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ID PMID Title PublicationDate abstract
8834287 Uncemented total knee arthroplasty: report of 109 titanium knees with cancellous-structure 1996 Feb One hundred twenty-three uncemented total knee arthroplasties were performed between November 1986 and November 1989. The implants were pure titanium with porous coating for bony ingrowth. One hundred nine of these knees were followed for 2 to 5 years (average: 31.5 months). Clinical evaluation of the results, using the Hospital for Special Surgery Knee Rating Scale, revealed an increase in the average knee score from 62.9 preoperatively to 92.5 postoperatively, with excellent or good results in 94.5% of the cases. Thirteen knees (12%) had 26 radiolucent lines or areas. There was no complete lucency underneath any implant, and no knees were revised for loosening. One knee required replacement of the tibial insert for instability. While titanium implants were successful in achieving secure fixation and high knee scores in the short term, longer follow up will be necessary for more definitive conclusions, especially in regard to the potential problems with titanium wear debris.
8906851 Selection of T cells reactive against autologous B lymphoblastoid cells during chronic rhe 1996 Nov 15 The repertoire and Ag specificity of T cells infiltrating inflamed joints from a chronic rheumatoid arthritis (RA) patient were studied in detail. Repertoire analysis demonstrated a reduced clonality of joint-infiltrating lymphocytes (JIL) as compared with patient's PBL, which was presumably due to an intra-articular expansion of T cell clones with recurrent TCR features. Strikingly, a large fraction of these JIL T cell clones, which were predominantly CD8+, proliferated in vitro when exposed to autologous B lymphoblastoid cells (BLC), unlike randomly chosen PBL clones derived from the same patient. This proliferative response was HLA-restricted, which confirmed a classical TCR-mediated recognition of BLC and was not observed against autologous PHA blasts, suggesting recognition of either EBV or B cell-specific Ags. Finally, a preliminary analysis of synovial lymphocytes derived from another chronic RA patient demonstrated a similar enrichment for T cells reactive against autologous BLC within JILs as compared with patient's PBLs. Taken together, these results, which suggest frequent expansions of autologous BLC-reactive T cells within inflamed joints of chronic RA patients, provide a basis for future studies evaluating the fine specificity and pathogenicity of these lymphocytes.
8911995 Immunosusceptibility genes in rheumatoid arthritis. 1996 Nov The polygenic predisposition to RA is conferred particularly by disease susceptibility sequences in the HVR3 of HLA DRB1 present in those subtypes of DR4 and DR1 that are associated with RA. The aim of this study was to examine predisposing interactions between genes encoding HLA and immunoglobulin molecules. Accordingly, we compared the genetic background of 114 Australian patients with RA with that of Australian controls of similar ethnic background. We identified HLA-A, B, and DR phenotypes serologically, HLA-DR, DQ alleles, and subtypes of DR4 by DNA typing, and Gm allogenotypes and immunoglobulin switch region polymorphisms by RFLP. For the subjects with RA, we confirmed previously reported observations that included an excess of females, 71%, a high frequency of HLA types DR4 or DR1 of 77% versus controls 47%, and a high frequency of the HVR3 susceptibility sequences of 76%, with 24% homozygous, and 52% heterozygous for the sequences. We observed other genetic correlations in RA that included increases in frequencies of DR4 in males, DR1 in females, the class I specificity HLA-B27 overall but more particularly in females, 24% in females, versus 5% of controls, HLA-DQB1*0302 (DQ8) in DR4*0401-positive patients, and the Gm allogenotype 1,2,3;23 +/- ; 5,10, 15% of patients versus 4% of controls. Examination of switch region genes gave no evidence of differences in the polymorphisms distributions. Thus, the major genetic risks for RA that are conferred by female gender and the HVR3 of HLA DRB1 are modulated by interactions between gender and HLA class I and class II alleles, and the Gm allogenotype.
