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Im Namen aller Beteiligten mochten wir Ihnen das Kompetenznetz Rheuma vorstellen. Dieser Artikel soll Ihnen einen ersten Einblick in die Aufgaben, Strukturen und Ziele unseres Projektes geben. Das Kompetenznetz Rheuma geht auf eine Initiative des Bundesministeriums fur Bildung und Forschung zuruck. Unter mehr als 150 Antragstellern hat das Ministerium im Rahmen eines Wettbewerbs neun Kompetenznetzwerke in der Medizin fur eine spezielle Forderung ausgewahlt. Das Ziel war, die in Deutschland vorhandene, aber bundesweit zersplitterte Kompetenz zu gesundheitspolitisch bedeutenden Krankheitsbildern zu bundeln und dadurch effizienter zu gestalten. Das Kompetenznetz Rheuma ist einer der Gewinner und wird uber einen Zeitraum von bis zu funf Jahren mit bis zu 5Mio. Mark jahrlich unterstutzt. Im Kompetenznetz Rheuma schliesen sich die verschiedenen Ebenen der Rheumatologie zusammen: die Grundlagenforschung, die Versorgungsforschung, die Universitatskliniken, die rheumatologischen Krankenhauser und Rehabilitationskliniken, die niedergelassenen Rheumatologen und die Hausarzte. Der Wissens- und Informationstransfer untereinander wird durch horizontale und vertikale Vernetzung sichergestellt. Ein wesentliches Ziel besteht darin, die Wege von der Laborbank bis zum Krankenbett zu verkurzen. Denn der enge Verbund von Grundlagenforschung, Krankenbetreuung und Dokumentation bietet einzigartige Moglichkeiten, neue Forschungsergebnisse zugig in die Patientenversorgung zu integrieren und bestehende Defizite zu erkennen und auszuschalten. Getragen und weiterentwickelt wird das Kompetenznetz Rheuma von den sechs antragstellenden rheumatologischen Kompetenzzentren in Berlin, Dusseldorf, Erlangen, Freiburg, Hannover und Lubeck/ Bad Bramstedt. Das Netzwerk soll aber kein in sich geschlossenes Projekt bleiben. Alle Interessierten sind herzlich eingeladen, sich daran zu beteiligen. Wir freuen uns also uber Ihre Vorschlage, Diskussionsbeitrage und Anfragen! Gezielte Informationen zu den Teilprojekten konnen Sie bei den in dieser Artikel genannten Ansprechpartnern gern anfordern.

Objective Recent studies suggest that giant cell arteritis (GCA) may be an antigen-driven disease. Since Chlamydia pneumoniae has been identified in arterial vessel walls, it was hypothesized that this organism might be associated with GCA. Methods Fourteen paraffin-embedded temporal artery biopsy specimens from 9 patients with GCA were examined by immunohistochemistry and by polymerase chain reaction (PCR) for the presence of C pneumoniae; for 5 patients, specimens were available from both the left and right arteries. Four temporal artery specimens from 3 patients with polymyalgia rheumatica (PMR) and 9 temporal artery specimens from 5 patients without GCA or PMR served as controls. Results C pneumoniae was detected by both immunohistochemistry and PCR in 6 GCA patient samples. One GCA patient sample was immunopositive only; another was PCR positive only. Thus, C pneumoniae was found in 8 of 9 GCA patients. One of 4 control samples from the PMR patients was immunopositive, but PCR negative, for C pneumoniae. The C pneumoniae–positive PMR patient also had respiratory symptoms. The remaining 9 control samples were negative for C pneumoniae by both immunohistochemistry and PCR. Immunohistochemistry showed that bacteria predominate in the adventitial layer of temporal arteries, in granulomatous infiltrates. Dendritic cells were examined by immunohistochemistry for their presence and localization in consecutive temporal artery specimens, and showed a strong topographic relationship with C pneumoniae. Like the bacterium, dendritic cells predominate in the adventitial layer of the arteries. Conclusion C pneumoniae was found in temporal artery specimens from most GCA patients, in 1 specimen from a PMR patient, and in no other control specimens; thus, it may play a role in the pathogenesis of the disease. Dendritic cells may represent the antigen-presenting cells in this situation.

by Moll et al. [2] the school of ‘lumpers’, who preferred Infection of the urogenital or gastrointestinal tract to group the so-called ‘variants of rheumatoid arthritis’ Alteration of the skin (psoriasiform skin or nail lesion, with rheumatoid arthritis itself, were overcome by the erythema nodosum) school of ‘splitters’, prompted by the idea that these Buccal ulceration of the mouth, small or large intestine and seronegative arthritides were, in fact, entirely separate urogenital tract Thrombophlebitis entities. This change was mirrored by the Nomenclature Pyoderma gangraenosum and Classification of the Rheumatic Diseases proposed Familial aggregation by the American Rheumatism Association in 1963 [1]. Association with HLA-B27 Rheumatoid arthritis, juvenile Still’s disease, ankylosing spondylitis, psoriatic arthritis, and Reiter’s syndrome 1. The term seronegative arthritis still survives and is were then classified under separate headings with the not completely out of use, which may be illustrated common denominator ‘polyarthritis of unknown origin’. by the fact that the Editor of this journal initially

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclo-oxygenase (COX), which leads to suppression of COX-1-mediated production of gastrointestinal-protective prostaglandins. Gastrointestinal injury is a common outcome. We compared the efficacy, safety, and tolerability of long-term therapy with celecoxib, a COX-1 sparing inhibitor of COX-2, with diclofenac, a non-specific COX inhibitor.655 patients with adult-onset rheumatoid arthritis of at least 6 months' duration were randomly assigned oral celecoxib 200 mg twice daily or diclofenac SR 75 mg twice daily for 24 weeks. Anti-inflammatory and analgesic activity and tolerability were assessed at baseline, every 4 weeks, and at week 24. We assessed gastrointestinal safety by upper-gastrointestinal endoscopy within 7 days of the last treatment dose at centres where the procedure was available. Analysis was by intention-to-treat.430 patients underwent endoscopy (celecoxib n=212, diclofenac n=218). The two drugs were similar in management of rheumatoid arthritis pain and inflammation. Gastroduodenal ulcers were detected endoscopically in 33 (15%) patients treated with diclofenac and in eight (4%) in the celecoxib group (p0.001). The rate of withdrawal for any gastrointestinal-related adverse event, most commonly abdominal pain, diarrhoea, and dyspepsia, was nearly three times higher in the diclofenac-treated group than in the celecoxib group (16 vs 6%; p0.001).Celecoxib showed sustained anti-inflammatory and analgesic activity similar to diclofenac, with a lower frequency of upper gastrointestinal ulceration or gastrointestinal adverse events, and tolerability was better.

