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ID PMID Title PublicationDate abstract
10220730 [Bilateral neuroretinitis with zoster infection]. 1999 Mar BACKGROUND: Infections with varicella zoster virus may involve the optic nerve and the retina. Different pathomechanisms have been discussed. We present a case with an autoimmune inflammatory reaction according to the clinical course. PATIENT: A 69-year-old female was referred to our clinic because of suspected bilateral anterior ischemic optic neuropathy. She complained of severe visual loss the day before admission. Her ophthalmological and general history was unremarkable apart from treatment with 5 to 7.5 mg prednisolone alternately because of rheumatoid arthritis. Best corrected visual acuity was 1/15 OD and 0.1 OS. A relative afferent pupillary defect on the right eye was present. Optic disc oedema with multiple hemorrhages of the retina extending into the peripheral funds, slightly attenuated retinal arteries and macular oedema were seen fundoscopically in both eyes. THERAPY AND CLINICAL OUTCOME: After immediate treatment with steroids (initial dose 250 mg prednisolone per day) visual acuity improved. Because of a clinically suspected and serologically proven active varicella-zoster infection an additional virostatic therapy with valaciclovir was started and steroids were lowered gradually. Within 2 months, visual acuity increased to 0.8 OD and 1.0 OS. Oedema of optic discs and macula resolved and retinal hemorrhages disappeared. CONCLUSION: A severe hemorrhagic neuro-retinitis involving the optic discs was seen in the course of a varicella-zoster infection, possibly reactivated by chronic steroid therapy of a rheumatoid arthritis. Because of the normalization of visual function an ischemic pathogenesis is unlikely. An autoimmune inflammatory reaction seems to be the predominant mechanism, supported by the good effect of steroid and valaciclovir therapy.
11420844 [The lack of awareness of the Israeli population regarding gastrointestinal complications 2001 Jun Non-steroidal anti-inflammatory drugs (NSAID) are potent analgesic agents. They are indicated for rheumatoid arthritis, osteoarthritis, severe acute and prolonged chronic pain. A wide range of analgesic agents are available. The objective of this study was to assess the patient's knowledge of his illness, his knowledge familiarity with NSAID medications and their side effects and thereupon, to evaluate the awareness, utilization, satisfaction and expectations associated with current available treatment. During the year 2000, a randomized telephone screening questionnaire, was completed over a 2 month period for a sample group of the general Israeli population over 50 years of age. Of the 3179 persons contacted, 2028 responded and 292 persons were treated with NSAIDs and further investigated. Fifty percent suffered from chronic musculoskeletal pain, 22% had osteoarthritis, 10% had rheumatoid arthritis, and 18% had undefined chronic pain. The average age of the respondent was 65 years old. The average duration of treatment was 11 years. The most common drugs used by the 292 respondents that were taking NSAIDs were diclofenac (Voltaren)--51% and naproxen (Naxyn)--21%. Only 4% were treated with COX-2 specific inhibitors. Twenty percent of the respondents utilized more than one NSAID simultaneously. Forty seven percent of the patients had peptic ulcer disease but only 39% of them were simultaneously treated with an NSAID and a gastroprotective agent. Sixty eight percent of patients expected amelioration of symptoms while taking NSAIDs. Seventy seven percent of respondents were dissatisfied with treatment. The patients expressed that they did not have a reliable easily accessible source of information on their disorder or on available treatment options. Many respondents were not aware of their medical diagnosis. In general, patients were not aware of all the available NSAIDs or the side effects of gastrointestinal complications. Enhancement of information available to the patient is warranted to improve the provision of efficient therapy, reduce side effects and increase patient satisfaction from therapy.
