Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
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| 11212174 | Secretion of anti-citrulline-containing peptide antibody by B lymphocytes in rheumatoid ar | 2001 Jan | OBJECTIVE: To understand the regulation of anti-citrulline-containing peptide antibody (anti-CCP) production in rheumatoid arthritis (RA), production of anti-CCP by B cells derived from peripheral blood (PB), bone marrow (BM), and synovial fluid (SF) was examined. METHODS: Purified PB and SF B cells were isolated by negative selection and then cultured in the absence or presence of L-CD40 ligand cells and interleukin-10 or anti-CD3-activated T cells. Total IgM and IgM-anti-CCP were detected after 14 days of culture by enzyme-linked immunosorbent assay. Enzyme-linked immunospot assays were performed to analyze the frequency of cells that spontaneously produced IgM-anti-CCP in BM and SF B cells. RESULTS: IgM-anti-CCP autoantibodies were induced in PB B cells from healthy controls and RA patients following coculture with activated T cells or application of the CD40 activation system, whereas no production could be detected when PB B cells were cultured in the absence of a stimulus. SF and BM B cells from anti-CCP-seropositive RA patients, but not anti-CCP-seronegative patients, actively produced IgM-anti-CCP without stimulation. The frequency of spontaneous production of IgM-anti-CCP among the IgM-secreting cells ranged from 2.2% to 25%. CONCLUSION: These results indicate the presence of B cell precursors for anti-CCP autoantibodies that are able to produce antibodies upon stimulation in the PB B cell repertoire of healthy controls and patients with RA. In contrast, B cells that actively secreted anti-CCP were specifically present in the BM and SF compartment of anti-CCP-seropositive RA patients. The local presence of anti-CCP-secreting cells in the inflamed joints provides evidence for an antigen-driven maturation of CCP-specific B cells at the site of inflammation in RA. | |
| 11350047 | Feedback control of the arachidonate cascade in rheumatoid synoviocytes by 15-deoxy-Delta( | 2001 May 18 | Rheumatoid arthritis (RA) is a chronic polyarticular joint disease associated with massive synovial proliferation, inflammation, and angiogenesis. PPAR-gamma ligands, both 15-deoxy-Delta(12,14)-prostaglandin J2 (15d- PGJ2) and troglitazone (TRO), can inhibit the growth of RA synoviocytes in vitro, and suppress the chronic inflammation of adjuvant-induced arthritis in rats, but the potency of 15d-PGJ2 is higher than TRO. Prostaglandin (PG) E2 plays important roles in joint erosion and synovial inflammation. In the present study, 15d-PGJ2, but not TRO and other prostanoids, suppressed interleukin (IL)-1beta-induced PGE2 synthesis in rheumatoid synovial fibroblasts (RSFs) through the inhibition of cyclooxygenase (COX-2) and cytosolic phospholipase A2 (cPLA2) expression. Furthermore, the inhibition was not affected by pretreatment with anti-PPAR-gamma antibody. It means that this anti-inflammatory effect of 15d-PGJ2 for PG synthesis may be independent of PPAR-gamma and 15d-PGJ2 is a key regulator of negative feedback of the arachidonate cascade on the COX pathway. These findings provide new insight into the feedback mechanism of the arachidonate cascade. | |
| 10217817 | Operative correction of swan-neck and boutonniere deformities in the rheumatoid hand. | 1999 Mar | A swan-neck or boutonniere deformity occurs in approximately half of patients with rheumatoid arthritis. The cause of boutonniere deformity is chronic synovitis of the proximal interphalangeal joint. Swan-neck deformity may be caused by synovitis of the metacarpophalangeal, proximal interphalangeal, or distal interphalangeal joints. Numerous procedures are available for the operative correction of these finger deformities. The choice of surgical procedure is dependent on accurate staging of the deformity, which is based on the flexibility of the proximal interphalangeal joint and the state of the articular cartilage. The patient's overall medical status and corticosteroid use, the condition of the cervical spine, the need for operative treatment of large joints, and the presence of deformities of the wrist and metacarpophalangeal joints must also be considered when planning treatment. In the later stages of both deformities, soft-tissue procedures alone may not result in lasting operative correction. | |
