One-year follow-up data from the German Cartilage Registry (KnorpelRegister DGOU) in the treatment of chondral and osteochondral defects of the talus.

INTRODUCTION: Chondral and osteochondral lesions of the talus (OLTs) remain a challenging issue with numerous operative treatments proposed to date. The aim of this study was to evaluate 1-year follow-up data in the German Cartilage Registry (KnorpelRegister DGOU). METHODS: Among 401 patients in the database, 114 patients with a complete 1-year Foot and Ankle Outcome (FAOS) score for subscale Pain as the primary variable were included. A total of 12 different surgical treatments were performed. However, 8 techniques were carried out in negligible numbers of patients (n = 1-3), leaving 89 patients treated with the following techniques: arthroscopic antegrade bone marrow stimulation (group A; n = 32), autologous chondrocyte implantation with autologous cancellous bone grafting (group B; n = 9), matrix-augmented bone marrow stimulation (group C; n = 22), and matrix-augmented bone marrow stimulation with autologous cancellous bone grafting (group D; n = 26). Group differences and possible influencing variables such as age and sex were evaluated. Level of significance was set at p < 0.05 for all statistical tests. RESULTS: All four treatment groups showed significant improvement of the FAOS scores at 1 year postoperatively compared with their preoperative scores. No significant differences were found with respect to score changes among the groups. A positive correlation between FAOS subscale Pain improvement and defect size volume and negative correlations between increasing age and FAOS subscales Sports/Rec and QoL were found. Concomitant ankle stabilization led to greater improvement in FAOS subscales Symptoms and ADL than in patients with no stabilization. FAOS subscale Pain showed greater improvement in women than in men. CONCLUSION: All analyzed treatment options were effective for treatment of OLTs. In particular, large defects appeared to benefit from treatment. In the presence of concomitant ankle instability, a stabilizing procedure appeared to have a positive impact on the outcome.

[Minimally invasive components of the treatment of tibialis posterior insufficiency in adults : Tendoscopy of the Achilles tendon, minimally invasive calcaneus displacement osteotomy and the sinus tarsi spacer]. / Minimal-invasive Komponenten der Therapie der Tibialis-posterior-Insuffizienz des Erwachsenen : Tendoskopie der Achillessehne, minimal-invasive Kalkaneusverschiebeosteotomie und Sinus-tarsi-Spacer.

Minimally invasive medializing calcaneal osteotomy, the implantation of a tarsi spacer and the tendoscopy of the posterior tibial tendon have been established as treatment options for tibialis posterior insufficiency grade II. The minimally invasive medializing calcaneal osteotomy allows a correction of the hindfoot valgus like an open procedure with a significantly lower risk of wound healing problems. It has gained increasing popularity within recent years. There is also good evidence for arthroereisis, with the use of the sinus tarsi spacer being primarily an addition to calcaneus sliding osteotomy. The possibilities for tendoscopy of the posterior tibial tendon are limited to debridement and synovectomy. Various papers report minimally invasive alternatives to the strayer procedure for a shortened gastrocnemius muscle. The proximal lengthening of the medial head of the gastrocnemius muscle is particularly popular as a soft tissue-sparing, less traumatic procedure. So far, no reports of a minimally invasive cotton osteotomy have been found in the literature.

[Hindfoot-centred X-ray technique for the evaluation of cavovarus deformity : A proposal for the optimization of radiologic delineation]. / Die "rückfußzentrierte Röntgentechnik" zur Erfassung von Cavovarusdeformitäten : Vorschlag zur Optimierung der radiologischen Darstellung.

In surgical correction of cavovarus deformity bony hindfoot procedures are required in most cases. For treatment planning X­rays in two or more planes are usually used. In conventional X­ray-techniques the hindfoot and ankle joint are presented in a more or less outward rotated position. Moreover, the peritalar complex is not delineated in the most corrected position. Therefore, the frequently used talus-metatarsal-I-angle (Meary angle) cannot be measured correctly. By application of the Coleman block test and additional adjustment of the malrotation in the lateral view, the peritalar complex and ankle joint can be evaluated in the corrected and "hindfoot-centred" position. Also, the frequently seen anterior ankle impingement can be observed precisely. Planning of osteotomies or corrective peritalar fusions is supported thereby. Some treatment examples are presented.

Therapeutic effect of methotrexate encapsulated in cationic liposomes (EndoMTX) in comparison to free methotrexate in an antigen-induced arthritis study in vivo.

