Rheumatoid Arthritis: Simmen BR

Simmen BR, Bogoch ER, Goldhahn J. · Upper Extremity Department, Schulthess Klinik in Zürich, Switzerland. · Nat Clin Pract Rheumatol. · Pubmed #18334981 No free full text.

Abstract: Longstanding rheumatoid arthritis (RA) leads to disability, caused mainly by joint destruction. The current goals of surgical intervention are to restore function and quality of life, prevent joint deterioration, relieve pain, and correct deformity. A number of different surgical treatment options are available to patients with RA, including synovectomy, arthrodesis, joint replacement, and soft tissue and special hand surgery; nonoperative management is also important. Decision-making and timing for orthopedic intervention are complex issues because of polyarticular involvement. Functional impairment, pain, and the subsequent loss of quality of life and inability to work have become the main considerations for surgical reconstruction. Early referral for orthopedic treatment can lead to improved functional benefit for patients with RA. The decision for orthopedic intervention should be established by an interdisciplinary team that includes rheumatologists and orthopedic surgeons experienced in the surgery of RA. Priority should be given to the joint that causes the greatest disability and pain. Disease progression and pharmaceutical treatment options should be taken into consideration when establishing an orthopedic intervention protocol.

Loehr JF, Gschwend N, Simmen BR, Katzer A. · Endo-Klinik, Hamburg, Germany. · Orthopade. · Pubmed #12955195 No free full text.

Abstract: Artificial joint replacement has found a firm place in orthopaedic surgery since its first introduction in the late 1960s. While the initial fixed bearing implants tended to progress to early loosening, the development of so-called "sloppy joints" has seen a major advance in the survival and success rate of this arthroplasty. The surgical approach and technique have also been modified in such a way as to allow a complete ventral release of a flexion contracture, while at the same time preserving the integrity of the extensor mechanism. In this way, the improvement of the biomechanics of the implant combined with diligent surgical technique have enhanced this procedure dramatically. Between 1978 and 1999, 305 GSB 3-type prosthesis were implanted, with the underlying pathologies being rheumatoid arthritis (77%), posttraumatic arthritis (21%) and degenerative arthritis (2%). The range of motion could be significantly improved from the pre-operative state for extension as well as flexion. This was even more obvious in the rheumatoid than in the posttraumatic situation. The survival rate for this type of implant was 90% at 10 years, with the implants after rheumatoid surgery faring somewhat better than those of the posttraumatics. Alternative treatment options, such as resection arthroplasty, distraction arthroplasty, or arthrodesis, are nowadays employed only in rare cases where a previous infection, personal preference or an inability by the patient to co-operate in a rehabilitation program have to be considered. The overall functional results of these types of treatments seem to be inferior to that of elbow arthroplasty. Therefore, this procedure is recommended not only for advanced degenerative and rheumatoid pathologies, but also in cases of posttraumatic arthrosis.

Pap G, Angst F, Herren D, Schwyzer HK, Simmen BR. · Schulthess Clinik, Zürich, Lengghalde 2, CH-8008 Zürich, Switzerland. · Hand Clin. · Pubmed #12945645 No free full text.

Abstract: Functional instruments in rheumatology should use standardized procedures and should be quantifiable, valid, reliable, and responsive/sensitive to change. For most assessment tools, these aspects have been considered and tested. One of the most important questions in assessing hand involvement in patients with RA is what the single assessment should be used for. There could be a substantial difference should hand assessment be done in a routine way in a hand practice or should it be performed within scientific studies on disease progression or the effect of operative interventions. Among other points, answering this question has a significant impact on the time the patient has to spend with the tests and on the time the hand therapist or hand surgeon is involved with it. In addition to aspects such as accuracy, reliability, and validity, therefore, in some evaluation tools the time needed to perform the clinical examination and assessment of hand function has also been considered to be of importance. In addition, it has to be considered that description of the anatomic status, measurements of impairment, and assessment of disability cannot simply be replaced by each other, and even measurements of single aspects often are not sufficient. It has been stated, therefore, that the combination of different discrete hand-function assessment methods provides a more complete picture of hand ability. Moreover, although better responsiveness of disability outcome measures over impairment measures has been demonstrated previously (eg, in patients treated for Colle fracture), the relationship between disability and impairment measures is not clearly established. Although some studies reported significant correlations between impairment and disability tests, other studies showed only poor or moderate correlations between disability scores, impairment, and disease activity measures when rheumatoid hands were assessed. It has been concluded that the relationship between impairment and disability is not straightforward. The new ICF-model addresses these two levels of health-related quality of life by different concepts of assessment. Because impairment reflects the consequences of the disease at the organ level, whereas disability reflects the consequences of the disease for functional performance and activity, for comprehensive assessment of hand handicap, measurement of disability is more comprehensive and closer to the patient's needs for performing ADLs.