| 10548505 | Activated T lymphocytes support osteoclast formation in vitro. | 1999 Nov | Osteoblastic stromal cells are capable of supporting osteoclast formation from hematopoietic precursors in the presence of osteotropic factors such as 1alpha,25(OH)(2)D(3), PTH, and IL-11. Osteoblastic stromal cells produce receptor activator of NF-kappaB ligand (RANKL), a type II membrane protein of the TNF ligand family, in response to these agents. Activated T lymphocytes also produce RANKL; however, the ability of this cell type to support osteoclast formation in vitro is unknown. Human PBMC-derived T cells, extracted using alphaCD3-coated magnetic beads, were cocultured with adherent murine spleen cells in the presence of Con A and a panel of cytokines. In the presence of Con A, bona fide osteoclasts were formed in vitro with activated T cells: IL-1alpha and TGFbeta further enhanced osteoclast numbers. PBMC-derived lymphocytes showed an increase in the mRNA expression of RANKL within 24 h of treatment with the same agents that were used to induce osteoclast formation. In synovial tissue sections with lymphoid infiltrates from RA patients, the expression of RANKL was demonstrated in CD3(+) T cells. The ability of activated T lymphocytes to support osteoclast formation may provide a mechanism for the potentiation of osteoclast formation and bone resorption in disease states such as rheumatoid arthritis. | |
| 9042931 | Detecting disease-predisposing variants: the haplotype method. | 1997 Mar | For many HLA-associated diseases, multiple alleles-- and, in some cases, multiple loci--have been suggested as the causative agents. The haplotype method for identifying disease-predisposing amino acids in a genetic region is a stratification analysis. We show that, for each haplotype combination containing all the amino acid sites involved in the disease process, the relative frequencies of amino acid variants at sites not involved in disease but in linkage disequilibrium with the disease-predisposing sites are expected to be the same in patients and controls. The haplotype method is robust to mode of inheritance and penetrance of the disease and can be used to determine unequivocally whether all amino acid sites involved in the disease have not been identified. Using a resampling technique, we developed a statistical test that takes account of the nonindependence of the sites sampled. Further, when multiple sites in the genetic region are involved in disease, the test statistic gives a closer fit to the null expectation when some--compared with none--of the true predisposing factors are included in the haplotype analysis. Although the haplotype method cannot distinguish between very highly correlated sites in one population, ethnic comparisons may help identify the true predisposing factors. The haplotype method was applied to insulin-dependent diabetes mellitus (IDDM) HLA class II DQA1-DQB1 data from Caucasian, African, and Japanese populations. Our results indicate that the combination DQA1#52 (Arg predisposing) DQB1#57 (Asp protective), which has been proposed as an important IDDM agent, does not include all the predisposing elements. With rheumatoid arthritis HLA class II DRB1 data, the results were consistent with the shared-epitope hypothesis. | |
| 9507267 | Coronal transacromial osteotomy surgical approach for shoulder arthroplasty. | 1998 Feb | Thirty-one shoulder arthroplasties in 24 patients were reviewed in which a coronal transacromial osteotomy surgical approach was used. Three total shoulder and 28 hemiarthroplasty procedures were performed. The average follow up was 5 years, 2 months. All patients underwent examination, interview, functional scoring, and radiographic studies. Twenty-seven shoulders (87%) were rated as excellent or good, and four were rated as fair or poor. Average postoperative active forward flexion and abduction measured 112 degrees and 103 degrees, respectively. Radiographs showed 87% of the osteotomies went on to union. The radiographic nonunions were stable, fibrous unions that were asymptomatic and did not have lower scores than the remainder of the group. The approach appears to be a viable option for shoulder arthroplasty. | |
| 9462756 | Silicone gel-filled breast implants and connective tissue diseases. | 1998 Feb | Recent worldwide press and media speculation that silicone implants may be linked to an increased incidence of breast cancer, other cancers, and connective tissue diseases-particularly systemic sclerosis-is a current cause for concern to the medical profession and public alike. We conducted a cross-sectional study of the prevalence of connective tissue diseases, as well as signs and symptoms associated with these conditions, in women who had received a silicone gel-filled breast implant for either breast augmentation or breast reconstruction following mastectomy for breast cancer compared with women without implants in South East Scotland. We compared 317 patients who had had a silicone gel-filled breast implant inserted with matched controls. We found no increased incidence of antinuclear antibodies or rheumatoid factor in the study groups. We detected one case of rheumatoid arthritis in the reconstruction group and one in matched controls, but no cases of any other connective tissue disease. No cases were found among the augmentation patients or their controls. No differences were found in symptoms or physical signs of connective tissue diseases between the study patients and their controls. This study has failed to find any case for a link between silicone gel-filled breast implants and connective tissue diseases. | |
