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ID PMID Title PublicationDate abstract
9574569 Transient gene transfer of IL-12 regulates chemokine expression and disease severity in ex 1998 May 1 Murine collagen-induced arthritis (CIA) is characterized by pannus formation, cell infiltration, and cartilage erosion, and shares histologic and immunologic features with rheumatoid arthritis. Numerous cytokines are reportedly associated with RA and/or CIA; however, their mechanistic role is not clear. To determine the role of IL-12 in CIA, DBA/1 LacJ mice were administered 3 x 10(8) plaque-forming units of mIL-12 i.p. in a nonreplicating adenoviral vector (AdIL-12) on day 25 following primary type II collagen immunization. Our studies demonstrated that systemic transient overexpression of IL-12 accelerated disease progression and augmented the arthritis severity relative to mice expressing a replication-deficient, E1-deleted Ad5 construct. A likely mechanism for this increase in pathology was the increase in the expression of cytokines and chemokines known to play a proinflammatory role in disease. In particular, levels of murine IFN-gamma were significantly increased in mice overexpressing AdIL-12 relative to the replication-deficient, E1-deleted Ad5 construct. Interestingly, the C-X-C chemokine murine macrophage inflammatory protein-2, as well as the C-C chemokines murine monocyte chemoattractant protein-1 and murine macrophage inflammatory protein-1alpha were up-regulated by AdIL-12 relative to controls. In an additional set of studies, neutralization of endogenous IL-12 in CIA mice was shown to delay disease onset and attenuate disease severity. IFN-gamma levels in the mice receiving anti-IL-12 were significantly decreased in joint homogenates. These studies demonstrate that IL-12 is an important cytokine involved in controlling the production of chemokines/cytokines leading to the evolution of experimental arthritis.
10654459 Outcome of total hip arthroplasty in small-proportioned patients. 2000 Jan In a prospective, consecutive series, 41 total hip arthroplasties were performed in 27 small-proportioned patients with small femoral dimensions. The 17 female and 10 male patients averaged 23.6 years (range, 14-47 years), and the mean height and weight were 157 cm (range, 132-183 cm) and 53.5 kg (range, 36-84 kg). The most common preoperative diagnosis was juvenile rheumatoid arthritis in 18 patients (28 hips). Most patients were severely disabled in their daily activity, and 68% of the patients were classified as Charnley functional class C. The femoral implants consisted primarily of the proximally porous-coated miniature Anatomic Medullary Locking femoral component (AML/CDH, Depuy, Warsaw, IN) in 33 hips in 22 patients (average stem diameter, 9.5 mm; range, 8-12.0 mm). A porous ingrowth acetabular cup fixed with screws was used in all procedures. At an average follow-up of 51 months, Harris Hip Scores improved significantly from 34 points (range, 0-65 points) preoperatively to 85 points (range, 33-100 points) after arthroplasty. There were no intraoperative complications. There was 1 revision because of femoral implant loosening. Three cementless femoral components showed evidence of nonprogressive subsidence. One patient had significant bilateral acetabular component polyethylene wear and underwent revision. All other femoral and acetabular components were radiographically stable. The relief of pain and improvement of function were dramatic. The miniature AML/CDH femoral component, combined with an uncemented acetabular cup, provides a promising, off-the-shelf alternative in small-proportioned patients.
