Publications by authors named "Jens Schaumburger"

30 Publications

  • Page 1 of 1

Lower Limb Malrotation Is Regularly Present in Long-Leg Radiographs Resulting in Significant Measurement Errors.

J Knee Surg 2021 Jan 29;34(1):108-114. Epub 2019 Jul 29.

Department of Orthopaedic Surgery, University of Regensburg, Regensburg, Germany.

Weight-bearing long-leg radiographs are commonly used in orthopaedic surgery. Measured parameters, however, change when radiographs are conducted in different rotational positions of the leg. It was hypothesized that rotational errors are regularly present in long-leg radiographs resulting in wrong measurements. In 100 consecutive long-leg radiographs conducted according to the method of Paley, rotation was assessed by fibular overlap. Angular parameters in radiographs (mechanical lateral proximal femoral angle (mLPFA), mechanical lateral distal femoral angle (mLDFA), angle between the anatomical and mechanical femoral axis (AMA), mechanical medial proximal tibia angle (mMPTA), mechanical lateral distal tibial angle (mLDTA), and the mechanical femoral and tibial axis (mFA-mTA) were measured and deviations related to malrotation calculated. An average internal rotation of 8 degrees was found in lower limbs showing a range between 29 degrees of internal and 22 degrees of external rotation. As a result, mean differences before and after rotational correction for measured parameters (mLPFA, mLDFA, AMA, mMPTA, mLDTA, mFA-mTA) ranged between 0.4 and 1.7 degrees (-2.1; 5.6 95% confidence interval [CI]). In conclusion, malrotation of lower limbs is regularly present in long-leg radiographs. As all measured parameters are influenced by malrotation, correct lower limb rotation needs to be verified.
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http://dx.doi.org/10.1055/s-0039-1693668DOI Listing
January 2021

Efficacy of antibiotic treatment of implant-associated infections with moxifloxacin, flucloxacillin, rifampin, and combination therapy: an animal study.

Drug Des Devel Ther 2017 14;11:1729-1736. Epub 2017 Jun 14.

Department of Orthopedics, University Medical Center Regensburg, Asklepios Klinikum Bad Abbach, Bad Abbach.

The efficacy of antibiotic monotherapy and combination therapy in the treatment of implant-associated infection by was evaluated in an animal study. The femoral medullary cavity of 66 male Wistar rats was contaminated with (ATCC 29213) and a metal device was implanted, of which 61 could be evaluated. Six treatment groups were studied: flucloxacillin, flucloxacillin in combination with rifampin, moxifloxacin, moxifloxacin in combination with rifampin, rifampin, and a control group with aqua. The treatment was applied for 14 days. After euthanasia, the bacterial counts in the periprosthetic bone, the soft tissue, and the implant-associated biofilm were measured. Both antibiotic combination treatments (moxifloxacin plus rifampin and flucloxacillin plus rifampin) achieved a highly significant decrease in microbial counts in the bone and soft tissue and in the biofilm. Mono-antibiotic treatments with either moxifloxacin or flucloxacillin were unable to achieve a significant decrease in microbial counts in bone and soft tissue or the biofilm, whilst rifampin was able to reduce the counts significantly only in the biofilm. Antibiotic resistance was measured in 1/3 of the cases in the rifampin group, whereas no resistance was measured in all other groups. The results show that combinations of both moxifloxacin and flucloxacillin plus rifampin are adequate for the treatment of periprosthetic infections due to infections with , whereas monotherapies are not effective or not applicable due to the rapid development of antibiotic resistance. Therefore, moxifloxacin is an effective alternative in combination with rifampin for the treatment of implant-associated infections.
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http://dx.doi.org/10.2147/DDDT.S138888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476658PMC
April 2018

A randomized controlled trial demonstrating sustained benefit of Autologous Matrix-Induced Chondrogenesis over microfracture at five years.

Int Orthop 2017 Apr 20;41(4):797-804. Epub 2017 Jan 20.

Department of Orthopedic Surgery, University of Regensburg, Asklepios Clinical Center Bad Abbach, Bad Abbach, Germany.

Purpose: Autologous Matrix-Induced Chondrogenesis (AMIC) utilizing a type I/III collagen membrane was compared with microfracture (MFx) alone in focal cartilage lesions of the knee at one, two and five years.

Methods: Forty-seven patients (aged 37 ± 10 years, mean defect size 3.6 ± 1.6 cm) were randomized and treated either with MFx, with sutured or glued AMIC in a prospective multicentre clinical trial.

Results: After improvement for the first two years in all subgroups, a progressive and significant score degradation was observed in the MFx group, while all functional parameters remained stable for least five years in the AMIC groups. At two and five years, MRI defect filling was more complete in the AMIC groups. No treatment-related adverse events were reported.

Conclusions: AMIC is an effective cartilage repair procedure in the knee resulting in stable clinical results significantly better than the MFx group at five years.
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http://dx.doi.org/10.1007/s00264-016-3391-0DOI Listing
April 2017

Appropriate sagittal femoral component alignment cannot be ensured by intramedullary alignment rods.

Knee Surg Sports Traumatol Arthrosc 2016 Aug 15;24(8):2453-60. Epub 2015 Feb 15.

Department of Orthopaedic Surgery, University of Regensburg, Regensburg, Germany.

Purpose: The intraoperative sagittal cutting block alignment when intramedullary alignment rods are used was investigated. Its absolute orthogonal orientation in relation to the mechanical femoral axis should be analysed. It was hypothesized that (1) alignment rods do not ensure a desired deviation within a range between 0° and 3° flexion as it has been shown to be favourable for clinical and functional outcome. Further, the degree of flexion cannot be (2) foreseen by the surgeon or (3) estimated by clinical or radiological parameters.

Methods: Forty knees allocated to total knee arthroplasty were included. The distal femoral cutting block was aligned using an intramedullary rod. By means of a navigation device, the sagittal alignment of the cutting block in degrees of flexion was measured.

Results: The mean measured flexion of the cutting block was 4.4° (3.6 SD). Twenty-five per cent (10/40) of the values were within a corridor between 0° and 3° of flexion. The mean difference between expected and measured flexion was -1.5° (-7.6 to 4.7 95 % limits of agreement). The dorsoventral diameter of the distal femur showed a significant influence on measured flexion (R (2) = 0.112, p = 0.035).

Conclusion: Intramedullary alignment rods used in the present study do not ensure a distal cutting block alignment between 0° and 3° of flexion in relation to the femoral mechanical axis. The extent of flexion could not be foreseen either by the surgeon. The dorsoventral diameter of the distal femur correlated with measured flexion. However, only limited data is available on influence of femoral component flexion on implant failure or clinical and functional outcome.