| 9146949 | Immunological abnormalities of chronic large granular lymphocytosis. | 1997 Mar | Chronic large granular lymphocytosis is a relatively common condition and comprises a clinically heterogenous group of patients. Phenotypically these can be divided into CD3+ (T cell) and CD3-(NK cell) expansions. They are characterized by a benign clinical course and a mild lymphocytosis, though a specific subgroup have a history of auto-immune disease and cytopenias. In order to develop a better understanding of the immunological abnormalities associated with this condition we examined systematically serum samples from 92 such patients for the presence of auto-antibodies, acute phase proteins and immunoglobulin levels. Auto-antibodies were found in 34% of patients and rheumatoid factor in 26%, though only half of these had active arthritis. Anti-neutrophil antibodies were negative in all cases. Quantitative immunoglobulin abnormalities were frequent with a distinct paraprotein present in three patients. The high incidence of multiple immunological abnormalities in these patients ranged from polyclonal hypergammaglobulinaemia and auto-antibodies through to monoclonal gammopathy. The aetiology of these abnormalities was unclear and undoubtedly complex, and should necessarily form part of the diagnostic investigations for all patients with persistent large granular lymphocyte expansions. | |
| 11438043 | Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human | 2001 | Interleukin-11 (IL-11) is a pleiotropic cytokine that regulates the growth and development of hematopoietic stem cells and decreases the proinflammatory mediators of cytokine and nitric oxide production. In animal models of arthritis, treatment with recombinant human IL-11 (rhIL-11) reduces both the level of synovitis and the histologic lesion scores in the joints. The goal of this phase-I/II study in adults with rheumatoid arthritis (RA) was to evaluate the safety and clinical activity of different doses and schedules of rhIL-11 in patients with active RA for whom treatment with at least one disease-modifying antirheumatic drug had failed. This was a multicenter, randomized, placebo-controlled trial that evaluated the safety and tolerability of rhIL-11 in 91 patients with active RA. rhIL-11 was administered subcutaneously; patients were randomized into one of five treatment groups (ratio of rhIL-11 to placebo, 4:1). Patients were treated for 12 weeks with either 2.5 or 7.5 microg/kg of rhIL-11 or placebo twice per week or 5 or 15 microg/kg of rhIL-11 or placebo once per week. The status of each subject's disease activity in accordance with the American College of Rheumatology (ACR) criteria was assessed before, during, and after completion of administration of the study drug. Administration of rhIL-11 was well tolerated at all doses and schedules. The most frequent adverse event was a reaction at the injection site. The data suggest a statistically significant reduction in the number of tender joints (P < 0.008) at the 15 microg/kg once-weekly dose schedule but showed no overall significant benefit at the ACR criterion of a 20% response. The trial showed rhIL-11 to be safe and well tolerated at a variety of doses and schedules over a 12-week treatment period in patients with active RA. The only adverse event clearly associated with rhIL-11 administration was reaction at the injection site. | |
| 10878294 | Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other | 2000 May | Leflunomide (Arava) has recently been approved by the Food and Drug Administration for the treatment of rheumatoid arthritis (RA). The drug, due to its protective effects on structural joint damage, has been classified as a disease modifying anti-rheumatic drug (DMARD). Leflunomide is structurally dissimilar from other drugs currently used to treat RA and exhibits a different mechanism of action. It has shown to be protective in a variety of animal models of arthritis and autoimmunity based on its immunomodulatory activity. Leflunomide is rapidly converted in vivo to its pharmacologically active metabolite A77 1726. This metabolite is a potent non-cytotoxic inhibitor