11511762 Bacterial DNA in synovial fluid cells of patients with juvenile onset spondyloarthropathie 2001 Aug OBJECTIVE: To identify bacterial DNA in synovial fluid cells of patients with active juvenile onset spondyloarthropathy (SpA). METHODS: The main group of study constituted 22 patients with juvenile onset SpA. In addition, five patients with adult onset SpA and nine with rheumatoid arthritis (RA) were studied. Polymerase chain reaction (PCR) with either genus- or species-specific primers was performed on synovial fluid cells to detect DNA sequences of Chlamydia trachomatis, Yersinia enterocolitica, Salmonella sp., Shigella sp., Campylobacter sp. and Mycobacterium tuberculosis. The presence of antibacterial antibodies in sera and synovial fluid was also determined by enzyme-linked immunoassay. RESULTS: The synovial fluid of nine patients with juvenile onset SpA, three with adult onset SpA and one with RA contained bacterial DNA. Five juvenile onset SpA samples had DNA of one single bacterium; two juvenile onset SpA and three adult onset SpA had DNA of two bacteria and two juvenile onset SpA had DNA of three bacteria. Overall, Salmonella sp. DNA was detected in seven synovial fluid samples, Shigella sp., Campylobacter sp. and M. tuberculosis were found in four samples each, and C. trachomatis was found in two. The bacterial DNA findings correlated with neither diagnosis nor disease duration. One RA synovial fluid had DNA of Campylobacter sp. Neither serum nor synovial fluid antibacterial antibodies correlated with DNA findings or clinical diagnosis. CONCLUSION: In this study, single and several combinations of bacterial DNA were identified in the synovial fluid of patients with long-term undifferentiated and definite juvenile onset SpA and adult onset SpA. Of relevance is that bacterial DNA corresponds to bacteria producing endemic disease in our population.
9836219 Anaesthesia for scoliosis surgery in a patient on anticoagulant therapy. 1998 Kyphoscoliosis surgery is frequently associated with major blood loss and coagulation disorders. A patient with juvenile rheumatoid arthritis, heart valve prosthesis and respiratory restrictive syndrome, was submitted to surgical correction of kyphoscoliosis. Current drug therapy included digitalis, oral anticoagulant and nonsteroidal anti-inflammatory drugs. After careful preoperative evaluation, oral anticoagulant and nonsteroidal anti-inflammatory drugs were discontinued (five and ten days before surgery, respectively), and intravenous heparin was introduced and maintained until two h before surgery. Bacterial endocarditis prophylaxis was obtained with ampicillin (50 mg.kg-1) and gentamicin (1.5 mg.kg-1). Anaesthetic management followed a general, balanced technique and the use of invasive monitoring devices. Clotting times were kept within the normal range--prothrombin time between 13 s and 14 s; partial thromboplastin time between 28 s and 30 s. Surgery was straightforward. The patient remained ventilated for 24 h and intravenous morphine (6 micrograms.kg-1.h-1) was used for nurse controlled analgesia. Afterwards, this was changed for patient controlled analgesia. Intravenous heparin was restarted 12 h after surgery and there were no complications postoperatively. Keeping the patient without anticoagulant therapy during this kind of surgery, was the less harmful option, taking into consideration that haemorrhage is inevitable and thromboembolism is a potential, though serious risk.
10516720 Intra-articular delivery of a herpes simplex virus IL-1Ra gene vector reduces inflammation 1999 Oct To evaluate the use of HSV-based vectors for arthritis gene therapy we have constructed a first-generation, ICP4 deficient, replication defective herpes simplex virus (HSV) vector (S/0-) and a second-generation HSV vector derivative (T/0-) deficient for the immediate-early genes ICP4, 22 and 27, each carrying a soluble TNF receptor or IL-1 receptor antagonist transgene cassette. A rabbit synovial-fibroblast line in culture, infected by either vector enabled high-level expression of the transgene product. However, following a single intra-articular injection of the vectors into rabbit knee joints, only the second-generation, HSV T/0- vector expressed detectable levels of soluble TNFR in synovial fluid. Synovial lavage fluid from inoculated joints con- tained up to 12 ng/ml of soluble receptor that persisted at detectable, but reduced levels for at least 7 days. When tested in an experimental model of arthritis generated by intra-articular overexpression of interleukin-1beta using retrovirus transduced synovial cells, the HSV T/0- vector expressing the interleukin-1 receptor antagonist was found to inhibit leukocytosis and synovitis significantly. The improved levels and duration of intra-articular transgene expression achieved via HSV-mediated gene delivery suggest that an HSV vector system could be used for therapeutic applications in patients with rheumatoid arthritis (RA) and other joint-related inflammatory diseases.
