A. König

Immunohistochemical analysis of proliferating and antigen-presenting cells in rheumatoid synovial tissue

We analysed the proliferative activity of synovial lining cells (SLCs), the distribution of proliferating B and T lymphocytes and the relationship of proliferating B and T lymphocytes to the pattern of antigen-presenting cells (APCs) within the rheumatoid synovial tissue (n=21). The immunohistochemical detection of the proliferation-associated antigen Ki 67 revealed low proliferative activity of SCL with and without expression of the Kim 8 (CD 68) antigen. Ki 67-positive B lymphocytes could be observed within secondary follicles (2/21), in small follicular dendritic reticulum cell (FDC)-containing follicle-like aggregates (7/21) and near the enlarged synovial intima (6/21). Ki 67-positive T lymphocytes could be detected in T-lymphocyte aaggregates (8/21), in the vicinity of blood vessels (18/21) and within the enlarged synovial intima (15/21). Semiquantitative analysis showed a strong correlation between the numbers of Ki 67-positive B lymphocytes and FDCs and between the numbers of Ki 67-positive T lymphocytes and interdigitating dendritic reticulum cells (IDC). There were significant differences in the number of Ki 67-positive B and T lymphocytes, IDCs and FDCs between the two groups of rheumatoid arthritis (RA) patients with different local clinical activity. These findings demonstrate a low proliferation of SLCs with and without expression of the monocyte-specific antigen Kim 8 and imply that B and T lymphocyte proliferation occurs in the presence of FDCs and IDCs. These results indicate that the RA synovial tissue is a site for antigen-dependent proliferation and maturation of B and T lymphocytes. The atypical pattern of FDC distribution within the rheumatoid synovial tissue “dysmorphic follicle” may be regarded as morphological substrate for a dysmaturation compartment of B lymphocytes leading to pathogenetic autoimmune phenomena in RA patients.

Balance Sheets of Knee and Functional Scores 5 Years After Total Knee Arthroplasty for Osteoarthritis A Source for Patient Information

To improve patient information on the results of total knee arthroplasty (TKA) for osteoarthritis, 253 primary TKAs of a prospective study with a mean follow-up of 5.3 years were analyzed. The increase or decrease of the individual variables of the Knee Society knee and function score and the percentage of operated knees in which these variables increased were determined. Improvement in pain rating had the largest increase of all variables, contributing 60% to the knee score increase. Pain improved in 95% of the knees. Alignment improved in about 90% of knees and accounted for 25% of knee score increase. Improvement in level walking contributed more to increase of function score than better stair-climbing abilities. Level walking improved in 80% of knees and stair climbing in 55%. Pain is the most rewarding indication for TKA, followed by deformity and poor walking ability. Key words: total knee arthroplasty, knee score, functional score, patient information.

German short musculoskeletal function assessment questionnaire (SMFA-D): comparison with the SF-36 and WOMAC in a prospective evaluation in patients with primary osteoarthritis undergoing total knee arthroplasty

Abstract. In a prospective clinical trial, the German short musculoskeletal function assessment (SMFA-D), the short form (SF)-36, and the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) were evaluated in 63 patients with primary osteoarthritis undergoing total knee arthroplasty. All instruments were sensitive to change, demonstrating the effect of total knee arthroplasty at 1-year follow-up. The SMFA-D effect sizes in comparable scales were bigger than in the SF-36 and similar to those of the WOMAC. Significant correlations of the SMFA-D indices with the SF-36 and WOMAC scales preoperatively could be shown. After 1-year follow-up, all correlations between the SMFA-D indices and SF-36 scales were significant. In other comparison, only the correlation between the SMFA-D function index and the WOMAC function scales remained significant. The correlation of the SMFA-D function index with external validation criteria was higher than that using the other instruments. We recommend the SMFA-D for assessing change in functional status of patients with primary osteoarthritis of the knee following arthroplasty.

Inflammatory infiltrate and interleukin-8 expression in the synovium of psoriatic arthritis : an immunohistochemical and mRNA analysis