11024117 Impaired gamma interferon responses against parvovirus B19 by recently infected children. 2000 Nov Parvovirus B19 is the causative agent of "fifth disease" of childhood. It has been implicated in a variety of conditions, including unsuccessful pregnancy and rheumatoid arthritis, and is a potential contaminant of blood products. There has been little study of immunity to parvovirus B19, and the exact nature of the protective humoral and cell-mediated immune response is unclear. Immune responses to purified virus capsid proteins, VP1 and VP2, were examined from a cohort of recently infected children and compared with responses from long-term convalescent volunteers. The results demonstrate that antibody reactivity is primarily maintained against conformational epitopes in VP1 and VP2. The unique region of VP1 appears to be a major target for cell-mediated immune responses, particularly in recently infected individuals. We confirm that antibody reactivity against linear epitopes of VP2 is lost shortly after infection but find no evidence of the proposed phenotypic switch in either the subclass of parvovirus B19-specific antibody or the pattern of cytokine production by antigen-specific T cells. The dominant subclass of specific antibody detected from both children and adults was immunoglobulin G1. No evidence was found for interleukin 4 (IL-4) or IL-5 production by isolated lymphocytes from children or adults. In contrast, lymphocytes from convalescent adults produced a typical type 1 response associated with high levels of IL-2 and gamma interferon (IFN-gamma). However, we observed a significant (P<0.001) deficit in the production of IFN-gamma in response to VP1 or VP2 from lymphocytes isolated from children. Taken together, these results imply that future parvovirus B19 vaccines designed for children will require the use of conformationally preserved capsid proteins incorporating Th1 driving adjuvants. Furthermore, these data suggest novel mechanisms whereby parvovirus B19 infection may contribute to rheumatoid arthritis and unsuccessful pregnancy.
11005517 Semiconstrained total elbow arthroplasty for ankylosed and stiff elbows. 2000 Sep BACKGROUND: Total elbow arthroplasty can be a valuable option for the treatment of ankylosed or very stiff elbows. METHODS: A semiconstrained total elbow arthroplasty was performed in thirteen patients (fourteen elbows) with a preoperative range of elbow motion of 30 degrees or less. Nine elbows were fused or ankylosed preoperatively. The mean age at the time of the surgery was fifty years (range, twenty-four to seventy-nine years). The etiology of the stiffness was trauma for eleven elbows, juvenile rheumatoid arthritis for two, and rheumatoid arthritis for one. RESULTS: After a mean duration of follow-up of sixty-three months, the result was excellent for four elbows, good for four, fair for one, and poor for five, according to the Mayo elbow performance score. The mean arc of flexion improved from 7 degrees (range, 0 to 30 degrees) preoperatively to 67 degrees (range, 10 to 115 degrees) after the surgery. The most important factor that influenced the final result was the presence of ectopic bone surrounding the elbow joint. There were seven complications. Infection developed in five elbows. Three elbows had a superficial infection, which did not compromise the final result in two and which was treated with a myocutaneous flap in one with skin necrosis, with an excellent result. Deep infection developed in two other elbows. Both had an unsatisfactory result, one after implant removal and one after several debridements and retention of the prosthesis. Two patients sustained a fracture because of a loose component, and the prosthesis was revised. Four patients who lost motion within the first month following the surgery had a manipulation under anesthesia. CONCLUSIONS: Semiconstrained total elbow arthroplasty is a useful option for patients with an ankylosed or a very stiff elbow and results in a considerable improvement of motion. Because of the nature of the underlying pathology, complications, including reoperation, are frequent, but the risk can be lessened by careful preoperative planning and surgical technique. Replacement is the preferred option in patients who are more than sixty years of age, but it is also a good choice in younger patients if there is no other viable option.
10525691 [The evolution of ankle arthroplasty]. 1999 Sep The results of ankle arthroplasty have generally been disappointing compared to other forms of arthroplasty. The present survey of results of ankle arthroplasty deals with the anatomical, the kinemasiological the biomechanical and the biological features of the ankle joint. These features all seem important prerequisites for a successful total ankle prosthesis design. From the study of the results displayed in the literature and those of my own series it can be stated that a modern ankle arthroplasty should respect the normal anatomy and kinemasiology. Biomechanically it should work as a normal ankle joint i. e. cylindrical mobility, congruency and a possibility for normal torque within the ankle mortise. The prosthesis components should only be fixed in solid subchondral bone, and preferably without cement. Only compressible forces should act at the bone-prosthesis interface. The axis of the ankle joint as well as of that of the hindfoot should be aligned to normal. Meticulous surgery and special guide instruments are absolute necessities. Restoration of muscle power and gait postoperatively are essential for a good and lasting result. The indication for ankle arthroplasty is mainly cases of osteoarthritis (primary or traumatic) and rheumatoid arthritis. Contraindications are talus necrosis, Charcot joints, extreme osteoporosis, severe arteriosclerosis, and very aggressive arthritis. Mental disorders and neurological disorders may also be contraindications. Furthermore, the patients should agree not to perform sports involving jumping and running or other ankle demanding activities. The average annual failure rate should not exceed 1 % if these recommendations are followed.