OBJECTIVES: Cationic lipid complexes bind to angiogenic endothelial cells of solid tumours and microvessels of chronic inflammatory tissue. Methotrexate (MTX) is one of the drugs used in the therapy of rheumatoid arthritis (RA); it is applied systemically but can have serious side-effects. The aim of this study was to investigate the impact of MTX encapsulated in cationic liposomes (EndoMTX) in comparison to treatment with free MTX. METHOD: We used an antigen-induced arthritis (AiA) model and investigated the leucocyte- and platelet-endothelial cell interaction in arthritic female C57/Bl6 mice and in healthy controls. The arthritic animals were divided into four different groups receiving either trehalose, free MTX, EndoMTX placebo, or EndoMTX. These parameters and functional capillary density (FCD) were measured and assessed by intravital microscopy (IVM). We controlled clinical parameters such as the knee joint diameter (KJD) throughout the observation period. RESULTS: Animals treated with EndoMTX showed a significant and superior reduction in leucocyte- and platelet-endothelial cell interaction, FCD, and KJD. Free MTX or empty liposomes also showed a reduction in these parameters but not to a significant level. FCD decreased in the EndoMTX group in comparison to using free drugs or empty carrier-like liposomes. CONCLUSIONS: This study demonstrates the advantage of using MTX encapsulated in cationic liposomes in contrast to free and generic MTX, with a higher efficacy in anti-inflammatory and anti-angiogenic abilities. Targeting with cationic liposomes may be a promising treatment option and should be elucidated in further experiments regarding dose reduction and side-effects due to MTX usage.

Simvastatin reduces leucocyte- and platelet-endothelial cell interaction in murine antigen-induced arthritis in vivo.

OBJECTIVES: The use of statins in the prevention and treatment of cardiovascular diseases is well established. Their use as anti-inflammatory and immunomodulatory agents in the treatment of rheumatoid arthritis (RA) has also been investigated, with several clinical and experimental studies indicating an anti-inflammatory effect of statins for RA, but other studies showing no effect or even the opposite. The current study was designed to examine the effect of simvastatin in an in vivo murine model of arthritis using intravital microscopy. METHOD: We assigned four groups (n = 7, female C57Bl6 mice), two with and two without antigen-induced arthritis (AiA), from which one of the non-AiA groups and one of the AiA groups were treated with simvastatin 40 mg/kg i.p. daily for 14 consecutive days after induction of arthritis. Platelet- and leucocyte-endothelial cell interaction was assessed by measurement of rolling and adherent fluorescence-labelled platelets and leucocytes, functional capillary density (FCD) was evaluated, and knee joint diameter was determined as a clinical parameter. RESULTS: In arthritic mice treated with simvastatin, a significant reduction in platelet- and leucocyte-endothelial cell interaction was observed in comparison to arthritic mice treated with vehicle. In addition, a significant reduction in FCD was seen in arthritic mice treated with simvastatin, along with a reduction in knee joint swelling of the AiA mice. CONCLUSIONS: Treatment of AiA mice with simvastatin showed significant reductions in platelet- and leucocyte-endothelial cell interactions, in FCD, and in the swelling of the knee joint. These results support the hypothesis of the anti-inflammatory effects of statins in the treatment of RA.

Biological activity and migration of wear particles in the knee joint: an in vivo comparison of six different polyethylene materials.

Wear of polyethylene causes loosening of joint prostheses because of the particle mediated activity of the host tissue. It was hypothesized that conventional and crosslinked polyethylene particles lead to similar biological effects around the knee joint in vivo as well as to a similar particle distribution in the surrounding tissues. To verify these hypotheses, particle suspensions of six different polyethylene materials were injected into knee joints of Balb/C mice and intravital microscopic, histological and immunohistochemical evaluations were done after 1 week. Whereas the biological effects on the synovial layer and the subchondral bone of femur and tibia were similar for all the polyethylenes, two crosslinked materials showed an elevated cytokine expression in the articular cartilage. Furthermore, the distribution of particles around the joint was dependent on the injected polyethylene material. Those crosslinked particles, which remained mainly in the joint space, showed an increased expression of TNF-alpha in articular cartilage. The data of this study support the use of crosslinked polyethylene in total knee arthroplasty. In contrast, the presence of certain crosslinked wear particles in the joint space can lead to an elevated inflammatory reaction in the remaining cartilage, which challenges the potential use of those crosslinked polyethylenes for unicondylar knee prostheses.

The free groin flap in the rat: a model for improving microsurgical skills and for microvascular perfusion studies.