A role for bacterial infection in the aetiology of inflammatory arthritis has been suspected for many years. Yet over that relatively long period of time only a few acute or chronic arthritides have been unequivocally linked to an infectious agent; these include septic arthritis, rheumatic fever, and, more recently, Lyme arthritis. The term reactive arthritis was first introduced to describe the association between Yersinia enterocolitica infection and arthritis, and it was intended to differentiate this form of acute, non-suppurative arthritis, which is characterised by negative joint culture, from infectious, purulent arthritis; the differentiation was meant to suggest an underlying sterile immune mediated pathomechanism.1 A few years later, immediately after discovery of the association between HLA-B27 and ankylosing spondylitis and Reiter’s syndrome, the term reactive arthritis was also related to this genetic marker; at this time the term was more strictly applied to the HLA-B27 associated reactive arthritides, following infections with enterobacteria and chlamydia.2 This concept has been widely recognised and accepted. However, non-HLA-B27 associated arthritides, such as Lyme disease induced by Borrelia burgdorferi , Neisseria gonorrhoeae induced reactive arthritis, post-streptococcal reactive arthritis, and rheumatic fever are viewed presently as reactive arthritides (see table1 for the spectrum of bacterial species triggering reactive arthritis). This inclusion is based on the observation that these arthritides also develop after a primary extra-articular infection, and that despite negative culture results, the organisms can be detected in the joint (for example, Borrelia ,7 Neisseria 9). View this table: Table 1 Bacteria triggering reactive arthritis–manifestations at the entry site (see references3–11,23,29,34) This brief historical outline demonstrates not only the changing definition of “reactive arthritis” over time, but also illuminates the lack of general consensus concerning the precise clinical and scientific conditions to which this term should be …

Objective Disease activity has been defined using a self-administered instrument, focusing on fatigue, axial pain, peripheral pain, enthesopathy and morning stiffness [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)]. This validated instrument is simple and takes 40 s to complete, but whether the index is an accurate expression of the component parts, or whether additional weighting would enhance its efficacy, is unclear. Methods Four hundred and seventy-three patients with ankylosing spondylitis received placebo or active non-steroidal anti-inflammatory drug (NSAID) for 6 weeks, and changes between entry and completion were captured by BASDAI and the individual components. Principle component analysis (PCA) was used to explore the best combinations of variables in decreasing order of explained total dispersion and to assess whether a single sum (or algebraic expression) best defined disease activity status. Results At entry, the correlation between BASDAI and the first axis was 0.99, 0.11 with the second, and zero thereafter. Data at study end and relating to change revealed a 100% correlation (R = 1) between the first axis and the sum, with zero for the remainder. Conclusions The data support BASDAI as being a valid and appropriate composite to define disease activity in ankylosing spondylitis. Developed as a simple sum of its components, BASDAI has excellent content validity.

Inflammatory joint disease can develop following an extra-articular infection. The term reactive arthritis was coined in order to differentiate this arthritis, which is often characterized by lack of culturable organisms in the joint, from septic arthritides. Bacteria known to trigger reactive arthritis include Campylobacter, Chlamydia, Salmonella, Shigella and Yersinia. Demonstration of bacteria or bacterial macromolecules in the joint has elicited the idea that reactive arthritis is a sterile process induced and maintained by antigenic material in the synovium. Continued synthesis of antigens to maintain synovial inflammation probably requires establishment of persistent bacterial infection in the joint, or at the primary site of infection. In the case of Chlamydia trachomatis, viable, metabolically-active organisms have been demonstrated to exist for extended periods in the joints of patients with reactive arthritis. In this chapter, we review the aetiological agents, and their molecular biology and phagocyte-host interactions, that are involved in reactive arthritis and spondylarthropathy.

The principal host cell for persistently infecting synovial Chlamydia trachomatis is the macrophage. During infection of human monocytes/macrophages in culture this bacterium displays aberrant morphology and produces no new elementary bodies, reflecting the situation in synovium. Here we investigate the metabolic status of C. trachomatis (serovar K) during an extended infection of human peripheral monocytes in vitro. Using reverse transcription-polymerase chain reaction assays, we have shown that primary transcripts from the chlamydial rRNA operons are present throughout a 10-day course of infection. Other assays targeting mRNAs from chlamydial genes encoding r-proteins S5 and L5, the glycyl-tRNA synthetase, the 60-kDa cysteine-rich outer membrane protein, and the KDO transferase indicate that these messengers are also present throughout the entire 10-day period. The gene encoding the 57-kDa heat-shock protein (hsp60) is expressed by the bacterium throughout the 10-day infection of cultured monocytes, but transcript levels from the gene encoding the major outer membrane protein (omp1) appear to be attenuated. Western analyses targeting these latter proteins confirm the presence of the hsp60 gene product, and the virtual absence of major outer membrane protein, in chlamydia-infected cultured human monocytes. Thus, during extended infection of human monocytes in vitro, chlamydia are non-productive but transcriptionally active; the pattern of transcriptional activity reflects that known for persistent C. trachomatis infection in vivo in synovial tissue.

SUMMARY Objective. This study compared the progression of joint damage in patients with early active severe rheumatoid arthritis (RA) treated with cyclosporin or parenteral gold. Methods. In this open, randomized, multicentre study with a blinded radiological endpoint, 375 patients who had suVered from active severe RA for

□ Wirkungsweise der nichtsteroidalen Antirheumatika Nichtsteroidale Antirheumatika (NSAR) uben ihre antiinflammatorischen, analgetischen und antipyretischen Wirkungen durch Hemmung der Prostanoidsynthese aus. Die typischen Nebenwirkungen der NSAR und deren Interaktionen mit Antihypertonika und Lithium sind ebenfalls durch diesen Wirkmechanismus bedingt. Erst 1990 wurde nachgewiesen, das die physiologische Prostanoidsynthese durch eine konstitutive Cyclooxygenase (COX-1) katalysiert wird, wahrend fur die proinflammatorische Prostanoidsynthese ein anderes Isoenzym, die induzierbare Cyclooxygenase (COX-2), verantwortlich ist.

Cat scratch disease (CSD) is a rarely recognized infectious disease in Germany. Only a few years ago the causative agent, Bartonella henselae, could be isolated. The typical clinical manifestations of CSD consist of skin changes at the inoculation site and a benign lymphadenopathy; other manifestations are rare. We report the case of a 47 year old woman, who developed a reactive spondylarthropathy with synovitis of finger joints, polyarthralgias of large- and medium-sized joints, and inflammatory spinal pain after a cat bite. The rheumatic manifestations resolved after 10 months by treatment with non-steroidal antirheumatic drugs. Only a few cases of rheumatic manifestations associated with CSD have been described in the literature. Because the prevalence of Bartonella henselae infection of cats is high in Europe, rheumatic manifestations might be more frequent. Diagnosis of CSD is now improved by the development of serological tests. We provide an overview of the clinical manifestations and the diagnostic criteria.

Borrelia burgdorferi– spezifische DNA last sich mittels Polymerase-Kettenreaktion (PCR) in verschiedenen Untersuchungsmaterialien von Patienten mit einer Lyme-Borreliose (LB) nachweisen. Ziel der vorliegenden Untersuchung ist es, den Wert der PCR-Untersuchungen von Urin im Hinblick auf die rheumatologische Diagnostik der Lyme-Borreliose zu uberprufen. Von 77 Patienten (LB n=34, undifferenzierte Arthritis (UA) n=25, Arthralgien/Myalgien (AM) n=18) und 15 Kontrollpersonen wurden Urinproben untersucht. Als Zielsequenzen dienten Flagellin-Gen (60 Proben) oder OspA-Plasmid (32 Proben). Es fand sich eine Sensitivitat der Flagellin-nested-PCR von 27%, mittels OspA-nested-PCR wurde dagegen nur ein positiver Befund erhoben. Trotz formal niedriger Sensitivitat konnte bei 2 Patienten mit einer UA erst durch die PCR die Diagnose LB gesichert werden. In Einzelfallen bietet die PCR somit diagnostisch wertvolle Hinweise bei klinischem Verdacht auf eine LB.