Level Of Evidence: Diagnostic study, Level II.
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http://dx.doi.org/10.1007/s00167-015-3541-8DOI Listing
August 2016

The influence of component alignment on patellar kinematics in total knee arthroplasty.

Acta Orthop 2015 13;86(4):444-50. Epub 2015 Jan 13.

Department of Orthopaedic Surgery and.

Background And Purpose: Postoperative anterior knee pain is one of the most frequent complications after total knee arthroplasty (TKA). Changes in patellar kinematics after TKA relative to the preoperative arthritic knee are not well understood. We compared the patellar kinematics preoperatively with the kinematics after ligament-balanced navigated TKA.

Patients And Methods: We measured patellar tracking before and after ligament-balanced TKA in 40 consecutive patients using computer navigation. Furthermore, the influences of different femoral and tibial component alignment on patellar kinematics were analyzed using generalized linear models.

Results: After TKA, the patellae shifted statistically significantly more laterally between 30° and 60°. The lateral tilt increased at 90° of flexion whereas the epicondylar distance decreased between 45° and 75° of flexion. Sagittal component alignment, but not rotational component alignment, had a significant influence on patellar kinematics.

Interpretation: There are major differences in patellar kinematics between the preoperative arthritic knee and the knee after TKA. Combined sagittal component alignment in particular appears to have a major effect on patellar kinematics. Surgeons should be especially aware of altering preoperative sagittal alignment until the possible clinical relevance has been investigated.
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http://dx.doi.org/10.3109/17453674.2015.1005907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4513599PMC
November 2015

Subchondral bone influences chondrogenic differentiation and collagen production of human bone marrow-derived mesenchymal stem cells and articular chondrocytes.

Arthritis Res Ther 2014 Oct 7;16(5):453. Epub 2014 Oct 7.

Introduction: Osteoarthritis (OA) is characterized by an imbalance in cartilage and underlying subchondral bone homeostasis. We hypothesized that signals from the subchondral bone may modulate production of matrix components, alter chondrogenic differentiation potential of cocultured bone marrow-derived mesenchymal stem cells (BMSC) and induce a phenotypic shift in differentiated OA chondrocytes.

Methods: We established a novel coculture model between BMSC, mixed cultures (BMSC and chondrocytes) and chondrocytes embedded in fibrin gel with OA and normal subchondral bone explants (OAB and NB). Tissues and cells were either derived from OA or trauma patients. In addition, we used adipose-derived stem cells (ASC) from liposuction. With gene expression analysis, biochemical assays, immunofluorescence and biomechanical tests we characterized the properties of newly generated extracellular matrix (ECM) from chondrocytes and chondrogenically differentiating BMSC cocultured with OAB or NB in comparison with monocultures (cultures without bone explants).

Results: Overall, gene expression of collagens of OAB and NB cocultured cells was reduced compared to monocultures. Concomitantly, we observed significantly lower collagen I, II and III and glycosaminoglycan (GAG) production in OAB cocultured cell lysates. In parallel, we detected increased concentrations of soluble GAGs and basic fibroblast growth factor (bFGF), interleukin (IL)-6 and IL-8 in supernatants of OAB and NB cocultures mainly at early time points. IL-1ß concentration was increased in supernatants of OAB cocultures, but not in NB cocultures. Cell-free NB or OAB explants released different amounts of IL-1ß, bFGF and soluble GAG into cell culture supernatants. In comparison to cocultures, monocultures exhibited higher Young's modulus and equilibrium modulus. Stimulation of monocultures with IL-1ß led to a downregulation of aggrecan (ACAN) gene expression and in general to induced matrix metalloprotease (MMP)2, MMP3 and MMP-13 gene expression while IL-6 and IL-8 stimulation partly reduced ACAN, MMP3 and MMP-13 gene expression.

Conclusions: Our results suggest an alteration of molecular composition and mechanical properties of the newly formed ECM in subchondral bone cocultures. We suggest that soluble factors, that is interleukins and bFGF, released in cocultures exert inhibitory effects on collagen and temporary effects on proteoglycan production, which finally results in a reduction of mechanical strength of newly formed fibrillar networks.
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http://dx.doi.org/10.1186/s13075-014-0453-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209060PMC
October 2014

Predicting knee rotation by the projection overlap of the proximal fibula and tibia in long-leg radiographs.

Knee Surg Sports Traumatol Arthrosc 2014 Dec 26;22(12):2982-8. Epub 2014 Sep 26.

Department of Orthopaedic Surgery, University of Regensburg, Regensburg, Germany,

Purpose: Rotation of the lower limbs in long-leg radiographs has a significant impact on imaging the mechanical femorotibial angle, the femoral anatomic mechanical angle, the mechanical lateral distal femoral angle (mLDFA) and the mechanical medial proximal tibial angle (mMPTA). In this study, we assessed the rotation of the lower limbs in conventional radiographs and hypothesized that the relative position of the proximal fibula to the proximal tibia on long-leg radiographs is related to the rotation of the knee joint.

Methods: Radiological examinations in different rotational positions of the knee joint (incremental 40° internal to 40° external rotation) were imitated by 50 computed tomography scans (50 patients, 25 men and 25 women). The extent of the projection overlaps of the fibula, the fibular tip and the distance from the fibular tip to the lateral cortex were determined for every rotational position.

Results: Multiple regression analysis showed a very strong correlation between the measured fibular parameters and knee rotation between 20° of internal rotation and 40° of external rotation (R (2) ~ 0.94, p < 0.001). By means of these results, we created a formula for predicting knee rotation: [Formula: see text]This strong correlation could not be found between 20° and 40° of internal rotation.

Discussion: Because incorrect internal and external rotation negatively influence the correct measurement of angles (mechanical femorotibial angle, femoral anatomic mechanical angle, the mLDFA and the mMPTA), long-leg radiographs should be assessed for proper rotation angles before measurement. Using the provided formula rotation of the lower limb in weight-bearing, long-leg radiographs can be reliably predicted.

Level Of Evidence: Diagnostic study, Level II.
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http://dx.doi.org/10.1007/s00167-014-3327-4DOI Listing
December 2014

Pinless navigation in total knee arthroplasty: navigation reduced by the maximum?

Int Orthop 2015 Mar 23;39(3):455-60. Epub 2014 Sep 23.

