Patella Infera in an HIV Positive Patient Following Total Knee Arthroplasty

A lowering of the patella after total knee arthroplasty is accompanied by pain and a restriction of the range of motion. With its etiology being unclear at present, a multifactorial genesis is under discussion. For the first time, we present a case report describing an HIV infection as a possible cause of patella infera

Chondrogenic differentiation of human subchondral progenitor cells is affected by synovial fluid from donors with osteoarthritis or rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>Microfracture is a first-line treatment option for cartilage repair. In microfracture, subchondral mesenchymal cortico-spongious progenitor cells (CSP) enter the defect and form cartilage repair tissue. The aim of our study was to investigate the effects of joint disease conditions on the <it>in vitro </it>chondrogenesis of human CSP.</p> <p>Methods</p> <p>CSP were harvested from the subchondral bone marrow. CSP characterization was performed by analysis of cell surface antigen pattern and by assessing the chondrogenic, osteogenic and adipogenic differentiation potential, histologically. To assess the effect of synovial fluid (SF) on chondrogenesis of CSP, micro-masses were stimulated with SF from healthy (ND), osteoarthritis (OA) and rheumatoid arthritis donors (RA) without transforming growth factor beta 3.</p> <p>Results</p> <p>CSP showed the typical cell surface antigen pattern known from mesenchymal stem cells and were capable of osteogenic, adipogenic and chondrogenic differentiation. In micro-masses stimulated with SF, histological staining as well as gene expression analysis of typical chondrogenic marker genes showed that SF from ND and OA induced the chondrogenic marker genes aggrecan, types II and IX collagen, cartilage oligomeric matrix protein (COMP) and link protein, compared to controls not treated with SF. In contrast, the supplementation with SF from RA donors decreased the expression of aggrecan, type II collagen, COMP and link protein, compared to CSP treated with SF from ND or OA.</p> <p>Conclusion</p> <p>These results suggest that in RA, SF may impair cartilage repair by subchondral mesenchymal progenitor cells in microfracture, while in OA, SF may has no negative, but a delaying effect on the cartilage matrix formation.</p

Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration

Rheumatoid arthritis (RA) leads to progressive destruction of articular cartilage. This study aimed to disclose major mechanisms of antirheumatic drug action on human chondrocytes and to reveal marker and pharmacological target genes that are involved in cartilage dysfunction and regeneration

Pathological Processing Techniques and Final Diagnosis of Breast Cancer Sentinel Lymph Nodes

Background: Recommendations for intraoperative and postoperative breast sentinel lymph node (SLN) processing differ widely. Micrometastases and isolated tumor cells (ITC) have recently been proposed as prognostically and therapeutically relevant. We compared 3 SLN protocols with regard to intraoperative and postoperative diagnosis. Materials and Methods: SLN in cohort I (270 patients) were intraoperatively assessed by stereomicroscopy. Intraoperative frozen section (IFS) was used only in stereomicroscopically suspicious SLN. In cohort II (197 patients), all SLN were examined with only 1 IFS. Final SLN workup in cohorts I and II consisted of complete step sectioning with immunohistochemistry. In cohort III (268 patients) 2 or more IFS were performed followed by 3 step sections and immunohistochemistry. Results: pN1 stages were significantly higher in cohorts I and II (33.3% and 34.0% respectively) than in cohort III (24.6%). Intraoperative false negativity for the detection of metastases (pN1) ranged from 54.4% (cohort I) and 35.8% (cohort II) to 21.2% (cohort III). In contrast, ITC were detected significantly more frequently in cohort I (9.3%) and cohort II (14.7%) than in cohort III (1.9%). Conclusions: Higher rates of SLN metastases and ITC in cohort I/II compared to cohort III suggest that IFS may result in tissue loss thus increasing the risk of missing metastases. Sparse IFS but complete postoperative SLN workup with step sectioning and immunohistochemistry provides more accurate information regarding minimal disease in SLN, but often results in delayed axillary lymph node dissection. This is important for preoperative patient information and recommendations in SLN processing protocol

B Cell Depletion Reduces the Number of Autoreactive T Helper Cells and Prevents Glucose-6-Phosphate Isomerase-Induced Arthritis

The therapeutic benefit of B cell depletion in patients with rheumatoid arthritis has provided proof of concept that B cells are relevant for the pathogenesis of arthritis. It remains unknown which B cell effector functions contribute to the induction or chronification of arthritis. We studied the clinical and immunological effects of B cell depletion in glucose-6-phosphate isomerase-induced arthritis. We targeted CD22 to deplete B cells. Mice were depleted of B cells before or after immunization with glucose-6-phosphate isomerase (G6PI). The clinical and histological effects were studied. G6PI-specific antibody responses were measured by ELISA. G6PI-specific T helper (Th) cell responses were assayed by polychromatic flow cytometry. B cell depletion prior to G6PI-immunization prevented arthritis. B cell depletion after immunization ameliorated arthritis, whereas B cell depletion in arthritic mice was ineffective. Transfer of antibodies from arthritic mice into B cell depleted recipients did not reconstitute arthritis. B cell depleted mice harbored much fewer G6PI-specific Th cells than control animals. B cell depletion prevents but does not cure G6PI-induced arthritis. Arthritis prevention upon B cell depletion is associated with a drastic reduction in the number of G6PI-specific effector Th cells