Inoculation of phorbol ester-differentiated U937 cells as a model for human macrophages with Chlamydia trachomatis of the urogenital serovar K resulted in a persistent infection, with maximal growth at day 7, until day 10 post-infection. At these times inclusion bodies were present in 0.5-2% of the cells. Typical inclusion bodies containing elementary bodies and reticulate bodies were observed by electron microscopy. Furthermore, single chlamydial particles resembling atypical elementary or intermediate bodies were identified in the cytoplasm in80% of the host cells. IFN-gamma exerts antichlamydial activity in epithelial and fibroblastoid cells, but the infection of U937 cells by C. trachomatis was not affected by IFN-gamma. The activity of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) was not detected in untreated or in IFN-gamma-treated or chlamydiae-infected or mock-infected U937 cells. The presence of atypical persisting chlamydiae and the lack of IDO expression in U937 cells indicates that the development of these atypical bacteria is independent from IFN-gamma-mediated tryptophan deprivation and other IFN-gamma-mediated effects. Evaluation of persistently infected cells revealed that the expression of the chlamydial major outer-membrane protein, heat-shock protein (hsp60) and lipopolysaccharide (LPS) antigens was not significantly altered in the course of the culture. An intense staining of the LPS on the surface of the host cells was demonstrated by immunofluorescence. The data show that phorbol ester-differentiated U937 cells restrict chlamydial growth strongly but not completely through a mechanism distinct from IDO-mediated tryptophan deprivation. The mechanisms of persistence of chlamydiae in monocytes, which differ considerably from those described for other cells, require further investigation.

B cell differentiation depends on cellular interactions with T lymphocytes and monocytes via adhesion molecules (AM). In order to characterize AM which are required for B cell differentiation immunoglobulin production using unseparated peripheral blood mononuclear cells (PBMC) was studied. Unstimulated human PBMC were cultured for 9 days with mAb directed at CD2/CD48, /CD58, CD59, CD5/CD72, CD11a-CD18/CD54, CD28/CD80, CD86, CD40/CD40L, or rat CD2 (control). B cell differentiation was quantified measuring IgM and in some cases IgA, IgG, and IgE production. IgM levels were significantly reduced by mAb against CD40, CD48, CD58 and CD80. The reduction was not due to isotype switching to IgA, IgG or IgE. The role of CD40, CD48, CD58 and CD80 was further investigated after depletion of different cell types. Depletion of monocytes and NK cells resulted in no detectable IgM production irrespective of added mAbs. In contrast, IgM production was still present after depletion of T cells and NK cells. Only mAb against CD80 and CD48 significantly reduced IgM production, the reduction of IgM production by anti-CD40 mAb was less than in the presence of T cells. Importantly, anti-CD58 mAb had no effect on IgM production after T cell and NK cell depletion. Taken together, the AM CD40, CD48, CD58, and CD80 are involved in Ig production of unseparated PBMCs. In this model of B cell differentiation only the AM CD58 depend on the presence of T cells while CD48 and CD80 help was found to be T cell independent.

Die Hepatitis C-Virus (HCV)-Infektion ist eine fur die rheumatologische Praxis relevante Infektionserkrankung. Sie ist Ursache der gemischten Kryoglobulinamie. Zusatzlich entwickeln viele HCV-Patienten rheumatische Begleitmanifestationen. Rheumatologisch relevante Manifestationen sind: Sicca-Syndrom, thromboembolische Ereignisse bei Vorliegen von Anti-Kardiolipin-Antikorpern und Fibromyalgiesyndrom. Ebenfalls HCV-assoziiert, ist eine zumeist seropositive polyartikulare Arthritis. Diese erfullt die klinischen Kriterien der chronischen Polyarthritis, nimmt aber einen anderen Verlauf. Remissionen werden haufig beobachtet, erosive Verlaufe sind die Ausnahme. Folgende Autoantikorper sind mit der HCV-Infektion assoziiert: Kryoglobuline, Rheumafaktoren, Anti-Nukleare-Antikorper (ANA), Antikorper gegen glatte Muskulatur (SMA), Anti-Phospholipid-Antikorper, Schilddrusenautoantikorper. Antikorper gegen Ro und La sind bei der HCV-Infektion nicht nachweisbar. Da die Leberentzundung zumeist okkult verlauft, ist auch bei normalen Lebertransaminasen eine HCV-Infektion nicht ausgeschlossen und die Indikation zur HCV-Testung gegeben, wenn bestimmte serologische und klinische Hinweise vorliegen. Bei positivem HCV-Nachweis sollte auf hepatotoxische Medikamente verzichtet und die Moglichkeit einer viruseradizierenden Therapie mit α-Inferferon erwogen werden.

Nichtsteroidale Antirheumatika gehoren zu den am haufigsten verordneten Medikamenten in den westlichen Landern. Die hohe Inzidenz gastrointestinaler Nebenwirkungen, die potentiell lebensgefahrlich sein konnen, erfordern Masnahmen zur Pravention in der Praxis. Vor der Applikation von NSAR ist die Indikation kritisch zu hinterfragen und bei Notwendigkeit des Einsatzes die Identifikation von Risikopatienten praktisch bedeutsam. Patienten mit einem hohen Risiko fur gastrointestinale Nebenwirkungen durch NSAR sollten als Prophylaxe Misoprostol in einer Dosis von 2- bis 3mal 200 μg/Tag erhalten. Misoprostol ist zur Zeit das einzige Medikament mit eindeutig gesicherter Wirksamkeit in der Prophylaxe der NSAR-induzierten Ulcera ventriculi und duodeni sowie deren Komplikationen. NSAR sind Inhibitoren des Schlusselenzyms der Prostaglandinsynthese, der Cyclooxygenase. Neuere Erkenntnisse zeigen, das zwei Isoenzyme der Cyclooxygenase existieren, von denen die Cyclooxygenase 1 fur die Aufrechterhaltung von Organfunktionen von groser Bedeutung ist und die Cyclooxygenase 2 im entzundeten Gewebe exprimiert wird. Mittlerweile wurden gezielt Substanzen entwickelt, die fast ausschlieslich die Aktivitat der Cyclooxygenase 2 inhibieren. Zukunftige Studien mussen zeigen, ob das pathophysiologische Konzept der selektiven Cyclooxygenase-2-Inhibition mit hoher antiinflammatorischer Wirksamkeit ohne gastrointestinale Nebenwirkungen vom Tiermodell auf den Menschen ubertragbar ist.