Department of Orthopaedic Surgery, University of Regensburg, Regensburg, Germany,

Purpose: Restoring a neutral mechanical axis in total knee arthroplasty (TKA) (within ±3° of varus/valgus) is associated with superior functional outcome and reduced early implant failure. Using conventional alignment jigs results in malalignment in >20 % of cases. In this study, we investigated the reduction of outliers within the threshold of ±3° of leg alignment using a "pinless" navigation system in comparison with conventional alignment jigs investigated.

Methods: In this randomised prospective study, 80 patients were randomly assigned/allocated to the pinless or conventional control group. After surgery, the two groups were compared regarding outliers > ±3° by means of hip-knee-ankle angle (HKA), mechanical medial proximal tibia angle (mMPTA), mechanical lateral distal femoral angle (mLDFA) and duration of surgery. Student's unpaired t test was used for quantitative variables, Fisher's exact test compared groups (pinless vs. control) and a two-sided p value of ≤0.05 was considered statistically significant.

Results: In the pinless group, outliers regarding HKA and mLDFA > ±3° was significantly reduced (p = 0.025 and p = 0.002 respectively). In the pinless group, the surgery duration was significantly longer (75.6 vs. 64.5 minutes, p < 0.001).

Conclusion: Pinless navigation is effective in reducing outliers > ±3° regarding HKA without risking pin-related complications, such as fractures, infections or breaking screws. However, not all tools for conventional navigation in TKA, such as real-time measurements of the tibiofemoral axis and gap balancing, are available.
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http://dx.doi.org/10.1007/s00264-014-2529-1DOI Listing
March 2015

Accuracy of bony landmarks for restoring the natural joint line in revision knee surgery: an MRI study.

Int Orthop 2014 Jun 26;38(6):1173-81. Epub 2014 Feb 26.

Department of Orthopaedic Surgery, University of Regensburg, Regensburg, Germany,

Purpose: Restoring the joint line (JL) improves clinical and functional outcome in total knee arthroplasty (TKA). Therefore, anatomical landmarks to approximate the JL have been published. So far, the natural deviation of the JL 90° to the mechanical tibial axis has not been considered. Thus, we designed this study to: (1) determine the natural JL of knees in healthy persons in respect to the mechanical tibial axis, (2) validate and double-check intra-operative bony landmarks already been published in respect to the natural JL and (3) find possible correlations between distances from bony landmarks to the JL and femoral and tibial width.

Methods: Eighty MRI scans of knees of healthy persons were examined by two independent observers. Distances from the tip of the fibular head (FH), the medial (ME) and lateral (LE) epicondyles and the adductor tubercle (AT) to the JL within the medial and lateral compartment were measured. Further, we determined the orientation of the JL in respect to the mechanical axis of the tibia. Interobserver correlations were calculated. Differences were analyzed using Student's t test. Linear regression models were calculated to analyze correlations.

Results: Interobserver correlation was excellent. Mean JL deviation was 4.2° varus. Distance between the FH, ME, LE and AT to the JL within the medial compartment was 12.2, 33.9, 33.4 and 45.4 mm, respectively. Within in the lateral compartment, distances were 15.3, 31.0, 30.6 and 42.3 mm to the JL. Strong correlation was found between femoral width and distances from the AT, ME and LE to the JL.

Conclusion: In TKA, the JL is usually altered due to the classic resection technique, which does not respect the natural deviation of the JL. Estimating the natural JL by adding absolute values to bony landmarks, as proposed in the literature, is not recommended. According to our data, the JL can be best estimated by adding the calculated value: 6.40 + (width femur [mm] × 0.49) to the AT.
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http://dx.doi.org/10.1007/s00264-014-2292-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4037526PMC
June 2014

Assessing patient-oriented results after revision total knee arthroplasty.

J Orthop Sci 2013 Nov;18(6):955-61

Background: Revision total knee arthroplasties (TKA) have been performed with increasing frequency over the last 25 years.

Methods: In this study, we retrospectively analyzed 78 patients who underwent 78 revision TKAs during the years 2003–2007 with an average follow-up of 81 months (range 60–108 months). All patients were treated with a standard rotating hinge prosthesis (TC3, DePuy, Warsaw, IN, USA) due to significant instability. We evaluated the postoperative results using the Knee Society clinical rating system and the WOMAC rating system.

Results: Clinical results revealed significant improvements in both scores. Complications occurred in almost one-third of the cases, with a reoperation rate of 26 %.

Conclusion: Our mid-term findings show that revision TKAs lead to an improvement in patient-perceived outcomes of physical variables. While revision TKA is a useful option for patients, procedure-associated complications should not be neglected. During the course of the procedure, it is important to collect patient-oriented data and focus on responsive and valid scores.
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http://dx.doi.org/10.1007/s00776-013-0467-1DOI Listing
November 2013

Comparing navigation-based in vivo knee kinematics pre- and postoperatively between a cruciate-retaining and a cruciate-substituting implant.

Int Orthop 2013 Mar 30;37(3):407-14. Epub 2013 Jan 30.

University of Regensburg, Orthopaedic Surgery, Regensburg, Germany.

Purpose: Individual physiological knee kinematics are highly variable in normal knees and are altered following cruciate-substituting (PS) and cruciate-retaining (CR) total knee arthroplasty (TKA). We wanted to know whether knee kinematics are different choosing two different knee designs, CR and PS TKA, during surgery using computer navigation.

Methods: For this purpose, 60 consecutive TKA were randomised, receiving either CR (37 patients) or PS TKA (23 patients). All patients underwent computer navigation, and kinematics were assessed prior to making any cuts or releases and after implantation. Outcome measures were relative rotation between femur and tibia, measured medial and lateral gaps and medial and lateral condylar lift-off.

Results: We were not able to demonstrate a significant difference in femoral external rotation between either group prior to implantation (7.9° CR vs. 7.4° PS) or after implantation (9.0° CR vs. 11.3° PS), both groups showed femoral roll-back. It significantly increased pre- to postoperatively in PS TKA. In the CR group both gaps increased, the change of the medial gap was significantly attributable to medial release. In the PS group both gaps increased and the change of the medial and of the lateral gap was significant. Condylar lift-off was observed in the CR group during 20° and 60° of flexion.

