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ID PMID Title PublicationDate abstract
10817564 Gene therapy that inhibits nuclear translocation of nuclear factor kappaB results in tumor 2000 May OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) increases the survival and proliferation of human rheumatoid arthritis (RA) cell lines. These experiments were designed to determine if inhibition of nuclear factor kappaB (NF-kappaB) nuclear translocation leads to increased apoptosis of TNFalpha-treated human RA cell lines. METHODS: We constructed an inhibitor of nuclear factor kappaB(IkappaB) dominant-negative adenovirus (AdCMVIkappaB-DN) and an X-linked inhibitor of apoptosis (XIAP) antisense adenovirus (AdCMVXIAP-AS). Primary RA synovial fibroblast (RASF) cell lines were transfected in vitro, and SV40-transformed RA synovial cell lines in SCID mice were transfected in vivo. Cells were treated with TNFalpha and analyzed for apoptosis. RESULTS: There was no apoptosis of primary RASF transfected in vitro with AdCMVIkappaB-DN alone. In contrast, there was apoptosis of >85% of cells treated with AdCMVIkappaB-DN plus TNFalpha. Primary RASF in SCID mice also exhibited high levels of apoptosis after in vivo transfection with AdCMVIkappaB-DN followed by treatment with TNFalpha. There was no apoptosis after treatment with AdCMVIkappaB-DN in the absence of TNFalpha. XIAP is an inhibitor of apoptosis which was up-regulated by TNFalpha, and this up-regulation was inhibited by AdCMVIkappaB-DN plus TNFalpha. Transfection of an AdCMVXIAP-AS gene therapy resulted in increased TNFa-induced apoptosis. CONCLUSION: AdCMVIkappaB-DN gene therapy greatly enhances apoptosis due to inhibition of an NF-kappaB-mediated antiapoptosis signaling pathway, and XIAP is a TNFalpha-inducible specific inhibitor of apoptosis in RA synovial cell lines. This and other modulators of TNF receptor or the Fas apoptosis pathway may be therapeutically beneficial in facilitating apoptosis of synovial tissue in patients with RA.
10068910 HLA-DR/DQ interaction in patients with erosive rheumatoid arthritis presenting articular a 1999 Feb In the present study we have analysed the effect of HLA-DRB1 and -DQB1 alleles on disease progression and genetic predisposition among 201 RA patients. We clearly confirm the association of RA with HLA class II alleles sharing the (Q)R/KRAA amino acid (AA) cassette in the third hypervariable region (HVR3) of the DR beta-chain. The HVR3 (Q)R/KRAA motif was significantly overrepresented among RA patients (79% vs. 40%, P < 0.001), with one third of the patients homozygous (28% vs. 6.7%, P < 10(-9)) and the number of rheumatoid factor positive (RF+) patients was significantly increased among HVR3 (Q)R/KRAA homozygous in comparison to HVR3 (Q)R/KRAA negative individuals. Erosive disease defined by the Larsen Score and personal disability determined using the Health Assessment Questionnaire (HAQ) was significantly increased among patients positive for the HVR3 motif with the worst outcome among HVR3 (Q)R/KRAA homozygous patients. In contrast, there was no association of the shared HVR3 AA cassette and disease severity in the majority of patients presenting systemic (extraarticular) disease. Homozygosity for the shared HVR3 motif was only marginally increased among patients presenting 'severe' extraarticular disease in comparison to patients with articular disease (33% vs. 43%, P = ns). Similarly, patients with nodular disease were not more often homozygous for the HVR3 (Q)R/KRAA motif. Furthermore, we observed no HLA-DR independent association of DQB1 alleles among HVR3 (Q)R/KRAA positive patients and controls. Our analysis supports the predominant role of HLA-DR for genetic susceptibility to RA. In the clinical setting, however, HLA-DR typing may be limited to assess the individual risk of patients for disease progression.