9361154 Pharmacology and pharmacokinetics of methotrexate in rheumatic disease. Practical issues i 1997 Nov Methotrexate (MTX) is among the most effective drugs for treatment of rheumatoid arthritis and has been proven valuable in the treatment of multiple other disorders of immune regulation. MTX has been administered at a wide range of doses and dose intervals, in conjunction with multiple other drugs, and in patients with a broad range of concomitant disorders. To design a safe and effective MTX treatment plan for an individual patient, the provider must have knowledge of the pharmacology and drug interactions of this effective but potentially dangerous medication. The first section of the article reviews MTX structure, pharmacology pharmacokinetics, and mechanisms of action in rheumatic disease. The second section examines factors that can be used to increase MTX efficacy and decrease toxicity.
18982482 Protective effect of DA-9601, an extract ofArtemisiae Herba, against naproxen-induced gast 1997 Oct Gastrointestinal irritation is the most frequent adverse effect in patients chronically taking nonsteroidal antiinflammatory drugs (NSAIDs) for the treatment of arthritic conditions. Gastroprotective effect of DA-9601, a new antiulcer agent fromArtemisiae Herba extract, against NSAID was evaluated in a rat model of arthritis that is similar in many aspects to human rheumatoid arthritis. Daily oral dosing of naproxen (30 mg/kg), one of the most commonly used NSAID, induced apparent gastric lesions as well as a significant decrease in mucosal prostaglandin E(2) (PGE(2)) and prostaglandin F(1alpha) (PGF(1alpha)) levels. Coadministration of DA-9601 prevents naproxen-induced mucosal injury and depletion, of prostaglandins, in a dose-related manner. DA-9601 did not alter the antiinflammatory or analgesic effect of naproxen. The present results suggest that DA-9601 may be useful as a mucoprotectant against NSAIDs in clinical practice.
11212147 Comparison of differentiated dendritic cell infiltration of autoimmune and osteoarthritis 2001 Jan OBJECTIVE: Infiltration of rheumatoid arthritis (RA) synovial tissue (ST) by differentiated dendritic cells (DC) is a consistent feature in patients with active disease. However, mononuclear cells (MNC), including DC, may be nonspecifically chemoattracted to inflammatory sites regardless of etiology. Therefore, to evaluate the specificity of ST infiltration by differentiated DC, synovial biopsies from patients with RA, spondylarthropathy (SpA), osteoarthritis (OA), and gout were examined. METHODS: Formalin-fixed ST sections were analyzed by double immunohistochemical staining for vascularity and infiltration by differentiated DC, lymphocytes, and macrophages. RESULTS: DC containing nuclear RelB were found in perivascular MNC aggregates from patients with all arthritides studied. Infiltration by differentiated DC was similar in RA and SpA ST, but reduced in OA ST. Differentiated DC were always observed in close association with lymphocytes, and the correlation between these variables suggested that the infiltration of inflammatory sites by DC and lymphocytes was associated. CONCLUSION: Perivascular infiltration by DC, lymphocytes, and macrophages is nonspecifically related to inflammation, but signals present in RA and SpA ST lead to more intense cellular infiltration and accumulation.
11199184 Determinants of bone mineral density in older men. 2000 Although osteoporosis in men is increasingly recognized as an important health issue and bone mass appears to be a major determinant of fracture, there remain few data concerning the determinants of bone mass in men. To determine the correlates of bone density in men, we studied a large group of older subjects recruited from three rural communities in the northwestern United States. Three hundred and fifty-five men over the age of 60 years (mean 71.5 +/- 7.4 years) without known disorders of mineral metabolism were recruited by community advertising. Bone mineral density was measured at the lumbar spine, proximal femur and radius by dual-energy X-ray absorptiometry, and factors potentially related to skeletal status were assessed by direct measurements or questionnaire. In univariate analyses weight (positively) and age (negatively) were associated with bone density. After adjustment for these two factors, alcohol intake, osteoarthritis and thiazide use were associated with higher bone density, while previous fractures, gastrectomy, peptic ulcer disease, rheumatoid arthritis, glucocorticoid use, hypertension, previous hyperthyroidism, height loss since age 20 years, chronic lung disease and smoking were related to lower density. In multivariate models, only weight and a history of cancer were related to higher bone mass, and age, previous fracture, rheumatoid arthritis, gastrectomy and hypertension were associated with lower density. These data contribute to the emerging field of osteoporosis in men, and may help in the clinical identification of men at higher risk of osteopenia.