Conclusion: This study did not reveal significant differences in navigation-based knee kinematics between CR and PS implants. Femoral roll-back was observed in both implant designs, but significantly increased pre- to postoperatively in PS TKA. A slight midflexion instability was observed in CR TKA. Intra-operative computer navigation can measure knee kinematics during surgery before and after TKR implantation and may assist surgeons to optimise knee kinematics or identify abnormal knee kinematics that could be corrected with ligament releases to improve the functional result of a TKR, whether it is a CR or PS design. Our intra-operative finding needs to be confirmed using fluoroscopic or radiographic 3D matching after complete recovery from surgery.
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http://dx.doi.org/10.1007/s00264-013-1798-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580100PMC
March 2013

Infusion, core decompression, or infusion following core decompression in the treatment of bone edema syndrome and early avascular osteonecrosis of the femoral head.

Rheumatol Int 2013 Jun 23;33(6):1561-5. Epub 2012 Dec 23.

Sportklinik Stuttgart, Taubenheimstr. 8, 70372 Stuttgart, Germany.

An increase in interstitial fluid is an expression of bone marrow edema (BME) and osteonecrosis (ON). The exact pathogenetic processes still remain unknown. Treatment options are mainly symptomatic with core decompression as surgical golden standard with immediate pain relief. Recently, it has been shown that intravenous iloprost can be used to achieve a reduction in BME and ON with a considerable improvement in the accompanying symptoms. The effect of intraveneously applied iloprost alone (12 patients) was studied against core decompression alone (12 patients) as well as iloprost following core decompression (12 patients). We could find a significant improvement in HHS, WOMAC score, SF-36 score and VAS 3 months and 1 year after therapeutical intervention in all treatment groups; however, statistically best results were obtained by combination. Concerning the MRI scans, we found a distinct reduction in BME in all groups again favoring the combination. Concerning ON, the results were not as promising as for BME. Intravenous prostacyclin and core decompression as monotherapy are of efficient therapeutical benefit in the treatment of BME, and the combination of both methods, however, seems to be most promising, also in the treatment of ON. Long-term results and higher number of patients are needed for final statements.
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http://dx.doi.org/10.1007/s00296-012-2597-8DOI Listing
June 2013

Bisphosphonates or prostacyclin in the treatment of bone-marrow oedema syndrome of the knee and foot.

Rheumatol Int 2013 Jun 10;33(6):1397-402. Epub 2012 Nov 10.

Department of Orthopaedic Surgery, University Hospital of Regensburg, Bad Abbach, Germany.

Bone-marrow oedema (BME) represents a reversible but mostly painful increase in interstitial fluid. The exact pathogenetic processes still remain unknown. Treatment options are mainly symptomatic with core decompression as golden standard leading to immediate pain relieve. Recently, it has been shown that intravenous prostacyclin and bisphosphonates are useful in achieving a reduction in BME with a considerable improvement in the accompanying symptoms. We compared the outcome of both intravenously applied prostacyclin (Ilomedin(®), 10 patients) and bisphosphonate (Bondronat(®), 10 patients) in treatment of BME of the knee and foot. We could find a significant improvement of WOMAC score, SF-36 score and VAS 3 months and 1 year after therapeutic intervention in both the prostacyclin and the bisphosphonate group. Concerning the MRI scans in both groups, we found a distinct reduction of BME in 47 % and a complete regression in 40 %. Comparing both groups, the improvement of the scores was greater in the prostacyclin group than in the bisphosphonate group; the difference, however, was not significant. Intravenous bisphosphonates as well as prostacyclin are of efficient therapeutic benefit in treatment of BME with a quicker and greater effect of prostacyclin.
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http://dx.doi.org/10.1007/s00296-012-2584-0DOI Listing
June 2013

Arthrodesis of the talonavicular joint using angle-stable mini-plates: a prospective study.

Int Orthop 2012 Dec 6;36(12):2491-4. Epub 2012 Oct 6.

Department of Orthopaedic Surgery, University of Regensburg, Bad Abbach, Germany.

Purpose: The talonavicular joint is a central connection of the human foot. Symptomatic talonavicular arthritis can be adequately addressed by isolated talonavicular fusion. However, non-union remains a relevant clinical challenge to the orthopaedic surgeon. The aim of this study was to analyse the clinicoradiological outcome of talonavicular fusion using angle-stable mini-plates.

Methods: We performed 30 talonavicular fusions in 30 patients (12 male, 18 female) with a mean age of 58.8 years (range, 22-74) between 2005 and 2007. Osseous joint fusion was achieved using mono- and multidirectional angle-stable mini-plates. The patients followed a standardised immobilisation and weight bearing protocol. The mean postoperative follow up was 15.8 months (6.1-23.8).

Results: The American Orthopedic Foot and Ankle Society AOFAS score increased significantly from 31.7 (19-42) to 82.3 points (55-97) (p < 0.001). Neither age at operation nor gender influenced the score results significantly, while the aetiology of talonavicular degeneration showed a significant effect. Mean visual analogue scale (VAS) pain intensity (0-10) reduced from 8.6 to 1.7 (p < 0.001). Good or excellent results were achieved in 26 patients, while two patients reported fair and another two poor results. Complete osseous fusion was observed at a mean of 10.9 weeks (8-13) postoperatively.

Conclusions: For the treatment of talonavicular arthritis, the application of mono- and multidirectional angle-stable mini-plates provided a strong fixation that led to high union rates and good to excellent overall outcome.
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http://dx.doi.org/10.1007/s00264-012-1670-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508057PMC
December 2012

Treatment of deep articular talus lesions by matrix associated autologous chondrocyte implantation--results at five years.

Int Orthop 2012 Nov 12;36(11):2279-85. Epub 2012 Aug 12.

Department of Orthopaedics, University of Regensburg, Regensburg, Germany.

Purpose: Treatment of focal full-thickness chondral or osteochondral defects of the talus remains a challenge. The aim of this study was to evaluate the postoperative success and the long-term efficacy of matrix associated autologous chondrocyte implantation in these defects.

Methods: Matrix associated autologous chondrocyte implantation (MACI) was applied in 22 consecutive patients (mean age 23.9 years) with full-thickness chondral or osteochondral lesions of the talus. The average defect-size was 1.94 cm² (range 1-6). In case of osteochondritis dissecans (n = 13) an autologous bone graft was performed simultaneously. Follow-ups were routinely scheduled up to 63.5 (±7.4) months, consisting of clinical evaluation and magnetic resonance imaging.