9986861 Human phaeohyphomycotic osteomyelitis caused by the coelomycete Phomopsis saccardo 1905: c 1999 Mar The Sphaeropsidales, coelomycetous fungi producing asexual conidia within enclosed conidiomata (pycnidia), are saprobic on numerous vascular plants. Despite their ubiquitous nature, only a limited number of genera have been documented as causing human disease. We report what we believe to be the first human case of osteomyelitis due to a Phomopsis species in a chronically immunosuppressed female. The patient developed a subcutaneous abscess on the distal phalanx of the right fourth finger complicated by osteomyelitis. Operative specimens revealed fungal hyphae and a pure culture of mould. The patient was treated with a 6-month course of itraconazole. At 16 months of follow-up, she remained free of recurrence. Phomopsis species differ from the similar, more frequently reported Phoma species by having immersed, thick-walled, multiloculate conidiomata and by the production of alpha (short, ellipsoidal) and beta (long, filamentous) conidia.
9010263 Modulation of hu/mu severe combined immunodeficient (SCID) mouse arthritis by local applic 1997 Jan The contribution of interleukins produced by most inflammatory cells to chronic arthritis is not well understood. Therefore, we investigated the influence of several human recombinant interleukins (IL-1beta, IL-2 and IL-6) on joint swelling, on the inflammatory process, and on serological parameters in a novel animal model of arthritis, the human/murine SCID arthritis. In this model an arthritis is induced by implanting human synovial tissue from patients with rheumatoid arthritis (RA) into the knee joint of mice with SCID. These mice tolerate the xenogeneic implant and develop a mixed human/murine pannus tissue. The interleukins were injected daily for 7 or 14 days after implantation. IL-1beta led to a significant increase in joint swelling. It intensified the inflammatory process accompanied by enhanced migration of murine inflammatory cells into the knee joint. The production of human IL-6 in the transplanted tissue was stimulated through the application of IL-1beta, and the serum level of human IL-6 was thus significantly higher than in controls. We could not observe a significant influence of IL-1beta on the production of human IgG or IgM by the implant. The application of human IL-2 had a weak effect similar to that of IL-1beta, but without statistical significance. Although IL-6 is a good marker for inflammation in RA, the application of recombined human IL-6 had no influence on the inflammatory process in this model.
9636191 Definition of MHC and T cell receptor contacts in the HLA-DR4restricted immunodominant epi 1998 Jun 23 Rheumatoid arthritis (RA) is an autoimmune disease associated with the HLA-DR4 and DR1 alleles. The target autoantigen(s) in RA is unknown, but type II collagen (CII) is a candidate, and the DR4- and DR1-restricted immunodominant T cell epitope in this protein corresponds to amino acids 261-273 (CII 261-273). We have defined MHC and T cell receptor contacts in CII 261-273 and provide strong evidence that this peptide corresponds to the peptide binding specificity previously found for RA-associated DR molecules. Moreover, we demonstrate that HLA-DR4 and human CD4 transgenic mice homozygous for the I-Abbeta0 mutation are highly susceptible to collagen-induced arthritis and describe the clinical course and histopathological changes in the affected joints.
10332977 Predominance of CD8+ T lymphocytes in psoriatic arthritis. 1999 May OBJECTIVE: To characterize the synovial fluid (SF) derived T cell populations in psoriatic arthritis (PsA) and compare with similar populations from rheumatoid arthritis (RA). METHODS: Paired peripheral blood (PB) and SF samples were analyzed by 3 color flow cytometry using monoclonal antibodies to CD3, CD4, CD8, HLA-DR, CD25, CD45RA, and CD45RO. RESULTS: There was a significantly increased CD8+ T cell population in PsA SF compared to RA: PsA mean 61% (range 35-93), RA mean 46% (range 6-72) (p < 0.005). This resulted in a reversal of the CD4:CD8 ratio in PsA SF compared to RA SF (p < 0.001). Patients with oligoarticular PsA had the most pronounced differences in SF derived T cell populations compared to RA (p < 0.0005) but these results were not significantly different from PsA patients with a polyarticular disease pattern. PB PsA T cell populations were not different from controls, in contrast to RA, where the CD4+ T cell population was increased (p < 0.0026), giving an exaggerated PB CD4:CD8 ratio. The majority of PsA SF CD8+ T cells expressed CD45RO, mean 73% (range 58-95), and HLA-DR antigen: mean 72% (range 38-94). Low levels of CD25 were detectable in this population, indicating a nonclassical activation pattern: mean 2% (range 0.3-4.4). CONCLUSION: In PsA, activated (HLA-DR+) and mature (CD45RO+) CD8+ T cells predominate in SE Analysis of this population may uncover clues to pathogenesis in this HLA class I mediated disease.