9669212 Long-term exposure to methotrexate induces immunophenotypic changes, decreased methotrexat 1997 Nov Methotrexate (MTX) treatment of rheumatoid arthritis may require increasing doses to maintain clinical efficacy. An overall plateau of clinical response is reached after only six months of treatment. To study the immunologic, biochemical and genetic effects of MTX on T cells, the Jurkat T cell line was made MTX-resistant by serial addition of methotrexate sodium into culture medium. Cells proliferated and divided successfully in MTX concentrations ranging to 15 microM. MTX resistance of Jurkat T cells in vitro was accompanied by significantly (P < 0.05) decreased expression of CD2, CD3, CD4, CD28, and CD69, IL-2 production, and MTX uptake assessed by cell association or disassociation of 3[H]-MTX or fluoresceinated MTX (FMTX), respectively. In addition, there was DHFR gene amplification and increased levels of DHFR in all resistant cell lines. Both permanent and transient phenotypic changes developed in resultant cell lines exposed to increasing concentrations of MTX in vitro. Expression of CD4 and CD25 and sensitivity to MTX returned to near-parental levels after removal of MTX from culture medium, whereas expression of CD26 and MTX uptake were significantly increased. Expression of CD2, CD3, CD69 and IL-2 production as well as the DHFR levels did not return to the parental phenotype after removal from MTX. We conclude that MTX-cultured cells express depressed levels of cell-surface markers vital for T cell function and activation. The return of enhancement of these cell-surface markers critical to T cell activation suggests a possible mechanism for the severe flares experienced by rheumatoid arthritis patients when drug treatment is discontinued.
11052465 Rheumatoid arthritis-related antigen 47kDa (RA-A47) is a product of colligin-2 and acts as 2000 We previously isolated RA-A47, which is recognized as an antigen of rheumatoid arthritis (RA), from a human chondrosarcoma-derived cell line (HCS-2/8). The N-terminal 21-amino-acid sequence of RA-A47 had 81% homology to the deduced amino acid sequence of the human heat-shock protein (HSP) 47 gene, the colligin gene, and 100% homology to that of the colligin-2 gene. Moreover, as is HSP47, RA-A47 was a heat-inducible collagen-binding protein. To further characterize RA-A47, we isolated ra-a47 cDNA from HCS-2/8 cells and human periodontal ligament fibroblast (HPLF) cells. The isolated ra-a47 cDNAs from both cells were almost the same as that of colligin-2. C504 and G505 in the cDNA sequences of both cells and C598 in the cDNA of HCS-2/8 were different from the corresponding bases of colligin-2 cDNA. These differences were also observed in genomic DNA. colligin cDNA was not isolated. To show that the isolated cDNA encodes RA-A47 protein, it was expressed in Cos-7 cells. The produced protein was 47kDa and was recognized both with RA sera and antirat HSP47 antibody, indicating that it is RA-A47 and has structural similarity to HSP47. These results taken together with our previous findings show that RA-A47 is the putative colligin-2 gene product and behaves as a human HSP47. Although colligin has been considered the human HSP47 gene, failure to detect the colligin gene and its mRNA suggests that colligin does not exist in human cells and that the HSP47 gene is identical with colligin-2, which encodes RA-A47.
