The effects of Celecoxib on inflammation and synovial microcirculation in murine antigen-induced arthritis.

OBJECTIVE: There is controversy about the effects of cyclooxygenase-2 (COX-2) on adhesion molecules and the microvasculature in inflamed tissue. Thus, the aim of this study was to assess COX-2-expression in Antigen-induced Arthritis (AiA) and to investigate the effects of selective COX-2 inhibition by Celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide) (CXB), on synovial microcirculation and adhesion molecule expression in arthritic as well as healthy mice. METHODS: Balb/c mice were allocated to 4 groups; 2 control groups with saline or CXB and 2 groups with AiA which also received saline or CXB (30 mg/kg BW in 0.3 ml solution). The severity of arthritis was assessed by changes in the transverse joint diameter On day 14 after AiA-induction, the patella tendon of the left knee joint was microsurgically resected and intravital fluorescence microscopy on synovial tissue was performed. Finally, the knee joint was removed for histology and immunohistochmistry. RESULTS: COX-2-expression in the inflamed synovium was demonstrated by immunohistochemistry. Application of Celecoxib resulted in a significant reduction in the rolling leukocyte fraction as well as in the number of leukocytes adherent to the endothelium (0.25 +/- 0. 1 and 96 +/- 34 cells/mm2 respectively) in comparison to the untreated animals with AiA (0.44 +/- 0.03 and 206 +/- 22 cells/mm2 respectively). Additionally, CXB-treated arthritic animals showed significantly less knee joint swelling and reduced adhesion molecule expression. CONCLUSION: In the present study, COX-2 expression in the synovial tissue of mice with AiA could be demonstrated. Selective COX-2 inhibition with CXB resulted in reduced leucocyte-endothelial cell interactions and decreased adhesion molecule expression. Evidence for a protective role of COX-2 in mouse AiA was not found.

Diagnostic value of increased diffusion weighting of a steady-state free precession sequence for differentiating acute benign osteoporotic fractures from pathologic vertebral compression fractures.

BACKGROUND AND PURPOSE: Differentiating acute benign from neoplastic vertebral compression fractures can pose a problem in differential diagnosis on routine MR sequences, as signal changes can be quite similar. Our purpose was to assess the value of increasing the diffusion weighting of a diffusion-weighted steady-state free precession (SSFP) sequence for differentiating these two types of vertebral compression fractures. METHODS: Twenty-nine patients with 32 acute vertebral compression fractures caused by osteoporosis (n = 15) or malignancy (n = 17) were examined with a diffusion-weighted SSFP sequence, a T1-weighted spin-echo sequence, and a short-inversion-time inversion recovery sequence. The SSFP sequence was performed with increased diffusion weighting (delta = 0.6, 3.0, 6.0, and 9.0 ms). The signal intensities of the fractured vertebral bodies were rated on a five-point scale from markedly hypointense to markedly hyperintense relative to normal adjacent vertebral bodies. Quantitative analysis was performed by region-of-interest measurements and by calculating the bone marrow contrast ratio. Statistical analysis was performed with the Mann Whitney U test and Student's t test. RESULTS: At delta = 3 ms, the osteoporotic fractures yielded hypointense signal in seven cases, isointense signal in six, and hyperintense signal in two. The fractures showed a progressive signal loss with increased diffusion weighting, so that hypointensity was reached in all but one case. All metastatic fractures had hyperintense signal with delta = 3 and 6.0 ms. With delta = 9.0 ms, four fractures became isointense. CONCLUSION: Increasing diffusion weighting can reduce false-positive hyperintense osteoporotic fractures or make hypointensity more obvious in cases of osteoporotic fractures.

[Accuracy of an image-free cup navigation system--an anatomical study]. / Genauigkeit eines bildfreien Navigationssystemes für die Hüftpfannenimplantation--eine anatomische Studie.

The position of the acetabular cup is of decisive importance for the function of a total hip replacement (THR). Using the conventional surgical technique, correct placement of the cup often fails due to a lack of information about pelvic tilt. With CT-based and fluoroscopically-assisted navigation procedures the accuracy of implantation has been significantly improved. However, additional radiation exposure, high cost and the increased time requirement have hampered the acceptance of these techniques. The present anatomical study evaluates the accuracy of an alternative procedure--image-free navigation. This method requires little extra effort, does not substantially delay surgery, and needs no additional imaging. Press-fit cups were implanted in 10 human cadaveric hips with the help of the image-free navigation system, and the position of the cups was checked intraoperatively with a CT-based navigation system and postoperatively by computed tomography. All cups were implanted within the targeted safe zone with an average inclination of 44 degrees (range 40 degrees-48 degrees, SABW 2.7 degrees) and an average anteversion of 18 degrees (range 12-24 degrees, SABW 4.1 degrees). Analysis of accuracy of the image-free navigation software revealed only a small, clinically tolerable deviation in cup anteversion and cup inclination in comparison with the CT-based navigation system and the post operative CT scans. The evaluated image-free navigation system appears to be a practicable and reliable alternative to the computer-assisted implantation of acetabular cups in total hip arthroplasty.