11072601 Development rate of mutilans fingers in patients with rheumatic disease. 2000 Sep OBJECTIVE: To describe arthritis mutilans (AM) deformity during the progression of rheumatic disease. METHODS: The development of mutilans-like hand deformities in 2 patients with juvenile chronic arthritis (JCA) and in 2 patients with adult onset rheumatoid arthritis (RA) are presented. The hands of these patients were evaluated at least at two time points during the course of disease using two different scoring methods based on differently summed Larsen grades of the hand joints. RESULTS: Two patients (one with JCA and one with RA) showed AM changes after a disease period of less than 10 years and 2 not until after 30 years. The patients with adult onset disease were young at the onset of joint disease. Early wrist fusions were performed on both patients showing a slow development rate. CONCLUSIONS: The development rate of AM is very variable, even in patients with the same diagnoses. Wrist fusion prevents shortening of the carpus and may decrease the development rate of AM.
10403258 Pharmacokinetics, safety, and efficacy of combination treatment with methotrexate and lefl 1999 Jul OBJECTIVE: To examine the safety and pharmacokinetics of and clinical response to leflunomide, a de novo pyrimidine synthesis inhibitor, when administered to patients with active rheumatoid arthritis (RA) who have been receiving long-term methotrexate therapy. METHODS: This was an open-label, 52-week study in which 30 patients with RA that remained active despite therapy with methotrexate at 17+/-4 mg/week (mean +/- SD) for > or =6 months were given leflunomide, 10-20 mg/day. Patients were assessed for adverse effects, pharmacokinetic measurements of leflunomide and methotrexate, and clinical response by American College of Rheumatology (ACR) 20% response criteria. RESULTS: Twenty-three patients completed 1 year of treatment. No significant pharmacokinetic interactions between leflunomide and methotrexate were noted. This combination therapy was generally well tolerated clinically, with the exception of elevations of liver enzyme levels. Seven patients withdrew from the treatment regimen: 2 withdrawals were voluntary, 3 were due to persistent elevation of plasma transaminase levels, and 2 were due to lack of efficacy. Of the patients, 16 (53%) met ACR 20% response criteria. Two met ACR criteria for remission after 1 year. CONCLUSION: The combination of methotrexate and leflunomide has therapeutic potential in RA.
11760396 Synovial fluid cytokine levels in Behçet's disease. 2001 Sep OBJECTIVE: To investigate the synovial fluid levels of interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), IL-1 receptor antagonist (IL-1ra), soluble IL-2 receptor (sIL-2r) and IL-8 in patients with Behçet's disease (BD) and to compare them to levels in rheumatoid arthritis (RA), and osteoarthritis (OA). METHODS: The cytokine levels of BD (n = 14), RA (n = 15) and OA (n = 15) patients were assessed by enzyme-linked immunosorbent method. RESULTS: Median synovial IL-1 beta and TNF-alpha levels were higher in RA compared to BD and OA patients. IL-1 beta levels were also higher in BD than OA whereas TNF levels were similar in these two groups. IL-1ra and TGF-beta activity in BD were higher than OA but lower than RA. sIL-2r and IL-8 levels were increased in BD and RA in comparison to OA patients. CONCLUSION: The arthritis of BD is non-erosive and accordingly, its synovial fluid contains lower levels of cytokines primarily involved in cartilage destruction, namely IL-1 beta and TNF-alpha, than RA. IL-1ra and TGF might serve as protective factors against erosion in the inflamed joints. High synovial fluid levels of sIL-2r and IL-8 probably reflect a non-specific inflammatory process.
11560031 [Clinical and laboratory support for multiple-modality treatment of rheumatic patients wit 2001 May In 158 rheumatic patients with mitral valvular disease (MVD), clinical-and-laboratory indices were studied together with a possibility for correction of the detected disorders in a multiple-modality staged treatment involving basic drug therapy, EHF-therapy, and sanatorium-health resort stage of rehabilitation. It has been found out that EHF-therapy and sanatorium-health resort treatment have a positive effect on the clinical course of the trouble and on the laboratory indices for the inflammatory process contributing to optimization of medicamentous treatment of rheumatic patients with MVD.