10805043 Drugs-nutrient interactions: a potential problem during adolescence. 2000 Mar The concept of drug-nutrient interactions is not new, but it has only recently gained currency in medicine. Although the elderly are normally considered to be at particular risk, other groups may also be at risk: infants, adolescents, pregnant women, alcohol and tobacco users, etc. In infants and adolescents there are several factors that may influence the possible interactions: firstly, nutrient needs are usually higher, mainly micronutrients; systems for detoxification of anutrients are not complete; the tendency to restricted diets (especially girls) that are unable to cover the actual recommended intakes for a number of micronutrients (i.e. vitamins); and the dangerous increase in alcohol consumption either in males or females. Administration of drugs in population with adequate vitamin intake is usually not a problem, but administration of drugs in those with borderline intake of vitamins or in patients with low nutritional status can result in symptomatic vitamin deficiency states. The groups at risk of poor vitamin status are smokers (a high proportion of adolescents are active smokers); dieters (skipping meals and dieting to lose weight frequently compromise micronutrient intake, and it should be considered that it is extremely difficult to meet all the requirements at intakes of less than 1,200 calories per day), oral contraceptive users, and pregnant and lactating women, excessive alcohol users, etc. The chapter also focuses on the case of folate: rapidly dividing tissues during the adolescent growth spurt increase requirements for folate. Because of this increased need, folate status appears to be of concern during the age of this rapid growth. A variety of drugs are known to interfere with vitamin utilization by blocking or altering transformation of the vitamin to its metabolically active form. Serum folate levels are known to be low in a high percentage of patients with rheumatoid arthritis, suggesting that aspirin alters the transport of folate by competition for binding sites on serum proteins. Methotrexate, a drug commonly used at low doses for the treatment of psoriasis, rheumatoid arthritis and certain liver disorders, limits the availability of methyl groups derived from one-carbon metabolism by inhibiting competitively a key enzyme in the intracellular folate metabolism. In humans, the antiepileptic drug valproic acid (VPA) is associated with two major adverse effects: teratogenicity and folate deficiency. The mechanisms by which VPA exerts the teratogenic or antifolate effect remain unclear, but an alteration in the methionine cycle is the strongest hypothesis proposed.
9458211 Clinical outcome of 149 patients with polymyalgia rheumatica and giant cell arteritis. 1998 Jan OBJECTIVE: To assess the clinical outcome of patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). METHODS: All charts of consecutive patients with a diagnosis of PMR and/or GCA attending a tertiary referral center from June 1989 to February 1996 were reviewed following a predetermined protocol. Subsequently, the majority of patients (90%) were assessed clinically or by telephone interview. Registered variables included demographic data, disease characteristics, prednisone dosage and duration, comorbidities, and clinical outcomes. RESULTS: There were 149 patients (133 with PMR alone, 7 with GCA alone, 9 with both); 94 (63%) were females; the mean age was 68 +/- 9 years, and the mean disease duration from the first symptom to the rheumatology consultation was 13 +/- 12 weeks (1-99). Typical clinical features of PMR were present in patients with PMR. Synovitis was observed in 26 patients. The presenting symptoms for GCA were typical features in 13 patients and blindness in 3 (2%) patients. Mean followup was 3.7 +/- 2 years. Comorbid conditions were present in 71 patients: 12 patients had hypertension, 13 had fractures, 8 diabetes, 29 cataract, 8 major infection, and 37 had other complications. Cancer was diagnosed in 4 patients and 6 patients had died. Prednisone was prescribed in 148 patients (mean dose 23 +/- 14 mg) for a mean time of 28 +/- 29 mo. Nonsteroidal antiinflammatory drugs were prescribed in 51 (34%) patients and methotrexate in 2. Disease remission was achieved in 81 (54%) patients (72 remissions, 9 presumed remissions) in whom steroid therapy had been stopped. Another 54 (36%) patients were still taking prednisone at the time of the interview, all were in clinical remission. Seventeen patients developed rheumatoid arthritis subsequent to the diagnosis of PMR. CONCLUSION: PMR and GCA should not necessarily be considered diseases with favorable outcome. In many of our patients, steroids were required for a prolonged period. Some patients developed significant complications attributable to steroid therapy. A significant number of patients progressed to rheumatoid arthritis.