Abstract Psoriatic arthritis is an inflammatory arthropathy that ultimately can lead to joint destruction. In this study, we investigated the immunophenotype of the inflammatory cells and the expression of interleukin-8 (IL-8), which is the hallmark chemoattractant cytokine of psoriasis in synovial membranes from patients exhibiting active psoriatic synovitis (n=9). The tissue samples were examined by immunohistochemistry, Western blot analysis and in situ hybridisation. The inflammatory infiltrate consisted predominantly of CD3+ T lymphocytes, with a higher proportion of CD4+ than CD8+ T lymphocytes in six cases. CD3+ T lymphocytes were focally distributed near small blood vessels and the enlarged synovial intima. CD1+ interdigitating reticulum cells were not detected. CD22+ B lymphocytes and plasma cells were found in small aggregates without KiM4+ follicular dendritic cells. KiM8+ macrophages were located in the synovial intima and were distributed in a diffuse pattern near the synovial lining cells. CD15+ neutrophil granulocytes were detected in four cases. They were preferentially located in the vicinity of blood vessels and the synovial intima. IL-8 was found at a high level in the synovial lining cells and to a lesser extent in cells located in the perivascular areas. Immunofluorescence double staining showed IL-8 to be expressed in KiM8+ multinucleated giant cells, KiM8+ macrophages and CD3+ T lymphocytes. IL-8 receptor A was demonstrated in the synovial lining and in macrophages and lymphocytes. IL-8 was detected by immunoblot analysis of the synovial tissue at 8.4 kD. Employing in situ hybridisation, IL-8 mRNA was strongly and preferentially expressed in the synovial intima, as well as in macrophages and lymphocytes. The immunophenotype of the psoriatic arthritis inflammatory cells shows great similarity to the inflammatory infiltrate found in the synovial tissue of patients with rheumatoid arthritis. The preferential expression of IL-8 and IL-8 mRNA in the enlarged synovial intima and in lymphocytes and macrophages suggests that IL-8 exerts its action through activated mononuclear cells and T lymphocytes. It seems to play a role in regulating leucocyte traffic into the enlarged synovial intima and may contribute to the aggressive synovitis of patients with psoriatic arthritis.

Human Monoclonal Rheumatoid Synovial B Lymphocyte Hybridoma with a New Disease-Related Specificity for Cartilage Oligomeric Matrix Protein

Joint-specific self-Ags are considered to play an important role in the induction of synovial T and B cell expansion in human rheumatoid arthritis (RA). However, the nature of these autoantigens is still enigmatic. In this study a somatically mutated IgG2λ B cell hybridoma was established from the synovial membrane of an RA patient and analyzed for its Ag specificity. A heptameric peptide of cartilage oligomeric matrix protein (COMP) could be characterized as the target structure recognized by the human synovial B cell hybridoma. The clonotypic VH sequences of the COMP-specific hybridoma could also be detected in synovectomy material derived from five different RA patients but in none of the investigated osteoarthritis cases (n = 5), indicating a preferential usage of VH genes closely related to those coding for a COMP-specific Ag receptor in RA synovial B cells. Moreover, the COMP heptamer was preferentially recognized by circulating IgG in RA (n = 22) compared with osteoarthritis patients (n = 24) or age-matched healthy controls (n = 20; both p < 0.0001). Hence, the COMP-specific serum IgG is likely to reflect local immune responses toward a cartilage- and tendon-restricted Ag that might be crucial to the induction of tissue damage in RA.

Results of posterior cruciate-retaining unconstrained total knee arthroplasty after proximal tibial osteotomy for osteoarthritis

The purpose of the study was to investigate the results of posterior cruciate ligament (PCL)-retaining total knee arthroplasty (TKA) after previous proximal closed wedge tibial osteotomy for degenerative arthritis according to the technique recommended by Coventry and Insall. Thirty-five patients with previous proximal tibial osteotomy were matched to 35 patients without previous osteotomy according to age, sex, and Knee Society patient category. TKA after osteotomy was technically more difficult, often requiring a more extensive exposure. Complications were similar in the two groups, but an extended hematoma was more common in patients with previous osteotomies (2 patients) than in those with primary arthroplasty (1 patient). Knee Society scores were significantly lower in those with previous osteotomy, primarily because of decreased anteroposterior stability and pain. No significant differences were found in function scores, range of motion, or alignment. However, overall results of this PCL-retaining unconstrained TKA did not match those reported after PCL-substituting TKA.

Low-molecular-weight heparin and partial thromboplastin time-adjusted unfractionated heparin in thromboprophylaxis after total knee and total hip arthroplasty

Thromboprophylaxis with heparins after total hip arthroplasty (THA) and total knee arthroplasty (TKA) is well established. The aim of this study was to compare low-molecular-weight heparin (enoxaparin) with partial thromboplastin time (PTT)-adjusted, unfractionated heparin (heparin sodium). In a prospective study of THA and TKA 246 patients, physical examination and compression and duplex ultrasound were performed 1 day before and 7 and 14 days after surgery. One hundred thirty patients received 40 mg enoxaparin subcutaneously once per day. One hundred sixteen patients received 5,000 IU heparin sodium subcutaneously 3 times daily. As the PTT did not reach 40 seconds, the heparin sodium dosage was increased to 7,500 IU 3 times daily. The overall thrombosis rate was 4% (n = 10). In the enoxaparin group, the rate was 2.9% of the 70 THAs and 10% of the 60 TKAs. Thrombosis also occurred in the group that received heparin sodium: 1.8% of the THAs and 1.7% of the TKAs. For TKA, the difference between the 2 heparin groups was statistically significant. In the thromboprophylaxis of TKA, PTT-adjusted unfractionated heparins are superior to fixed doses of low-molecular-weight heparins.

