate doses of MTX (orally and intravenously) were assessed (dosage 10 mg/m2). No substantive differences in the pharmacokinetics were found between pre‐ and post‐cholecystotomy MTX treatment, including clearance rates, volumes of distribution, and terminal half‐lives. The results, however, demonstrated a change in the bioavailability of the drug (decreasing from 84.7% to 38.9%). Based on extrapolations of the data, with assumed rates of bile flow, the findings also suggest that there is substantial biliary elimination of MTX (8.7–26.0%) and its principal 7‐hydroxy metabolite (1.5–4.6%).
Hla‐dr alleles with naturally occurring amino acid substitutions and risk for development of rheumatoid arthritis
Authors: Gao Xiaojiang , Olsen Nancy J. , Pincus Theodore , Stastny Peter 
Published: February 2007

AbstractTo determine the HLA‐DR4 subtypes associated with rheumatoid arthritis (RA), we performed amplification of DR4 DRB1 genes by the polymerase chain reaction and dot‐blots with oligonucleotide probes. In 52 HLA‐DR4+ RA patients, Dw4 was the predominant subtype. This subtype was found in 45 of 52 patients (86.5%) compared with 33 of 59 DR4+ controls (55.9%; P < 0.001). In the whole population, Dw4 also gave the highest relative risk for RA (RR = 5.31). Relative risk was also associated with DR1.1, the common white DR1 (Dw1) type, which has a third hypervariable region amino acid sequence similar to some forms of DR4 and has glycine at position 86. Variants of DR1 (DR1.2) or DR4 (Dw14.1, Dw14.1) with valine at position 86 appeared less able to confer risk for RA. Substitution of residues in the third hypervariable region of the first domain of DRB1 appeared to correlate with relative risk for RA. Among subjects having 0–1 amino acid substitutions, RA developed in 53%, whereas in subjects with 2–4 amino acid changes, RA was present in only 17.4% (P < 0.00001). DQw7 (formerly DQw3.1) was slightly increased in DR4+ RA patients compared with controls, but a striking excess of Dw4,DQw7 homozygous patients was observed. The results suggest that DQw7 may have an additional effect, possibly with a recessive mechanism, since it was observed only in DR4 homozygous patients.
Altered immune response to glycine‐rich sequences of epstein‐barr nuclear antigen‐1 in patients with rheumatoid arthritis and systemic lupus erythematosus
Authors: Petersen Jorgen , Rhodes Gary , Roudier Jean , Vaughan John H. 
Published: February 2007

AbstractPrior studies have shown that patients with rheumatoid arthritis (RA) have an increased number of circulating Epstein‐Barr virus–infected B lymphocytes and elevated titers of antibody to Epstein‐Barr nuclear antigen–1 (EBNA‐1), the major nuclear antigen expressed in latently infected B cells. However, it is not known whether antibodies from RA patients recognize the same epitopes as antibodies from normal subjects. Most of the anti–EBNA‐1 antibodies in normal subjects are directed at the glycine‐alanine repeating region of the molecule. Antibodies specific for this region are also somewhat more prevalent in RA patients than in normal subjects. A panel of synthetic peptides derived from EBNA‐1 was used to analyze the immune response to antigenic epitopes outside the glycine‐alanine region, using the peptides as solid‐phase antigen. Sera from RA patients and from systemic lupus erythematosus patients contained elevated levels of IgG antibodies to 2 non–glycine‐alanine peptides and to 3 non–glycine‐alanine peptides, respectively. Two of the 3 peptides are glycinerich, but antibodies that react with them are distinct from each other, as well as from those that react with the glycine‐alanine epitope. Eight other peptides from the C‐terminal portion of EBNA‐1 either do not react with sera or show no difference between normal subjects and patient groups. The antibodies to the glycine‐alanine peptide are enriched with k light chains, whereas antibodies to epitopes outside the glycinealanine region are not so restricted among k and λ light chains. Thus, RA patients and systemic lupus erythematosus patients have different antibody responses than do normal subjects, both quantitatively and qualitatively.
Long‐term disability and prolonged sick leaves as outcome measurements in ankylosing spondylitis: possible predictive factors
Authors: Guillemin Francis , Briançon Serge , Pourel Jacques , Gaucher Alain 
Published: February 2007

