Expression patterns of CD44 and CD44 splice variants in patients with rheumatoid arthritis.

OBJECTIVES: It has been suggested that CD44 is involved in the pathogenesis of rheumatoid arthritis (RA). By alternative splicing, numerous CD44 isoforms can be generated which may play different roles the inflammatory process. We therefore studied the expression of various CD44 splicevariants in the circulation and synovial tissue of patients with RA and correlated expression with clinical features. METHODS: Expression of distinct CD44 splice variants was analysed by FACS in peripheral monocytes of 46 RA patients and 36 healthy controls. Expression of CD44 splice variants in synovial tissue of RA and OA patients was analysed by immunohistochemistry and the effects of blocking CD44v4 on RA-fibroblast like synoviocytes (FLS) were studied. RESULTS: On monocytes, the expression of CD44 and CD44v3 was significantly lower in patients with erosive disease than in those without radiographic progression (p<0.05 for CD44 and p<0.01 for CD44v3). CD44v6 on monocytes was significantly associated with the clinical disease activity index (r=0.34, p<0.05) and CRP-levels (r=0.37, p<0.02). Immunhistochemical analyses revealed that most variants were expressed to a significantly higher extent in RA than in OA synovial membranes. Particularly the variants CD44v4, CD44v6 and CD44v7-8 were highly expressed in the RA lining and also abundantly in the endothelium. Blocking CD44v4 in RA-FLS reduced the proliferation to 68±8% (p<0.02) when compared to control experiments and led to a reduction in IL-1ß mRNA expression (p<0.05). CONCLUSIONS: Expression of CD44 splice variants is generally increased in the synovial lining of RA patients when compared to OA. The inverse association of CD44v3 expression on monocytes with the development of erosive disease and the functional impacts of CD44v4 blockade in RA-FLS suggests a pathogenetic role of this splice variants which needs to be further investigated.

Ten-year follow-up of the non-porous Allofit cementless acetabular component.

Cementless acetabular fixation has demonstrated superior long-term durability in total hip replacement, but most series have studied implants with porous metal surfaces. We retrospectively evaluated the results of 100 consecutive patients undergoing total hip replacement where a non-porous Allofit component was used for primary press-fit fixation. This implant is titanium alloy, grit-blasted, with a macrostructure of forged teeth and has a biradial shape. A total of 81 patients (82 hips) were evaluated at final follow-up at a mean of 10.1 years (8.9 to 11.9). The Harris Hip Score improved from a mean 53 points (23 to 73) pre-operatively to a mean of 96 points (78 to 100) at final review. The osseointegration of all acetabular components was radiologically evaluated with no evidence of loosening. The survival rate with revision of the component as the endpoint was 97.5% (95% confidence interval 94 to 100) after 11.9 years. Radiolucency was found in one DeLee-Charnley zone in four acetabular components. None of the implants required revision for aseptic loosening. Two patients were treated for infection, one requiring a two-stage revision of the implant. One femoral stem was revised for osteolysis due to the production of metal wear debris, but the acetabular shell did not require revision. This study demonstrates that a non-porous titanium acetabular component with adjunct surface fixation offers an alternative to standard porous-coated implants.

[Six to ten year results of use of the alloclassic hip prosthesis--a multicentre survival analysis]. / 6 - 10-Jahres-Ergebnisse des zementfreien Alloclassic-Hüftsystems--Eine multizentrische Survival-Studie.

AIM: This prospective study describes This retrospective multicenter study was undertaken to calculate mid- and long-term survival rates of the cementless Zweymüller/Alloclassic total hip prosthesis. MATERIAL AND METHODS: The rectangular titanium stem and threaded cup have been in use since 1986. The ball head is made of alumina ceramic, the inlay of UHMW polyethylene. Five hospitals in Austria, France and Germany cooperated in the follow-up of 848 patients operated between October 1986 and September 1990 (mean age 62.2 years, 62% women, 38% men, mean patient weight 73.8 kg, body mass index 26.8). 468 patients were followed clinically, 320 patients interviewed on the phone, 29 sent a letter. No information was available concerning the remaining 31 patients. Probabilities of implant survival were estimated with the Kaplan-Meier method. RESULTS: 98 patients (11.5%) had died at a median follow-up time of 81.1 months. The probability of survival at 81.1 months was 98.6% looking at stem and cup. There was no significant association of survival of the prosthesis and patient weight, gender or body mass index. CONCLUSION: Our results are in accordance with previously published data of smaller series using the Zweymüller/Alloclassic( total hip. The survival rate of this cementless rectangular titanium prosthesis for the reported follow-up time compares favorably with contemporary cemented hip prostheses.