Simmen BR, Schwyzer HK, Flury MP, Goldhahn J. · Abteilung Obere Extremität, Schulthess Klinik, Lengghalde 2, 8008, Zürich, Switzerland. · Oper Orthop Traumatol. · Pubmed #19326066 No free full text.

Abstract: OBJECTIVE: Exact restoration of the glenohumeral joint, especially in the case of complex pathologies, due to high prosthesis modularity and in situ assembly; later conversion to inverse design with same shaft possible. INDICATIONS: Primary shoulder osteoarthritis, secondary joint destruction after previous fracture or its treatment, humeral head necrosis, or inflammatory processes, revisions of defect situations such as hemiprostheses. CONTRAINDICATIONS: General contraindications of total shoulder arthroplasty, additionally, functional loss of the rotator cuff, advanced osteoporosis, narrow medullary canal, e.g., in patients with juvenile rheumatoid arthritis. SURGICAL TECHNIQUE: After deltopectoral approach free resection of the humeral head along landmarks, stepwise rasping of the humeral medullary canal, insertion of the rectangled stem, realignment of humeral height with the body, realignment of inclination and possible retroversion with the inclination set. The asymmetric head ensures exact restoration of the joint center. Implantation of the cemented glenoid, test of range of motion and soft-tissue tension, and exchange of components in situ, if necessary. RESULTS: A prospective evaluation of the first 146 consecutive patients with 1-year follow-up revealed significant improvements of about 151% regarding pain and of about 98% in function without significant differences between different indications. Four shaft fissures were observed and treated with intraoperative cerclages during the learning period. No further fissures were noted after adaptation of the surgical procedure and subsequent guidelines. One traumatic and one atraumatic head rotation were observed but should be prevented with a new torque wrench. Similar functional results can be achieved even in complex shoulder pathologies due to the high modularity of the prosthesis.

Simmen BR, Bachmann LM, Drerup S, Schwyzer HK, Burkhart A, Flury MP, Goldhahn J. · Upper Extremity Department, Schulthess Clinic, Zurich, Switzerland. · J Shoulder Elbow Surg. · Pubmed #18818102 No free full text.

Abstract: The purpose of this report is to assess the association of concomitant biceps tenodesis in total shoulder arthroplasty with treatment success 1 year after total shoulder arthroplasty. Of 136 consecutive shoulders (124 patients) undergoing primary total shoulder arthroplasty between 2003 and 2006, 54 (39.7%) underwent biceps tenodesis. For each patient, we obtained potential preoperative confounding data, such as age; gender; presence of rheumatoid arthritis; Short Form 36; number of previous shoulder operations; Disabilities of the Arm, Shoulder and Hand score; Shoulder Pain and Disability Index score; and insurance status. At the 1-year follow-up, we calculated the Constant score of all patients (ranging from 0 [worst] to 100 [best]). We first determined the crude association of concomitant biceps tenodesis with 1-year treatment success (Constant score > or =80) and then fitted a multivariate model correcting for potential confounders to assess the adjusted association of the biceps tenodesis on treatment success. The total number of treatment successes was 46 of 136 shoulders (33.8% of all prosthesis implantations). The crude association (odds ratio) of a concomitant biceps tenodesis with treatment success was 2.38 (95% confidence interval [CI] 1.15 to 4.93; P = .02). When adjusting for potential confounders, we found that this association slightly increased to 2.97 (95% CI 1.00 to 8.85; P = .05). Concomitant biceps tenodesis appears to have a favorable effect on 1-year treatment success after total shoulder arthroplasty.