OBJECTIVE—The purpose of this study was to investigate the therapeutic potential of the anti-CD2 mAb OX34 first with regard to bone protection in established rat adjuvant arthritis (AA) and secondly with regard to prevention of AA induction. METHODS—Established AA was treated with dexamethasone (1 mg/kg body weight) for two days plus OX34 mAb or control mAb over three days (2 mg and then 1 mg) starting at different time points of the disease. For prevention studies animals were injected as above with mAb before induction of AA. Arthritis score (AS), hindpaw thickness, and body weight were blindly measured three times per week. Flow cytometry and hindpaw radiography were performed at the end of the study (day 29). RESULTS—Treatment of early AA with OX34 mAb combined with dexamethasone but not dexamethasone plus control mAb dramatically suppressed established AA as assessed by AS and hind paw thickness (>65% and >80% reduction, respectively; p

SUMMARY Anti-CD2 MoAbs have previously been shown to induce tolerance and to block B cell differentiation, T cell and monocyte activation. Since these immune functions are important in joint inflammation, we asked whether administration of the anti-CD2 MoAb OX34 has a beneficial effect on established rat adjuvant arthritis, a model of human rheumatoid arthritis, and how it affects CD2-bearing leucocyte subsets. Female Lewis rats with established adjuvant arthritis received a total of 5 mg OX34 or isotype-matched control MoAb starting on day 15 after adjuvant injection. Weight and arthritis score (AS) were measured in a blinded fashion. Peripheral blood cells were analysed for numbers of leucocyte subsets at various time points. Animals were killed on day 30 and lymphatic organs were processed for immunohistology. Clinically, OX34 treatment led to increased body weight and reduced AS. Although OX34 binds to CD4+ and CD8+ T cells in a comparable fashion, OX34 treatment reduced CD4+ T cells, but not CD8+ T cells. Among CD4+ T cells CD45RC+ (‘naive’) T cells virtually disappeared; CD45RC− (‘recently activated’) T cells were slightly reduced. A reduction of CD4+ T cells was also found in the lung, liver, bone marrow, spleen and lymph nodes. Down-modulation of the CD2 molecule by OX34, again, affected CD4+ T cells, suggesting a specific signal for CD4+ but not CD8+ T cells. In conclusion, the anti-CD2 MoAb OX34 attenuates established rat adjuvant arthritis. In spite of similar binding to CD4+ and CD8+ T cells, OX34 depletes only CD4+ T cells and down-modulates the CD2 molecule on these cells. These results suggest a therapeutic benefit from CD2-directed therapy for chronic types of arthritis.

Zielsetzung: Ziel der Studie war die Ubersetzung und die Validierung einer deutschen Version des Health Assessment Questionnaire Disability Index (HAQ) und der Vergleich seiner psychometrischen Eigenschaften mit der Version-P und der Version-PR des Funktionsfragebogens Hannover. Methoden: Nach der Ubersetzung wurde die Test-Retest-Reliabilitat bei 32 ambulanten Patienten der Abteilung Rheumatologie der Medizinischen Hochschule Hannover mit Hilfe der Pearson-Korrelation uberpruft. Eine Woche nach der ersten Beantwortung wurde den Patienten der Fragebogen erneut zugesandt. Zur Validierung wurden 110 stationaren Patienten in 3 verschiedenen Kliniken vorgelegt. Alle Patienten erfullten die Kriterien des American College of Rheumatology von 1987 oder die Rom-Kriterien der inaktiven chronischen Polyarthritis (cP). Zur Beurteilung der Kriteriumsvaliditat zogen wir den Keitel-Funktionstest (KFT) und die modifizierte Steinbrocker-Klassifikation (mSK) der funktionellen Behinderung heran. Die interne Konsistenz wurde mit Hilfe des Cronbach Koeffizienten Alpha (CKA) bestimmt. Zur Erfassung der Konstruktvaliditat wurden die HAQ- und FFbH-Scores mit verschiedenen klinischen und laborchemischen Variablen verglichen und zur Aufklarung der Varianz multiple Regressionen berechnet. Ergebnisse: Die Test-Retest-Reliabilitat des HAQ betrug r=0,94. Es zeigte sich ein CKA von 0,91 (HAQ), 0,90 (FFbH-P) und 0,93 (FFbH-PR). Im Vergleich zum KFT ergab sich ein Korrelationskoeffizient von r=–0,73 (HAQ), r=+0,74 (FFbH-P) und r=+0,71 (FFbH-PR) im Vergleich zur mSK ein r=+0,75 (HAQ), r=–0,72 (FFbH-P) und r= –0,70 (FFbH-PR). Der Korrelationskoeffizient des HAQ/FFbH-P betrug r=–0,87 bzw. r=–0,88 beim HAQ/FFbH-PR. Die Korrelationen zwischen den klinischen und laborchemischen Parametern reichten von r=±0,58 (Schmerz/HAQ) bis r=±0,11 (Anzahl der geschwollenen Gelenke/FFbH-PR). In multiplen, ruckwartsgerichteten Regressionsanalysen fanden sich r2-Werte von 0,64 (HAQ), 0,61 (FFbH-P) und 0,59 (FFbH-PR). Der Schmerz erklarte etwa 1/3 und die Bewegungseinschrankung 16–21% der Varianz. Schlusfolgerung: Die hier vorgestellte deutsche Version des HAQ und die zwei verschiedenen Versionen des FFbH erwiesen sich als reliable und valide Instrumente zur Messung der funktionellen Behinderung in einem deutschsprachigen Patientenkollektiv mit cP. Das mit dem HAQ und den beiden Versionen des FFbH gemessene Konstrukt zeigte eine hohe Ubereinstimmung.

Previous studies have suggested that monocytes may play a role in the dissemination ofChlamydia trachomatis, and in establishment of persistent infection with this bacterium. Infection of cultured human peripheral blood monocytes withC. trachomatisserovar K produced persistent, non-productive infection. Transmission electron microscopy of such infected cultures revealed single or multipleChlamydiain monocyte inclusions over a culture period of 10 days. Those inclusions were aberrant, and normal reticulate bodies within the inclusions were not observed. Immunoelectron microscopy showed the chlamydial major outer membrane protein and lipopolysaccharide to be associated with the bacterial plasma membrane. Lipopolysaccharide was also identified in the monocyte cytoplasm. Molecular analyses of primary chlamydial rRNA transcripts demonstrated that the organism is viable and metabolically active within monocyte inclusions. However, attempts to overcome chlamydial growth arrest by incubation ofChlamydia-infected monocytes with tryptophan, and antibodies against alpha interferon, gamma interferon, or tumor necrosis factor, were all ineffective, suggesting that known mechanisms of growth inhibition do not hold in human monocytes. These observations indicate that infection of human peripheral blood monocytes withC. trachomatismay be involved in the genesis/maintenance of extra-urogenital inflammation, since non-culturable, metabolically active bacteria persist in those cells.

The association between rheumatoid arthritis (RA) and the HLA-DR4 is known since 1978. However, the significance of the HLA-DR4 for the pathogenesis of RA has not been uniformly accepted. Further studies revealed that also other HLA-DR alleles were associated with RA. With the application of molecular biology techniques, it could be demonstrated that the serologically typed HLA-DR4 allele consists of different alleles. Only some of them predispose for RA. These predisposing alleles share a conserved aminoacid sequence of the 3rd hypervariable region of the HLA-DRB1 gene at positions 70-74 and 86. This RA-associated sequence is called "Shaped Epitope" (SE). This SE is conserved not only between associated HLA-DR4 alleles, but between all HLA-DR-alleles which predispose for RA. Patients homozygous for the SE appear to have a more severe disease course than heterozygous patients. These data are based mainly on the results of cross-sectional studies. The value of HLA-DR alleles as prognostic markers for RA has to be investigated further in prospective studies. Seit Ende der siebziger Jahre wird ein Zusammenhang zwischen dem HLA-DR4 und der chronischen Polyarthritis (cP) diskutiert. Der Beitrag des HLA-DR4 Gens zur Pathogenese wurde zunachst unterschiedlich bewertet. Mit Hilfe der Molekularbiologie konnte gezeigt werden, das das serologisch definierte HLA-DR 4 Allel aus unterschiedlichen Subtypen besteht. Nur diejenigen Subtypen pradisponieren einen ungunstigen Verlauf der cP, die in der dritten hypervariablen Region der HLA-DRB1 Kette an Positionen 70-74 und 86 eine konservierte Aminosauresequenz aufweisen. Diese cP-assoziierte Sequenz wird in der angloamerikanischen Literatur als "Shared Epitope" (SE) bezeichnet. Alle weiteren HLA-DR Allele, die mit der cP assoziiert sind, z.B. HLA-DR1 Allele, besitzen ebenfalls diese Aminosaurensequenz. Trager des SE auf beiden Chromosomen weisen im Vergleich zu Heterozygoten einen ungunstigeren Krankheitsverlauf auf. Diese Ergebnisse wurden vorwiegend im Rahmen von Querschnittsstudien erarbeitet. Die Wertigkeit als Prognosemarker bei der cP mus noch in prospektiven Studien gezeigt werden.