AbstractPrognostic factors for the occurrence of longterm disability and prolonged sick leave were determined in 182 patients with ankylosing spondylitis. A significant relationship appeared between functional disability (determined by the Stanford Health Assessment Questionnaire) and sex, age at disease onset, and the number of peripheral joints involved. Using a life‐table approach, the probability of prolonged sick leaves was associated with peripheral joint involvement and work that involved carrying heavy loads. Long‐term disability was more frequent after work involving exposure to cold conditions (relative risk [RR] = 2.01) and prolonged standing postures (RR = 1.34), while sedentary work (RR = 0.35) and formal vocational rehabilitation programs (RR = 0.57) seemed to protect against long‐term disability.
Interleukin‐1α, interleukin‐2, and soluble interleukin‐2 receptors in polymyositis
Authors: Wolf Robert E. , Baethge Bruce A. 
Published: February 2007

AbstractCell‐mediated immunity has been implicated in the pathogenesis of polymyositis (PM). We conducted a prospective study in which serum levels of soluble interleukin‐2 receptors (IL‐2R), IL‐1α, and IL‐2 were correlated with creatine kinase (CK) levels and clinical disease activity. Cytokines and IL‐2R were quantitated in 133 serum samples from 14 patients by use of an enzyme‐linked immunosorbent assay. In patients with acute PM (9 patients), soluble IL‐2R and IL‐1α levels were elevated initially, but declined rapidly with therapy. A significant linear relationship was found between soluble IL‐2R levels and CK levels. IL‐2 was initially detectable in only 3 patients, and it disappeared with therapy in all 3. The levels of cytokines and IL‐2R were consistently normal in patients with inactive PM (2 patients). In patients with chronic PM (3 patients), the cytokines and soluble IL‐2R levels were normal despite persistently abnormal CK levels and/or muscle weakness. Cellular IL‐2R levels correlated positively with serum levels of soluble IL‐2R. Our studies substantiate a pathogenic role for cellular immunity in PM, with the finding of activation of lymphocytes. The finding of increased levels of IL‐1α demonstrates for the first time that there is monocyte activation in PM. Persistent elevation of CK levels after normalization of the levels of cytokines and IL‐2R may be prognostic of impending chronic disease. Serum soluble IL‐2R appear to be a sensitive indicator of improvement or exacerbation of disease activity in patients with PM.
Elevated substance p and accelerated cartilage degradation in rabbit knees injected with interleukin‐1 and tumor necrosis factor
Authors: O'Byrne Elizabeth M. , Blancuzzi Vincent , Wilson Douglas E. , Wong Mary , Jeng Arco Y. 
Published: February 2007

AbstractCytokines, interleukin‐1 (IL‐1), tumor necrosis factor α, and the neurotransmitter, substance P, have been implicated in the pathogenesis of arthritis because they stimulate synovial cells to secrete prostaglandin E2 and collagenase in vitro. We investigated in vivo changes in intraarticular substance P and the degradation of cartilage proteoglycan in response to intraarticular cytokine injections in rabbits. Twenty‐four hours after a single injection of 10 ng, 30 ng, or 100 ng of recombinant human IL‐1α (rHuIL‐1α) per joint, the mean ± SEM levels of substance P detected in the cell‐free joint lavage fluid were 250 ± 67 fmoles, 480 ± 60 fmoles, and 530 ± 130 fmoles (n = 4–5), respectively. The level of substance P in the contralateral knees injected with diluent was 58 ± 8 fmoles (n = 12). The level of substance P had increased by 2 hours after IL‐1 injection and remained elevated in the joint 48 hours after injection. Cytokineinduced proteoglycan depletion was also time‐ and dose‐dependent. Proteoglycan concentrations in articular cartilage dissected from the weight‐bearing condyles were calculated as the ratio of sulfated glycosaminoglycan measured using 1,9‐dimethylmethylene blue: hydroxyproline. After 48 hours, 10 ng, 30 ng, or 100 ng of rHuIL‐la per joint decreased proteoglycan levels by 9 ± 4%, 14 ± 4%, and 21 ± 3% (n = 8), respectively. Likewise, the injection of recombinant human tumor necrosis factor α induced depletion of intraarticular substance P and cartilage proteoglycan.
Metabolic and ultrastructural changes in articular cartilage of rats fed dietary supplements of omega‐3 fatty acids
Authors: Lippiello Louis , Fienhold Margery , Grandjean Carter 
Published: February 2007