Results: The AOFAS score improved significantly from 70.1 to 87.9/92.6/93.5/95.0/95.5 and 95.3 points at three, six, 12, 24, 36 and 63.5 months, respectively. On a visual analogue scale, pain intensity decreased from 5.7 (±2.6) to 0.9 (±0.8) while subjective function increased from 5.3 (±2.3) to 8.9 (±0.9) at final follow-up (each p < 0.001). The Tegner score rose significantly from 2.4 (±1.2) to 4.7 (±0.6). The MOCART score improved from 62.6 (±19.4) at three months to 83.8 (±9.4) at final follow-up. No significant differences were found between lesions caused by osteochondritis dissecans or trauma and between first- or second-line treatments. For all scores, the most benefit was seen within the first 12 months with stable results afterwards. No major complications were noted.

Conclusions: Matrix associated autologous chondrocyte implantation is capable of significant and stable long-term improvement of pain and functional impairment caused by focal full-thickness chondral and osteochondral talus lesions.
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http://dx.doi.org/10.1007/s00264-012-1635-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479272PMC
November 2012

Fluoroscopy-guided retrograde core drilling and cancellous bone grafting in osteochondral defects of the talus.

Int Orthop 2012 Aug 11;36(8):1635-40. Epub 2012 Apr 11.

Department of Orthopedics, University of Regensburg, Regensburg, Germany.

Purpose: In undetached osteochondral lesions (OCL) of the talus both revitalisation of the subchondral necrosis and cartilage preservation are essential. For these cases, we assess the results of minimally invasive retrograde core drilling and cancellous bone grafting.

Methods: Forty-one osteochondral lesions of the talus (12x grade I, 22x grade II and 7x grade III according to the Pritsch classification, defect sizes 7-14 mm) in 38 patients (mean age 33.2 years) treated by fluoroscopy-guided retrograde core drilling and autologous cancellous bone grafting were evaluated by clinical scores and MRI. The mean follow-up was 29.0 (±13) months.

Results: The AOFAS score increased significantly from 47.3 (±15.3) to 80.8 (±18.6) points. Lesions with intact cartilage (grades I and II) had a tendency to superior results than grade III lesions (83.1 ± 17.3 vs. 69.4 ± 22.2 points, p = 0.07). First-line treatments and open distal tibial growth plates led to significantly better outcomes (each p < 0.05). Age, gender, BMI, time to follow-up, defect localisation or a traumatic origin did not influence the score results. On a visual analogue scale pain intensity reduced from 7.5 (±1.5) to 3.7 (±2.6) while subjective function increased from 4.6 (±2.0) to 8.2 (±2.3) (each p < 0.001). In MRI follow-ups, five of the 41 patients showed a complete bone remodelling. In two cases demarcation was detectable.

Conclusions: The technique reported is a highly effective therapeutic option in OCL of the talus with intact cartilage grades I and II. However, second-line treatments and grade III lesions with cracked cartilage surface can not be generally recommended for this procedure.
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http://dx.doi.org/10.1007/s00264-012-1530-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535023PMC
August 2012

Chemical synovectomy with sodium morrhuate in the treatment of symptomatic recurrent knee joint effusion.

Rheumatol Int 2012 Oct 17;32(10):3113-7. Epub 2011 Sep 17.

Department of Orthopedic Surgery, University of Regensburg, Asklepios Klinikum Bad Abbach, Kaiser Karl V Allee 3, 93077 Bad Abbach, Regensburg, Germany.

The aim of this study was to assess the efficacy and safety of intra-articular sodium morrhuate injections in the treatment of recurrent knee joint effusions. Ninety-eight knees of 92 patients (f = 59, m = 33) with knee arthritis of heterogeneous etiology were treated with chemical synovectomy (CSO). Of those, 39 patients suffered from rheumatoid arthritis (RA). The mean follow-up was 29.8 months. Clinical outcome was evaluated by analyzing subjective patient satisfaction, activity level, pain severity on the basis of the Visual Analogue Pain Scale (VAS), Lysholm and Gillquist score, and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Fifty-seven percent of all patients and 67% of patients diagnosed with RA were satisfied with CSO. No significant effects on patient satisfaction by CSO were noted in patients older than 40 years. Overall, VAS, Lysholm and Gillquist score, and KOOS improved significantly at final review. The intra-articular application of sodium morrhuate is an effective and safe measure in the treatment of recurrent symptomatic knee joint effusions in young patients suffering from recurrent knee joint effusions.
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http://dx.doi.org/10.1007/s00296-011-2142-1DOI Listing
October 2012

Clinical outcome after Chevron-Akin double osteotomy versus isolated Chevron procedure: a prospective matched group analysis.

Arch Orthop Trauma Surg 2012 Jan 28;132(1):9-13. Epub 2011 Aug 28.

Klinik und Poliklinik für Orthopädie und Orthopädische Chirurgie, für die Universität Regensburg, Asklepios Klinikum Bad Abbach, Kaiser Karl V Allee 3, 93077 Bad Abbach, Germany.

Background: Hallux valgus is a frequent condition of the forefoot, resulting in cosmetic deformity and pain. Chevron osteotomy (CO) is widely employed for the treatment of hallux valgus. Chevron-Akin double osteotomy (CAO) was previously described and superiority over an isolated Chevron procedure was assumed. The objective of this study was to compare the short-to-middle term outcomes of CO and CAO.

Patients And Methods: This study included 72 patients with established diagnosis of mild-to-moderate hallux valgus, treated by either isolated CO or CAO. The CO group included 46 patients (mean 51.5 years) with a mean hallux valgus angle of 27°, while the CAO group included 26 subjects (mean 53.1 years) and a mean hallux valgus angle of 32° preoperatively. All patients were reviewed by physical examination, and standardized questionnaire, and pre- and postoperative standing X-rays were performed. Matched group analysis was carried out to analyze statistical differences of both techniques.

Results: The patients were assessed and group matched at a mean of 1.37 years for the CO group and 1.04 years for the CAO group, postoperatively. Mean improvement of HVA (hallux valgus angle) was 10.6° in the CO group and the CAO group improved by 17.5°. DMAA (distal metatarsal articular angle) improved in the CO group by 5.4° and in the CAO by 13.7°. Mean AOFAS score improved by 27.9 (CO) and 21.5 (CAO). Patient satisfaction was high in both groups, with a tendency towards higher values within the CAO group.

Conclusions: These findings indicate that Chevron-Akin double osteotomy is a save and practicable procedure for the treatment of mild-to-moderate hallux valgus. Superiority of combined Chevron-Akin procedure over an isolated Chevron osteotomy might be limited to distinct clinical settings, but should not be generally assumed.
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http://dx.doi.org/10.1007/s00402-011-1385-3DOI Listing
January 2012

The oncofetal gene survivin is re-expressed in osteoarthritis and is required for chondrocyte proliferation in vitro.