Lengthening of the iliotibial band by femoral detachment and multiple puncture. A cadaver study.

BACKGROUND: Lengthening of the iliotibial band by various methods such as distal detachment, Z-plasty, or multiple puncture are common procedures for balancing the contracted valgus knee in total knee arthroplasty. This study was performed to measure the lengthening effect of multiple puncture and release of the distal femoral attachment of the iliotibial tract. METHODS: In a cadaver study on 14 knees, we studied the possible elongation of the iliotibial band by distal femoral detachment (release of Kaplan's fibers) and multiple puncture of the distal half of the tract. Maximum elongation was measured under a constant tension of 60 N. RESULTS: The average gain in length of the combination of both procedures was 16.3 mm (range 12-23 mm) with a tension force of 60 N applied. CONCLUSION: The results show that a sufficient release of the iliotibial band can be achieved with the techniques except for severe cases of valgus deformation, where more effective methods to release the iliotibial band such as Z-plasty or complete dissection should be performed.

Overexpression of transcription factor Ets-1 in rheumatoid arthritis synovial membrane: regulation of expression and activation by interleukin-1 and tumor necrosis factor alpha.

OBJECTIVE: To investigate the expression of the transcription factor Ets-1 in synovial tissue and cultured synovial fibroblasts from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to study the regulation of Ets-1 expression and activation in synovial fibroblasts by proinflammatory cytokines. METHODS: In situ expression of Ets-1 in synovial tissue from RA and OA patients was examined by double immunohistochemistry. The effects of interleukin-1 (IL-1) or tumor necrosis factor alpha (TNFalpha) on Ets-1 expression and activation (DNA binding) in cultured synovial fibroblasts were analyzed by Western blotting and DNA gel shift assay, respectively. In addition, the intracellular location of Ets-1 in synovial fibroblasts was determined by immunofluorescence. RESULTS: Pronounced expression of Ets-1 was detected in synovial tissues from all RA patients evaluated, particularly in the synovial lining layer and the sublining areas. Ets-1 was expressed by both fibroblasts and macrophages as well as by endothelial cells, while only a few T cells stained positive for Ets-1. In synovial specimens from OA patients, Ets-1 expression was much less frequently observed and was largely restricted to vascular cells. Ets-1 was expressed to a similar degree in cultured synovial fibroblasts from RA and OA patients, as demonstrated by reverse transcriptase-polymerase chain reaction and Western blotting. Both IL-1 and TNFalpha induced pronounced up-regulation of Ets-1 in synovial fibroblasts. Moreover, binding of Ets-1 to its specific DNA binding site was induced by both cytokines, although with different time courses. Immunofluorescence staining revealed a dominant nuclear localization of Ets-1 in IL-1- or TNFalpha-stimulated synovial fibroblasts. CONCLUSION: The overexpression of Ets-1 observed in RA synovial tissue appears to be caused by TNFalpha and IL-1, suggesting that Ets-1 may be an important factor in the cytokine-mediated inflammatory and destructive cascade characteristic of RA.

Activation, differential localization, and regulation of the stress-activated protein kinases, extracellular signal-regulated kinase, c-JUN N-terminal kinase, and p38 mitogen-activated protein kinase, in synovial tissue and cells in rheumatoid arthritis.

OBJECTIVE: To investigate whether stress- and mitogen-activated protein kinases (SAPK/MAPK), such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK, are significantly activated in rheumatoid arthritis (RA) synovial tissue compared with their activation in degenerative joint disease; to assess the localization of SAPK/MAPK activation in rheumatoid synovial tissue; and to search for the factors leading to stress kinase activation in human synovial cells. METHODS: Immunoblotting and immunohistology by antibodies specific for the activated forms of SAPK/MAPK were performed on synovial tissue samples from patients with RA and osteoarthritis (OA). In addition, untreated and cytokine-treated human synovial cells were assessed for SAPK/MAPK activation and downstream signaling by various techniques. RESULTS: ERK, JNK, and p38 MAPK activation were almost exclusively found in synovial tissue from RA, but not OA, patients. ERK activation was localized around synovial microvessels, JNK activation was localized around and within mononuclear cell infiltrates, and p38 MAPK activation was observed in the synovial lining layer and in synovial endothelial cells. Tumor necrosis factor alpha, interleukin-1 (IL-1), and IL-6 were the major inducers of ERK, JNK, and p38 MAPK activation in cultured human synovial cells. CONCLUSION: Signaling through SAPK/MAPK pathways is a typical feature of chronic synovitis in RA, but not in degenerative joint disease. SAPK/MAPK signaling is found at distinct sites in the synovial tissue, is induced by proinflammatory cytokines, and could lead to the design of highly targeted therapies.