9062950 Hepatitis C virus infection and autoimmunity. 1997 Feb Hepatitis C virus (HCV) infection has been associated with a plethora of immune and autoimmune perturbations. We review serological and clinical autoimmune manifestations associated with HCV infection, discuss treatment regimens for HCV-related autoimmune diseases, and present a framework for understanding HCV-associated autoimmune disease by performing a computerized literature search from which representative articles were used and referenced. The immune response to HCV may include the development of cryoglobulins, rheumatoid factor, antinuclear antibodies (ANA), anticardiolipin, antithyroid, anti-liver/kidney/microsomal antibodies (anti-LKM), as well as HCV/anti-HCV immune complex formation and deposition. HCV infection is a significant cause of mixed essential cryoglobulinemia, which may then be complicated by cryoglobulinemic glomerulonephritis, vasculitis, or neuropathy. It has also been associated with membranous and membranoproliferative glomerulonephritis. Subsets of autoimmune hepatitis patients are infected with HCV and evidence suggests that HCV is a causative agent of antithyroid antibodies and autoimmune thyroid disease. Although cause-and-effect remain to be proved, there are reports of HCV infection preceding or coincident with polyarthritis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and polymyositis/dermatomyositis (PM/DM). HCV-infected patients also have a high incidence of sialoadenitis, and reports of low-grade lymphoproliferative malignancies have emerged. However, HCV is not a major causative factor for most autoimmune diseases. Optimal treatment for HCV-related autoimmune disease remains to be determined. Interferon alpha (IFN alpha) has successfully reduced viremia/transaminitis, cryoglobulins, proteinuria, and nephritis, but recurrent disease manifestations are frequent after discontinuation of therapy. Moreover, IFN alpha may precipitate or exacerbate autoimmune disease symptoms. HCV-related autoimmune disease also has been treated successfully with corticosteroids, azathioprine, and cyclophosphamide, although HCV viremia persists and may worsen.
9558182 Gastric administration of recombinant 65 kDa heat shock protein delays the severity of typ 1998 Apr OBJECTIVE: The 65 kDa heat shock protein (HSP) chaperonin is a highly conserved intracellular protein. HSP are involved in the pathogenesis of arthritis, but are not able to induce experimental arthritis. T cell clones recognizing the 180-188 amino acid sequence of 65 kDa HSP are present in inflamed synovium of both adjuvant arthritis and rheumatoid arthritis (RA). Oral administration of bovine collagen II or co-chaperonin 10 kDa HSP has been shown to induce an immune tolerance state to collagen induced arthritis (CIA). We investigate the effect of oral gavage with 65 kDa HSP on CIA. METHODS: We immunized 6-8-week-old DBA1 male mice with bovine type II collagen. A group of 25 mice were given oral recombinant mycobacterial 65 kDa HSP before immunization (30 microg in 200 microl phosphate buffered saline (PBS) at Days -7, -5, -2) while PBS alone was administered in 27 controls. A 3rd group was fed 65 kDa HSP according to the same protocol but was not immunized with collagen II (n = 8). The clinical arthritis score was recorded 3 times/week until Day 60. Antibodies to collagen II were determined by ELISA. RESULTS: The incidence of arthritis was comparable in the 2 groups (72 vs 70%). The onset of arthritis was not delayed in mice fed HSP. However, the severity of arthritis was lower 10 days after arthritis onset in animals fed 65 kDa HSP (clinical score 1.83 +/- 0.79 vs 2.74 +/- 1.1; p < 0.0001). No animals in Group 3 had arthritis. Serum IgG anti-type II collagen levels were decreased in HSP treated mice (optical density 0.33 +/- 0.21 vs 0.46 +/- 0.21; p < 0.0001). However, the ratio of IgG1/IgG2a antitype II collagen antibody response remained unchanged in the mice fed 65 kDa HSP. CONCLUSION: These results suggest that oral administration of 65 kDa HSP may diminish collagen induced arthritis.