[MRI based volumetric assessment of knee cartilage after ACL-reconstruction, correlated with qualitative morphologic changes in the joint and with clinical outcome. Is there evidence for early posttraumatic degeneration?]. / MRT-basierte Knorpelvolumetrie nach Kreuzbandersatzplastik in Korrelation mit qualitativen Gelenkveränderungen und dem klinischen Outcome. Gibt es Hinweise auf frühzeitige posttraumatische degenerative Veränderungen?

PURPOSE: The purpose of this study was to analyze potential quantitative and qualitative changes of the knee cartilage and joint indicative of early posttraumatic OA 4 years after ACL-reconstruction and to correlate the MRI-findings with the clinical outcome (CO). MATERIALS AND METHODS: 1.5 T MRI-scans were performed on 9 patients post-op and 4 years later. Using a high-resolution T 1-w-fs-FLASH-3D-sequence cartilage volume (cVol) and thickness (mTh) were quantified. Using standard PD-w fs and T 1-w sequences qualitative changes of the joint structures were analyzed based on the WORMS-score. CO was rated by an orthopaedic surgeon using Lysholm-score, OAK-score, Tegner-activity-score (TAS), and Arthrometer KT-1000 testing. RESULTS: Mean changes of cVol were -1.8 % (range: -5.9 %; + 0.7 %) and of mTh -0.8 % (range: -3.0 %; + 1.1 %). No significant change (95 %-CI) could be identified for any compartment. Three patients developed new peripatellar ostheophytes, acute trauma related changes mostly decreased. Mean outcome of Lysholm-score and OAK-score were 90 pts and 86 pts, mean TAS was 4.3 pts. Average maximum tibial translation reached 5.2 mm comparing to 6.7 mm on the healthy contralateral side. CONCLUSION: Despite a tendency towards decreased cVol and mTh 4 years after ACL-reconstruction qMRI revealed no significant cartilage loss. Newly developing osteophytes did not match with the observed good CO. This small pilot study motivates future quantitative and qualitative-structural MRI-based assessment of articular cartilage and other joint structures in order to improve diagnostic tools for the detection of early OA.

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.

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.

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.

Head-up-tilt testing in children: new perspectives using beat-to-beat blood-pressure monitoring.

The head-up-tilt-test in pediatric patients for the evaluation of syncope shows a sensitivity of 35-85% and often requires pharmacological stimulation in order to improve its diagnostic value. We used a new device for beat-to-beat blood pressure monitoring combined with impedance cardiography in a 12-year-old girl during tilt testing. A seven seconds asystolia was provoked. The haemodynamic parameters showed clearly the drop in heart rate as well as in cardiac output, and returned to normal values after tilting back the patient. With the help of this new monitoring device, the sensitivity and specificity of head-up-tilt-testing can probably be improved.

Particles of all sizes provoke inflammatory responses in vivo.

The aim of this study was to investigate whether all sizes of wear particles are capable of provoking inflammatory responses and whether there are different responses among different particle sizes. The knees of 40 female Balb/c mice were injected with polystyrene particles of three different diameters, 0.5 microm, 2.0 microm, and 75 microm, using a 0.1% vol/vol concentration. Seven days after particle injection, assessment of the synovial microcirculation using intravital microscopy, and histologic examination, were done. All the mice injected with polystyrene particles had enhanced leukocyte-endothelial cell interactions and histologic scores regardless of particle size when compared with control animals injected with sterile phosphate buffered saline. Polystyrene particles 0.5 microm in size provoked stronger membrane thickening and increased leukocyte-endothelial cell interactions than 75-microm particles. The fraction of rolling leukocytes was enhanced in the 2.0-microm particle group when compared with the 75-microm particle group. These results indicate that polystyrene particles of all sizes (0.5 microm, 2.0 microm, and 75 microm) are capable of inducing an inflammatory response. Small particles (0.5 microm, 2.0 microm) seem to provoke a stronger inflammatory response than larger particles (75 microm) in conditions with equal particle volume.