of the enzyme dihydroorotate dehydrogenase (DHODH), a key enzyme in the de novo synthesis of uridine monophosphate (UMP). Activated lymphocytes depend on the pyrimidine de novo syntheses to fulfill their metabolic needs for clonal expansion and terminal differentiation into effector cells. De novo synthesis of pyrimidines is not only essential to provide precursors for new RNA and DNA synthesis, but also for phospholipid synthesis and the pyrimidine sugars necessary for protein glycosylation, which support the massive expansion in membrane biosynthesis to form daughter cells. This mechanism likely contributes to leflunomide's action as a DMARD in RA and other autoimmune diseases. This review is a summary of current in vivo and in vitro data, focussing primarily on the mechanism of action of leflunomide in RA. | |
| 11205854 | Complications of elbow arthroscopy. | 2001 Jan | BACKGROUND: Although the potential complications of elbow arthroscopy, including nerve injuries, have been described, the prevalence of their occurrence has not been well defined. The purpose of this paper is to describe the serious and minor complications in a large series of patients treated with elbow arthroscopy. METHODS: A retrospective review of 473 consecutive elbow arthroscopies performed in 449 patients over an eighteen-year period was conducted. Of the 473 cases, 414 were followed for more than six weeks. The most common final diagnoses were osteoarthritis (150 cases), loose bodies (112), and rheumatoid or inflammatory arthritis (seventy-five). The arthroscopic procedures included synovectomy (184), debridement of joint surfaces or adhesions (180), excision of osteophytes (164), diagnostic arthroscopy (154), loose-body removal (144), and capsular procedures such as capsular release, capsulotomy, and capsulectomy (seventy-three). RESULTS: A serious complication (a joint space infection) occurred after four (0.8%) of the arthroscopic procedures. Minor complications occurred after fifty (11%) of the arthroscopic procedures. These complications included prolonged drainage from or superficial infection at a portal site after thirty-three procedures, persistent minor contracture of 20 degrees or less after seven, and twelve transient nerve palsies (five ulnar palsies, four superficial radial palsies, one posterior interosseous palsy, one medial antebrachial cutaneous palsy, and one anterior interosseous palsy) in ten patients. The most significant risk factors for the development of a temporary nerve palsy were an underlying diagnosis of rheumatoid arthritis (p < 0.001) and a contracture (p < 0.05). There were no permanent neurovascular injuries, hematomas, or compartment syndromes in our series, and all of the minor complications, except for the minor contractures, resolved without sequelae. CONCLUSIONS: Our results indicate that the prevalence of temporary or minor complications following elbow arthroscopy may be greater than previously reported. However, serious or permanent complications were uncommon. | |
| 11775830 | Role of protein tyrosine kinase in IL-1 beta induced activation of mitogen-activated prote | 2000 Oct | OBJECTIVES: To study mitogen-activated protein kinase (MAPKs) activation in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) under the stimulation of IL-1 beta, and to elucidate the role of protein tyrosine kinase (PTK) in the activation of MAPKs. METHODS: Primary cultures of RA FLS were used. Western blot was applied to examine transient changes in protein tyrosine phosphorylation status and MAPKs activation in RA FLS stimulated with IL-1 beta at various doses, and over different periods. Genistein, the specific PTK inhibitor, was used to evaluate the inhibitory role in activation of MAPKs by IL-1 beta. RESULTS: IL-1 beta transiently increased protein tyrosine phosphorylation, and activated the MAPKs cascades (mainly ERK2, JNK2 and P38) in RA FLS. There was no obvious difference in MAPKs activation among different doses of IL-1 beta (1 IU/ml, 10 IU/ml, 100 IU/ml), but the peak activation of ERK2, JNK2 and P38 took place at 5 min, 15 min and 1 min, respectively, after stimulation with IL-1 beta. The activation of ERK2 was inhibited by genistein, but the inhibitory role on that of JNK and P38 was relatively weak. CONCLUSIONS: During signal transduction of IL-1 beta in RA FLS, tyrosine phosphorylation was increased transiently, the MAPKs cascade was activated in a few minutes, and there was heterogenicity in the activation among three subfamily members. PTK had a role in the activation of ERK, but had weak effects on that of JNK and P38. | |