Simmen BR, Bachmann LM, Drerup S, Schwyzer HK, Burkhart A, Goldhahn J. · Orthopedics Department, Schulthess Clinic, Lengghalde 2, 8008 Zürich, Switzerland. · Osteoarthritis Cartilage. · Pubmed #18061485 No free full text.

Abstract: OBJECTIVE: To Estimate the probability of treatment success 1 year after a total shoulder arthroplasty by developing a model based on preoperative clinical factors. METHOD: Between June 2003 and December 2006, 140 patients undergoing shoulder operations were assessed for age, gender, current rheumatoid arthritis, Short Form (SF) 36 physical and mental sum scores, previous shoulder operations, the Disabilities of Arm, Shoulder and Hand (DASH) symptom and function scores, the Shoulder Pain and Disability Index (SPADI), and insurance status. One year after the operation a Constant score of 80 or more out of 100 indicated successful treatment. Patient variables were analyzed with a logistic regression model augmented in a stepwise manner and bootstrapped 100 times. Variables selected at least 33 times were incorporated into a final model and the Area under the Receiver Operating Characteristics Curve (aROC) was calculated. RESULTS: There were 47/140 (33.6%) successful treatments. The probability of success was reduced in patients with previous shoulder operations (Odds Ratio [O.R.] 0.17, 95% Confidence Interval (95%CI) 0.04-0.85; P=0.03) and older than 75 years (O.R. 0.21, 95%CI 0.05-0.77; P=0.02). The probability of success increased in patients with a higher SF 36 mental sum score (O.R. 1.03, 95%CI 0.96-1.09, P=0.42) and a higher DASH function score (O.R. 1.05, 95%CI 1.02-1.07, P=0.001). The aROC was 0.79 (0.70-0.88) indicating that the model has a high predictive capacity. CONCLUSION: Once validated this model based on four preoperative clinical factors offers a prediction of whether a patient will respond to treatment 1 year after total shoulder arthroplasty.

Engler A, Aeschlimann A, Simmen BR, Michel BA, Gay RE, Gay S, Sprott H. · Center of Experimental Rheumatology, Department of Rheumatology and Institute of Physical Medicine, University Hospital, Gloriastrasse 25, Zurich, Switzerland. · Biochem Biophys Res Commun. · Pubmed #17560936 No free full text.

Abstract: The transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel, which is mainly expressed by nociceptive neurons in dorsal root and trigeminal ganglia. However, there is increasing evidence that TRPV1 expression is not limited to primary afferent neurons but that the receptor is expressed in various cell types throughout the body. Here, we demonstrate the expression of TRPV1 in synovial fibroblasts (SF) from patients with symptomatic osteoarthritis (OA) and rheumatoid arthritis (RA). In addition, the mRNA expression of TRPV1 was shown in PBMCs from healthy controls and from OA patients. The presence of TRPV1 was confirmed at the protein level. Stimulation of cultured OA- and RA-SF with the TRPV1 agonist capsaicin led to increased expression of IL-6 mRNA as well as of IL-6 protein in the cell culture supernatants. IL-6 protein expression could be antagonized with capsazepine. Thus, we hypothesize that TRPV1 may play a role in non-neuronal mechanisms that might modulate nociception in symptomatic OA and RA patients.

Goldhahn J, Kolling C, Gay S, Simmen BR. · Upper Extremity Department, Schulthess Clinic, Zürich, Switzerland. · Nat Clin Pract Rheumatol. · Pubmed #17299449 No free full text.