9099902 Transcriptional regulation of the human 'leukemia inhibitory factor' gene: modulation by g 1997 Mar 14 Leukemia inhibitory factor (LIF) is a pleiotropic cytokine implicated in various pathological conditions, such as rheumatoid arthritis and osteoporosis. Despite its possible importance as a therapeutic target, very little is known about the regulation of human LIF. In particular, its regulation at the promoter level has not been studied so far, and was, therefore, the focus of the present work. After showing that Jurkat T lymphoma cells can be induced to express endogenous LIF mRNA, we used this cell line as a model to study the regulation of the human LIF promoter in transient transfection assays. For this purpose, a 666 bp fragment of the human LIF 5'-flanking region, amplified from genomic DNA by nested polymerase chain reaction (PCR), was used for the construction of a luciferase reporter plasmid (hLIF666-Luc). In unstimulated Jurkat cells, the human LIF promoter showed low constitutive activity. The promoter was induced upon stimulation with phorbol ester (TPA). Combined stimulation with TPA and the calcium ionophore ionomycin resulted in strong synergistic induction of luciferase activity from the LIF promoter. Transfection experiments with deletion constructs (hLIF274-Luc and hLIF82-Luc) located the region required for this induction to a 192 bp portion of the promoter, which carries two putative c-ets binding sites. We then investigated the effect of glucocorticoids and estradiol by cotransfecting the respective receptors. Both hormones strongly inhibited the stimulation of the LIF promoter by TPA and ionomycin. Since LIF is implicated in the pathogenesis of inflammatory and degenerative conditions, such as rheumatoid arthritis and osteoporosis, the finding that therapeutic agents employed in the treatment of such conditions, i.e. glucocorticoids and estrogens, can modulate the induction of LIF at the transcriptional level, is of particular interest.
11067959 Leflunomide suppresses TNF-induced cellular responses: effects on NF-kappa B, activator pr 2000 Nov 15 Leflunomide is a pyrimidine biosynthesis inhibitor that has recently been approved for treatment of rheumatoid arthritis. However, the mechanism of leflunomide's antiarthritis activity and is not fully understood. The critical role that TNF plays in rheumatoid arthritis led us to postulate that leflunomide blocks TNF signaling. Previously, we have demonstrated that leflunomide inhibits TNF-induced NF-kappaB activation by suppressing I-kappaBalpha (inhibitory subunit of NF-kappaB) degradation. We in this study show that leflunomide also blocks NF-kappaB reporter gene expression induced by TNFR1, TNFR-associated factor 2, and NF-kappaB-inducing kinase (NIK), but not that activated by the p65 subunit of NF-kappaB, suggesting that leflunomide acts downstream of NIK. Leflunomide suppressed TNF-induced phosphorylation of I-kappaBalpha, as well as activation of I-kappaBalpha kinase-beta located downstream to NIK. Leflunomide also inhibited TNF-induced activation of AP-1 and the c-Jun N-terminal protein kinase activation. TNF-mediated cytotoxicity and caspase-induced poly(ADP-ribose) polymerase cleavage were also completely abrogated by treatment of Jurkat T cells with leflunomide. Leflunomide suppressed TNF-induced reactive oxygen intermediate generation and lipid peroxidation, which may explain most of its effects on TNF signaling. The suppressive effects of leflunomide on TNF signaling were completely reversible by uridine, indicating a critical role for pyrimidine biosynthesis in TNF-mediated cellular responses. Overall, our results suggest that suppression of TNF signaling is one of the possible mechanisms for inhibitory activity of leflunomide against rheumatoid arthritis.
11549370 Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage co 2001 There is mounting evidence for a role of the growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) in inflammatory disease, including arthritis. In the present study, we examined the effectiveness of treatment of collagen-induced arthritis (CIA) with a neutralizing mAb to GM-CSF. DBA/1 mice were immunized for the development of CIA and treated at different times, and with different doses, with neutralizing mAb to GM-CSF or isotype control mAb. Anti-GM-CSF mAb treatment prior to the onset of arthritis, at the time of antigen challenge, was effective at ameliorating the ensuing disease. Modulation of arthritis was seen predominantly as a reduction in overall disease severity, both in terms of the number of limbs affected per mouse and the clinical score of affected limbs. Importantly, anti-GM-CSF mAb treatment ameliorated existing disease, seen both as a reduction in the number of initially affected limbs progressing and lower numbers of additional limbs becoming affected. By histology, both inflammation and cartilage destruction were reduced in anti-GM-CSF-treated mice, and the levels of tumor necrosis factor-a and IL-1beta were also reduced in joint tissue washouts of these mice. Neither humoral nor cellular immunity to type II collagen, however, was affected by anti-GM-CSF mAb treatment. These results suggest that the major effect of GM-CSF in CIA is on mediating the effector phase of the inflammatory reaction to type II collagen. The results also highlight the essential role of GM-CSF in the ongoing development of inflammation and arthritis in CIA, with possible therapeutic implications for rheumatoid arthritis.