Biomolecular and histopathologic classification and typification of chronic joint diseases

Um die Aussagekraft histopathologischer Untersuchungen in der Diagnostik von Gelenkerkrankungen zu erhöhen, wurden zwei neue Evaluierungssysteme etabliert: 1. Der Synovialitis-Score und 2. die Konsensus-Klassifikation der periprothetischen Membran. Mit dem Synovialitis-Score wurde ein Graduierungssystem definiert, welches anhand der semiquantitativen Beurteilung der drei Kriterien a) Deckzellschichtverbreiterung, b) Aktivierung des synovialen Stromas und c) Entzündungszellinfiltrat eine Beurteilung chronischer Synovialitiden jedweder Genese ermöglicht. Es zeigt eine gute Reproduzierbarkeit zwischen unabhängigen Untersuchern und eine gute Korrelation mit klinischen Diagnosen, wobei niedriggradige Befunde für das Vorliegen einer degenerativen, und hochgradige Befunde für eine rheumatische Gelenkerkrankung sprechen. Für die Diagnostik periprothetischer Membranen gelockerter Endoprothesen wurde ein histopathologisches Klassifikationssystem erstellt, welches vier Typen unterscheidet: Abriebinduzierter Typ (I), infektiöser Typ (II), Mischtyp (III) und Indifferenzytp (IV). Diese Typisierung korreliert mit mikrobiologischen Untersuchungsbefunden. Die histopathologische Untersuchung wird durch die Anwendung dieser Klassifikation die Diagnostik von Endoprothesenlockerungen ergänzen. Als wesentliches Kriterium für die Diagnose einer periprothetischen Infektion wurde die Detektion von insgesamt mindestens 23 neutrophilen Granulozyten in zehn mikroskopischen Gesichtsfeldern definiert. Die histologische Untersuchung kann als intraoperativer Schnellschnitt durchgeführt werden, wobei eine eingeschränkte Beurteilbarkeit in etwa einem Viertel der Fälle in Kauf genommen werden muss. Zusätzlich ermöglicht die histologische Untersuchung der periprothetischen Membran die Dokumentation des Prothesenabriebs, was der Qualitätskontrolle des Implantats dient. Genexpressionsprofile von abriebinduzierten und infektiösen Lockerungsmembranen wurden erstellt und zum großen Teil validiert, wobei letztlich die klinische Relevanz dieser Untersuchungen hinter den Erwartungen zurückblieb. Chitinase-1 wird in abriebinduzierten Membranen deutlich überexprimiert, und die chitinolytische Enzymaktivität ist im Serum von Patienten mit abriebinduzierter Prothesenlockerung signifikant höher als in der Kontrollgruppe. Allerdings ist die Varianz der Messwerte so groß, dass sich dieser Parameter nicht für einen Test zur Früherkennung einer Prothesenlockerung eignet.In order to enhance the informative value of histopathologic examinations in joint diseases, two new evaluation systems were established: First, the synovitis score and second, the consensus classification of the periprosthetic membrane. The synovitis score is a grading system for the severity of chronic joint diseases, irrespective of the etiology. It is based on the semiquantitative grading of the a) enlargement of the synovial lining, b) activation of synovial stroma and c) inflammatory infiltrate. Its use showed a good reproducibility and good correlation with clinical diagnoses, low-grade scores being in favour of degenerative diseases, while high-grade scores are diagnostic of rheumatic joint diseases. For the diagnostic workup of periprosthetic membranes from loose endoprostheses, a classification system was established, which discriminates between four types: Wear-particle induced (I), infectious (II), combined (III) and indeterminate type (IV). The histological typing correlates well with the results of microbiological testing. As essential criterion for the diagnosis of a periprosthetic infection, the detection of at least 23 neutrophilic granulocytes in ten high- power fields could be defined. The histopathologic examination can be executed as intraoperative frozen section, however the evaluation will not be possible in about one fourth of the cases due to the impaired morphology in frozen sections. Furthermore, the histopathological examination allows for the detection of prosthesis wear, which is helpful for the quality control of the implants. Gene expression profiles from wear-particle induced and from infectious periprosthetic membranes were generated and partially validated by RT-PCR and immunohistochemistry. However, the relevance of these examinations for clinical practice underachieved. For example, Chitinase-1 was strongly overexpressed in wear-particle induced periprosthetic membranes, and its enzymatic activity was significantly higher in patients with wear-particle induced loosening; but the great variability of the enzymatic activity impedes the use of this parameter as a test for screening or differential diagnostics in endoprosthesis loosening