Abstract: BACKGROUND: A 46-year-old, nonsmoking, nulliparous woman with a 23-year history of rheumatoid arthritis presented with severely destructed right shoulder, right elbow, and right wrist joints, which resulted in a complete loss of working ability. INVESTIGATIONS: Physical examination, X-ray, MRI, ultrasound, functional staging using the Shoulder Pain and Disability Index, the Patient Rated Elbow Evaluation, the Disabilities of the Arm, Shoulder and Hand, and the health-related quality-of-life Short Form 36 questionnaire, determination of the c-reactive protein level, erythrocyte sedimentation rate, Disease Activity Score 28 and the metalloproteinase profile, and histology of removed synovial tissue. DIAGNOSIS: Severe destruction of the right shoulder and elbow (Larsen grade IV) resulting from late-stage seropositive rheumatoid arthritis. MANAGEMENT: Reconstruction of the elbow and ipsilateral shoulder in a two-step procedure: replacement of the elbow joint with a semiconstrained Gschwend-Scheier-Bahler III (GSB III) elbow prosthesis (Zimmer, Inc., Warsaw, IN) followed by replacement of the shoulder with the Promos Modular Shoulder System (Plus Orthopedics AG, Rotkreuz, Switzerland) 1 month later. The patient received 4 weeks of inpatient rehabilitation.

Kistler U, Weiss AP, Simmen BR, Herren DB. · Department of Hand Surgery, Schulthess Clinic, Zurich, Switzerland. · J Hand Surg Am. · Pubmed #16344189 No free full text.

Abstract: PURPOSE: The surgical treatment of the rheumatoid wrist is key in managing the affected hand. Wrist fusion is often the treatment of choice in cases of severe destruction and deformation although most patients would prefer a motion-preserving procedure. The implantation of a wrist prosthesis might be an alternative to partial arthrodesis for selected cases. In this series we analyzed the long-term results (minimum follow-up period, 10 y) of the Swanson silicone spacer for the wrist in patients with rheumatoid arthritis. METHODS: Sixteen patients with rheumatoid arthritis with 18 silicone spacers for the wrists were reviewed after a minimum follow-up period of 10 years (average, 15 y). Subjective evaluation, clinical examination, and radiographic analysis were included. An additional 9 patients (9 wrists) were interviewed by telephone. RESULTS: In 12 of the patients the subjective result was good or very good, mostly because of adequate pain relief. The average range of motion for flexion (average, 28 degrees )/extension (average, 15 degrees ) was 43 degrees with a wide variation within the series. Radiologically all wrists had diminished residual carpal height at follow-up evaluation and 9 of the wrists had evidence of osteolysis and foreign-body granuloma. The initial good correction of the ulnar translation of the wrist was lost partially in the follow-up period (1.1 vs 4.0 mm). Three of the patients needed surgical revision within the follow-up period; all were converted to wrist fusion. CONCLUSIONS: These long-term results suggest that the silicone wrist spacer still may be considered as an alternative to wrist fusion or more complex wrist joint prostheses in patients with rheumatoid arthritis, especially in severe cases and in patients with low demands. In the long term osteolysis caused by foreign-body granulation is to be expected and has to be considered.

Jüngel A, Baresova V, Ospelt C, Simmen BR, Michel BA, Gay RE, Gay S, Seemayer CA, Neidhart M. · Centre of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, Gloriastrasse 25, CH 8091 Zurich, Switzerland. · Ann Rheum Dis. · Pubmed #16284094 links to  free full text

Abstract: BACKGROUND: Histone acetylation/deacetylation has a critical role in the regulation of transcription by altering the chromatin structure. OBJECTIVE: To analyse the effect of trichostatin A (TSA), a streptomyces metabolite which specifically inhibits mammalian histone deacetylases, on TRAIL-induced apoptosis of rheumatoid arthritis synovial fibroblasts (RASF). METHODS: Apoptotic cells were detected after co-treatment of RASF with TRAIL (200 ng/ml) and TSA (0.5, 1, and 2 micromol/l) by flow cytometry using propidium iodide/annexin-V-FITC staining. Cell proliferation was assessed using the MTS proliferation test. Induction of the cell cycle inhibitor p21Waf/Cip1 by TSA was analysed by western blot. Expression of the TRAIL receptor-2 (DR5) on the cell surface of RASF was analysed by flow cytometry. Levels of soluble TRAIL were measured in synovial fluid of patients with RA and osteoarthritis (OA) by ELISA. RESULTS: Co-treatment of the cells with TSA and TRAIL induced cell death in a synergistic and dose dependent manner, whereas TRAIL and TSA alone had no effect or only a modest effect. RASF express DR5 (TRAIL receptor 2), but treatment of the cells with TSA for 24 hours did not change the expression level of DR5, as it is shown for cancer cells. TSA induced cell cycle arrest in RASF through up regulation of p21Waf1/Cip1. Levels of soluble TRAIL were significantly higher in RA than in OA synovial fluids. CONCLUSION: Because TSA sensitises RASF for TRAIL-induced apoptosis, it is concluded that TSA discloses sensitive sites in the cascade of TRAIL signalling and may represent a new principle for the treatment of RA.