10648018 Serum amyloid A in the assessment of early inflammatory arthritis. 2000 Jan OBJECTIVE: Acute phase serum amyloid A (A-SAA) has been reported to be more sensitive than C-reactive protein (CRP) as a marker of disease activity. It may function in immune regulation and is linked to the development of secondary amyloidosis. We investigated the profile of A-SAA in early inflammatory arthritis and compared A-SAA with CRP and erythrocyte sedimentation rate (ESR) in relation to diagnosis and disease activity. METHODS: Using a sensitive and specific ELISA, A-SAA was measured in the serum of 140 patients with early arthritis (disease duration 2 weeks to 24 mo, mean 6 mo). CRP was determined using a standard ELISA; ESR and clinical disease activity variables were also recorded. RESULTS: Sixty-four patients had rheumatoid arthritis (RA), 19 psoriatic arthritis (PsA), 28 undifferentiated arthritis (UA), and 29 other forms of arthritis. A-SAA levels correlated with both CRP (r = 0.73, p = 0.0001) and ESR (r = 0.6, p = 0.0001). The magnitude of the A-SAA response was greater than either the CRP or ESR, and very high A-SAA levels were observed in disease as early as 2 weeks. Highest A-SAA concentrations occurred in RA (median 70.3 mg/l, maximum 1542) compared with the other groups (medians, PsA: 33 mg/l; UA: 12.3 mg/l; other arthritis: 11.2 mg/l), with values > 520 mg/l observed exclusively in RA. A-SAA, unlike CRP or ESR, could distinguish patients with a final diagnosis of RA from those who had persistent UA. In RA, A-SAA provided the strongest correlations with clinical measurements of disease activity. Clinical improvement was also best represented by A-SAA, while disease deterioration was associated with a significant increase in A-SAA values, but not CRP or ESR. CONCLUSION: Compared with ESR or CRP, A-SAA correlates best with markers of disease activity, and in patients with recent onset arthritis, very high levels of SAA occur exclusively in RA. As A-SAA is sensitive to change and accurately reflects alterations in disease status, it is the best marker available for the assessment of inflammatory joint disease.
11687037 Methotrexate for treating juvenile idiopathic arthritis. 2001 BACKGROUND: In both adult rheumatoid arthritis (RA) and juvenile arthritis, the focus has shifted from 'inflammation parameters' to more patient centered disability outcomes. In RA this resulted in the development of the Outcome Measures in Arthritis Clinical Trials (OMERACT), and in juvenile arthritis the Pediatric Rheumatology International Trials Organization (PRINTO) core set. This PRINTO-core set was established using a combination of statistical and consensus formation techniques. This core set contains a number of patient centered disability measures. This review systematically searched the available literature and reports the available evidence of efficacy of MTX, with special focus on patient centered disability measures in Juvenile Idiopathic Arthritis (JIA). OBJECTIVES: To perform a systematic review on the effects of MTX on functional ability, range of motion, quality of life, overall well-being and pain for patients with JIA. SEARCH STRATEGY: The Cochrane Controlled Trials Register (CCTR) and MEDLINE were searched up to March 2001, using the search strategy sensitive for randomised controlled trials, used by the Cochrane Collaboration. SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials comparing MTX against placebo or standard care in patients with Juvenile Idiopathic Arthritis (JIA) were selected. DATA COLLECTION AND ANALYSIS: Two reviewers (TT, JN) determined the studies to be included in this review and extracted the data of patient centered disability measures. The data were pooled using standardized mean differences (SMD) for limited joint range score, number of joints with swelling, and number of joints with pain on motion. Physicians global assessment and parents global assessment were evaluated with pooled odds ratios (OR). MAIN RESULTS: Only two studies with a total 165 JIA patients under 18 years of age were included in this review. For JIA patients, MTX therapy had small to moderate effects on patients centered disability. The effect on joint range of motion, number of joints with pain and swelling and parent's assessment of disease activity showed a relative percentage improvement from 3 to 18% greater with MTX than with placebo. REVIEWER'S CONCLUSIONS: Current evidence suggests that MTX does not have clinically significant effects (>20%) on patient centered disability measures in JIA patients.