1333966 Beta 2-adrenergic receptors on peripheral blood mononuclear cells in patients with rheumat 1992 Oct In order to investigate the influence of the autonomic nervous system on the immune response in rheumatic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), we determined the number and the dissociation constants of beta 2-adrenergic receptors (beta 2R) on peripheral blood mononuclear cells (PBMC) in patients with RA characterized by either low or high disease activity, patients with SLE, and healthy age-matched controls by means of a radioligand binding assay with [125I]iodocyanopindolol. The number of beta 2R was significantly decreased in all three patient groups as compared with the healthy controls. In SLE patients, a significant negative correlation between beta 2R and the anti-ds-DNA antibody titre was observed (r = -0.57, P < 0.01). These data demonstrate the close correlation between the number of beta 2R on PBMC and the extent of disease activity in patients with RA and SLE and suggest an involvement of the autonomic nervous system in the pathogenesis of rheumatic disorders.
1337027 [A case of malignant rheumatoid arthritis with corticosteroid-reactive subacute myelopathy 1992 Aug We reported a 64-year-old man who had malignant rheumatoid arthritis (MRA) and developed subacute myelopathy and peripheral neuropathy. He had suffered from seropositive rheumatoid arthritis for 4 years, and developed weakness of four limbs, dysuria and constipation two months before the admission. Neurological examination revealed the diffuse muscle wasting and weakness in four limbs. Deep tendon reflexes were hyperactive in four limbs, but not in jaw jerk. Babinski sign was positive bilaterally. Deep sensation was decreased in four limbs and superficial sensation was decreased below the neck. Dysuria and constipation were noted, but anal and bulbocavernosus reflexes were present. On laboratory examination, RF and RAHA increased markedly. Serum complements decreased and immune complexes were positive. Nerve conduction study demonstrated multiple entrapment neuropathy in addition to mononeuritis multiplex. Histological examination of the biopsied sural nerve disclosed the obliterating endarteritis in the epineurium, and marked decrease in number of myelinated fibers. No compressive lesions were seen in the spinal canal by spine X-ray and MRI. Assuming that inflammatory process induced cervical myelopathy, corticosteroid therapy (predonisolone 60 mg/day) was administered and alleviated neurological symptoms, in accordance with the improvement of serological abnormalities. Therefore, an inflammatory process associated with MRA was supposed to damage the spinal cord as well as peripheral nerves in the present case.
7743743 Comparison of blood and synovial fluid lymphocyte subsets in rheumatoid arthritis and oste 1995 Jan Immunoregulatory T-cell deficiency is thought to underlie pathogenesis of rheumatoid arthritis (RA) as a systemic autoimmunopathy. The aim of this study was a simultaneous analysis of peripheral blood and synovial lymphocyte subsets (Ly-SS) of RA patients as compared to patients with locally active osteoarthritis (OA). Peripheral blood Ly-SS and paired synovial fluid Ly-SS from 87 RA patients were analysed by two dimensional flow cytometry (Simulset Becton Dickinson) as compared to 15 OA patients. The control group consisted of 32 healthy subjects. The peripheral blood analysis from RA and OA patients revealed a significant decrease of CD8+ T-cells and increase of CD4+: CD8+ ratio when compared to the control group. The blood of RA patients showed a significant increase of HLA DR+ and IL 2R+ T cells as compared to OA group. The synovial fluid from RA and OA patients showed a significant increase of CD3+, CD8+, HLA DR+ T-cells and decrease of CD4+:CD8+ ratio and CD19+ cells in comparison to the peripheral blood. This study shows, that the OA T-cell system seems not to be activated in peripheral blood in opposition to RA patients. Synovial fluid Ly-SS in OA, however, showed only quantitative but not qualitative differences. OA seems to be mainly a local inflammatory response depending on T-cells, when lymphocyte T activity in blood is diminished.