Shen H, Aeschlimann A, Reisch N, Gay RE, Simmen BR, Michel BA, Gay S, Sprott H. · University Hospital Zurich, Zurich, Switzerland. · Arthritis Rheum. · Pubmed #15880345 links to  free full text

Abstract: OBJECTIVE: To investigate the expression and regulation of the kappa-opioid receptor (KOR) and the delta-opioid receptor (DOR) in fibroblast-like synoviocytes (FLS) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA), and to explore the potential antiarthritic mechanisms of peripheral KORs. METHODS: FLS isolated from synovial tissues of 6 OA patients, 8 RA patients, and 2 healthy individuals were exposed to the selective KOR agonist U69593, the selective DOR agonist SNC 80, and kappa-opioid dynorphin A in the presence or absence of the KOR antagonist nor-binaltorphimine, the DOR antagonist naltrindole, and the proinflammatory cytokines tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta). The expression of KOR and DOR in OA and RA FLS was evaluated on the messenger RNA (mRNA) and protein levels with TaqMan real-time reverse transcriptase-polymerase chain reaction and immunofluorescence staining, respectively. KOR/DOR-mediated activation of ERK-1 and ERK-2 was investigated by Western blotting. RESULTS: We detected functional KOR and DOR in normal FLS and observed a reduction of both receptors in OA and RA FLS, which was more distinct in RA FLS. U69593 enhanced KOR mRNA expression in both OA and RA FLS in a KOR antagonist-reversible manner. However, the dose required for maximal enhancement in RA FLS was 10 times higher than that required in OA FLS. TNFalpha and IL-1beta both suppressed the expression of DOR and KOR mRNA in both OA and RA FLS. CONCLUSION: DOR and KOR are constitutively present in normal FLS and are suppressed under inflammatory conditions, such as RA and OA. Most interestingly, the KOR agonist U69593 may exert an antiarthritic effect via up-regulation of KOR in OA and RA FLS.

Angst F, Goldhahn J, John M, Herren DB, Simmen BR. · Obere Extremitäten- und Handchirurgie, Schulthess-Klinik, Zürich, Schweiz. · Orthopade. · Pubmed #15856166 No free full text.

Abstract: BACKGROUND: Patients with elbow destruction due to rheumatoid arthritis (RA) or trauma (PT) were compared to population-based normative data and to each other after total elbow arthroplasty. PATIENTS AND METHODS: Pain, function, and biopsychosocial health were multidimensionally assessed by the generic Short Form 36 (SF-36), the condition-specific Disabilities of the Arm, Shoulder and Hand questionnaire (DASH), and the Patient Related Elbow Evaluation form (PREE) instrument and analyzed by uni- and multivariate methods. RESULTS: Compared to normative values, the examined 59 RA patients were significantly affected in the function scales of the SF-36 and in all DASH scales. The 20 PT patients were worse than the norm only in the DASH function. Function was lower in RA than in PT in the SF-36 scales and in the DASH (RA: 44.4, PT: 70.3, p<0.001). This difference was less distinct in the PREE. CONCLUSION: Total elbow arthroplasty led to a pain-free outcome and normal quality of life, but failed to restore complete function. Functional deficits were larger in the RA patients and could also be measured by the SF-36, possibly due to polyarticular affection.