AbstractA “marginally deficient” essential fatty acid state was produced in male Sprague‐Dawley rats by dietary supplementation with Ω3 fatty acids. Animals fed diets containing the highest amounts of these fatty acids (10% menhaden fish oil) demonstrated a 70% maximum decrease in the linoleic and arachidonic acid content of articular cartilage, a 30–40% decrease in cartilage hexosamine content, with little effect on hydroxyproline levels, and a 32% inhibition of proteoglycan synthesis. Histologic analysis revealed an occasional surface irregularity and localized depletion of Safranin O and toluidine blue staining of articular cartilage on the femoral heads from animals taking the higher doses. Electron microscopic analysis revealed a marked decrease in “dark‐staining” chondrocytes relative to “light‐staining” cells in all animals fed menhaden fish oil. The cartilaginous changes noted in this study reflect a causal relationship between chondrocyte metabolism and an altered unsaturated fatty acid content. The observed responses of chondrocytes to Ω3 fatty acids may be similar to those commonly associated with the development of early osteoarthrosis. It is not known whether similar changes are induced in other species, including humans, but these observations suggest that some caution must be taken in the long‐term adminitration of menhaden fish oil or other Ω3 fatty acid‐containing preparations in rheumatoid arthritis patients.
MULTICENTRIC RETICULOHISTIOCYTOSIS IN A PATIENT WITH MALIGNANT MELANOMA: A RESPONSE TO CYCLOPHOSPHAMIDE AND A UNIQUE CUTANEOUS FEATURE
Authors: Kenik Jay G. , Huerter Christopher J. , Hurley John A. , Stanosheck James F. 
Published: February 2007

AbstractWe describe a patient with multicentric reticulohistiocytosis and a history of malignant melanoma. His widely disseminated disease did not affect the site of surgical removal of the malignant melanoma nor the donor site of a skin graft. The multicentric reticulohistiocytosis progressed while the patient was taking nonsteroidal antiinflammatory agents, but showed significant response during a 10‐month course of cyclophosphamide. While he was taking the cyclophosphamide, however, his melanoma recurred, and the patient subsequently died.
SCINTIGRAPHIC EVALUATION OF LUMBOSACRAL PAIN IN BRUCELLOSIS
Authors: Cordero‐Sánchez M. , Alvarez‐Ruiz S. , López‐Ochoa J. , Garcia‐Talavera J. R. 
Published: February 2007

AbstractLow back pain is the most frequent rheumatologic manifestation of brucellosis. The diagnosis of brucellar sacroiliitis is hampered by the poor specificity of the clinical data and the poor sensitivity of the radiologic data. In this report, we show that scintigraphy not only increases the sensitivity but also allows an earlier diagnosis of disease and permits the detection of osteoarticular brucellar involvement in areas adjacent to the sacroiliac joint.
The longitudinal course of hand osteoarthritis in a male population
Authors: Kallman Douglas A. , Wigley Fredrick M. , Scott William W. , Hochberg Marc C. , Tobin Jordan D. 
Published: February 2007