7788147 The therapeutic effects of an engineered human anti-tumour necrosis factor alpha antibody 1995 Apr Pro-inflammatory cytokines such as tumour necrosis factor alpha (TNF alpha) have been implicated in the pathogenesis of rheumatoid arthritis (RA), and have therefore become therapeutic targets. An engineered human antibody, CDP571, that neutralizes human TNF alpha was administered intravenously in single doses of 0.1, 1.0 or 10 mg/kg to patients with active RA (n = 24). The effects of the antibody were compared in a double-blind fashion with those of placebo (n = 12). In an open continuation phase patients were given either 1.0 or 10 mg/kg. We found that CDP571 was well tolerated and caused reductions in markers of disease activity such as erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP): this was confirmed by a reduction in the disease activity score (DAS). There was a reduction in the number of tender joints, maximal in degree and duration after 10 mg/kg. Patients also documented a reduction of pain and relief of arthritis symptoms. The effects of 10 mg/kg CDP571 on ESR, CRP, tender joints, pain and symptom relief compared to placebo were statistically significant at weeks 1 or 2. The continuation phase, although open, confirmed both the safety and the beneficial effects of CDP571 in active RA. In conclusion CDP571, an engineered human anti-TNF alpha antibody, is well tolerated and, after a single dose of 10 mg/kg, provides improvements in symptoms, signs and serological markers of disease activity in patients with active RA.
7748221 Dysregulation of the in vivo production of interleukin-1 receptor antagonist in patients w 1995 May OBJECTIVE: Patients with rheumatoid arthritis (RA) have defective hypothalamic responses to inflammation, possibly because of excessive production of cytokine inhibitor, which could blunt the effects of cytokines on the hypothalamus, or because of an imbalance between interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL-1Ra), which could create a mainly proinflammatory state. The present study was undertaken to investigate these possibilities. METHODS: The in vivo kinetics of IL-1 beta and IL-1Ra secretion were studied in patients with RA, osteoarthritis (OA), and chronic osteomyelitis (OM), and in normal controls before and after surgery. RESULTS: The 24-hour levels of IL-1Ra were significantly increased in RA (P < 0.001), but there was no diurnal variation in any group. Preoperative levels of IL-1Ra were higher in RA and OA sera (P = 0.001). After surgery, IL-1Ra behaved like an acute-phase reactant protein in all subjects. IL-1 beta was 10-20 times higher in RA than in OM and OA patients at baseline, but the percentage increase in all groups postoperatively was the same. RA patients had an IL-1Ra:IL-1 beta ratio of 26.2 +/- 3.7 (mean +/- SEM) at baseline (OM patients 89.2 +/- 5.8 and OA patients 1,310 +/- 363); this increased to 66.5 +/- 19.8 after surgery (OM patients 120 +/- 6.7 and OA patients 325.8 +/- 106). CONCLUSION: RA patients have a dysregulation of IL-1Ra production, and it seems unlikely that the defective hypothalamic response seen in RA is due to a functional deficit of IL-1 beta.
8124909 Thyroid involvement in chronic inflammatory rheumatological disorders. 1993 Dec The association between rheumatological and thyroid disorders has long been known, the most common being the association of rheumatoid arthritis and autoimmune thyroiditis. Little is known as to possible thyroid involvement in other rheumatological disease of possible autoimmune aetiology, such as psoriatic arthritis and ankylosing spondylitis. We measured thyroid volume and function as well as the prevalence of anti-microsome and anti-thyroglobulin antibodies in 107 consecutive patients with rheumatoid arthritis, 42 patients with psoriatic arthritis, and 12 male patients with ankylosing spondylitis. Fifty-two normal subjects were used as controls. The average thyroid volume, measured at ultrasounds, was increased in all groups of patients, and the prevalence of thyroid enlargement (A-P diameter > 20 mm) was 2-3 fold higher in rheumatological disorders in comparison to controls. Both, patients with rheumatoid arthritis and psoriatic arthritis had higher-than-normal fT4 levels and an increased prevalence of anti-microsome antibodies. In the rheumatoid arthritis group alterations in thyroid volume and function were present irrespective of disease activity, whereas in psoriatic arthritis thyroid involvement was confined to patients with active disease. Our data are consistent with a significant thyroid involvement in rheumatological disorders, which is not limited to diseases with a definite autoimmune aetiology.