9550474 Soluble Fas ligand in the joints of patients with rheumatoid arthritis and osteoarthritis. 1998 Apr OBJECTIVE: To investigate the expression and function of Fas ligand (FasL),which can be in a membrane-bound or soluble form, in the joints of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: The concentration of soluble FasL (sFasL) in serum and synovial fluid (SF) from 24 OA and 38 RA patients was measured using an enzyme-linked immunosorbent assay. The expression of FasL on SF lymphocytes (SFL) and peripheral blood lymphocytes (PBL) was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. A cytotoxic killing assay of membrane-bound FasL and purified sFasL against cultured synovial cells was also performed. RESULTS: Soluble FasL was detected in the SF of patients with RA and OA, but not in their serum. The concentration of SF sFasL was remarkably higher in patients with severe RA than in patients with mild RA or with OA. RT-PCR showed that SFL, but not PBL, from RA patients expressed messenger RNA for FasL. Membrane-bound FasL induced apoptosis in cultured synovial cells from the RA and OA patients, but naturally processed human sFasL did not. CONCLUSION: SFL from RA patients expressed FasL, and cleaved sFasL accumulated in the SF of inflamed joints. The different killing activity of membrane-bound FasL and sFasL against synovial cells may regulate Fas-mediated apoptosis in synovial cells.
10342329 The role of N-acetylcysteine in protecting synovial fluid biomolecules against radiolytica 1999 May High field proton (1H) NMR spectroscopy has been employed to evaluate the abilities of the antioxidant thiol drug N-acetylcysteine and exogenous cysteine to protect metabolites present in intact inflammatory synovial fluid samples against oxidative damage arising from gamma-radiolysis (5.00 kGy) in the presence of atmospheric O2. Although oxidation of urate to allantoin by radiolytically-generated *OH radical was readily circumventable by pre-treatment of synovial fluids with N-acetylcysteine (1.00 or 3.00 x 10(-3) mol x dm(-3)) or cysteine (1.00, 2.00 or 5.00 x 10(-3) mol x dm(-3)), both thiols offered only a limited protective capacity with respect to hyaluronate depolymerisation and the production of formate from carbohydrates in general. Radiolytic products generated from the added thiols (predominantly their corresponding disulphides) were simultaneously detectable in 1H Hahn spin-echo spectra of gamma-irradiated synovial fluids, permitting a quantitative evaluation of the radioprotective capacity of these agents. It is concluded that the multicomponent analytical ability of high field 1H NMR spectroscopy provides much useful molecular information regarding mechanisms associated with the radioprotectant actions of thiols in intact biofluids.
9890339 Evaluation of an ELISA test for determination of the serum transferrin receptor. Demonstra 1998 Nov We undertook this study to evaluate a recently introduced ELISA kit for determining serum transferrin receptor (TfR) concentration (TfR, Ramco Laboratories, Inc.), to produce reference values for healthy adults, and to compare the results with another commercially available reagent system. The mean (SD) recovery of added TfR was 88% (6%). In dilution studies, the ratio between the measured and expected values was 0.98 (0.11). The intra-assay and interassay coefficients of variation were from 5% to 7% and from 6% to 9% in a physiological and a supraphysiological concentration range, respectively, and from 13% to 16% in a subnormal concentration range. In healthy adults between 20 and 60 years of age, we observed no age- or sex-related differences in TfR values. Thus, the same reference interval, 3.0-8.2 mg l(-1), may be used for this population. The correlation between the results obtained with the Ramco TfR test and the Amgen Diagnostics Clinigen test was satisfactory (r=0.79). The Ramco TfR test produced higher values (Tf=0.40 (-0.45-1.25)+1.46 (1.16-1.75)* Clinigen). The number of samples that fell within the same concentration interval with both methods (low, normal or high in relation to the respective reference interval) was only 45% (27/60). The Ramco TfR test had fewer values falsely suggesting iron deficiency than the Clinigen test. Serum TfR methods need to be uniformly standardized.