BMC Musculoskelet Disord 2011 Jul 5;12:150. Epub 2011 Jul 5.

Department of Orthopedic Surgery, University of Regensburg, Asklepios Klinikum Bad Abbach, Kaiser Karl V Allee 3, 93077 Bad Abbach, Germany.

Background: Regulation of cell death and cell division are key processes during chondrogenesis and in cartilage homeostasis and pathology. The oncogene survivin is considered to be critical for the coordination of mitosis and maintenance of cell viability during embryonic development and in cancer, and is not detectable in most adult differentiated tissues and cells. We analyzed survivin expression in osteoarthritic cartilage and its function in primary human chondrocytes in vitro.

Methods: Survivin expression was analyzed by immunoblotting and quantitative real-time PCR. The localization was visualized by immunofluorescence. Survivin functions in vitro were investigated by transfection of a specific siRNA.

Results: Survivin was expressed in human osteoarthritic cartilage, but was not detectable in macroscopically and microscopically unaffected cartilage of osteoarthritic knee joints. In primary human chondrocyte cultures, survivin was localized to heterogeneous subcellular compartments. Suppression of survivin resulted in inhibition of cell cycle progression and sensitization toward apoptotic stimuli in vitro.

Conclusions: The present study indicates a role for survivin in osteoarthritic cartilage and human chondrocytes. In vitro experiments indicated its involvement in cellular division and viability. Learning more about the functions of survivin in chondrocyte biology might further help toward understanding and modulating the complex processes of cartilage pathology and regeneration.
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http://dx.doi.org/10.1186/1471-2474-12-150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141611PMC
July 2011

The oncofetal gene survivin promotes cell proliferation and survival in primary human osteoblastic cells.

Calcif Tissue Int 2011 Sep 15;89(3):211-20. Epub 2011 Jun 15.

Department of Orthopedic Surgery, University of Regensburg, Asklepios Klinikum Bad Abbach, Germany.

Survivin, the smallest member of the inhibitor of apoptosis gene family, is critical for the regulation of mitosis and maintenance of cell viability during embryonic development and cancer, while not being detectable in most adult differentiated tissues. We know little about whether survivin plays any physiological or pathophysiological role in the adult musculoskeletal system. We studied the expression of survivin in primary human osteoblastic cells and its biological functions in vitro. Survivin was detected by immunoblotting and real-time PCR. Subcellular localization was analyzed by immunofluorescence. Transfection of siRNA and plasmids coding for wild-type survivin was performed to study survivin function, i.e., proliferation and apoptosis assays. Survivin mRNA and protein are expressed in primary human osteoblastic cells. During interphase survivin localizes predominantly to the cytoplasmic compartment, which is relevant for the organization of the spindle apparatus during mitosis. Survivin knockdown resulted in an arrest of the cell cycle at the G(2)/M phase and increased rates of apoptosis. Elevated levels of survivin in primary human osteoblasts enhanced proliferation and cell viability. Taken together, we demonstrate for the first time that survivin is expressed in primary human osteoblastic cells on the mRNA and protein levels. Our results indicate that survivin is a critical factor for cell division and cell viability in primary human osteoblastic cells. Learning more about survivin's role in human osteoblasts could be an important step toward understanding the complex processes involved in bone homeostasis and remodeling.
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http://dx.doi.org/10.1007/s00223-011-9508-yDOI Listing
September 2011

The antiapoptotic gene survivin is highly expressed in human chondrosarcoma and promotes drug resistance in chondrosarcoma cells in vitro.

BMC Cancer 2011 Apr 2;11:120. Epub 2011 Apr 2.

Department of Orthopedic Surgery, Regensburg University Medical Center, Asklepios Klinikum Bad Abbach, Bad Abbach, Germany.

Background: Chondrosarcoma is virtually resistant to chemotherapy and radiation therapy. Survivin, the smallest member of the inhibitor of apoptosis protein family, is a critical factor for tumor progression and resistance to conventional therapeutic approaches in a wide range of malignancies. However, the role of survivin in chondrosarcoma has not been well studied. We examined the importance of survivin gene expression in chondrosarcoma and analysed its influences on proliferation, apoptosis and resistance to chemotherapy in vitro.

Methods: Resected chondrosarcoma specimens from which paraffin-embedded tissues could be extracted were available from 12 patients. In vitro experiments were performed in human chondrosarcoma cell lines SW1353 and Hs819.T. Immunohistochemistry, immunoblot, quantitative PCR, RNA interference, gene-overexpression and analyses of cell proliferation and apoptosis were performed.

Results: Expression of survivin protein was detected in all chondrosarcoma specimens analyzed, while undetectable in adult human cartilage. RNA interference targeting survivin resulted in a G2/M-arrest of the cell cycle and led to increased rates of apoptosis in chondrosarcoma cells in vitro. Overexpression of survivin resulted in pronounced resistance to doxorubicin treatment.

Conclusions: These findings indicate that survivin plays a role in the pathogenesis and pronounced chemoresistance of high grade chondrosarcoma. Survivin antagonizing therapeutic strategies may lead to new treatment options in unresectable and metastasized chondrosarcoma.
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http://dx.doi.org/10.1186/1471-2407-11-120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076263PMC
April 2011

In-vitro investigation of a noninvasive referencing technology for computer-assisted total hip arthroplasty.

Orthopedics 2010 Apr 16;33(4). Epub 2010 Apr 16.

Department of Orthopedic Surgery, Regensburg University Medical Center, Asklepios Klinikum Bad Abbach, Kaiser-Karl V.-Allee 3, 93077 Bad Abbach, Germany.

The use of surgical navigation to aid in total joint replacement requires the bony fixation of reference marker arrays. In this context, a number of potential complications have been reported, including pin-site infection, soft tissue morbidity, and stress fracture. This study was performed to determine whether a femoral pinless, imageless navigation method for total hip arthroplasty (THA) is an accurate alternative method of measuring leg-length and offset change intraoperatively. Computer-assisted THA was simulated on a Sawbones bench test model including a femoral soft tissue model. Leg-length and offset changes were calculated by an imageless navigation system using the pinless measurement algorithm, in which the calculation of leg-length and offset changes is based on a specific realignment of the leg and then compared to corresponding measurements on a millimeter scale at the level of the femoral condyles. Mean difference in leg-length measurement (navigation versus millimeter paper) was 0.9 mm (95% confidence interval [CI]: 0.03-1.7 mm, P=.043), and the corresponding mean difference in offset was 1 mm (95% CI: 0.06-1.9 mm, P=.038). A noninvasive, pinless femoral system is a reliable tool for controlling leg length and offset during THA in an in-vitro setup. This system could lead to a reduction of potential risks associated with navigation techniques.
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http://dx.doi.org/10.3928/01477447-20100225-10DOI Listing
April 2010

Analysis of bone matrix composition and trabecular microarchitecture of the femoral metaphysis in patients with osteonecrosis of the femoral head.