Stable bony integration with and without short-term indomethacin prophylaxis.A 5-year follow-up.

We included in a prospective study of a standardized indomethacin protocol 134 consecutive patients undergoing primary cementless endoprosthetic hip replacement between January and June 1990. Periarticular heterotopic ossification (HO) was graded according to the Arcq classification (grades 0 to III). At final follow-up, all patients were analyzed clinically and radiographically for HO and aseptic loosening. A similar group of 44 patients (mean age of 64 years, range 38-82 years) undergoing total hip replacement (THR) with the same prosthesis and technique in 1987 did not receive HO prophylaxis and served as a control group. The average age of the 134 prophylaxis patients was 66.5 years (range 32-85 years), and the average follow-up was 65 months (range 60-71 months). Thirty patients (25%) were lost to final follow-up (19 died, 10 unknown, 1 amputation). In the study group, 77% had HO grade 0, while none had HO grade III, compared with 18% HO grade 0 and 16% HO grade III in the control goup. These differences were statistically significant (P = < 0.001). At a minimum of 60 months follow-up, clinical and radiographic evaluation revealed no aseptic loosening in the study group: 4 cases of prosthesis subsidence during the first year did not progress. In the control group, there was a higher incidence of radiolucency around the femoral component, and one patient met all criteria for radiographic evidence of aseptic loosening. Statistical analysis revealed no significant difference between the two groups (P = 0.104). Based on our clinical and radiological results, indomethacin does not inhibit stable bony integration of the femoral component.

Stable bony integration with and without short-term indomethacin prophylaxis. A 5-year follow-up.

We included in a prospective study of a standardized indomethacin protocol 134 consecutive patients undergoing primary cementless endoprosthetic hip replacement between January and June 1990. Periarticular heterotopic ossification (HO) was graded according to the Arcq classification (grades 0 to III). At final follow-up, all patients were analyzed clinically and radiographically for HO and aseptic loosening. A similar group of 44 patients (mean age of 64 years, range 38-82 years) undergoing total hip replacement (THR) with the same prosthesis and technique in 1987 did not receive HO prophylaxis and served as a control group. The average age of the 134 prophylaxis patients was 66.5 years (range 32-85 years), and the average follow-up was 65 months (range 60-71 months). Thirty patients (25%) were lost to final follow-up (19 died, 10 unknown, 1 amputation). In the study group, 77% had HO grade 0, while none had HO grade III, compared with 18% HO grade 0 and 16% HO grade III in the control group. These differences were statistically significant (P = < 0.001). At a minimum of 60 months follow-up, clinical and radiographic evaluation revealed no aseptic loosening in the study group: 4 cases of prosthesis subsidence during the first year did not progress. In the control group, there was a higher incidence of radiolucency around the femoral component, and one patient met all criteria for radiographic evidence of aseptic loosening. Statistical analysis revealed no significant difference between the two groups (P = 0.104). Based on our clinical and radiological results, indomethacin does not inhibit stable bony integration of the femoral component.

Cytokine production by synovial T cells in rheumatoid arthritis.