9376997 Relationship between urinary excretion of modified nucleosides and rheumatoid arthritis pr 1997 Sep The levels of the five methylated nucleosides pseudouridine (psi-Urd), 1-methyladenosine (1-MeAdo), 4 acetylcytidine (4-AcCyd), 1 methylinosine (1-Melno) and 7 methylguanosine (7-MeGuo) resulting from RNA degradation were examined in the urine of rheumatoid arthritis (RA) patients. Of these five, 1-MeAdo and psi-Urd were correlated with the active phase of the disease, while two others (4-AcCyd and 1-Melno), which require further evaluation, appeared to be linked to the prognosis of the disease. As RNA turnover is closely associated with cell proliferation, including that of lymphocytes in RA, there may be a hitherto unsuspected benefit in measuring 1-MeAdo and psi-Urd as biochemical markers of RA disease activity.
11828419 Synthesis of a C-glycoside analogue of beta-D-galactosyl hydroxynorvaline and its use in i 2000 Nov 17 A C-linked isostere of beta-D-galactosylated hydroxynorvaline has been prepared in eight steps from per-O-benzylated galactopyranolactone. Addition of a homoallylic Grignard reagent to the lactone, reduction of the resulting hemiacetal with triethylsilane, and a Wittig reaction with Garner's aldehyde were key steps in this synthesis. The C-linked building block was then incorporated at position 264 into the fragment CII(256--270) from typeII collagen by solid-phase synthesis using a combination of the tert-butoxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc) protective group strategies. Deprotection of the benzylated C-linked galactosyl moiety was achieved simultaneously with cleavage of the glycopeptide from the solid phase by using triethylsilyl trifluoromethanesulfonate in TFA. Helper T-cell hybridomas obtained in a mouse model for rheumatoid arthritis responded to the C-linked glycopeptide when presented by classII MHC molecules. However, 10- to 20-fold higher concentrations were required as compared to when O-linked beta-D-galactosylated hydroxynorvaline or hydroxylysine (Hyl) were present at position 264 of CII(256--270). Thus, replacement of a single oxygen atom by a methylene group in the carbohydrate moiety of a glycopeptide antigen had a substantial influence on the T-cell response. This reveals that T cells are able to recognize the carbohydrate moiety of glycopeptide antigens with high specificity. Finally, the results suggest that structural modifications of beta-D-Gal-Hyl(264) in CII(256--270) may give altered peptide ligands that can be used for induction of tolerance in autoimmune rheumatoid arthritis.
11055825 Significance of low mRNA levels of interleukin-4 and -10 in mononuclear cells of the synov 2000 Our objective was to investigate the clinical significance of Th1 and Th2-type cytokines, such as interferon-gamma (IFNgamma) interleukin (IL)-12, IL-4 and IL-10, in the mononuclear cells (MNC) of the synovial fluid (SF) in patients with rheumatoid arthritis (RA). The cytokine production in the MNC obtained from the SF (SF-MNC) in 30 patients with RA and 10 with gout was examined by measuring the mRNA levels of IFNgamma, IL-12, IL-4 and IL-10 by semiquantitative RT-PCR. The mRNA levels of IFNgamma, IL-4 and IL-10 were significantly higher in the SF-MNC of RA patients than in those of gout patients (p<0.001, p<0.01 and p<0.001, respectively). Correlations between mRNA levels were significant for IL-12 and IL-4, IL-12 and IL-10, and IL-4 and IL-10 (p<0.05). The mRNA levels of IL-4 and IL-10 were very low compared to those of IL-12 in seven of the 30 patients with RA; all of these patients were in stage 4, and serum levels of CRP, ESR and blood platelet count which are considered as indices of the severity of inflammation, were significantly elevated in these seven patients compared to the other 23 RA patients. The markedly reduced synthesis of both IL-4 and IL-10 mRNA could be considered to be related to the progression and/or activity of RA. The results of this study therefore indicate an imbalance in the levels of Th1 and Th2 cytokines at the site of inflammation in RA, and draw attention to the possibility of treatment of progressive or intractable RA with IL-4 and/or IL-10.