Objectives. Several sets of criteria for the diagnosis of axial SpA (including non-radiographic axial spondyloarthritis) have been proposed in the literature in which scores were attributed to relevant findings and the diagnosis requests a minimal sum of these scores. To quantitatively estimate the probability of axial SpA, multiplying the likelihood ratios of all relevant findings was proposed by Rudwaleit et al. in 2004. The objective of our proposal is to combine the advantages of both, i.e. to estimate the probability by summing up scores instead of multiplying likelihood ratios. Methods. An easy way to estimate the probability of axial spondyloarthritis is to use the logarithms of the likelihood ratios as scores attributed to relevant findings and to use the sum of these scores for the probability estimation. Results. A list of whole-numbered scores for relevant findings is presented, and also threshold sum values necessary for a definite and for a probable diagnosis of axial SpA as well as a threshold below which the diagnosis of axial spondyloarthritis can be excluded. In a diagram, the probability of axial spondyloarthritis is given for sum values between these thresholds. Conclusion. By the method proposed, the advantages of both, the easy summing up of scores and the quantitative calculation of the diagnosis probability, are combined. Our method also makes it easier to estimate which additional tests are necessary to come to a definite diagnosis.

Recently, we demonstrated that smoking status itself is an independent predictor of radiographic spinal progression over 2 years in patients with axial SpA (axSpA).1 Here we report in more detail the relationship between tobacco smoking and development of structural damage in the spine in patients with axSpA with a focus on a dose-dependent association and a relationship between smoking and activity of systemic inflammation. In total, 210 patients with axSpA (115 with ankylosing spondylitis (AS) and 95 with non-radiographic axSpA (nr-axSpA)) from the GErman SPondyloarthritis Inception Cohort (GESPIC)1 ,2 were included. Detailed description of the patients and radiographs scoring has been reported elsewhere.1 In the current analysis, we used an extended syndesmophytes count, which included lateral views of the cervical and lumbar spine, and also antero-posterior views of the lumbar spine. Significant radiographic spinal progression was defined as (1) worsening of the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) by ≥2 units after 2 years and (2) development of a new syndesmophyte or progression of existing syndesmophytes (formation of a bridging syndesmophyte from two single syndesmophytes) after 2 years. Smoking status and smoking intensity (non-smoker, 10 cigarettes a day and less, 11–20 cigarettes, and more than 20 cigarettes …

Objective. Allelic TAP polymorphism has been linked to susceptibility to Reiter's syndrome and was suggested to influence disease phenotype in HLA-B27 positive patients with ankylosing spondylitis. In the present study, we examined whether the human TAP alleles functionally differ in their translocation specificity for HLA-B27-binding nonamers. Methods. TAP translocation of a panel of HLA-B27-binding peptides was measured with a labeled reporter peptide containing an N-linked glycosylation acceptor site in streptolysin O-permeabilized cells with different TAP alleles. Results. The different human TAP alleles tested did not measurably differ in their peptide specificity. Conclusion. The polymorphism of human TAP does not affect the translocated repertoire of HLA-B27 ligands and is therefore unlikely to play a decisive role in the development of HLA-B27-associated disease.

SUMMARY Reduced levels of a soluble form of the adhesion receptor and CD2 ligand CD58 (sCD58) were previously described in RA patients. In order to understand the biological significance of this finding we biochemically characterized sCD58 in RA and asked how well sCD58 binds to CD2. sCD58 concentrations were measured in serum and synovial fluid (SF) samples of RA patients by two ELISAs, one detecting domain 1 of CD58 (CD58-D1), and the other one the complete molecule (CD58-D1 + D2). Small amounts of split sCD58-D1 were found in most RA sera, but not SF. In addition, split sCD58-D2 was detected in SF by affinity chromatography, SDS–PAGE, and Western blotting. Gel filtration gave similar peaks at 95–125 kD for RA sera, SF, and normal serum. Binding of SF-sCD58 to the CD2+ Jurkat variant JBB1 or recombinant CD2 was stronger than urinary sCD58 and reached binding of oligomeric recombinant CD58 at low concentrations. In conclusion, sCD58-split products were found in RA sera and SF. At concentrations as they occur in vivo, SF-sCD58 binds to CD2 much more strongly than urinary sCD58. It is conceivable that locally released sCD58 blocks the CD2/CD58 interaction under physiological conditions. Insufficient release of sCD58, e.g. in synovitis, might result in T cell accumulation and perpetuation of inflammation.

Ro 15-8081, a substituted cyclohexanol hydrochloride, inhibits the re-uptake of norepinephrine and of serotonin. Its antinociceptive properties have been demonstrated in animals and then confirmed in humans after single-dose administration. The objective was to determine the analgesic efficacy and the safety of Ro 15-8081 in osteoarthritis of the hip and knee (femoro-tibial location) after multiple-dose application. The design for studying dosage employed 5 parallel groups in an international multicenter, double-blind, randomized trial having a duration of 2 weeks. Drugs studied were: 20 mg Ro 15-8081 (divided into 2 doses), 50 mg Ro 15-8081 (divided into 2 doses), 100 mg Ro 15-8081 (divided into 2 doses), placebo twice daily or 20 mg/day piroxicam (piroxicam in the morning and placebo in the evening). Piroxicam was used as a reference drug in order to validate clinical testing. Assessment criteria were pain (100-mm VAS) and function (Lequesne's index). A responder (main assessment criterion) was defined as a patient exhibiting a reduction of at least 30% of pain (VAS) during the study (intention-to-treat analysis). A total of 522 patients were enrolled in the study. A clear beneficial effect of piroxicam was observed when compared with placebo (70% and 48% of responders in piroxicam and placebo groups respectively; P < 0.0001). Multigroup comparison showed a statistically significant difference between Ro 15-8081 groups and the placebo group regarding mean change in pain between D1 and Dend and the rate of VAS responders. Comparison (Dunnett's t or χ2 tests) between each individual Ro 15-8081 and the placebo group reached statistical significance for the 100 mg Ro 15-8081 group (mean change in pain between D1 and Dend: P = 0.05; percentage of responders: P = 0.0008) but no statistically significant difference for the other dosages of Ro 15-8081. Fifty-three patients withdrew from the study because of adverse events and/or inefficacy, mainly in 50 and 100 mg Ro 15-8081 groups and in a dose-related manner. The adverse events which appeared to be drug related were mainly dryness of the mouth, insomnia, headache, constipation, nausea, dizziness, nervousness, palpitation. This study suggests that 100 mg Ro 15-8081 per day divided into 2 doses has (1) an analgesic effect in hip or knee osteoarthritis and (2) poor acceptability in the conditions of the study regimen application.