AbstractIn this prospective analysis of the natural history of osteoarthritis (OA) of the hand, the incidence and progression of various radiographic features of OA were examined in 177 men who participated in the Baltimore Longitudinal Study of Aging. Subjects who were less than 60 years old were selected based on the availability of at least 4 hand radiographs taken during at least 20 years of followup, while subjects who were age 60 or older were required to have had at least 4 hand radiographs taken during only 14 years of followup. Individual joints of the hands were graded for the presence and severity of 5 features of OA: osteophytes, joint space narrowing, subchondral sclerosis, lateral deformity, and cortical collapse. They were also graded according to the global Kellgren/Lawrence scale. The incidence and rate of progression of OA, as measured by all scales, increased in progressively older age groups. Cox's proportional hazards models showed that isolated doubtful osteophytes (Kellgren/Lawrence grade 1) and isolated joint space narrowing predicted the development of the radiographic features of OA. The rate of OA progression slowed as the severity increased. We conclude that, in men, the incidence of radiographic features of hand OA increases with age. Regardless of age, the earliest radiographic signs of OA are joint space narrowing and doubtful osteophytes.
Synovitis and osteoarthritic changes in canine articular cartilage after anterior cruciate ligament transection. Effect of surgical hemostasis
Authors: Myers Stephen L. , Brandt Kenneth D. , O'Connor Brian L. , Visco Denise M. , Albrecht Marjorie E. 
Published: February 2007

AbstractAnterior cruciate ligament transection (ACLT) in the dog produces changes in the articular cartilage of the unstable knee that are consistent with those of osteoarthritis (OA). To determine whether the degrees of severity of OA cartilage changes, of synovitis, and of synovial iron deposition were related to adequacy of hemostasis at the time of ACLT, a modified surgical technique was devised, whereby electrocautery was used to obtain meticulous control of bleeding when the ligament was severed and irrigation was used to remove intraarticular blood before closure of the joint. When no particular attention was given to hemostasis, 69% of the dogs showed synovitis in the OA knee 10 weeks after ACLT; when electrocautery and irrigation were used to maintain hemostasis, synovitis was present in only 24% of the OA knees 10 weeks after ACLT (P < 0.01). Iron deposits were present in 75% of synovial samples obtained after routine ACLT, but in only 6% (P < 0.001) when attention was given to hemostasis.Hypertrophy of articular cartilage, chondrocyte cloning, fibrillation, and changes in tangential zone chondrocytes were less prominent in the OA knee when electrocautery and irrigation were used. However, the water content, uronic acid concentration, and rate of net 35S‐labeled glycosaminoglycan synthesis were similarly increased regardless of the surgical technique used, and presumably, these changes reflect the reaction of joint cartilage to mechanical instability in this model of OA.
Vitamin e status during dietary fish oil supplementation in rheumatoid arthritis
Authors: Tulleken Jacob E. , Limburg Pieter C. , Muskiet Frits A. J. , Rijswijk Martin H. Van 
Published: February 2007

AbstractThe primary objective of this study was to determine whether it is the fish oil itself or the α‐tocopherol that is added to the fish oil preparations (to prevent peroxidation) that is responsible for the beneficial effects of dietary supplementation with fish oil in patients with rheumatoid arthritis (RA). One group of RA patients took fish oil supplements and another group took α‐tocopherol‐enriched coconut oil supplements (placebo controls), both for 3 months. Clinical and laboratory indices of RA activity in relation to cellular and plasma vitamin E levels were assessed at the beginning and the end of the trial. The results of the study provide evidence that the beneficial effects of fish oil supplementation cannot be ascribed to the antioxidizing properties of the α‐tocopherol per se.
The analysis of antinuclear and antinucleolar autoantibodies of scleroderma by radioimmunoprecipitation assays
Authors: Kipnis Robert J. , Craft Joe , Hardin John A. 
Published: February 2007

AbstractWe have characterized autoantibodies to nuclear and nucleolar antigens in 112 patients with diffuse scleroderma, CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), scleroderma overlap syndromes, or primary Raynaud's phenomenon by indirect immunofluo‐rescence and radiolabeled immunoprecipitation assays. We noted for the first time that anti‐Th RNP antibodies represent a common antibody specificity in scleroderma (occurring in 13% of patients with scleroderma‐like illnesses) and that anti‐NOR 90 antibodies are quite rare in American patients (none found). In addition, we describe 3 new scleroderma‐associated autoantibodies.