11298065 Anti-TNF agents for rheumatoid arthritis. 2001 Mar Rheumatoid arthritis (RA) is a chronic inflammatory, autoimmune disease with a prevalence of approximately 1% and an annual incidence of 0.04%. Up to 50% of patients with RA are unable to work 10 years after diagnosis. The disease is associated with significant morbidity and mortality with associated medical costs to the UK of between £240 m and £600 m per year. Non steroidal anti-inflammatory drugs (NSAIDs) have little effect on the underlying course of RA, but they have some anti-inflammatory and analgesic properties. Disease modifying antirheumatic drugs (DMARDs) have been shown to slow progression of RA and are currently recommended early in the course of treatment of RA which is when disease progression is most rapid. Etanercept and infliximab belong to a new group of parentally administered antitumour necrosis factor (TNF) drugs. Etanercept is licensed in the UK for the treatment of active rheumatoid arthritis in patients who have not responded to other DMARDs and in children with polyarticular-course juvenile arthritis who have not responded to or are intolerant of methotrexate. In adults it produces significant improvements in all measures of rheumatic disease activity compared to placebo. In patients whose disease remains active despite methotrexate treatment, further improvement in control is obtained with the addition of etanercept without an increase in toxicity. In one small trial, etanercept was found to be more effective than placebo in a selected group of children. Infliximab is a monoclonal antibody which is currently licensed in the UK for Crohn's disease and, in combination with methotrexate for the treatment of rheumatoid arthritis in patients with active disease when the response to disease-modifying drugs, including methotrexate, has been inadequate. In clinical trials infliximab produced significant improvements in all measures of rheumatic disease activity compared with placebo. Infliximab in combination with methotrexate was shown to be superior to methotrexate or infliximab alone. There are currently no predictors of a good response to anti-TNF drugs and a percentage of patients fail to respond to treatment (25% to 38% of etanercept patients; 21% to 42% of infliximab patients). Infliximab monotherapy induces the production of anti-infliximab antibodies, which may reduce its effectiveness. Adding methotrexate to infliximab therapy may prevent this response. Anti-TNF drugs may affect host defences against infection and malignancy; whether these agents affect the development and course of malignancies and chronic infections is unknown and safety and efficacy in patients with immunosuppression or chronic infections has not been investigated. With infliximab, upper respiratory tract infections, general infections and those requiring antimicrobial treatment were more common in patients than placebo. Likewise, upper respiratory tract infections were more common in patients treated with etanercept than with placebo. Injection site reactions occur with both infliximab (16%–20%) and etanercept (37%). There are approximately 600 000 patients with RA in the UK, and of these between 2% and 3.5% may have severe disease which has failed to respond to conventional treatment and who might be eligible for anti-TNF therapy. If between 50% and 70% of patients treated with anti-TNF drugs respond and continue on long-term treatment then the recurrent annual cost to the NHS could be between £48 m and £129 m.
11380136 Hip disease and the prognosis of total hip replacements. A review of 53,698 primary total 2001 May We studied the rates of revision for 53,698 primary total hip replacements (THRs) in nine different groups of disease. Factors which have previously been shown to be associated with increased risk of revision, such as male gender, young age, or certain types of uncemented prosthesis, showed important differences between the diagnostic groups. Without adjustment for these factors we observed an increased risk of revision in patients with paediatric hip diseases and in a small heterogeneous 'other' group, compared with patients with primary osteoarthritis. Most differences were reduced or disappeared when an adjustment for the prognostic factors was made. After adjustment, an increased relative risk (RR) of revision compared with primary osteoarthritis was seen in hips with complications after fracture of the femoral neck (RR = 1.3, p = 0.0005), in hips with congenital dislocation (RR = 1.3, p = 0.03), and in the heterogenous 'other' group. The analyses were also undertaken in a more homogenous subgroup of 16,217 patients which had a Charnley prosthesis implanted with high-viscosity cement. The only difference in this group was an increased risk for revision in patients who had undergone THR for complications after fracture of the femoral neck (RR = 1.5, p = 0.0005). THR for diagnoses seen mainly among young patients had a good prognosis, but they had more often received inferior uncemented implants. If a cemented Charnley prosthesis is used, the type of disease leading to THR seems in most cases to have only a minor influence on the survival of the prosthesis.