J Orthop Res 2009 Sep;27(9):1175-81

Department of Orthopaedic Surgery, University of Regensburg, ZMB/BioPark, Regensburg, Germany.

Osteonecrosis of the femoral head (ONFH) usually affects young individuals. In advanced stages of ONFH, total hip replacement is the golden standard. However, survivorship after total hip replacement has been reported to be poorer in patients with ONFH compared to patients with primary osteoarthritis (OA). In radiological and histological studies, an impaired bone quality was found not only for the femoral head, but also for the intertrochanteric and metaphyseal region. We hypothesize that alterations of bone quality in the femoral metaphysis might contribute to early stem loosening. The objective of this study was to assess the gene expression levels of factors regulating bone formation and remodeling of the intertrochanteric regions and the proximal femoral canal in patients with ONFH and those with primary OA. The cellular and macromolecular composition of the bone matrix was assessed by osteocalcin immunohistochemistry, and the three-dimensional organization of trabecular bone was characterized by microCT analysis. Gene expression of BMP-2 is twofold higher in the proximal femur in the region of the greater trochanter of patients with ONFH compared to those with OA. The number of osteoblasts in the greater trochanter of patients with ONFH (253/mm(2)) is increased compared to patients with OA (156/mm(2)). Trabecular properties in ONFH bone are altered for bone volume (OA: 32 mm(3), ONFH: 51 mm(3)) and structure model index (OA: 2.2, ONFH: 1.6) in the proximal femoral canal, but not in the trochanteric regions. These alterations in bone metabolism and architecture might contribute to the higher rates of stem loosening after total hip replacement in patients with ONFH, however, further experimental and clinical studies are needed to support our findings.
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http://dx.doi.org/10.1002/jor.20873DOI Listing
September 2009

[Matrix-associated autologous chondrocyte transplantation (MACT). Minimally invasive technique in the knee].

Oper Orthop Traumatol 2008 Sep;20(3):208-19

Orthopädische Klinik für die Universität Regensburg, Asklepios Klinikum Bad Abbach, Bad Abbach.

Objective: Repair of localized cartilage defects in the knee.

Indications: Localized partial or full-thickness cartilage defects in the knee or osteochondral lesions (osteochondritis dissecans [OD]).

Contraindications: Generalized cartilage defects, osteoarthritis, bacterial and rheumatoid arthritis, uncorrected axis deformities, ligament instability, patella instability, meniscectomy.

Surgical Technique: Two-step procedure. 1. Diagnostic arthroscopy and cartilage biopsy for cell cultivation. 2. Minimalized arthrotomy. Defect debridement. Autologous cancellous bone grafting in OD. Glueing of the cell-loaded scaffold into the defect.

Postoperative Management: Early functional rehabilitation with knee orthosis. Partial weight bearing (20 kg) for 6 weeks.

Results: 50 patients (24 female, 26 male, age 14-44 years, mean 30.3 years) with 58 focal cartilage defects (III-IV degrees) of the knee in the medial (n = 32) or lateral condyle (n = 5), patella (n = 14) and/or trochlea (n = 7) underwent matrix-associated autologous chondrocyte implantation (MACI). The mean follow-up was 24 months (21-29 months). The mean defect size was 4.1 cm2(1.6-6.1 cm2). The Lysholm Score improved from 57.3 to 87.4 points, the DGKKT (German Society of Autologous Cartilage and Bone Cell Transplantation) Score from 55.3 to 85.5 points. Pain on a visual analog scale (VAS) diminished from 5.5 to 2.1, while subjective function enhanced from 4.5 to 7.6. All scores were significant (p < 0.01; t-test). In eleven patients (twelve defects), a second-look arthroscopy revealed a mostly fibrocartilaginous regenerative tissue in 41.7% (5/12) and a mixed fibrous/hyaline regenerative tissue in 33.4% (4/12). 54% (27/50) of the patients estimated their result as excellent, 28% (14/50) as good, 16% as fair, and 2% (1/50) as poor.
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http://dx.doi.org/10.1007/s00064-008-1303-1DOI Listing
September 2008

Cementing technique in femoral resurfacing.

Arch Orthop Trauma Surg 2009 Oct 18;129(10):1317-25. Epub 2008 Sep 18.

University of Regensburg, Regensburg, Germany.

Introduction: The cementing technique is one of the various speculated factors that might contribute to the failures of resurfacing arthroplasty of the hip. The influence of bony preparation by jet lavage or lavage only in combination with different cementing techniques and cements of different viscosity in a study on fresh human femoral heads has not been evaluated so far.

Materials And Methods: Sixty fresh human femoral heads were prepared for resurfacing following manufacturers' instructions and divided into 12 groups. The different groups received either syringe lavage or jet lavage and either a low-, medium- or high-viscosity cement with either packing or quarter filling of the implant with recess of the femoral stem in each case. Application of the implant was standardized. After polymerization, the femoral heads were cut into quarters and polished. Cement penetration was assessed using a square millimeter grid under optical zoom.

Results: Manual packing with high viscosity cement is a reproducible method in resurfacing arthroplasty. Syringe lavage and jet lavage mainly showed comparable cement penetration patterns when applied same cementing techniques. The penetration depth ranged from a mean of 0.6 to 3.2 mm with 0.4 being the lowest and 4.0 being the deepest. The mantle thickness ranged from 0.8 to 2.4 mm with statistically significant thicker mantles with filling, compared to packing.

Conclusion: Our results showed distinct less penetration depth than previously reported and that just medium viscosity cement reached reliable results in the supposed range of penetration depth and cement mantle thickness. Jet lavage should be recommended for the low-viscosity cement but avoided in combination with a cement filling technique of lower viscosity cements. Filling of the implant caused the greatest penetration depth and a higher number of incomplete seatings and should therefore be avoided.
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http://dx.doi.org/10.1007/s00402-008-0753-0DOI Listing
October 2009

Tissue concentrations of vancomycin and Moxifloxacin in periprosthetic infection in rats.

Acta Orthop 2007 Dec;78(6):766-73

Department of Orthopedic Surgery, Institute of Medical Microbiology and Hygiene, University of Regensburg, Landshut, Germany.