[Macerated human hip bone preparation as a substitute for fresh frozen preparations for testing the primary stability and frictional torques of cementless hip cups]. / Mazerierte Hüftpfannenpräparate als Ersatz für fresh-frozen-Präparate zur Testung von Primärstabilität und Einschraubverhalten zementfreier Hüftpfannen.

AIM: The aim of the study was to validate macerated human acetabuli as replacement for fresh frozen preparations for testing primary stability and the screwing in moments of cementless threaded hip cups. METHOD: Three fresh frozen human pelvis were tested. One half of each pelvis was macerated whereas the other half was preserved as fresh frozen preparation. In the side of every pelvis the moments of screwing-in, the micromotions, the maximum expressing force and the maximum pull-out torque were determined. RESULTS: The screwing in moments, the maximum expressing forces and the maximum pull-out torques did not change. The micromotions were reduced to half. CONCLUSION: Considering the reduction of the micromotions, macerated human acetabuli are valid replacements for fresh frozen preparations for testing the primary stability and the screwing-in behaviour of screwed pans.

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.

Operative or conservative treatment of the acutely torn anterior cruciate ligament in middle-aged patients. A follow-up study of 133 patients between the ages of 40 and 59 years.

In all, 133 patients with an acute rupture of the anterior cruciate ligament (ACL) were reviewed (aged 40 to 59 years). Average follow-up was 29 +/- 10 months. Thirty-one patients underwent conservative therapy, 35 patients were treated by primary suture, while in 67 the primary suture was augmented with the semitendinosus tendon. The patients with primary repair and semitendinosus tendon augmentation showed significantly better results according to OAK and Lysholm scores, the Lachman test, pivot-shift testing, and KT-1000 arthrometer measurements than those treated conservatively or with primary suture. The physical activity level was significantly higher in the patients with augmented ACL repair than in the conservatively treated patients. There was no significant difference between the patients with augmented ACL repair and conservative treatment in the assessment of range of motion, while the patients with primary suture had a significantly greater loss of flexion than those in the other two treatment groups. Increasing age was not found to have a negative effect on either operative or conservative treatment. The results indicate that patients between the ages of 40 and 59 years can be treated successfully by ACL surgery.

Tripled semitendinosus anterior cruciate ligament reconstruction with Endobutton fixation: a 2-3-year follow-up study of 35 patients.

We evaluated the clinical outcome of tripled semitendinosus tendon ACL reconstruction with femoral Endobutton (Acufex, Smith&Nephew, Andover, MA) and tibial Suture Washer (Acufex, Smith&Nephew, Andover, MA) (n 29) or post screw fixation (n 6) in 35 patients on an average of 28 (20-37) months after surgery. On the basis of IKDC criteria, 22 patients showed a normal or nearly normal knee function and 25 patients had a KT 1000 maximal manual side-to-side difference of < or =5 mm at follow-up. Subjectively, 28 patients graded their knee function as normal or nearly normal. The average Lysholm score was 88 points, average OAK score 90 points and average modified HSS score 93 points. 19 patients reached their preinjury level of activity at follow-up. The postoperative Lachman test was < or =1+ in 24 patients and 24 patients also showed an absent pivot shift. Significant bone tunnel enlargement occurred in 26 patients on the femoral side and in 23 patients on the tibial side. We found no correlation between bone tunnel enlargement and clinical outcome. The clinical outcome of tripled semitendinosus tendon ACL reconstruction with Endobutton fixation on the femoral side was not entirely satisfactory. The procedure was associated with a high incidence of bone tunnel enlargement in this series.

[Acute tissue toxicity of PMMA bone cements]. / Akute Gewebetoxizität von PMMA-Knochenzementen.

AIM: Local toxic reactions are one possible reason for fibrous tissue formation at the interface between bone and PMMA bone cement. Most of the numerous in vitro studies have shown severe cytotoxicity of bone cements and their components. However, in vivo investigations of the local tissue toxicity of bone cements have so far seldom been performed. METHODS: The in-vivo hens-egg chorion-allantoic-membrane test (HET-CAM), a well established replacement procedure for experiments with higher vertebrates, is used for the testing of potentially toxic solid and fluid substances. It was performed with PMMA bone cements, their components and their monomer extracts to measure in vivo biocompatibility. RESULTS: We showed that local toxic tissue reactions occurred, especially at the beginning of the processing phase of PMMA bone cements. We also proved that certain components of PMMA bone cements have poor tissue compatibility and sometimes cause severe local tissue changes. CONCLUSIONS: In the development of PMMA bone cements and when drafting the recommendations for their use, attention should be paid to their biocompatibility as well as their mechanical properties.