9563375 Neer hemiarthroplasty and Neer total shoulder arthroplasty in patients fifty years old or 1998 Apr Seventy-eight Neer hemiarthroplasties and thirty-six Neer total shoulder arthroplasties were performed at our institution, between January 1, 1976, and December 31, 1985, in ninety-eight patients who were fifty years old or less. Two patients (two shoulders) died, and four patients (four shoulders) were lost to follow-up. The remaining seventy-four hemiarthroplasties (95 per cent) in sixty-four patients and thirty-four total shoulder arthroplasties (94 per cent) in thirty-one patients were included in the clinical analysis as the preoperative and operative records were complete and the patients had been followed for at least five years (mean, 12.3 years) or until revision. All 114 shoulders were included in the survivorship analysis. Both total shoulder arthroplasty and hemiarthroplasty resulted in significant long-term relief of pain (p < 0.0001) as well as improvement in active abduction (p < 0.0001) and external rotation (p < 0.0001). However, with the numbers available, we could not detect a significant difference between the two procedures with respect to these variables. A complete set of radiographs was available for sixty-eight (92 per cent) of the seventy-four shoulders that had a hemiarthroplasty and for thirty-two (94 per cent) of the thirty-four shoulders that had a total shoulder arthroplasty. A radiolucent line around the humeral component was noted after sixteen (24 per cent) of the hemiarthroplasties and after seventeen (53 per cent) of the total shoulder arthroplasties. A radiolucent line around the glenoid component was seen after nineteen (59 per cent) of the total shoulder arthroplasties. Erosion of the glenoid was found after forty-six (68 per cent) of the hemiarthroplasties. The results were graded according to a modification of the system of Neer et al. and of Cofield. Fifteen hemiarthroplasties led to an excellent result; twenty-four, a satisfactory result; and thirty-five, an unsatisfactory or unsuccessful result. Four total shoulder arthroplasties were followed by an excellent result; thirteen, a satisfactory result; and seventeen, an unsatisfactory or unsuccessful result. The estimated survival of the hemiarthroplasty prostheses (with 95 per cent confidence intervals) was 92 per cent (86 to 98 per cent) at five years, 83 per cent (75 to 93 per cent) at ten years, and 73 per cent (59 to 88 per cent) at fifteen years. Analysis of the results in association with the two major diagnoses revealed that the risk of revision was higher for the thirty shoulders that had the hemiarthroplasty for the treatment of the sequelae of trauma than for the twenty-eight that had the procedure for the treatment of rheumatoid arthritis (p = 0.017). The estimated survival of the total shoulder prostheses (with 95 per cent confidence intervals) was 97 per cent (92 to 100 per cent) at five years, 97 per cent (91 to 100 per cent) at ten years, and 84 per cent (70 to 100 per cent) at fifteen years. The risk of revision was higher for the seven shoulders that had had a tear of the rotator cuff at the time of the operation than for the twenty-seven that had not had one (p = 0.029). The data from the present study indicate that a shoulder arthroplasty provides marked long-term relief of pain and improvement in motion; however, nearly half of all young patients who have a shoulder arthroplasty have an unsatisfactory result according to a rating system. Care should be exercised when either a hemiarthroplasty or a total shoulder arthroplasty is offered to patients who are fifty years old or less.
10232393 Human T lymphocyte populations which bind to P- or E-selectin are enriched with cells expr 1999 Apr 1 The present study was undertaken to investigate whether core 2 O-glycans are involved in binding of resting human T lymphocytes to P- or E-selectin and in recruitment of these cells to inflammatory sites. Freshly isolated human peripheral blood T lymphocytes were incubated with P- or E-selectin-coated dishes, and expression of core 2 O-glycans by the adherent and nonadherent cells was examined using the anti-1D4 mAb, which specifically recognizes human CD43 modified with core 2 O-glycans. The results indicated that both the P-selectin/adherent and E-selectin/adherent populations were significantly enriched with ID4+ cells, as compared with the initial population. An enrichment of ID4+ cells in the P- and E-selectin/adherent populations was observed in both CD4 and CD8 T cell subsets and even in the CD45RO+ memory CD4 T-cell subset. However, the anti-1D4 mAb did not inhibit binding of human T lymphocytes to P- or E-selectin, indicating that the 1D4 antigen itself is not directly involved in selectin binding. We also found that the percentage of ID4+ cells in synovial fluid T lymphocytes of rheumatoid arthritis patients was significantly increased as compared with normal peripheral blood T lymphocytes. Taken together, our results support the notion that core 2 O-glycans, which are located apart from the ID4 antigen, are involved in binding of human resting T lymphocytes to both P- and E-selectin, and these interactions may contribute to preferential recruitment of human memory CD4 T lymphocytes to inflammatory sites, including the synovium of rheumatoid arthritis patients.