Routine microbiological diagnosis of Chlamydia-induced reactive arthritis is based mainly on the detection of Chlamydia trachomatis with urogenital swabs or in urine. Because chlamydial antigen, rRNA, and DNA are present in low quantities in the inflamed joint, highly sensitive assays are needed to detect C. trachomatis not only at the primary site of infection but also in peripheral blood and peripheral blood leukocytes, which are suspected carriers for dissemination, and in synovial fluid. To evaluate possible tools for this purpose, the sensitivities of PCR, MicroTrak, Chlamydia EIA, IDEIA, and PACE 2 for the detection of defined numbers of purified C. trachomatis elementary bodies (EB) in urine, peripheral blood, peripheral blood leukocytes, and synovial fluid were determined. In urine, PCR detected 2, MicroTrak and ChlamydiaEIA detected 2 x 10(3), and PACE 2 and IDEIA detected 2 x 10(4) EB per ml. In peripheral blood, only PCR and MicroTrak detected C. trachomatis, with detection limits of 100 and 2 x 10(7) EB per ml, respectively. For peripheral blood leukocytes, the detection limits were 2 EB per ml for PCR and 2 x 10(4) EB per ml for MicroTrak, ChlamydiaEIA, IDEIA, and PACE 2. In synovial fluid, PCR detected 200, MicroTrak and IDEIA detected 2 x 10(5), and PACE 2 detected 10(6) EB per ml. ChlamydiaEIA was unable to detect 2 x 10(6) EB per ml in synovial fluid. In summary, PCR was found to be the most sensitive method. The sensitivities of the other methods tested were at least 1,000 times lower than that of PCR. PCR should therefore be considered a most promising tool for routine diagnosis of Chlamydia-induced arthritis.

Objective. To assess the efficacy and tolerability of sulfasalazine (SSZ) in the treatment of spondyl-arthropathy. Methods. We conducted a 6-month randomized, placebo-controlled, double-blind, multicenter study of patients with spondylarthropathy whose disease had remained active despite treatment with nonsteroidal antiinflammatory drugs. Patients were treated with SSZ (3 gm/day) or placebo. The primary efficacy variables were the physician's and patient's overall assessments, pain, and morning stiffness. End points were analyzed in the intent-to-treat and completer patient populations; the time course of effect was analyzed in the completer patient population. Results. Of the 351 patients enrolled, 263 (75%) completed the 6-month treatment period. The withdrawal rates were 35 (20%) and 53 (30%) in the placebo and SSZ groups, respectively. In the intent-to-treat analysis of end point efficacy, the between-treatment difference reached statistical significance only for 1 of the 4 primary outcome variables, the patient's overall assessment of disease activity, for which 60% of the patients taking SSZ improved by at least 1 point on a 5-point scale, in contrast to 44% of the patients taking placebo. Laboratory markers of inflammation also showed statistically significant change in favor of SSZ. In subgroup analysis, the most impressive effects were seen in patients with psoriatic arthritis, both for the 4 primary efficacy variables and for secondary efficacy variables such as the number of inflamed joints. Adverse events were more frequent in the SSZ group than the placebo group, but all were transient or reversible after cessation of treatment. Conclusion. The results of this study show that SSZ had greater efficacy than placebo in the treatment of active spondylarthropathy, notably in patients with psoriatic arthritis.

We investigated the usability of anisotropic materials as inserts in aluminum-matrix-composite baseplates for typical high performance power semiconductor modules using finite-element simulations and transient plane source measurements. For simulations, several physical modules can be used, which are suitable for different thermal boundary conditions. By comparing different modules and options of heat transfer we found non-isothermal simulations to be closest to reality for temperature distribution at the surface of the heat sink. We optimized the geometry of the graphite inserts for best heat dissipation and based on these results evaluated the thermal resistance of a typical power module using calculation time optimized steady-state simulations. Here we investigated the influence of thermal contact conductance (TCC) between metal matrix and inserts on the heat dissipation. We found improved heat dissipation compared to the plain metal baseplate for a TCC of 200 kW/m2/K and above.To verify the simulations we evaluated cast composite baseplates with two different insert geometries and measured their averaged lateral thermal conductivity using a transient plane source (HotDisk) technique at room temperature. For the composite baseplate we achieved local improvements in heat dissipation compared to the plain metal baseplate.

Das von der EU geförderte Forschung- und Entwicklungsprojekt Thermaco zielt auf die Entwicklung von Materialen und Fertigungstechnologien für extrem effiziente Lösungen zur Wärmeabfuhr ab. Im Mittelpunkt der Untersuchungen steht die Kombination von Aluminium mit Kohlenstoff-basierten Einsätzen, die die Wärmeleitfähigkeit signifikant erhöhen. Das Ziel ist die definierte Wärmeabfuhr für Anwendungen in kritischen Bereichen, wie in der Mikroelektronik, der Elektromobilität, der (erneuerbaren) Energieerzeugung sowie bei Höchstleistungs-Verbrennungsmotoren.

The French artist Niki de Saint Phalle (1930-2002) is one of the most famous female painter and sculptor of the 20th century. Her eventful live was full of emotional and physical burdens such as abuse by the father as a adolescent, early separation from family, nervous collapse, turbulent relationship with the artist Jean Tinguely, and last not least serious diseases. The psychological trauma of sexual abuse together with a "nervous breakdown" years later was the start of a life as an artist and is also a key to her art of the early years. She was affected from rheumatoid arthritis (RA) and was treated over 20 years with prednisolone and antimalarials leading to a good functional outcome and limited erosions of the wrist joint. Additionally, she had lifelong pulmonary disorders finally leading to death, which she attributed to polyester, the material used for her sculptures. An analysis of medical documents collected by her and provided by treating physicians gives another surprising explanation: selective IgA deficiency with multiple recurrent respiratory infections, asthma, milk intolerance, autoimmune thyroiditis, and RA compatible with hypogammaglobulinemia. Very unique in case of Niki de Saint Phalle is that IgA deficiency was transient. Nevertheless, it may be possible that the occupational exposure with art materials (polystyrene, polyester) has contributed in part or temporarily to her health problems. Altogether, her enormous artistic productivity represents an outstanding example of creative coping with RA and other lifelong health problems.

The treatment of active rheumatoid arthritis (RA) usually requires different therapeutic options used sequentially in case of an insufficient response (IR) to previous agents. Since there is a lack of clinical trials comparing biologic treatment sequences, simulation models might add to the understanding of optimal treatment sequences and their cost-effectiveness. The objective of this study was to assess the cost-effectiveness of different biologic treatment strategies in patients with an IR to anti-TNF agents, based on levels of disease activity from the German public payer's perspective.A cost-effectiveness sequential model was developed in accordance with local RA treatment strategies, using DAS28 scores as dichotomous effectiveness endpoints: achieving remission/no remission (RS/no RS) or a state of low disease activity (LDAS/no LDAS). Costs were estimated using resource utilisation data obtained from a large observational German cohort. Advanced simulations were conducted to assess the cost-effectiveness over 2 years of four sequential biologic strategies composed of up to 3 biologic agents, namely anti-TNF agents, abatacept or rituximab, in patients with moderate-to-severe active RA and an IR to at least one anti-TNF agent.Over two years, the biological sequence including abatacept after an IR to one anti-TNF agent appeared the most effective and cost-effective versus (vs.) use after two anti-TNF agents (€633 vs. €1,067/day in LDAS and €1,222 vs. €3,592/day in remission), and vs a similar sequence using rituximab (€633 vs. €728/day in LDAS and €1,222 vs. €1,812/day in remission). The sequence using a 3rd anti-TNF agent was less effective and cost-effective than the same sequence using abatacept (€2,000 vs. €1,067/day in LDAS and €6,623 vs. €3,592/day in remission). All differences were statistically significant (p0.01).The results suggest that in patients with an IR to at least one anti-TNF agent, biologic sequences including abatacept appear more efficacious and cost-effective than similar sequences including rituximab or only cycled anti-TNF agents.