Schindele S, Herren D, Flury M, Simmen BR. · Abteilung für Obere Extremität und Handchirurgie, Schulthess-Klinik, Zürich, Schweiz. · Handchir Mikrochir Plast Chir. · Pubmed #15744652 No free full text.

Abstract: For the reconstruction of destroyed metacarpophalangeal (MP) joints in rheumatoid arthritis, the Swanson silicon spacer is still the golden standard. However, long-term follow-up reveals an increasing number of complications, particularly mechanical failure. In order to deal with these problems a number of new, biomechanically different silicone implants have been designed. Among these, the NeuFlex prosthesis has a preflexed hinge of 30 degrees in relation to the shaft axis, a more palmar lying center of rotation and a rectangular hinge with a collarlike platform against the bony surfaces. In a prospective study, the early results of the first thirteen patients operated with the NeuFlex arthroplasty are reported. All patients suffered from rheumatoid arthritis with destruction of the MP joints. The mean follow-up was 12.3 months. A total of 37 joints were replaced. All patients were female with an average age of 56 years. Postoperative reduction of pain, measured on a visual analog scale with the maximum of 10 (VAS), decreased from 6.6 to 0.7 (p < 0.001). Jamar grip strength improved from 4.2 kg preoperatively to 9.9 kg postoperatively (p < 0.005). Range of motion improved from 37 degrees to 57 degrees (p < 0.0001) as a result of a reduction in active extension deficit which reduced from 35 degrees to 15 degrees postoperatively. Ulnar drift was reduced from 20.2 degrees to 3.4 degrees at follow-up (p < 0.005). Radiological evaluation showed no implant failure, no subsidence, and no signs of inflammatory reaction. Overall the NeuFlex silicone implants show encouraging early results which must be confirmed in the long term.

Angst F, John M, Pap G, Mannion AF, Herren DB, Flury M, Aeschlimann A, Schwyzer HK, Simmen BR. · Schulthess Klinik, Zurich, Switzerland. · Arthritis Rheum. · Pubmed #15696556 links to  free full text

Abstract: OBJECTIVE: To assess quantitatively the outcome and to explore the physiometric and psychometric properties of clinical, generic, and condition-specific instruments after total elbow arthroplasty. METHODS: Seventy-nine patients were assessed in a 6-19-year cross-sectional catamnesis by means of 6 widely used questionnaires, clinical examinations, and radiographic examinations. RESULTS: With regard to pain, general physical health, and all the mental health dimensions of the Short Form 36 (SF-36), the patients showed scores comparable to normative values. Elbow joint stability and satisfaction were both good. Significant functional limitation was evidenced by the low mean scores of the SF-36 physical functioning measure (48.7, normative 69.9) and the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) function measure (51.1, normative 89.3). The SF-36 physical component summary and the DASH correlated highly (r = 0.76) and, in factor analysis, loaded on the factor "physical unspecific." The patient and clinical modified American Shoulder and Elbow Surgeons questionnaire (mASES) correlated with the Patient Related Elbow Evaluation form (r = 0.92 with the patient mASES) and loaded on "physical specific." The SF-36 mental component summary loaded on "mental quality of life." CONCLUSION: The patients' self-rated health, quality of life, and clinical outcome were good and were not affected by impairment in some specific functional abilities. A questionnaire set comprising the SF-36 and the patient and clinical mASES is proposed for the comprehensive and specific assessment of outcome after elbow arthroplasty.

Angst F, Pap G, Mannion AF, Herren DB, Aeschlimann A, Schwyzer HK, Simmen BR. · Schulthess Klinik, Zurich. · Arthritis Rheum. · Pubmed #15478159 links to  free full text

Abstract: OBJECTIVE: To explore the physiometric and psychometric properties of clinical, generic, and condition-specific assessment instruments. To describe patients' outcome after total shoulder arthroplasty. METHODS: Forty-three patients were assessed in a 5-6-year cross-sectional catamnesis. RESULTS: With regard to shoulder joint stability, pain, general physical health, and mental health, the patients showed scores comparative to normative scores. Significant functional limitation was evidenced by low mean scores on the specific function scales (e.g., Disability of the Arm, Shoulder and Hand questionnaire score = 64.0, normative score = 86.6). There were high correlations among the joint-specific scales (up to 0.93) and moderate correlations between these and the generic and clinical scales. Factor analysis identified 3 different assessment domains. CONCLUSION: The patients' quality of life (QOL) was high and not affected by impairment in some specific functional abilities. Physical QOL, mental QOL, clinical assessment, condition-specific measures, and generic measures were identified as separate domains, all of which are required for a comprehensive and sophisticated assessment in practical clinical routine.