[The architecture of the subacromial space after full thickness supraspinatus tears]. / Die Architektur des subakromialen Raumes bei Supraspinatussehnenruptur.

AIM: The etiology of rotator cuff tears is multifactorial. An important factor is the damage of the rotator cuff by narrowing of the subacromial space. The purpose of this investigation was to estimate the influence of various metrical parameters on the size of the subacromial space. METHOD: We investigated 161 human macerated scapulae, 36 of them had a known tear of the supraspinatus tendon. All scapulae were photographed in two standard positions from the front and the lateral side. Defined distances and angles were measured using an image analyzing system followed by statistical analysis. RESULTS: Shoulders with a tear of the supraspinatus tendon showed a trend towards higher incidences of hooked acromions. Furthermore we found a significant higher incidence of elongated oval shaped glenoids in the group with supraspinatus tendon tear. In comparison to normal shoulders a significantly smaller distance from the top of the glenoid to the tip of the acromion and a greater distance from the top of the glenoid to the tip of the coracoid process was measured. In addition there was a significantly smaller coracoid angle and a smaller glenoid-spinal angle in this group. CONCLUSION: The width of the subacromial space depends on various parameters. Our data suggest that besides the acromion type the shape of the coracoid, the acromial angle, the spine-scapula angle and the cavitas-spine angle should be taken into account for diagnostic and therapeutic decisions.

Tunnel enlargement and changes in synovial fluid cytokine profile following anterior cruciate ligament reconstruction with patellar tendon and hamstring tendon autografts.

There is growing evidence that cytokines such as tumor necrosis factor (TNF) alpha, interleukin (IL) 1beta, IL-6, bone morphogenetic proteins (BMP), and nitric oxide (NO) play an important role in the pathogenesis of bone tunnel enlargement following anterior cruciate ligament (ACL) reconstruction. Furthermore, the release of these mediators has been considered a possible reason for the higher incidence of bone tunnel enlargement following hamstring tendon (HST) than following patellar tendon (PT) ACL reconstruction observed in several studies. In this investigation synovial fluid samples from 13 patients were collected immediately before (24+/-7 days after ACL rupture) and 7 days after ACL surgery and values of TNF-alpha, IL-1beta, IL-6, NO, and BMP-2 were analyzed. Furthermore, the incidence of bone tunnel enlargement was assessed using radiographs 38+/-7 weeks after surgery. Six patients underwent autologous HST ACL reconstruction, and in seven patients an PT autograft was used. In the overall patient population there were significantly higher synovial fluid concentrations of IL-6 and BMP-2 postoperatively than preoperatively; TNF-alpha showed a trend towards lower postoperative levels while IL-1beta and NO remained unchanged. The concentrations of NO, TNF-alpha, and IL-6 found in the present study were clearly higher than normal values given in the literature. Assessment of bone tunnel enlargement revealed an average increase in tibial tunnel width of 28.4+/-3.1% with comparable values for HST and PT ACL reconstructions. There was no significant correlation between bone tunnel enlargement and postoperative synovial fluid concentrations of TNF-alpha, IL-1beta, IL-6, NO, and BMP-2. However, all patients with bone tunnel enlargement had higher postoperative concentrations of TNF-alpha, IL-6, and NO in the synovial fluid. There were no significant differences in concentrations between HST and PT groups. In conclusion, we observed an association between tibial bone tunnel enlargement and elevated synovial fluid concentrations of IL-6, TNF-alpha, and NO 7 days after ACL surgery indicating the potential involvement of these biological mediators in the pathogenesis of bone tunnel enlargement. However, there was no difference between HST and PT ACL reconstructions regarding synovial fluid contents of IL-6, TNF-alpha, IL-1beta, NO, and BMP-2, suggesting a comparable biological response between these autografts following their use in ACL reconstruction.

Diffusion-weighted imaging of tumor recurrencies and posttherapeutical soft-tissue changes in humans.