The goal of this study was to evaluate the free groin flap in the rat transplanted to the neck as a tool for extending microsurgical skills and to assess its suitability as a model for microvascular perfusion studies following secondary venous ischaemia. An analysis of 60 consecutive groin flap transplantations was performed in male Sprague Dawley rats with special regard to anatomy and operation times (Part I, animals No. 1-60). Following flap transplantation, the animals No. 10-30 (n = 21) were used for the determination of the critical time period of a complete venous stasis of the free groin flap resulting in a total flap loss (Part II). The flaps of animals No. 31-41 (n = 11) were used for assessing the feasibility and reproducibility of intra-vital video microscopy (IVM) of the flaps (Part III). The mean total operation time decreased from 166 (± 26) minutes ins the first 10 animals to 126 (± 21) minutes and 130 (± 12) minutes in the latter two groups of 10 animals, respectively. After a critical period of 35 minutes of a complete artificial venous stasis a complete flap necrosis occurred. IVM detected a higher functional capillary density of the skin of the transplanted groin flaps in the animals in which the flaps were rinsed with 1 ml of Ringer's lactated solution prior to I/R. In conclusion, this model is simple and reliable. The model may be a useful tool for evaluating and comparing the effects of various anticoagulants or vasomotor drugss on microvascular perfusion in critically compromised free flaps.

Selective inhibition of platelets by the GPIIb/IIIa receptor antagonist Tirofiban reduces leukocyte-endothelial cell interaction in murine antigen-induced arthritis.

OBJECTIVE: Inflammation is associated with the invasion of leukocytes into affected tissues and with the up-regulation of platelet activation and adhesion. Assuming that leukocyte accumulation is linked to platelet aggregation, the aim of our study was to examine the effects of selective platelet inhibition by the glycoprotein (GP) IIb/IIIa receptor antagonist Tirofiban on the leukocyte-endothelial cell interaction. MATERIAL AND METHODS: We used the model of antigen-induced arthritis (AiA) to induce inflammatory changes in the synovial microcirculation. Ex vivo labelled platelets and in vivo fluorescence-labelled leukocytes were visualized by intravital microscopy (IVM). C57/Bl6 mice were allocated to four groups; two control groups with saline or Tirofiban and two groups with AiA that also received either saline or Tirofiban (0.5 microg/g BW) intravenously. RESULTS: There was no significant change in platelet- or leukocyte- endothelial cell interaction in the endothelium in healthy control animals. In contrast, after selective inhibition of platelets, the platelet- and leukocyte-endothelial cell interaction was significantly reduced in arthritic mice and reached the level of the healthy control groups. CONCLUSION: Selective platelet inhibition by Tirofiban resulted in reduced leukocyte-endothelial cell interactions in AiA. Consequently, platelets contribute to leukocyte adhesion in AiA via GPIIb/IIIa and therefore platelet inhibition could become an additional therapy option in chronic arthritic disease.

In vivo interactions of platelets and leucocytes with the endothelium in murine antigen-induced arthritis: the role of P-selectin.

OBJECTIVE: Platelets are thought to participate in the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis (RA). We showed recently an in vivo increase in platelet-endothelial cell interactions in mice with antigen-induced arthritis (AiA). The underlying mechanisms are not yet clear. The aim of this study was to investigate the impact of P-selectin in AiA by means of intravital fluorescence microscopy (IVM). METHODS: C57/Bl6 mice and P-selectin-deficient mice were divided into four groups (n = 7; control/AiA per strain). The extent of AiA was assessed by measuring knee joint swelling and by histological scoring. Rolling and adherent fluorescence-labelled platelets and leucocytes were investigated by IVM. RESULTS: In arthritic P-selectin-deficient mice (rolling: 0.05+/-0.01; adherent: 130+/-20 mm(-2)), compared to arthritic C57/Bl6 mice (rolling: 0.20+/-0.04; adherent: 1910+/-200 mm(-2)), platelet interaction was significantly reduced (p<0.05) and reached the level of both control groups without AiA. In addition, interaction of leucocytes in P-selectin-deficient arthritic animals (rolling: 0.12+/-0.06; adherent: 387+/-37 mm(-2)) was significantly decreased in comparison to arthritic C57/Bl6 animals (rolling: 0.21+/-0.06; adherent: 1492+/-284 mm(-2); p<0.05). Swelling of the knee joint and histological scoring were reduced in arthritic P-selectin-deficient mice compared to arthritic C57/Bl6 mice. CONCLUSION: We have demonstrated for the first time in vivo a significant decrease in the interaction of platelets and leucocytes with the endothelium in P-selectin-deficient mice with AiA and a reduction in clinical and histological symptoms of arthritis. These findings suggest that leucocyte-endothelial cell interactions depend at least partially on platelet P-selectin and therefore platelets may be responsible for the leucocyte tissue damage in AiA.

Platelet P-selectin is significantly involved in leukocyte-endothelial cell interaction in murine antigen-induced arthritis.