8180316 Monoclonal IgM rheumatoid factors generated from synovial B cells of rheumatoid arthritis 1993 Four of 15 monoclonal human IgM rheumatoid factors (RF) derived from synovial B cells of patients with rheumatoid arthritis showed positive ELISA reactions with human beta 2-microglobulin. These findings were different from those previously noted using IgM RF derived from monoclonal Waldenstrom's paraproteins or the IgM components of mixed cryoglobulins, and resembled the anti-beta 2 microglobulin specificity of polyclonal IgM RF from patients with rheumatoid arthritis. Reactions of monoclonal IgM synovial RF with overlapping 7-mers of beta 2m sequence indicated major regions of positive reactivity at positions 57-64 and 89-95 which were maintained in the presence of high salt (300 mM NaCl) conditions. Glycine substitution of each residue within RF-reactive beta 2m regions indicated that tryptophanes at position 60 and 95, lysine at 58, phenylalanine at 62, valine at 93 and arginine at 97 constituted important single amino acids for the reactive epitopes. These findings indicate that clonally restricted human IgM RF derived from diseased tissues of patients with RA show anti-beta 2m reactivity similar to polyclonal RF from the same patients. This particular fine specificity is not present in monoclonal RF derived from patients with Waldenstrom's or mixed cryoglobulins showing anti-gamma-globulin activity.
8151586 Efficacy of additive DMARD therapy in patients with rheumatoid arthritis. Double blind con 1994 Jan OBJECTIVE: To examine the efficacy of the addition of small doses of additional disease modifying antirheumatic drugs (DMARD) to ongoing DMARD treatment [additive DMARD therapy (ADT)]. METHODS: A 3-month prospective, double blind, randomized, placebo controlled study was performed using either 100 mg/day of bucillamine (Buc) or an inactive placebo (P1). Two groups of 12 patients each who had experienced an insufficient benefit from gold sodium thiomalate (GSTM) alone were enrolled in the study. RESULTS: The addition of Buc proved more beneficial than P1 regarding improvement in disease activity (p = 0.0032) and drug usefulness (p = 0.0025). A significant within group improvement was observed in joint swelling count, the Lansbury activity index, erythrocyte sedimentation rate and C-reactive protein. However, the difference in the clinical variables between the 2 groups was minimal. CONCLUSION: The usefulness of ADT was suggested by this trial; however, further confirmation by additional studies is still needed.
1409100 Osteologic standardization of human coxarthrosis using histomorphometry and its relevance 1992 Jun Using bone histomorphometry, in this study the osteologic status of 107 patients with coxarthrosis and femoral neck fracture [FNF] was assessed and compared with bone parameters from patients revised for aseptic loosening. Bone biopsies of the acetabulum and the proximal femur from patients with primary coxarthrosis [pCoxA] (69), dysplastic coxarthrosis [CDH] (19), rheumatoid arthritis [RA] (9), femoral head necrosis [FHN] (8), femoral neck fracture [FNF] (4) and aseptic loosening (12) were taken during hip alloarthroplastic surgery, prepared undecalcified and analysed using histomorphometry (according to MERZ). In pCoxA the following average figures of bone parameters of the acetabular biopsy were determined: trabecular bone volume (TBV) 39.6%, osteoid volume (OV) 3.9%, active osteoblastic surface (AOS) 6.5%, osteoclastic resorption surface (ORS) 2.4%, osteoid surface (OS) 17.4% and resorption surface (RS) 7.0%. As average figures of the femoral biopsy in pCoxA were assessed: TBV = 17.2%, OV = 1.3%, AOS = 0.9%, ORS = 0.4%, OS = 6.5% and RS = 2.5%. These data were compared with bone parameters of secondary coxarthrosis, osteoporosis (FNF) and aseptic loosening. Based on the study of Oettmeier et al. on femoral heads (Skel Radiol 18: 165-174, 1989), the investigated groups were subdivided into three osteologic types of the hip. The osteopenic type was found in 10% of pCoxA, 43% of RA and 28% of CDH. The hyperostotic type, predominantly occurring in males, was mostly demarcated in FHN (38%) and pCoxA (12%). The results demonstrate the individual osteologic status of patients before hip alloarthroplasty. This could influence planning of the operation and the bone-implant interface as well as long-term prognosis of artificial joints.