10358204 The role of an epithelial neutrophil-activating peptide-78-like protein in rat adjuvant-in 1999 Jun 15 The chemokine, epithelial neutrophil-activating peptide-78 (ENA-78), is a potent neutrophil chemotaxin whose expression is increased in inflamed synovial tissue and fluid in human rheumatoid arthritis compared with osteoarthritis. Since ENA-78 has been implicated in the pathogenesis of RA, we examined the expression of an ENA-78-like protein during the development of rat adjuvant-induced arthritis (AIA). Using an ELISA assay, we found increased levels of antigenic ENA-78-like protein in the sera of AIA animals compared with control normal animals by day 7 postadjuvant injection. ENA-78-like protein levels continued to increase as AIA developed. ENA-78-like protein levels in joint homogenates were increased in AIA animals later in the development of the disease, by day 18 during maximal arthritis, compared with control animals. Expression of ENA-78-like protein in both the AIA serum and joint correlated with the progression of inflammation of the joints. Anti-human ENA-78 administered before disease onset modified the severity of AIA, while administration of anti-ENA-78 after clinical onset of AIA did not modify the disease. These data support a role for an ENA-78-like protein as an important chemokine in the progression and maintenance of AIA.
9870873 Enhanced and coordinated in vivo expression of inflammatory cytokines and nitric oxide syn 1998 Dec OBJECTIVE: To evaluate the sites of expression of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha), and inducible nitric oxide synthase (iNOS) in patients with inflammatory and degenerative joint diseases. METHODS: Cytokines and iNOS were detected by immunohistochemistry analysis of synovial and cartilage biopsy specimens obtained at knee arthroscopy in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), osteoarthritis (OA), and traumatic knee arthritis. Cytokine and iNOS expression was quantified using computerized image analysis. RESULTS: IL-1beta, TNFalpha, and iNOS were highly expressed by synovial cells (lining layer cells, infiltrating leukocytes, endothelial cells) from patients with inflammatory arthritides and significantly less by synovial cells from patients with OA and traumatic arthritis. In contrast, the latter patients showed high chondrocyte expression of cytokines and iNOS while RA and PsA patients had only minor chondrocyte positivity. In both joint compartments, IL-1beta expression, TNFalpha expression, and iNOS expression were strongly correlated. CONCLUSION: The enhanced and coordinated expression of IL-1beta, TNFalpha, and iNOS by chondrocytes strongly supports the hypothesis that chondrocytes are the major site of production of mediators of inflammation in human OA, thus playing a primary role in the pathogenesis of this disease.
9418130 T cell response of I-Aq mice to self type II collagen: meshing of the binding motif of the 1997 Nov Type II collagen (CII) is of immunological interest because of its repetitive structure and properties as an autoantigen. The mouse gene has recently been cloned, thus enabling T cell-defined epitopes to be identified. Multiple novel epitopes on mouse CII are here detected in the autoreactive T cell response. The major response is directed to an epitope with residues 707-721 located on the CB10 fragment. Some 25 other epitopes are also recognized, including the autologous homologue of the 256-270 epitope which dominates in the response to foreign collagen. The cells reactive with mouse collagen peptides were of Th1 type, as judged by release of IFN-gamma. No significant reactivity was detected to mouse CII peptides during ongoing disease. Alignment of the mouse epitopes revealed a sequence motif with characteristic side chains at residues P1, P4 and P7, and to a lesser extent at P5, within a nonamer core sequence. Binding of these epitopes was simulated in a computer model of the I-Aq molecule, where peptides with anchor residues at P1, P4 and P7 were indeed found to fit the binding groove best. The spacing of pockets and the fine structure of the binding surface of the I-Aq molecule meshes with the repetitive structure of the collagen (X-Y-Gly), thus providing a likely explanation for the occurrence of multiple epitopes. Comparison with human DR binding motifs showed that the I-Aq motif resembles most closely that of the DR4 subtypes which predispose for rheumatoid arthritis.