To investigate the influence of non-steroidal anti-inflammatory drugs (NSAIDs) intake on radiographic spinal progression over 2 years in patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (SpA).164 patients with axial SpA (88 with AS and 76 with non-radiographic axial SpA) were selected for this analysis based on availability of spinal radiographs at baseline and after 2 years of follow-up and the data on NSAIDs intake. Spinal radiographs were scored by two trained readers in a concealed randomly selected order according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) system. An index of the NSAID intake counting both dose and duration of drug intake was calculated.High NSAIDs intake (NSAID index≥50) in AS was associated with lower likelihood of significant radiographic progression defined as an mSASSS worsening by ≥2 units: OR=0.15, 95% CI 0.02 to 0.96, p=0.045 (adjusted for baseline structural damage, elevated C reactive protein (CRP) and smoking status) in comparison with patients with low NSAIDs intake (NSAID index50). This effect was most pronounced in patients with baseline syndesmophytes plus elevated CRP: mean mSASSS progression was 4.36±4.53 in patients with low NSAIDs intake versus 0.14±1.80 with high intake, p=0.02. In non-radiographic axial SpA, no significant differences regarding radiographic progression between patients with high and low NSAIDs intake were found.A high NSAIDs intake over 2 years is associated with retarded radiographic spinal progression in AS. In non-radiographic axial SpA this effect is less evident, probably due to a low grade of new bone formation in the spine at this stage.

We describe a 35-year old patient with nodular fasciitis, erythema migrans, and gonarthritis four months after a bite of a Borrelia afzelii infected tick. The Borrelia afzelii infection was identified by a polymerase chain reaction and direct sequencing of the amplification product. Borrelia-specific DNA was also detectable in nodular fasciitis tissue. We therefore conclude that Borrelia afzelii can be a causative agent of nodular fasciitis and Lyme arthritis in a highly endemic region of Northern Germany.

Early rheumatoid arthritis (RA) and very early RA are major targets of research and clinical practice. Remission has become a realistic goal in the management of RA, particularly in early disease. The 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) RA classification criteria, the EULAR treatment recommendations for RA, and the EULAR recommendations for the management of early arthritis focus on early disease and translate the knowledge related to early RA into classification and management. Nevertheless, there is a need for further improvement and progress. Results from 6 recent studies are summarized, evaluating the performance of the 2010 ACR/EULAR RA classification criteria. The data show a significant risk of misclassification, and highlight that overdiagnosis and underdiagnosis may become important issues if the criteria recommend synthetic and biological disease-modifying antirheumatic drugs. Therefore, some considerations are presented on how the current problems and limitations could be overcome in clinical practice and future research. A consensus is needed to better define the early phase of RA and differentiate from other early arthritis. The possible effect of misclassification on spontaneous and drug-induced remission of early and very early RA awaits further elucidation. Such research will eventually lead to more reliable diagnostic and classification criteria for new-onset RA.

Objective.In a pilot study, a distinct T cell cytokine pattern associated with HLA-B27 status and a tumor necrosis factor-α (TNF-α) promoter gene polymorphism was found at –308 (TNF–308). The objective of our study was to assess these associations in a different cohort of patients with ankylosing spondylitis (AS) and to evaluate any effect on clinical measurements.Methods.Peripheral T cell cytokine production of patients with AS (n = 121) from the German Spondyloarthritis Inception Cohort was assessed by flow cytometry and correlated with HLA-B27, TNF–238, and TNF–308, and with clinical measurements.Results.In HLA-B27-positive, anti-TNF-naive patients with AS, the percentages of TNF-α-producing (5.02%) and interleukin 10-producing (0.31%) CD8+ cells were significantly lower in comparison to HLA-B27-negative patients (9.52%, p = 0.048, and 0.46%, p = 0.037, respectively). A nonsignificant trend was found for a lower production of TNF-α by CD4+ and interferon-γ by both CD4+ and CD8+ T cells, as compared to HLA-B27-negative patients with AS (p > 0.05 for all comparisons). The A allele at TNF–308 was associated with a lower percentage of TNF-α-producing CD4+ T cells. No significant correlations were found between clinical or radiological measurements and cytokine production or with TNF-α promoter gene polymorphisms.Conclusion.Modulation of T cell cytokines by HLA-B27 might play a role in AS pathogenesis in B27-positive individuals. No conclusive data were obtained for the TNF–308 polymorphism on cytokine production, and no effect of cytokines or genetic polymorphisms on clinical manifestations was observed.

Objective To assess the progression of radiographic sacroiliitis in a cohort of patients with early axial spondyloarthritis over a period of 2 years and to explore predictors of progression. Methods 210 patients with axial spondyloarthritis from the German Spondyloarthritis Inception Cohort have been selected for this analysis based on availability of radiographs at baseline and after 2 years of follow-up. Radiographs were centrally digitised and the sacroiliac joints were scored independently according to the grading system of the modified New York criteria for ankylosing spondylitis (AS) by two trained readers. The readers scored both time points simultaneously but were blinded for the time point and for all clinical data. Results 115 patients (54.8%) fulfilled the modified New York criteria for AS in their radiographic part in the opinion of both readers at baseline, while 95 patients (45.2%) were classified as non-radiographic axial spondyloarthritis. More patients with non-radiographic spondyloarthritis (10.5%) compared with AS (4.4%) showed an estimated ‘true’ progression by at least one grade according to both readers, although the difference between the two groups was statistically non-significant. The rate of progression from non-radiographic axial spondyloarthritis to AS was 11.6% over 2 years. An elevated level of C-reactive protein (CRP) at baseline was a strong positive predictor of radiographic sacroiliitis progression in non-radiographic axial spondyloarthritis and AS (OR 3.65 and 5.08, respectively, p Conclusion Progression of radiographic sacroiliitis by at least one grade after 2 years occurs only in a small percentage of patients with early axial spondyloarthritis. An elevated level of CRP was found to be a strong positive predictor of sacroiliitis progression.

Purpose of review The history of ankylosing spondylitis, the main representative of the spondyloarthritides, is dating back to several thousand years BC and recently proven for medieval skeleton by HLA-B27 typing with modern molecular techniques. In modern time, the history of spondyloarthritis (SpA) is characterized by fluctuation between lumping and splitting. Actually, the recent advent of new classification criteria demands to discuss the consequences and clinical implications in the historical context of the development of the concept of SpA including the controversy of lumping and splitting. Recent findings The new Assessment of SpondyloArthritis International Society classification criteria for axial and peripheral SpA are primarily developed to provide support for clinical trials with biologicals and other treatment modalities, which intend to cover the whole spectrum, especially early clinical manifestations of spondyloarthritides. New insights into genetics and the evolving etiological role of Chlamydia in SpA including the most recent finding of the effective combination antibiotic therapy are major advances in the evolving history of SpA. Summary The concept of SpA is well accepted for the classification, diagnosis, and therapeutic management of a high proportion of individuals with inflammatory rheumatic conditions. For further advances research technologies are now available to enlarge the current body of clinical, immunologic, and genetic studies using pivotal microbiologic research and new antimicrobial therapeutic strategies.