| 9549450 | Meta-analysis of short-term low dose prednisolone versus placebo and non-steroidal anti-in | 1998 Mar 14 | OBJECTIVE: To determine whether short-term, oral low dose prednisolone (< or = 15 mg daily) is superior to placebo and non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis. DESIGN: Meta-analysis of randomised trials of oral corticosteroids compared with placebo or a non-steroidal anti-inflammatory drug. SETTING: Trials conducted anywhere in the world. SUBJECTS: Patients with rheumatoid arthritis. MAIN OUTCOME MEASURES: Joint tenderness, pain, and grip strength. Outcomes measured on different scales were combined by using the standardised effect size (difference in effect divided by SD of the measurements). RESULTS: Ten studies were included in the meta-analysis. Prednisolone had a marked effect over placebo on joint tenderness (standardised effect size 1.31; 95% confidence interval 0.78 to 1.83), pain (1.75; 0.87 to 2.64), and grip strength (0.41; 0.13 to 0.69). Measured in the original units the differences were 12 (6 to 18) tender joints and 22 mm Hg (5 mm Hg to 40 mm Hg) for grip strength. Prednisolone also had a greater effect than non-steroidal anti-inflammatory drugs on joint tenderness (0.63; 0.11 to 1.16) and pain (1.25; 0.26 to 2.24), whereas the difference in grip strength was not significant (0.31; -0.02 to 0.64). Measured in the original units the differences were 9 (5 to 12) tender joints and 12 mm Hg (-6 mm Hg to 31 mm Hg). The risk of adverse effects during moderate and long term use seemed acceptable. CONCLUSION: Prednisolone in low doses (< or = 15 mg daily) may be used intermittently in patients with rheumatoid arthritis, particularly if the disease cannot be controlled by other means. | |
| 10460187 | Characterisation of T cell clonotypes that accumulated in multiple joints of patients with | 1999 Sep | OBJECTIVE: To investigate whether identical T cell clonotypes accumulate in multiple rheumatoid joints, the clonality of T cells that had infiltrated into synovial tissue (ST) samples simultaneously obtained from multiple joints of patients with rheumatoid arthritis (RA) was analysed. METHODS: T cell receptor (TCR) beta gene transcripts, amplified by reverse transcription-polymerase chain reaction from ST and peripheral blood lymphocytes of five RA patients, were subjected to single strand conformation polymorphism analysis and DNA sequencing. RESULTS: Approximately 40% of accumulated T cell clonotypes found in one joint of a patient were found in multiple joints in the same patient. Furthermore, identical amino acid sequences were found in TCR beta junctional regions of these clonotypes from different patients with at least one HLA molecule match. CONCLUSIONS: The T cell clonotypes accumulating in multiple rheumatoid joints may be involved in the perpetuation of polyarthritis by reacting to antigens common to these multiple joints. | |
| 10939298 | Free radicals in chronic fatigue syndrome: cause or effect? | 2000 | We have demonstrated that certain morphological and biochemical changes occur in chronic fatigue syndrome (CFS) and in rheumatoid arthritis (RA). These changes in RA can be explained by the well-established inappropriate increase in free radical generation. The similar changes in CFS suggest a similar explanation and a possible role for free radicals in the aetiology of this condition. | |
| 10743792 | IgG antibodies to type II collagen reflect inflammatory activity in patients with rheumato | 2000 Mar | OBJECTIVE: To determine the clinical significance of IgG antibodies to type II collagen (CII) and to define any correlation of antibodies to CII with the inflammatory response in patients with rheumatoid arthritis (RA). METHODS: IgG antibodies to native human type II collagen (IgG anti-CII) were measured in sera and synovial fluid (SF) from patients with RA, patients with osteoarthritis (OA), and healthy controls by an improved ELISA. Demographic, clinical, and laboratory data including tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) levels were also obtained at the time of sampling in patients with RA. RESULTS: The median level and positivity for circulating IgG anti-CII were higher in patients with RA (n = 297) than patients with OA (n = 34) and healthy controls (n = 50) (p < 0.001). The titers of IgG anti-CII in SF were also higher in RA (n = 45) than in OA (n = 16) (p < 0.001). In paired samples, the levels of IgG anti-CII were significantly higher in SF compared to the sera in patients with RA (n = 45) (p < 0.001), but levels were not different in patients with OA (n = 16). Circulating IgG anti-CII converted from positive to negative in 13 patients (10.7%) and from negative to positive in 18 patients (14.8%) among 122 patients with RA in whom IgG anti-CII were monitored sequentially at a mean interval of 12.2 months. IgG anti-CII positive