Masuda K, Masuda R, Neidhart M, Simmen BR, Michel BA, Müller-Ladner U, Gay RE, Gay S. · Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zürich, Gloriastrasse 25, Switzerland. · Arthritis Res. · Pubmed #12223111 links to  free full text

Abstract: The aim of this study was to explore the molecular profile of proliferating rheumatoid arthritis synovial fibroblasts (RA-SF). Total RNA was extracted from two cultures of RA-SF (low-density [LD] proliferating cells and high-density [HD] nonproliferating cells) and suppression subtractive hybridization was performed to compare differential gene expression of these two cultures. Subtracted cDNA was subcloned, and nucleotide sequences were analyzed to identify each clone. Differential expression of distinct clones was confirmed by semiquantitative RT-PCR. The expression of certain genes in synovial tissues was examined by in situ hybridization. In both LD and HD cells, 44 clones were upregulated. Of the 88 total clones, 46 were identical to sequences that have previously been characterized. Twenty-nine clones were identical to cDNAs that have been identified, but with unknown functions so far, and 13 clones did not show any significant homology to sequences in GenBank (NCBI). Differential expression of distinct clones was confirmed by RT-PCR. In situ hybridization showed that certain genes, such as S100A4, NFAT5, unr and Fbx3, were also expressed predominantly in synovial tissues from patients with RA but not from normal individuals. The expression of distinct genes in proliferating RA-SF could also be found in RA synovium, suggesting that these molecules are involved in synovial activation in RA. Most importantly, the data indicate that the expression of certain genes in RA-SF depends on the stage of proliferation; therefore, the stage needs to be considered in any analysis of differential gene expression in SF.

Herren DB, Simmen BR. · Upper Extremity Unit, Schulthess Klinik, Zürich, Switzerland. · Clin Orthop Relat Res. · Pubmed #11795731 No free full text.

Abstract: The results of a new subcapital shortening osteotomy for correction of metacarpophalangeal joint deformity in patients with rheumatoid arthritis of the hands are presented. Seven patients (16 joints) were followed up for a mean of 33.5 months. The mean shortening of the metacarpal bone was 4.6 mm (range, 4-8 mm), and seven joints had additional intrinsic release. Only four (25%) joints held the correction of the deformity; all other joints had recurrence of palmar subluxation with or without additional ulnar drift. The range of motion of the joints with preserved correction after surgery was 80 degrees compared with 28 degrees of the joints with recurrent deformity. The possible mechanism of failure was analyzed. The results of the current series suggest that subcapital shortening osteotomy may not be indicated for treatment of severe metacarpophalangeal joint deformity in patients with rheumatoid arthritis.

Shigeyama Y, Pap T, Kunzler P, Simmen BR, Gay RE, Gay S. · WHO Collaborating Center for Molecular Biology and Novel Therapeutic Strategies for Rheumatic Diseases, University Hospital, Zurich, Switzerland. · Arthritis Rheum. · Pubmed #11083276 links to  free full text