The aim of this study was to examine soft tissue tumor recurrences and posttherapeutic soft tissue changes in humans with a diffusion-weighted steady-state free precession (SSFP) sequence. Twenty-four patients with 29 pathologies of the pelvis or the extremities were examined. The lesions were classified as follows: group 1, recurrent viable tumors (n = 10); group 2, postoperative hygromas (n = 7); and group 3, posttherapeutic reactive inflammatory muscle changes (n = 12). The sequence protocol in these patients consisted of short tau inversion recovery images, T2-weighted spin-echo (SE), pre- and postcontrast T1-weighted SE images and the diffusion-weighted SSFP sequence. The signal loss on diffusion-weighting was evaluated visually on a four-grade scale and quantitatively. The signal intensities were measured in regions of interest and a regression analysis was performed. Statistical analyses was performed utilizing the Student's t-test. The signal loss was significantly higher for hygromas and edematous muscle changes than for recurrent tumors (p < 0.001) indicating higher diffusion of water protons. The regression coefficient was -0.11 (mean) for tumors. Hygromas had a significantly higher signal loss than inflammatory edematous muscle changes (p < 0.01). The regression coefficients were -0.29 (mean) for hygromas and -0.22 (mean) for edematous muscle changes. The SSFP sequence seems to be a suitable method for diffusion-weighted imaging of the musculoskeletal system in humans. These preliminary results suggest that the signal loss and the regression coefficients can be used to characterize different types of tissue.

[Inflammatory responses to wear particles in vivo: a novel model in the murine knee joint]. / Inflammatorische Reaktion auf Abriebpartikel von Endoprothesen in vivo. Ein experimentelles Modell an der Maus.

Although it is now widely recognized that the inflammatory response to implant wear particles plays an important role in aseptic loosening of total joint replacements, the precise mechanisms of this process remain unclear. The aim of this study was to establish an animal model for the study of the adverse response to particulate wear debris and the effects on the synovial microcirculation as well as the leukocyte-endothelial cell interaction in the murine knee joint in vivo. Balb/c mice were injected with 50 microl of a 0.5-microm polystyrene particle suspension (0.1% v/v) into the knee joint. The severity of the inflammatory response was evaluated at days 1, 2, 3, 5, 7 (acute), 21 (intermediate), and 63 (chronic) after particle injection. Histological examination as well as assessment of the synovial microcirculation using intravital microscopy was performed. For the intravital microscopy measurements, the patella tendon was partially resected for visualization of the synovial tissue of the knee joint and the fluorescent markers FITC-dextran and rhodamine 6G were injected intravenously. There was a significantly enhanced leukocyte-endothelial cell interaction beginning at day 3 after particle injection with a maximum in the acute phase (days 5-7) and a subsequent decline in the intermediate (day 21) and chronic (day 63) phases. Functional capillary density was significantly increased from day 3 until day 21 after particle application. The histological examination showed an inflammatory reaction that complied widely with the temporal course of the microvascular parameters and resembled the histological appearance of the synovial-like membrane around loose joint prostheses. A novel model was established for the qualitative and quantitative investigation of the particle-induced inflammatory response in the joint environment. It was shown for the first time that there is a significantly enhanced leukocyte-endothelial cell interaction in the synovial tissue after intra-articular particle injection. This model seems to be suitable for further investigations, e.g., dealing with the biocompatibility of different particle materials.

The value of desoxypyridinoline in the diagnostics of loosened arthroplasty.

According to several reports in the last few years, desoxypyridinoline (Dpd) in urine increases significantly in cases of loosened arthroplasty. Therefore, this marker was suggested as useful in the diagnostics of implant loosening. In this study, the level of Dpd was determined in 69 patients with arthroplasty of the hip or the knee joint. Thirty-four of these patients received revision surgery following implant loosening. In 35 of these 69 patients, there were no clinical or radiological signs of loosening (control group). The mean age of the patients with loosened implants (22 women, 13 men) was 67.9 years and of the control group (22 women, 12 men) 66.9 years. In the group with arthroplastic loosening, as well as in the control group, 14 patients had increased levels of Dpd. There were 20 patients in the group with loosened arthroplasty and 19 patients in the control group that had normal levels of Dpd. The female patients had a mean Dpd level of 8.6 nmol/mmol creatinine (4.3-24 nmol/mmol creatinine) in the urine in cases of loosening and 10.1 nmol/mmol creatinine (2-33 nmol/mmol creatinine) in the control group. The male patients had a mean Dpd level of 7.8 nmol/mmol creatinine (3.2-19.2 nmol/mmol creatinine) in the urine in cases of loosening and 5.8 nmol/mmol creatinine (0.3-11.7 nmol/mmol creatinine) in the control group. In conclusion there was no significant increase in Dpd in patients with implant loosening compared with the control group. Furthermore, older patients often suffer from diseases causing increased bone resorption that may falsify the test results. We cannot confirm that Dpd is helpful in the diagnostics and screening of implant loosening.