OBJECTIVE: To investigate the production of cytokines by T cells in patients with rheumatoid arthritis (RA), reactive arthritis (REA) and osteoarthritis (OA). METHODS: The lymphokines interleukin (IL)-2, IL-4, interferon gamma (IFN-gamma) and tumour necrosis factor beta (TNF-beta), as well as the monokines IL-1, IL-6 and TNF-alpha, were measured by immunoassays in sera and synovial fluid (SF) from patients with RA, REA and OA. In addition, cytokine expression was studied by immunohistochemistry in synovial membrane tissue sections from patients with RA and OA. RESULTS: Almost 60% of RA sera contained at least one of the cytokines investigated, though in low concentrations, whereas cytokines were generally not detectable in sera from REA and OA patients. In contrast, cytokines were found in virtually all SF; thus, the majority of SF from RA patients contained IFN-gamma (median level 17 pg/ml) in addition to the monokines IL-6 (4700 pg/ml) and TNF-alpha (157 pg/ml). IFN-gamma and IL-6 (but not TNF-alpha) were also frequently measured in SF from REA patients, whereas OA samples typically contained only IL-6. Immunohistochemical analysis of tissue sections from RA patients revealed lymphokine expression in 0.1-0.3% of T cells, particularly IL-2 and IFN-gamma, and to a lesser extent also IL-4. Interestingly, the expression of TNF-alpha and IL-6 by synovial T cells was also observed. The majority of cytokine-expressing T cells were CD4-positive T-helper cells typically found in perivascular areas, whereas cytokine-producing CD8-positive T cells were found distributed throughout the synovium. As expected, in specimens from OA patients, T cells were much less abundant and expression of cytokines could not be detected. CONCLUSION: These data clearly demonstrate production of cytokines by T cells in RA synovial tissue, indicating that activated T cells play a role in the pathophysiological events of RA.

[Mannerfelt arthrodesis of the wrist joint in patients with chronic polyarthritis. A retrospective analysis of 24 cases]. / Die Arthrodese des Handgelenkes nach Mannerfelt bei Patienten mit chronischer Polyarthritis. Eine retrospektive Analyse von 24 Fällen.

AIM: Mannerfelt established his technique of wrist arthrodesis with stabilisation by an intraosseous rushpin as a secure method for patients with rheumatoid arthritis. This study was performed to evaluate the mid-term results in a consecutive group of patients. METHODS: Out of a group of 39 operations 24 wrist arthrodeses (61%) in 19 patients have been followed 12-96 months postoperatively (average 44 mths) by clinical testing and radiographic examination. All operations were performed in the original technique. All patients suffered from rheumatoid arthritis in an advanced stage (Larsen III-V). RESULTS: All but one patient were free of pain. Function and strength of the hand increased significantly in all patients. All patients had additional resection of the ulnar head that led to normal pro-supination of the forearm. 18 patients were very satisfied with the result of the procedure. All but one of the wrists showed complete fusion. In one case there was an intraoperative perforation of the pin through the radial cortex, in another case we saw a fissure of the shaft of the third metacarpal bone. One patient showed a dysesthesia in the third finger. CONCLUSION: The results in this group of patients confirmed the advantages of Mannerfelt's technique such as simple operative technique, high fusion rate and low incidence of complications.

The role of T-lymphocytes and cytokines in rheumatoid arthritis.

In this review the involvement of T cells, in addition to that of the monocyte/macrophage lineage, in the pathogenesis of rheumatoid arthritis is discussed. The evidence for the pathogenetic importance of T cells is based upon their state of activation in the synovial membrane and the cytokines produced. These cytokines can be detected in synovial fluids as well as in the synovial membrane by both immunohistochemistry and in situ hybridization. However, cytokine production can be detected only in a minor fraction of the T cells which contrasts the number of non-T cells observed to synthesize cytokines. Nevertheless, it can be assumed that the small amount of lymphokines is sufficient to activate a cytokine cascade derived from other cells. The cytokine profile secreted is indicative for a T cell response that primarily involves Th1-like cells.

[Rheumatoid orthopedics and endoprosthetics of the shoulder joint]. / Rheumaorthopädie und Endoprothetik am Schultergelenk.

The first part of the present article gives a comprehensive description of the pathology, diagnostics and forms of therapy of rheumatically impaired shoulder joints. Improved operative methods and methods such as bursectomy, synovectomy, reconstructive soft-tissue management and joint replacement depending on the stage of impediment have enhanced the use of surgery in the treatment of rheumatic shoulder joints. The second part gives a critical evaluation of indications, methods and results of modern shoulder joint replacement. A survey of written publications on the results of hemi- and total endoprostheses on the one hand, our own clinical experiences on the other, have shown that the use of modular hemiendoprostheses produces clinically excellent results with no problems of loosening of the glenoid part.

[10 years of cementless implantation of total hip endoprosthesis using Zweymüller's stem]. / 10 Jahre zementfreie Implantation von Hüfttotalendoprothesen unter Verwendung des Zweymüller-Schaftes.