7570205 [Bone mineral density of the radius in patients with rheumatoid arthritis measured by dual 1995 Jun Bone mineral density (BMD) of the radius was measured in 181 female patients with rheumatoid arthritis (RA) and 255 control subjects using dual energy X-ray absorptiometry (DXA). The BMD of RA patients was assessed according to patients' age and menopause and was compared with age-matched controls for various activity factors of RA and duration of the disease that might correlate with BMD. At stages I and II of premenopausal RA, generalised osteoporosis was not observed. At stages III and IV, the BMD decreased considerably in premenopausal RA patients at age of 45 years or older. There were significant correlations between the BMD of postmenopausal RA and all factors examined, many of which did not affect premenopausal RA. These results suggest that osteoporosis of female patients with RA is influenced only slightly by the disease itself, but it is secondary osteoporosis induced by decreased activities of daily living due to RA.
7705437 Vascular somatostatin receptors in synovium from patients with rheumatoid arthritis. 1994 Dec 27 The peripheral nervous system and its neuropeptidergic pathways may play an important role in the pathogenesis and development of rheumatoid arthritis. In the present study, the role of the neuropeptide somatostatin (SRIF), which was recently shown to be implicated in inflammatory diseases of the gastrointestinal tract, was evaluated by measuring the expression of somatostatin receptors in synovium from patients with rheumatoid arthritis. Somatostatin receptors were detected using in vitro receptor autoradiography in the synovium from five patients with active disease. No receptors were found in one case, a successfully treated patient with quiescent disease. The receptors were of high affinity and specific for biologically active somatostatin analogs. Displacement by nanomolar concentrations of somatostatin-14, somatostatin-28, and octreotide was observed, suggesting that most of the receptors identified belong to the SRIF1A subtype. The somatostatin receptors were preferentially located in blood vessels, with specific labeling of the veins but not of the arteries. The whole vessel wall was homogeneously labeled including the smooth muscle cells and probably the endothelium. These data suggest that the synovium in active rheumatoid arthritis expresses a high density of somatostatin receptors. Somatostatin may act through these venous receptors to influence the inflammatory process by induction of vasoconstriction, inhibition of plasma extravasation and cell migration, or inhibition of neovascularization.
7818579 Elevated interleukin-10 levels in patients with rheumatoid arthritis. 1995 Jan OBJECTIVE: Interleukin-10 (IL-10) has been shown to exert both antiinflammatory and immunostimulatory effects in vivo and in vitro. We therefore sought to examine the role of this cytokine in rheumatoid arthritis (RA) by assessing serum and synovial fluid IL-10 levels. METHODS: Serum and synovial fluid samples were collected from patients with RA and patients with various inflammatory, infectious, and noninflammatory arthritides (controls). IL-10 was assayed using an IL-10-specific enzyme-linked immunosorbent assay, and messenger RNA (mRNA) levels were assessed by semi-quantitative polymerase chain reaction (PCR) techniques. RESULTS: Both RA serum and synovial fluid contained significantly elevated IL-10 levels compared with levels in normal subjects or in control patients (P < 0.01). Some patients with spondylarthropathy also manifested increased serum levels of IL-10. Serum levels of IL-10 did not correlate with standard measures of clinical activity, but were shown to correlate significantly with serum rheumatoid factor (RF) titers and in vitro levels of spontaneous IgM-RF production (P < 0.05). PCR analyses demonstrated the constitutive expression of IL-10 mRNA by the non-T cell population, and semiquantitative PCR analysis documented elevated levels of IL-10 mRNA in circulating mononuclear cells of those RA patients who were not treated with slow-acting antirheumatic drugs. Analysis of IL-10 mRNA revealed the cytokine to be of human, and not viral, origin. CONCLUSION: These data suggest that there is increased production of IL-10 by non-T cells in patients with RA. This may contribute to the diminished T cell function and increased antibody and RF production in these patients.
1513040 [Renal and neurologic symptoms due to cryoglobulinemia complicated with rheumatoid arthrit 1992 Jun A 55-year-old woman with rheumatoid arthritis and Sjögren's syndrome developed complications of acute renal failure and symmetrical polyneuropathy. Laboratory examination revealed macroglobulinemia, positive cryoglobulin, and low complement levels. Kidney biopsy specimen revealed "thrombi" in glomerular capillary loops that were positive for PAS stain and negative for Congo red stain. Sural nerve biopsy specimens showed axonal degeneration and subsequent myelin loss due to vasculitis. We, therefore, diagnosed renal failure and polyneuropathy due to cryoglobulinemia, and treated the patient with double filtration plasmapheresis. Moreover, lymph node biopsy specimen revealed malignant lymphoma of the follicular, small-cell lymphoplasmocytic type which seemed to be related to the macroglobulinemia. The complication of cryoglobulinemia must be taken into consideration in patients with autoimmune disease or lymphoproliferative disorder complicated with renal or neurologic symptoms.