There is growing evidence that platelets play an important role in the development and maintenance of rheumatoid arthritis. Activation and adherence of platelets in the synovial microcirculation might be in part responsible for endothelial damage and activation of leukocytes. Recent findings show a direct influence of P-selectin on platelet- and leukocyte-endothelial cell interaction in mice with Antigen-induced Arthritis (AiA). P-selectin is only expressed by platelets and endothelial cells, not by leukocytes. Therefore, the aim of the present study was to investigate the differential influence of platelet and endothelial P-selectin on the extent of inflammation in AiA. AiA was induced in wild-type mice and in P-selectin-deficient mice from the same genetic background (four groups: each n = 7). Intravital fluorescence microscopy (IVM) was used to visualize platelets and leukocytes in the synovial microcirculation at day 8 after AiA. Platelets from either strain were fluorescence-labelled ex vivo and transferred into either strain. We were able to demonstrate a significant decrease of platelet- and leukocyte-endothelial cell interaction in P-selectin-deficient mice with AiA in comparison to wild-type mice with AiA. When wild-type platelets were donated into P-selectin-deficient AiA recipients, the leukocyte-endothelial cell interaction was significantly increased compared to the group consisting of P-selectin-deficient recipient and donor mice. These are the first in vivo results showing that the P-selectin stored in platelets is at least partly responsible for the leukocyte-endothelial cell interaction and the resulting tissue damage in AiA. In the future, a suppression of platelet P-selectin could potentially become a treatment option for reducing the effects of rheumatoid arthritis.

Endothelial iNOS versus platelet iNOS: responsibility for the platelet/leukocyte endothelial cell interaction in murine antigen induced arthritis in vivo.

OBJECTIVE: Since an increase of platelet-endothelial cell interactions has been observed in mice with Antigen- induced-Arthritis (AiA) as well as an increase of NO expression, the aim of our study was to investigate in vivo the influence of NO, especially the platelet and endothelial inducible NO Synthase, on the platelet- and leukocyte endothelial cell interaction. MATERIAL AND METHODS: C57/Bl6 mice and iNOS deficient mice were disposed in 6 groups (each=7). After induction of AiA, rolling and adherent fluorescence labelled platelets and leukocytes were investigated by intravital microscopy (IVM) on day 8 after AiA. Rank SUM Test and ANOVA on ranks have been performed regarding the data. RESULTS: All arthritic mice presented an increase in platelet and leukocyte interaction with the endothelium compared to control groups. The arthritic iNOS deficient mice showed a more intense interaction of platelets and leukocytes with the endothelium in comparison with the wild-type arthritic mice. The group using arthritic wild-type recipient and iNOS deficient donor mice showed an increase in cell-interactions, leading to an endothelial effect, compared to the group using iNOS deficient arthritic recipient and wild-type donor mice. CONCLUSION: The IVM data lead to an anti-inflammatory effect of NO, since NO followed an increase in platelet- and leukocyte- endothelial cell interaction in iNOS deficient mice with AiA. In addition, we have shown for the first time in vivo that platelet NO produced by iNOS seems to have a minor influence on the leukocyte induced tissue damage in contrast to endothelial iNOS. Therefore, selective platelet inhibition would not interfere with the protective effect of NO.

Platelet-endothelial cell interactions in murine antigen-induced arthritis.

OBJECTIVES: Growing evidence supports the substantial pathophysiological impact of platelets on the development of rheumatoid arthritis. At present there are no methods for studying these cellular mechanisms in vivo. The aim of this study was to visualize and investigate platelet-endothelial cell interaction in the knee joint of mice with antigen-induced arthritis (AiA) by means of intravital microscopy. METHODS: In 14 mice (Balbc) intravital microscopic assessment was performed on day 8 after AiA induction in two groups (controls, AiA). The severity of AiA was assessed by measuring knee joint swelling and by histological scoring. Ex vivo fluorescently labelled rolling and adherent platelets and leucocyte-endothelium interactions were investigated by intravital fluorescence microscopy. RESULTS: Swelling of the knee joint as well as histological score was significantly enhanced in arthritic animals compared with controls. In control mice intravital microscopy revealed low baseline rolling and sticking of leucocytes and fluorescently labelled platelets. AiA induced a significant increase in the fraction of rolling leucocytes (3 times) and rolling platelets (6 times) compared to the control group. Furthermore, AiA induction resulted in a significantly enhanced number of adherent leucocytes (3-fold) and adherent platelets (12-fold) in comparison with control animals. CONCLUSIONS: Platelet kinetics were directly analysed using intravital microscopy in the arthritic microcirculation in vivo for the first time. We provide the first evidence that platelets accumulate in arthritic vessels, indicating platelet activation due to AiA. Platelet recruitment and subsequent activation might play an important role in the pathogenesis of rheumatoid arthritis.