The German Short Musculoskeletal Function Assessment questionnaire: reliability, validity, responsiveness, and comparison with the Short Form 36 and Constant score—a prospective evaluation of patients undergoing repair for rotator cuff tear

In a prospective clinical trial, first the German Short Musculoskeletal Function Assessment questionnaire (SMFA-D) was tested for reliability, validity, and responsiveness in 23 patients with rotator cuff tears, and secondly the Short Form (SF)-36, and the Constant score were evaluated comparatively in 45 patients with rotator cuff tear undergoing open repair. Retest reliability was excellent for the functional index of the SMFA-D and satisfactory for the bother index. The SMFA-D showed good validity and responsiveness. All three instruments demonstrated significantly the positive effect of rotator cuff repair at 12-month follow-up. Using comparable scales, effect sizes were bigger with the SMFA-D than with the SF-36 and as big as the Constant score. Significant correlations of the SMFA-D indices with the SF-36 scales and the Constant score could be shown preoperatively. At 12-month follow-up, all correlations between SMFA-D indices, SF-36 scales, and Constant score function scales were still significant. We recommend use of the SMFA-D to assess changes in functional status concerning patients with rotator cuff tear undergoing open repair.

Hybrid total knee arthroplasty.

Abstract A prospective study of a hybrid total knee arthroplasty (TKA) with an uncemented femoral component and cemented tibial and patellar components was performed to combine the advantage of a press-fit femur while avoiding the problems in uncemented tibial and patellar implants. A total of 329 posterior cruciate-preserving TKA were studied at an average of 4.7 years after surgery: 84% of the knees had at most mild or occasional pain, 68% had good or excellent knee scores, and 62% could walk more than 1000 m. The function scores were 40% good or excellent in this collective, with an average age of 69.4 years at surgery. The component position and alignment were biomechanically correct. Radiolucent lines were observed regularly at the edges of the tibial and femoral components. There were no revisions for aseptic loosening. Hybrid TKA provides good results comparable to cemented TKA.

[Reliability, validity and responsiveness of the German short musculoskeletal function assessment questionnaire (SMFA-D) in patients with osteoarthritis of the hip undergoing total hip arthroplasty].

Zusammenfassung.Einleitung:Ziel der vorliegenden Arbeit ist die Überprüfung der Reliabilität, Validität und Responsivität des Funktionsfragebogen Bewegungsapparat (SMFA-D) bei Patienten mit Coxarthrose und totalendoprothetischem Gelenkersatz.Patienten und Methode:Bei 51 Patienten wurde der SMFA-D, der SF- 36 und der Harris Hip Score sowie ein Gehtest und die Funktionsfähigkeit nach Arzteinschätzung in einer prospektiven Studie erfasst.Ergebnisse:Die Reliabilität war mit r=0,78 für den Funktionsindex und r = 0,84 für den Beeinträchtigungsindex gut. Der SMFA-D konnte Patienten in ihrer Erkrankungsschwere nach ärztlicher Einschätzung unterscheiden (diskriminative Validität). Die Indizes des SMFA-D korrelieren signifikant mit dem Harris Hip Score, den Skalen des SF-36, der Arzteinschätzung und der Gehgeschwindigkeit als Ausdruck der Konstruktvalidität. Im Dreimonatsverlauf konnte die Responsivität mit großen Effektstärken (1,04 Funktionsindex und 1,02 Beeinträchtigungsindex) gezeigt werden.Zusammenfassung:Der SMFA-D stellt auch bei Patienten mit Coxarthrose und totalendoprothetischem Gelenkersatz ein reliables, valides und änderungssensitives Instrument dar und wird als patientenzentriertes Funktionsmaß empfohlen.Summary.Background:The aim of the present study was to check for reliability, validity and responsiveness of the Musculoskeletal Function Assessment questionnaire (SMFA-D) in patients with coxarthrosis undergoing total hip replacement.Patients and method:In a prospective clinical trial the SMFA-D, the SF-36, the Harris Hip score, test of walking speed and the functional impairment according to the physican assessment were recorded.Results:The reliability of the instrument could be demonstrated by a correlation coeffizient of r = 0.78 for the function index and r = 0.84 for the bother index. Patients could be distinguished by the physican’s assessment to show discriminative validity. Both indices correlated significantly with the Harris Hip score, scales of the SF-36 and the walking speed supporting the construct validity. The responsiveness could be shown with large effect sizes (1.04 for the function index and 1.02 for the bother index) at the three-month follow-up.Conclusions:The SMFA-D was found to be a reliable, valid and responsive instrument in patients with coxarthrosis undergoing hip replacement and the use of this instrument can be recommended.