1380988 Analysis of lymphocyte phenotype and T cell receptor genotype in Felty's syndrome. 1992 Jul Natural killer (NK) cells and CD3+ large granular lymphocytes (LGL) were investigated in patients with Felty's syndrome (FS), rheumatoid arthritis (RA) and healthy controls. In most patients with FS, NK cell number and activity were decreased. CD3+ LGL were unchanged. However, in one patient a marked expansion of CD3- CD16+ CD56+ (NK) cells was seen and in a second, an expansion of CD3+ LGL. In FS there was also an increase in HLA- DR+ and CD8+ but not gamma delta+ T cells. Three of 11 patients with FS studied demonstrated a dominant rearrangement of the T cell receptor beta gene constant region consistent with oligoclonal T cell expansion.
8325555 [Nerve compression syndromes in the area of the elbow joint in patients with chronic polya 1993 Mar This review of the literature reveals pathology responsible for the occurrence of entrapment neuropathies at the elbow associated with rheumatoid arthritis. Clinical symptoms and surgical treatment of ulnar, radial, and median nerve palsies are described.
8838507 Potential pathogenicity of deglycosylated IgG cross reactive with streptokinase and fibron 1996 Jan OBJECTIVE: Fibronectin (FN) and the streptococcal plasminogen activator streptokinase (SK) share the epitope LTSRPA. This epitope is not reactive in native FN and it reacts with anti-SK antibodies only after plasmin digestion of the protein. To investigate a potential correlation between the high levels of anti-LTSRPA antibodies in sera of patients with rheumatoid arthritis (RA) and the perpetuation of the immune response characteristic of this disease, we analyzed their capacity to activate complement and the process of binding to the serum lectin mannan binding protein (MBP). METHODS: We used a radioimmunoassay to evaluate immune complexes between anti-LTSRPA IgG and FN, plasmin degraded FN, or the LTSRPA peptide for their capacity to activate complement C5 to C5a. Purified human serum lectin MBP was used to quantify the degree of exposed mannose or N-acetylglucosamine residues in the Fc region of anti-LTSRPA IgG of patients with RA and healthy controls. RESULTS: Anti-LTSRPA IgG from patients with RA have a greater capacity to activate complement C5 to C5a when bound to either the LTSRPA peptide or plasmin degraded FN in vitro. We found a very strong correlation between the complement activating capacity of the RA immune complexes and their binding to MBP. CONCLUSION: The enhanced capacity of RA anti-LTSRPA IgG immune complexes to activate complement C5 to C5a is directly correlated with their binding capacity to MBP. As MBP binding depends on exposed mannose or N-acetylglucosamine residues in the Fc region of the IgG molecule, these studies suggest that defective glycosylation of circulating anti-SK IgG may play a role in the etiology of RA.
1384441 Characteristics of immunocompetent cells in synovial membranes from multiple sites in pati 1992 Sep The phenotypic characterization of enzymatically dissociated mononuclear cells in synovial membrane samples from multiple sites in two patients with rheumatoid arthritis (RA) were examined by fluorescence activated flow cytometry. In synovial membrane samples from each patient there was a consistent increase in the proportion of CD8+ cells (suppressor/cytotoxic), CD14+ cells (monocytes/macrophages), and HLA-DR+ cells compared with paired peripheral blood mononuclear cells. The proportion of CD4+ cells (helper/inducer) in synovial membrane was variable. Studies of in vitro production of IgM and IgM rheumatoid factor in one patient showed strikingly similar values for synovial membrane rheumatoid factor production at the two sites, which was enhanced compared with production in peripheral blood. These results suggest that in individual patients with RA the intra-articular immune response is comparable at multiple anatomical sites and that it is distinct from that in peripheral blood.