11508588 Anti-agalactosyl IgG antibodies in sera from patients with systemic sclerosis. 2001 Aug OBJECTIVE: To determine the prevalence and clinical correlations of anti-agalactosyl IgG antibodies (anti-AG IgG) in patients with systemic sclerosis (SSc). METHODS: Serum samples from patients with limited cutaneous SSc (lSSc; n = 49), diffuse cutaneous SSc (dSSc; n = 21), rheumatoid arthritis (RA; n = 10), systemic lupus erythematosus (SLE; n = 20), and healthy individuals (n = 20) were examined by lectin-enzyme immunoassay using human agalactosyl IgG as antigen. RESULTS: Anti-AG IgG were detected in 52 (74%) of 70 patients with SSc, which was much higher than the frequency of rheumatoid factor positivity in SSc (16%). Levels of anti-agalactosyl IgG antibodies were significantly higher than in healthy controls or patients with SLE, but lower than patients with RA. Levels of anti-AG IgG in patients with dSSc were significantly higher than in lSSc. SSc patients with anti-topoisomerase I antibodies had significantly higher levels of anti-AG IgG than SSc patients with anticentromere antibodies. Concerning clinical correlation, patients with pulmonary fibrosis showed elevated levels of anti-AG IgG compared to those without pulmonary fibrosis. Patients with decreased %VC or %DLCO showed increased levels of anti-AG IgG. Elevated levels of anti-AG IgG were associated with the presence of contracture of phalanges or cutaneous calcinosis, but not the presence of arthritis/arthralgia. CONCLUSION: The results suggest that anti-agalactosyl IgG antibody is frequently detected in SSc and is a serological indicator for more severe SSc.
12461572 [Hematopoietic stem cell transplantation in autoimmune diseases. Pros and cons]. 2001 New therapeutics have clearly advanced our chances of inducing remission in several aggressive autoimmune diseases like rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Despite this, subgroups of patients with RA or SLE or of other diseases like systemic sclerosis (SSc) or multiple sclerosis (MS) still present a poor response to conventional drugs. In this kind of patients, haematopoietic stem cell transplantation (HSCT) provided important clinical benefits in several studies. This might depend upon several possible mechanisms such as purging of autoreactive T cells during conditioning or changes of the TH1/TH2 biological milieu. An overview of the results obtained so far, the drawbacks and the perspectives in this field are presented.
11339045 [Surgical rehabilitation of a patient with corneal perforation in keratoconjunctivitis sic 2001 Jan The authors describe effective surgical rehabilitation of a female patient with corneal perforation and subsequent complicated cataract developing against the background of chronic deficiency of lacrimal production associated with Sjogren's syndrome which developed in the presence of rheumatoid arthritis. Treatment with artificial tears during complex pre- and postoperative therapy prevented serious complications and made unnecessary the preliminary interventions aimed at inhibition of lacrimal production. Long remission of the underlying disease and stability of visual functions during 2 years evidence the efficiency of rehabilitative measures.
10992733 A case of parasymphyseal and associated insufficiency fractures of pubic rami in a patient 2000 Jul Parasymphyseal insufficiency fractures are uncommon. Furthermore, none have been reported in systemic rheumatic diseases other than rheumatoid arthritis. In this article we report on parasymphyseal insufficiency fractures in a patient with mixed connective tissue disease.
10751011 Update on outcome assessment in rheumatic disorders. 2000 Mar Outcome assessment in rheumatic disorders is getting more and more attention. A series of Outcome Measures in Rheumatology (OMERACT) conferences has provided a good impulse for further research in the field. In this chapter we will review the results of the last OMERACT 4 conference in detail. This conference was focused on longitudinal/observational studies, rheumatoid arthritis (response criteria and imaging), and core sets for ankylosing spondylitis and systemic lupus erythematosus. Moreover, an overview of recent literature on measures of disease activity, quality of life measures, and imaging is presented. For the various rheumatic disorders, several new instruments and/or further validation steps are described.
10564325 Acute myocardial infarction following toxic epidermal necrolysis? 1999 Sep We describe a 29-year-old woman with rheumatoid arthritis who suffered an acute myocardial infarction 70 days after an initial presentation with toxic epidermal necrolysis (TEN). The trigger for the TEN was probably an over-the-counter anti-influenza treatment containing tipepidine hibenzate. Although the patient had familial hypercholesterolemia, we believe that thrombocytosis, induced by the inflammatory response and metabolic stress resulting from the TEN, may also have played a significant role in the pathogenesis of the myocardial infarction. Although TEN manifests itself principally as a skin disease, the potential for systemic morbidity, including cardiovascular abnormalities, should also be remembered.