patients (n = 98) had shorter disease duration (p = 0.04) and less frequent deformity (p = 0.013), and higher median erythrocyte sedimentation rate (ESR) (p = 0.001) and C-reactive protein (CRP) (p < 0.001) than IgG anti-CII negative patients (n = 120). The levels of IgG anti-CII correlated with CRP (r = 0.270) and ESR (r = 0.253). CRP decreased significantly in patients (n = 13) who converted from IgG anti-CII positive to negative (p = 0.013). IgG anti-CII positive patients (n = 40) had higher levels of TNF-alpha and IL-6 than negative patients (n = 40) (p < 0.001). Levels of IgG anti-CII correlated well with TNF-alpha (r = 0.617) and IL-6 (r = 0.347). CONCLUSION: Increased IgG anti-CII in sera and SF in RA correlated directly with acute phase reactants and the proinflammatory cytokines TNF-alpha and IL-6. Our data suggest that IgG anti-CII could reflect inflammatory activity with a potential to destroy cartilage in the early stages of RA. | |
| 9058651 | Home exercise and compliance in inflammatory rheumatic diseases--a prospective clinical tr | 1997 Mar | OBJECTIVE: To survey and to compare the one year effects of dynamic muscle training and progressive muscle relaxation as home exercise for patients with inflammatory rheumatic diseases; and to identify predictors for compliance with a longterm home exercise regimen. METHODS: Fifty-four patients (mean age 54 yrs, mean symptom duration 14 yrs) were assessed for health related quality of life, exercise motivation, joint tenderness, and physical capacities. After randomization into 2 groups, every patient was instructed on one occasion in a 30 min program of either dynamic training or muscle relaxation to carry out at home, 5 times a week during 3 months, and then 2-3 times a week for another 9 months. RESULTS: Seventeen patients in each group completed the one year exercise protocol, while 10 from each group did not. Compliance with the one year exercise regimen seemed to be predicted by high self-efficacy for exercise, regular range-of-motion exercises before the intervention, and being unmarried. After one year, minor improvements in physical effect (p < or = 0.05) and work effect (p < or = 0.05) were found in the dynamic training group, while minor improvements in pain effect (p < or = 0.05), emotional reactions (p < or = 0.05), and arm endurance (p < or = 0.01) were found in the muscle relaxation group. No differences between the groups regarding changes in health status, joint tenderness, or physical capacities during the intervention period were found. CONCLUSION: These results may improve the selection of patients for home exercise, and form a basis for improved administration of home exercise programs. | |
| 9622037 | Anticardiolipin antibodies in clinical conditions associated with a risk of thrombotic eve | 1998 Feb 1 | Anticardiolipin antibodies (ACAs) of IgA, IgG, and IgM isotypes were measured using an enzyme-linked immunosorbent assay (ELISA) in patients with SLE, and in other groups of subjects with a higher or lower risk of developing thrombosis. IgA ACAs were present in high titers in all groups and had little discriminant value in predicting thrombotic risk. In patients without the lupus anticoagulant (LAC) with conditions in which a thrombotic tendency was a feature (primigravidae with preeclampsia or intrauterine growth retardation, patients with angina or acute myocardial infarction, those on anticoagulant therapy for apparently spontaneous thrombosis, and patients with Behcet's syndrome in whom there was a history of thrombosis) ACAs of all isotypes were present in 44/191 (23%). In patients in whom a thrombotic tendency was not a feature (normal controls, primigravidae with normal deliveries, patients with rheumatoid arthritis, and with Behcet's syndrome in whom there was no thrombotic history) 22/241 (9%) had ACAs. Although ACAs were more likely to be present in a subset of patients without systemic lupus erythematosus (SLE) and/or the LAC, their presence was a poor discriminator of increased risk of thrombosis. | |