The surface integrity of components considerably influences the reliability of technical systems. According to the application of the components, their surfaces have to meet different demands. Cutting processes with geometrically defined cutting edge are often used as final machining processes. They offer the opportunity to influence the surface integrity by means of the process kinematics, process parameters and tool geometry. In the case of realising a predefined surface integrity, for example the generation of microstructures, these machining processes reach their limits very fast. For this reason, the influence of ultrasonic vibration assistance in cutting is investigated with focus on achieved surface integrity. Different vibration directions of the tool are examined. This paper investigates the effect of ultrasonic vibration assistance on the surface integrity, obtained in turning processes. Several possibilities for generating predefined surface microstructures are identified. In turning with ultrasonic vibration assistance in the cutting direction, the mean cutting force is markedly reduced in comparison to conventional machining. The examinations show that turning with ultrasonic vibration assistance enables a specific setting of the surface integrity within a wide range. It is expected that the results can be applied to other, also difficult to machine materials. Der Oberflachenzustand von Bauteilen beeinflusst die Funktionstauglichkeit technischer Systeme masgeblich. In Abhangigkeit von der konkreten Anwendung der Komponenten werden unterschiedliche Anforderungen an die Oberflachen gestellt. Zu den fur die Endbearbeitung am haufigsten eingesetzten Verfahren gehoren die spanenden Prozesse mit geometrisch bestimmter Schneide. Diese bieten die Moglichkeit, den Oberflachenzustand durch die Verfahrenskinematik, die Bearbeitungsparameter sowie die Werkzeuggeometrie zu beeinflussen. Bei der Erzielung definierter Oberflacheneigenschaften, zum Beispiel der Erzeugung von Mikrostrukturen, stosen diese Methoden jedoch schnell an ihre Verfahrensgrenzen. Aus diesem Grund wird der Einfluss von dem Werkzeug uberlagerten Ultraschallschwingungen auf den Oberflachenzustand untersucht. Es werden unterschiedliche Schwingungsrichtungen des Werkzeugs am Beispiel der Langsdrehbearbeitung betrachtet und verschiedene Moglichkeiten zur Erzeugung definierter Oberflachenstrukturen dargestellt. Diese Untersuchungen zeigen, dass sich durch eine Uberlagerung von Ultraschallschwingungen in Schnittrichtung die mittleren Schnittkrafte im Vergleich zur konventionellen Bearbeitung erheblich reduzieren lassen. Des Weiteren wird durch eine ultraschallunterstutzte Drehbearbeitung eine gezielte Beeinflussung der Oberflachenfeingestalt in weiten Grenzen moglich. Es ist zu erwarten, dass sich diese Ergebnisse auf weitere, auch schwer zerspanbare Werkstoffe, ubertragen lassen.

EDM is a known process for machining of hard and brittle materials. Due to its noncontact and nearly forceless behaviour, it has been introduced into micro manufacturing and through constant development it is now an important means for producing high‐precision micro geometries. One restriction of EDM is its limitation to electrically conducting materials.Today many applications, especially in the biomedical field, make use of the benefits of ceramic materials, such as high strength, very low wear and biocompatibility. Common ceramic materials such as Zirconium dioxide are, due to their hardness in the sintered state, difficult to machine with conventional cutting techniques. A demand for the introduction of EDM to these materials could so far not be satisfied because of their nonconductive nature.At the Chemnitz University of Technology and the Fraunhofer IWU, investigations in the applicability of micro‐EDM for the machining of nonconductive ceramics are being conducted. Tests are undertaken using micro‐...

Micro Electro Discharge Machining is a well known process for machining microstructures with highest precision in hard and brittle or tough materials. The deeper the structures and therefore higher the aspect ratio, the more difficult it is to remove the ablated particles from the discharge zone and keep the process in stable condition. Flushing can be aided by vibration of either tool or workpiece. Thus, applying ultrasonic vibration to micro EDM has proven to enhance the process significantly. The vibration is most efficiently induced via the tool or workpiece directly to the discharge zone. However, to achieve an ultrasonic vibration of the tool or workpiece, a complex vibration system that operates in resonant mode is needed. Any crucial change of the vibrating parts results in a demanding and therefore expensive adjustment of the vibrating system. With this setup, the application of ultrasonic vibration is only profitable for large scale serial production. In this work a different approach of ultrasonic superposition to the EDM is proposed. A highly focused ultrasonic vibration is induced into the dielectric in a way to directly influence the discharge zone. This indirect ultrasonic superposition can be easily applied since it is independent of the tool or workpiece geometry. Experiments are carried out to examine the effects of the indirect ultrasonic superposition on the EDM process. First results show the possibility of enhancing micro-EDM by this approach.Copyright © 2011 by ASME

OBJECTIVE Chlamydia trachomatis and Borrelia burgdorferi infections are frequently the cause of unexplained oligoarthritis, as shown by identification of bacteria specific DNA in joint material from patients with reactive arthritis, Lyme arthritis, and undifferentiated oligoarthritis. The aim of this study was to determine whether the two organisms occur simultaneously in joint material from patients with arthritis. METHODS Seventy six patients with unexplained arthritis were prospectively studied. Synovial fluid was obtained from all patients and examined for DNA from C trachomatis and B burgdorferi using specific polymerase chain reaction (PCR) protocols. Data concerning prior genitourinary infection or a history of tick bite were recorded and serum antibodies to C trachomatis and B burgdorferi were determined. RESULTS Six patients (8%) had DNA from both C trachomatis and B burgdorferi in the same synovial fluid specimen (mean leucocyte count 11.925/mm 3 , 65% granulocytes). These patients (four men, two women; mean age 33.7 years) all had oligoarthritis of the knee, ankle, or both (mean disease duration 11.3 months). From the history and serological examination, four patients had some evidence of actual or previous infection with one or other of the bacteria, while the other two patients had a positive serological test for Chlamydia only. CONCLUSIONS DNA from two different microorganisms which are known to be triggering agents for arthritis may be present simultaneously in joint material from patients with unexplained oligoarthritis. This finding raises the question as to whether, in such cases, one or both bacteria contribute to the pathogenesis of the disease or whether they are only innocent bystanders.

OBJECTIVE Comparison of overall RA-related costs and of relative contribution of single-cost domains before and after the introduction of TNF-blocking agents in Germany. METHODS Two cohorts of RA outpatients (ACR '87 criteria) with long-standing disease are assessed in terms of disease-related costs and cost composition (n = 106 patients in 1997-98 and n = 180 patients in 2002 with similar patient characteristics). Full-cost analyses are performed including direct disease-related costs (medical and non-medical) and productivity costs as collected by patient questionnaires. Absolute costs (€/patient/year) are compared and the impact of single-cost domains on overall costing in RA is estimated (relative proportions of cost components within samples). RESULTS Overall costs are comparable (1997-98: €4280; 2002: €3830; not significant). Differences can be observed in medication (1997-98: €550; 2002: €1580; P