Abstract: OBJECTIVE: To analyze the expression pattern of osteoclast differentiation factor (ODF) and its contribution to osteoclastogenesis in rheumatoid arthritis (RA). METHODS: The expression of ODF was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) in RA synovial fibroblasts (RASF) isolated from 7 RA patients and in normal skin fibroblasts. Using RNA probes specific for ODF, in situ hybridization was performed. Immunohistochemical double labeling for CD68 was applied to characterize the ODF-expressing cells. ODF protein and messenger RNA (mRNA) expression by RASF with or without 1,25(OH)2D3 was studied by Western blot analysis and quantitative real-time PCR. In addition, we performed coculture experiments with RASF and normal peripheral blood mononuclear cells with or without 1,25(OH)2D3. RESULTS: By RT-PCR, ODF mRNA expression was found in all RASF investigated, but not in normal skin fibroblasts. In situ hybridization revealed that in RA synovial tissues, ODF mRNA was expressed mainly in the lining layer and at sites where synovium was attached to bone. Immunohistochemical double labeling demonstrated ODF mRNA expression mainly in CD68-fibroblast-like synoviocytes and CD68+ multinucleated osteoclast-like cells. By Western blotting, all RASF expressed ODF protein. However, different levels of ODF expression were found in the RASF from different patients. Interestingly, RASF expressing higher levels of ODF induced a larger number of osteoclast-like cells than did RASF expressing only low levels of ODF. Although 1,25(OH)2D3 did not alter the levels of ODF expression in RASF on either Western blot or quantitative real-time PCR, osteoclastogenesis required the presence of 1,25(OH)2D3. CONCLUSION: The present results suggest that activated RASF, by expressing ODF, play an important role in rheumatoid bone destruction. Moreover, the data provide evidence that RASF not only activate osteoclasts, but also contribute directly to osteoclastogenesis.

Herren DB, Simmen BR. · Schulthess Klinik, Department of Orthopaedics and Handsurgery, Zürich, Switzerland. · Clin Orthop Relat Res. · Pubmed #10693559 No free full text.

Abstract: Joint replacement is an established method in the treatment of destroyed, painful, proximal interphalangeal joints. A palmar approach was used in which the main collateral ligaments were preserved, allowing immediate active rehabilitation with enhanced primary lateral stability. Fifty-nine proximal interphalangeal joint silicone arthroplasties in 38 patients with a minimum followup of 12 months were reviewed. Thirty-eight of the 59 joints had implantation from a palmar approach and 21 joints from a dorsal approach. The two groups were well-matched in terms of indication, preoperative range of motion, and patient age. No significant increase in the range of motion was found in either of the patient groups, with an overall average range of motion of 51 degrees postoperatively. There was also no significant difference in the postoperative stability in the two patient groups. The choice of surgical approach at the proximal interphalangeal joint level for the silastic type of implants does not appear to be important. With more sophisticated types of implants in which the integrity of the collateral ligaments is crucial, a palmar approach might be beneficial.

Flury MP, Herren DB, Simmen BR. · Upper Extremity Unit, Schulthess Klinik, Zurich, Switzerland. · Clin Orthop Relat Res. · Pubmed #10627720 No free full text.

Abstract: The authors introduce a new functional classification of rheumatoid arthritis of the wrist. Unlike the classifications used today, it includes the aspect of the natural course of rheumatoid arthritis. The goal of this paper is to identify radiologic indicators that will classify rheumatoid arthritis into stable forms of the disease (Types I and II) and unstable forms of the disease (Type III). Of 144 wrists examined, the first available radiograph and the radiograph obtained at the time of the first surgery were assessed. The indicators measured were: carpal height ratio, ulnar translocation, radial rotation, and scapholunate dissociation. Noting the changes that occurred each year in these indicators, it was possible to identify a significant difference between stable forms (Types I and II) and unstable forms (Type III) for the parameters carpal height ratio, ulnar translocation, and scapholunate dissociation. The distribution of the indicators allowed the definition of three values: the 100% value, the cut off point, and the lower threshold value. Combining the three radiologic parameters at those values markedly enhanced the possibility to classify rheumatoid arthritis of the wrist. With the help of the three radiologic indicators carpal height ratio, ulnar translocation, and scapholunate dissociation, it is possible to classify wrists with an early stage of rheumatoid arthritis according to the Schulthess classification. The early identification of destabilizing forms of rheumatoid arthritis becomes possible, making the choice and timing of the surgical intervention easier. Wrists with a progressive unstable form of rheumatoid arthritis may be stabilized earlier.

Kolling C, Herren DB, Simmen BR, Goldhahn J. · No affiliation provided · Ann Rheum Dis. · Pubmed #19605747 No free full text.

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