| 10428123 | Analysis of routine histological evaluation of tissues removed during primary hip and knee | 1999 Jul | BACKGROUND: It has often been hospital policy to send all resected specimens obtained during a total hip or knee arthroplasty for histological evaluation. This practice is expensive and may be unnecessary. We sought to determine the ability of surgeons to diagnose primary joint conditions correctly, and we attempted to identify any possible risks to the patient resulting from the omission of routine histological evaluation of specimens at the surgeon's discretion. Our objective was to ascertain whether routine histological evaluation could be safely omitted from the protocol for primary hip and knee arthroplasty without compromising the care of the patient. METHODS: A total of 1388 consecutive arthroplasties in 1136 patients were identified from a database of primary total hip and knee arthroplasties that was prospectively maintained by the senior one of us. Follow-up data obtained at a mean of 5.5 years (range, two to ten years) were available after 92 percent (1273) of the 1388 arthroplasties. The preoperative diagnosis was determined from the history, findings on clinical examination, and radiographs. The intraoperative diagnosis was determined by gross inspection of joint fluid, articular cartilage, synovial tissue, and the cut surfaces of resected specimens. The combination of the preoperative and intraoperative diagnoses was considered to be the surgeon's clinical diagnosis. All resected specimens were sent for routine histological evaluation, and a pathological diagnosis was made. Attention was given to whether a discrepancy between the surgeon's clinical diagnosis and the pathological diagnosis altered the management of the patient. The original diagnoses were updated with use of annual radiographs and clinical assessments. The cost of histological examination of specimens obtained at arthroplasty was determined by consultation with hospital administration, accounting, and pathology department personnel. RESULTS: A pathological fracture or an impending fracture was diagnosed preoperatively and confirmed intraoperatively during twelve of the 1388 arthroplasties. Histological analysis demonstrated malignancy in specimens obtained during eleven of these arthroplasties and evidence of a benign rheumatoid geode in the specimen obtained during the twelfth arthroplasty. The preoperative and intraoperative diagnoses made before and during the remaining 1376 arthroplasties were benign conditions, which were confirmed histologically in all patients. No diagnosis changed during the follow-up period. As demonstrated by a comparison with the histological diagnosis, the surgeon's clinical diagnosis of malignancy had a sensitivity of 100 percent (95 percent confidence interval, 74.0 to 100 percent), a specificity of 99.9 percent (95 percent confidence interval, 99.6 to 100 percent), a positive predictive value of 91.7 percent (95 percent confidence interval, 64.6 to 98.5 percent), and a negative predictive value of 100 percent (95 percent confidence interval, 99.7 to 100 percent). There was a discrepancy between the preoperative and intraoperative diagnoses associated with eleven arthroplasties. All eleven intraoperative diagnoses were correct, as confirmed histologically. Excluding the patients who had a pathological or impending fracture, the accuracy of the surgeon's preoperative diagnosis was 99.2 percent (95 percent confidence interval, 98.6 to 99.5 percent). When the intraoperative and preoperative diagnoses were combined, the accuracy was 100 percent (95 percent confidence interval, 99.7 to 100 percent). Histological evaluation at our hospital resulted in total charges, including hospital costs and professional fees, of $196.27 and a mean total reimbursement of $102.59 per evaluation. In our series of 1136 patients with 1388 arthroplasties, these costs could have been eliminated for all but the twelve patients who had a suspected malignant lesion and the one patient in whom pigmented villonodular synovitis was found. (ABSTRACT | |
| 10403931 | Oligoclonal T cell expansions in patients with Behçet's disease. | 1999 Jul | Behçet's disease (BD) is a multisystem disorder with oral and genital ulcers, mucocutaneous, ocular, joint, vascular and central nervous system involvement. In this study, the peripheral T cell repertoire was analysed in patients with BD with MoAbs against T cell receptor (TCR) Vbeta gene products in CD4+ and CD8+ T cell compartments, and these were compared with rheumatoid arthritis (RA) patients and healthy controls (HC). In the CD4+ T cell compartment, oligoclonal TCR Vbeta expression was observed in 56% of BD (10/18), 71% of RA (5/7) patients and 21% (3/14) of HC. In the CD8+ T cell group 50% of BD (9/18), 57% of RA patients and 28% of HC (4/14) had an oligoclonal TCR repertoire. An increase of TCR Vbeta5.1 subset was observed in five BD patients among CD8+ T cells. Other elevations of TCR Vbeta subsets were heterogeneously distributed with one to three different Vbeta subsets. Our results suggest an antigen-driven oligoclonal increase of T cells in BD. There was no overall increase in any Vbeta group to suggest a superantigen effect. Analysis of the responsible antigens causing the increase in T cell subsets may give insights into the aetiopathogenesis of BD and immunomodulation of these T cells may lead to new treatments. |