A retrospective study of the first consecutive 111 cementless Zweymüller Stems has been performed. 56 cases have been followed clinically and radiologically with an interval of 10-11 years. The average harris hip score was 90.7 pts, the cumulative success rate of the stem was 97.96% after 10-11 years. The frequency of bony reactions around the stem and their changes during the course of time could be followed in 40 implants with a complete radiologic documentation at 5 and 10 years postoperative. Hypertrophic changes of the bone around the tip of the stem remained unchanged from the fifth to the tenth year but there was an increase of proximal lucencies (27% at 5 yrs, 35 at 10 yrs), widening of the calcar (20% at 5 yrs, 25% at 10 yrs) and stress shielding (30% at 5 yrs, 47% at 10 yrs).

[Results 2 to 5 years after implantation of the cement-free "APS" total knee prosthesis. A retrospective study of the first 160 cases]. / Zwei bis fünf Jahresergebnisse nach Implantation der zementfreien "APS" Knietotalprothese. Eine retrospektive Studie der ersten 160 Fälle.

One hundred-and-forty-seven out of 160 cementless APS total knees replacements have been clinically and radiologically evaluated with a mean follow-up period of 38 (24-60) months. Primary diagnosis has been osteoarthrosis in two thirds and rheumatoid arthritis in one. Reoperations have been performed in 4.9% due to aseptic loosening of the tibial tray, and in 3.7% due to patellar problems (aspetic loosening in 1.2% and luxation in 2.5%). There have been three late infections of the joint leading to arthrodesis in two or exchange operation in one case. The radiologic course of the remaining 126 implants showed excellent or good osseous integration of the implants in more than 80%. We were able to show that rheumatoid arthritis as well as malimplantation of the prosthesis can decrease the rate of osseous integration.

[Radiologic and sonographic screening study of shoulder joints of patients with rheumatoid arthritis]. / Radiologische und sonographische Screening-Untersuchung an Schultergelenken von Patienten mit Rheumatoid-Arthritis (RA).

In the course of a prospective study at our department the shoulder joints of 50 RA-patients were examined. Two criteria have been applied: only righthanded patients have been examined in order to ascertain any prevalence of changes in the dominant extremity, and only patients who were primarily admitted to our department because of complaints other than those of the shoulder. Examination consisted of anamnesis, clinical tests, radiography and sonography. Reports in the literature concerning involvement of 60%. This percentage was confirmed in our clinical and radiological examinations. If, however, sonography is used, it increases to 96%. Lesions of the rotator cuff can be demonstrated, beginning on the synovial side above bone erosions, without any clinical signs or radiographic changes. Radiographic changes have been rated according to Larsen stages 0-5. Upward migration of the humeral head already before massive bone destruction of the shoulder seems to confirm an early involvement of the rotator cuff. Involvement of the acromioclavicular joint begins with Larsen stage 2 and often includes a distension of the joint cavity. The dominant extremity was not found to be affected predominantly. The therapeutic consequences resulting from this examination are discussed.

Longterm analysis of Sheehan total knee arthroplasty.

Sheehan total knee arthroplasty was carried out in 405 knees at two centres. The patients were followed up from two to eleven years. The clinical results were assessed, the complications documented and the influence of specific factors on the result was evaluated. The principal complications arose from the patella and the femorotibial articulation. The low rate of loosening and the achievement of satisfactory alignment lead the authors to support the concept of a long stem.

Long-term results after implantation of McKee-Farrar total hip prostheses.

From 1973 to 1976, McKee-Farrar total hip arthroplasties were performed in the Orthopaedics Department at the Centre of Pulmology. In the present study, only patients with a complete record of radiological changes at the bone/implant or bone/cement interface were evaluated. A series of 81 patients with 100 total hip prostheses in situ according to the Mayo Clinic hip score and 36 patients who had undergone 36 revision operations were studied. The design of the metal cup with metal studs at the outer surface has a favourable effect on the stability of the implant/cement combination: loosening at the implant/cement interface did not occur in any of these cases and there were few cement fractures. In spite of the metal-to-metal combination, abrasion is slight and there is no danger of metallosis.

The APS knee joint prosthesis. A review of 32 patients.

First clinical and radiographic results with a new knee joint prosthesis, implanted without cement, are reported and the characteristics of the implant (dowel fixation and special instrumentation) presented. The first series of 35 joints with a follow-up period of 1-3 years shows excellent results. Radiographically, primary osseous integration cannot be positively identified in all cases, but it could be proved in most instances. Cement-free implantation requires good preoperative bone quality and an operative technique which inserts the implant anatomically. If these two conditions are met, there is every probability of successful implantation. No problems specific to the implant have been encountered.