Background: A one-step exchange of an endoprosthesis with periprosthetic infection requires effective antibiotics at high concentrations around the endoprosthesis. We evaluated the tissue distribution of vancomycin and Moxifloxacin in a standardized in vivo model of periprosthetic infection.

Methods: 36 male rats with periprosthetic infection of the left hind leg, induced by a standardized procedure, received either antibiotic treatment with vancomycin or Moxifloxacin twice daily for 2 weeks, or a sham treatment. After the last administration, different tissues from each animal were evaluated for concentrations of antibiotic.

Results: Compared to plasma, the tissue concentrations of Moxifloxacin were higher in all tissues investigated (lung, muscle, fat, bone) and the tissue-plasma ratio of Moxifloxacin was considerably higher than that of vancomycin. The concentrations of Moxifloxacin were equally high in the infected and the uninfected hind leg, whereas the vancomycin concentrations were significantly higher in the infected leg.

Interpretation: The standardized model of periprosthetic infection described here can be extrapolated to different bacterial and mycotic pathogens, and also to different antibiotics or therapeutic regimes. It provides a way of correlating tissue concentrations with clinical outcome in future studies.
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http://dx.doi.org/10.1080/17453670710014536DOI Listing
December 2007

Treatment of implant-associated infections with moxifloxacin: an animal study.

Int J Antimicrob Agents 2006 May 18;27(5):444-8. Epub 2006 Apr 18.

Department of Orthopedic Surgery, University of Regensburg, Kaiser-Karl V.-Allee 3, D-93077 Bad Abbach, Germany.

The efficacy of moxifloxacin in the treatment of an implant-associated infection by Staphylococcus aureus was compared with vancomycin in an animal study. The femoral medullary cavity of 36 Wistar rats was contaminated with S. aureus (ATCC 29213) and a metal device was implanted. After treatment for 14 days with moxifloxacin (2 x 10 mg/kg/day) or vancomycin (2 x 15 mg/kg/day), the bacterial counts (colony-forming units) in the periprosthetic bone, the soft tissue and the implant-associated biofilm were measured. Compared with the control group, moxifloxacin achieved a highly significant decrease in the microbial counts in the bone and soft tissue and in the biofilm (P<0.001). Moreover, the efficacy of moxifloxacin was significantly greater than that of vancomycin (P<0.01). Vancomycin did not reduce the microbial count significantly compared with the control group (P>0.05). The results justify further investigations of the treatment of implant-associated infections due to S. aureus with moxifloxacin.
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http://dx.doi.org/10.1016/j.ijantimicag.2005.12.003DOI Listing
May 2006

Pro-MMP-9 is a specific macrophage product and is activated by osteoarthritic chondrocytes via MMP-3 or a MT1-MMP/MMP-13 cascade.

Exp Cell Res 2004 Jul;297(2):303-12

Department of Physiological Chemistry and Pathobiochemistry, University Hospital of Münster, Münster, Germany.

In joint diseases of both the inflammatory (rheumatoid arthritis, or RA) or the degenerative variety (osteoarthritis, or OA), matrix metalloproteinases (MMPs) are essential mediators of irreversible tissue destruction. MMP-9 is secreted as a stable, inactive zymogen and is proteolytically converted to the active enzyme. To understand the activation mechanism of MMP-9 in joint diseases, the process was investigated in serum-free cocultures of human articular chondrocytes and macrophages. Macrophages extensively expressed and secreted pro-MMP-9 whereas chondrocytes failed to produce the enzyme. However, efficient activation of pro-MMP-9 required soluble and membrane-associated chondrocyte proteinases. Two alternative activation pathways mainly involved MMPs and, marginally, serine or cysteine proteinases. MT1-MMP (MMP-14), the only MT-MMP expressed in chondrocytes, converted pro-MMP-13 which, in turn, cleaved pro-MMP-9. Alternatively, pro-MMP-9 was activated less efficiently by MMP-3, which was converted by autocatalysis or by serine or cysteine proteinases. Both pathways were triggered by chondrocytes from OA, but not normal joints. Therefore, articular chondrocytes are not innocent bystanders in joint diseases. They not only produce destructive enzymes guided by environmental cues but also they can instruct inflammatory cells or cells from surrounding tissues to do so by converting in several ways zymogens produced but not activated by these cells themselves.
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http://dx.doi.org/10.1016/j.yexcr.2004.02.027DOI Listing
July 2004

Increased prevalence of semaphorin 3C, a repellent of sympathetic nerve fibers, in the synovial tissue of patients with rheumatoid arthritis.

Arthritis Rheum 2004 Apr;50(4):1156-63

University Hospital Regensburg, Regensburg, Germany.

Objective: The presence of selective sympathetic nerve repellents, i.e., semaphorins, may be responsible for the observed reduction of sympathetic innervation in the synovial tissue of patients with rheumatoid arthritis (RA). This study was undertaken to investigate the presence of different semaphorins in synovial tissue of patients with RA, patients with osteoarthritis (OA), and control subjects without inflammation.

Methods: In situ hybridizations with digoxigenin-labeled RNA probes directed against different semaphorins were performed. The presence of semaphorin 3C (S3C) in the synovial tissue of 10 RA, 10 OA, and 5 control subjects was investigated using a polyclonal antiserum directed against S3C.

Results: All in situ hybridizations revealed the presence of S3C messenger RNA, but no other investigated semaphorin (i.e., against primary afferent sensory nerve fibers), in the synovial tissue of RA and OA patients. Immunohistologic double staining demonstrated that macrophages and fibroblasts were positive for S3C protein. Quantitative analysis of S3C protein staining showed an increased density of S3C-positive cells in the synovial tissue of RA patients (mean +/- SEM 339 +/- 65 cells/mm(2)) in comparison with OA patients (168 +/- 27/mm(2); P = 0.031 versus RA) and controls (126 +/- 26/mm(2); P = 0.027 versus RA). Studies of the relationship between sympathetic nerve fiber density and S3C-positive cell density in the tissue of all patients showed that RA patients generally had lower densities of sympathetic nerve fibers and higher densities of S3C-positive cells than OA patients and control subjects.

Conclusion: These findings suggest that S3C from macrophages and fibroblasts, which is selectively directed against sympathetic nerve fibers, could be one element responsible for reduced sympathetic innervation in RA tissue. The inability of sympathetic nerve fibers to reinnervate synovial tissue could contribute to the chronic nature of RA.
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http://dx.doi.org/10.1002/art.20110DOI Listing
April 2004