9719493 Estrogen-mediated immunosuppression in autoimmune diseases. 1998 Jul Gender affects the susceptibility to many autoimmune diseases. Women have an increased risk of developing diseases such as rheumatoid arthritis and multiple sclerosis compared with men. The female preponderance is believed to depend in part on the influence of sex hormones on the immune system. The mechanism of estrogen-induced immune suppression both in human autoimmune diseases and their experimental animal model counterparts is discussed. In addition, the mechanisms of estrogen and anti-estrogens are discussed in relation to their possible use as future therapeutic anti-inflammatory agents.
9230935 Annexins in cancer and autoimmune diseases. 1997 Jun Several annexins have been implicated in the pathogenesis of benign and malignant neoplasms of different origins. In some tumours a suppressive action of annexins has been shown, whereas studies of other tumours indicate an involvement of annexins in tumour progression. In the light of the expression of annexins at distinct episodes of fetal development these observations point towards a functional role of annexins in cellular development and differentiation. This view is supported by data that link certain annexins to distinct pathways of signal transduction. Auto-antibodies against several annexins have been detected in patients with autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel disease. Until now it is unclear whether their presence reflects a relevant pathogenetic mechanism or merely represents an unspecific expression of a raised autoimmunity in these patients.
9933419 Methotrexate specifically modulates cytokine production by T cells and macrophages in muri 1999 Jan Immunosuppressive therapy with methotrexate (MTX) has been established as effective treatment for patients with rheumatoid arthritis. To analyse the therapeutic potential and mechanisms of action of MTX, we determined serum cytokine levels and cytokine production by splenic T cells and macrophages in untreated and MTX-treated mice. Furthermore, we assessed the role of MTX in a murine model of experimental arthritis induced by collagen type II (CIA). MTX reduced spontaneous and IL-15-induced tumour necrosis factor (TNF) production by splenic T cells but not by macrophages from healthy mice in vitro in a dose-dependent manner. In contrast, interferon-gamma (IFN-gamma) production was less strikingly reduced and IL-4 production was virtually unaffected. In addition, treatment of healthy mice with MTX in vivo led to reduced TNF serum levels and diminished TNF production by splenic T cells and macrophages. Intraperitoneal administration of MTX prior to the onset of arthritis completely prevented clinical and pathological signs of CIA. This was associated with a striking reduction of TNF production by spleen cells from MTX-treated mice. The role of TNF in MTX-mediated effects on cytokine production was further underlined by the finding that MTX effects on IFN-gamma production were augmented in TNF-transgenic mice but abrogated in mice in which the TNF-alpha gene had been inactivated by homologous recombination. Thus, MTX specifically modulates spontaneous and IL-15-induced TNF-alpha production in mice and prevents experimental murine CIA. These data suggest that TNF production by T cells is an important target of MTX and may serve as a basis to understand and further analyse MTX-mediated mechanisms of immunosuppression in patients with RA.
17039083 Early onset methotrexate-induced pancytopenia and response to G-CSF: a report of two cases 2001 Feb Methotrexate (MTX) is one of the most widely used antirheumatic drugs for the treatment of rheumatoid arthritis. Whereas the hepatotoxicity of methotrexate is well recognized, the hematologic toxicity, namely, pancytopenia, is still a concern and is potentially fatal. We report two cases of early-onset methotrexate-induced pancytopenia that were successfully treated with granulocyte colony-stimulating factor (G-CSF). The pancytopenia improved with 3 days of administration. A review of the literature revealed at least 146 reported cases of MTX-induced pancytopenia. Significant risk factors for myelotoxicity included renal impairment, infection, and hypoalbuminemia. Successful management includes prompt discontinuation of MTX, intravenous folinic acid, high-dose steroids and, as in our case, G-CSF.