11145023 Regulatory effects of interleukin-4 and interleukin-10 on human neutrophil function ex viv 2000 Dec OBJECTIVE: To assess the capacity of interleukin-4 (IL-4) and IL-10 to block polymorphonuclear neutrophil (PMN) activation in an ex vivo human model system, and to confirm their effect on neutrophil function in an animal model of arthritis. METHODS: The ex vivo phagocytic capacity of cytokine-activated human PMNs was assessed by use of assays for measuring the ingestion of heat-killed yeast and by subsequent hexose-monophosphate shunt activation using nitroblue tetrazolium reduction. The in vivo activity of IL-4 and IL-10 was measured using a rat adjuvant arthritis model in which the mycobacterial antigen concentration was titrated to modify disease intensity. RESULTS: IL-4 and IL-10 suppressed the ex vivo activation state of interferon-gamma- and tumor necrosis factor alpha-activated human neutrophils. In the rat adjuvant arthritis model, treatment with systemic murine IL-10 (mIL-10) effectively suppressed all disease parameters in rats that received the lower concentrations of mycobacteria, whereas systemic mIL-4 was effective against even the most severe disease. Both cytokines were effective in lowering the absolute PMN cell number recovered and the PMN activation state in the joint synovia. We also observed lower levels of the messenger RNA transcript for CINC protein (cytokine-induced neutrophil chemoattractant; a rat homolog for human IL-8) in the synovia. CONCLUSION: IL-10 is an effective antiarthritic agent and has a major effect on the presence and function of PMNs in the joint synovia when disease intensity is not severe. IL-4 has an inhibitory profile that is similar to that of IL-10, but is effective in modifying even the most severe disease. Both cytokines reduced the phagocytic activation of human PMNs in response to proinflammatory cytokines. These data demonstrate that IL-4 and IL-10 can exert powerful regulatory effects on neutrophil function that translate into a therapeutic response in a disease model of arthritis. Treatment with these cytokines alone or in combination may therefore be very useful in the management of patients with rheumatoid arthritis.
11196525 Evidence for immune activation against oxidized lipoproteins in inactive phases of juvenil 2001 Jan OBJECTIVE: Oxidative stress contributes to joint inflammation and damage in rheumatoid arthritis. In a mobile inflamed joint, exercise induced multiple cycles of hypoxia-reperfusion injury may lead to the creation of a redox environment in which oxido-reductase systems, by NADPH mechanisms, produce highly reactive chemical species (i.e., oxygen free radicals). We investigated 2 endproducts of lipid peroxidation, malonildialdehyde (MDA) and diene conjugates (DC), and the formation of antibodies against oxidized low density lipoproteins (Ab oxLDL) in juvenile chronic arthritis (JCA), and assessed the role of oxidative phenomena in different phases and subsets of this disease. METHODS: To assess the role of oxidative stress in JCA, we measured the endproducts of lipid peroxidation, MDA and DC, by the increase of absorbance at 586 nm and 234 nm, respectively, and the levels of Ab oxLDL by ELISA in the sera of 58 patients with JCA and 21 healthy controls. Due to crossreactivity between Ab oxLDL and anticardiolipin antibodies (aCL), the sera were also tested by a standard ELISA for IgG-aCL. The patients were divided into 3 subsets: 29 with pauciarticular (pauci), 15 with polyarticular (poly), and 14 with systemic (sys) onset disease, and then were subdivided, according to different variables appropriate to each subset, reflecting active and inactive disease, into 30 active (14 pauci, 8 poly, 8 sys) and 28 inactive (15 pauci, 7 poly, 6 sys). RESULTS: Levels of Ab oxLDL were significantly increased in the whole group of patients (566.6 +/- 263.0 vs 206.6 +/- 136.3 mU/ml; p < 0.001) and in each of the type of onset (pauci 660.8 +/- 272.1, p < 0.001; poly 341.3 +/- 134.7, p < 0.01; sys 497.8 +/- 114.8, p < 0.001) compared to controls. Ab oxLDL were higher in the inactive than in the active group (743.5 +/- 231.9 and 404.4 +/- 169.9; p < 0.001). MDA and DC levels were not increased significantly in patients' sera. No patient was positive for IgG-aCL. CONCLUSION: These findings suggest that MDA and DC cannot be considered major markers of oxidative stress in JCA and that the Ab oxLDL may represent a delayed sign of oxidative stress previously induced by the inflammatory process in patients with JCA.