Varying development of femoral and tibial subchondral bone tissue and their interaction with articular cartilage during progressing osteoarthritis.

INTRODUCTION: Differences between tibial and femoral joint surfaces and knee compartments concerning coupled bone and cartilage turnover or bone-cartilage cross talk have not been previously examined, although the mechanical and biological interaction of the mineralized subchondral tissues with articular cartilage is of great importance for advancing osteoarthritis. MATERIALS AND METHODS: Therefore, with the help of immunohistochemistry and real-time polymerase chain reaction (RT-PCR), human knee joint cartilage tissue was investigated for expression of key molecules of the extracellular matrix and cartilage composition (collagen type I and II, aggrecan) plus proteoglycan content (colorimetric analysis). Furthermore, we correlated the results with 3D microcomputed tomography of the underlying subchondral bone (high-resolution micro-CT system). Measurements were performed in dependence of the anatomical site (femoral vs. tibial, medial and lateral each) to identify regional differences during the osteoarthritic process. From an enduring series of 108 patients undergoing implantation of TKA, 34 osteochondral samples with lesions macroscopically classified as ICRS grade 1b (group A) and 34 samples with ICRS grade 3a/3b lesions (group B) were compared with 21 healthy controls. RESULTS: Concerning 3D analysis, the medial femoral condyle and tibia showed the most significant increase in bone volume fraction and a decrease in the trabecular number in group B frequently accompanied by subchondral bone resorption pits and enchondral ossification. Under physiological conditions, tibia plateaus show lower bone volume fraction than the corresponding femoral site and this difference enlarges with advancing OA. Partially even contradictory behavior was observed such as trabecular separation at the lateral tibial and medial plateau in osteochondral OA samples of the same patients. Collagen type II expression levels show faster and varying changes than type I during the OA process, leading to a lower positive or negative correlation with bone microstructural analysis, especially on the tibia plateau. CONCLUSIONS: Structural bone and cartilage parameter changes showed varying developments and correlations among each other in the different compartments of the knee. As a clinical conclusion, therapies to postpone or prevent cartilage degeneration by influencing the loss of mineralized bone could be site dependent.

Regional differences of tibial and femoral cartilage in the chondrocyte gene expression, immunhistochemistry and composite in different stages of osteoarthritis.

The function of articular cartilage as an avascular tissue is mainly served by collagen type II and proteoglycan molecules. Within this matrix homeostasis between production and breakdown of the matrix is exceptionally sensitive. The current study was conducted to identify regional differences in specific alterations in cartilage composition during the osteoarthritic process of the human knee joint. Therefor the changes in the expression of the key molecules of the extracellular matrix were measured in dependence of the anatomical side (femoral vs tibial) and associated with immunohistochemistry and quantitative measurement. 60 serial osteochondral femoral condyle and the tibial plateau samples of patients undergoing implantation of total knee endoprosthesis of areas showing mild (Group A, macroscopically ICRS grade 1b) respectively advanced (Group B, macroscopically ICRS grade 3a/3b) (30 each) osteoarthritis according to the histological-histochemical grading system (HHGS) were compared with 20 healthy biopsies with immunohistochemistry and histology. We quantified our results on the gene expression of collagen type I and II and aggrecan with the help of real-time (RT)-PCR. Proteoglycan content was measured colorometrically. In group A slightly increased colour intensity was found for collagen II in deeper layers, suggesting a persisting but initially still intact repair process. But especially on the medial tibia plateau the initial Col II increase in gene expression is followed by a decrease leading to the lowest over all Col II expression on the medial plateau, here especially in the central part. There in late stage diseases the collagen type I expression was also more pronounced. Markedly decreased safranin O staining intensity was observed in the radial zone and less reduced intensity in the transitional zone with loss of zonal anatomy in 40% of the specimens in group A and all specimens in group B. Correlation between colorometrically analysed proteoglycan GAG content and aggrecan Real Time PCR is mainly weak. Tibial and femoral cartilage in contrast to patellar cartilage both are preferential exposed to compressive stresses, but presence of menisci affects the load distribution at the tibial side, which creates varying conditions for the different cartilage surfaces in the knee. As directly measured Poissons ratio in tibial cartilage is higher but Younǵs modulus is lower than in femoral cartilage, different resulting feedback amplification loops interact with proceeding cartilage damage. The initial loss of aggrecan may support Matrix metalloproteinases (Mmps) in the access to the collagen network and the considerably differing mechanical properties at both joint surfaces result in varying increased synthesis and release of matrix degrading enzymes. The present study has identified a selection of events which reflect the response of cartilage structure and composite, chondrocytes itself and their productivity to changes in mechanical stress depending on the anatomical site.

[Important Aspects of Diagnosis and Minimally Invasive Treatment of Metastases in the Spine Through the Plasma Field Therapy (Cavity Coblation Method)]. / Besonderheiten der Diagnostik und der minimalinvasiven chirurgischen Behandlung von multiplen Metastasen an der Wirbelsäule durch Plasmafeldtherapie (Cavity-Coblation-Methode).

Background and objectives: Until recently, it was almost impossible to perform major surgery on metastases in the spine. This is especially the case for multiple spinal metastases and for older multi-morbid patients with higher OP risks. It is very important in such cases that the operation should be as minimally invasive as possible, and should aim to reduce pain, treat fractures and to improve the quality of life. The aim of this publication is to present and discuss the specific features of the methodology, problems, surgical techniques, as well as the effectiveness of the modernised cavity/coblation method and results of the treatment of 240 patients with spine metastases. Patients/Material and Method: Patients: Patients of every age with bone destruction were treated, with osteolysis and pathological fractures of vertebrae caused by metastases. The pre-operative diagnosis was evaluated by X-Ray, MRT, CT, whole-body F18-FDG-PET, whole-body bone scintigraphy, histology. Cavity/coblation method: Tumour resection was carried out by the plasma field (42 °C, cold energy) over the percutaneous trans-/extrapedicular access and was followed by balloon kyphoplasty. Tumour tissue was removed, deformation corrected and stability enhanced. The treatment clearly reduced the risks of recurrence, fracture and compression of the neural structures. Local radiotherapy and chemotherapy were performed post-operatively. Clinical and radiological follow-ups, included tumour staging, were performed regularly after the OP (after 2 and 14 days and 3, 6,12, 24, 36, 48 and 60 months), including data on pain and improvement in quality of life. Results: Within 6 years (03/08-04/14), we treated 240 patients with multiple spinal metastases (146 female, 94 male, age range 31-92 years, average age 65.5 years) or 784 vertebral bodies. 61 patients were also given dorsal percutaneous instrumentation and straightening. All patients experienced a significant reduction in pain, and improvements in satisfaction and quality of life. Treatment was combined with chemotherapy and local radiotherapy to reduce tumour cell growth or recurrence rate. Patients could be rapidly mobilised after surgery, blood loss was minimal, and the next oncology treatment could be initiated immediately. Discussion/Conclusions: Cavity/coblation is a safe and minimally invasive procedure, as confirmed by our own short- and long-term results, as well as by reports/publications of other workers. OP risks, blood loss, and surgical time are lower and shorter. This new method is very promising for the future. It is important that the indication is correct and the treatment strategy must be adapted individually. Prognosis must be assessed and the surgical technique must be precise.

[Tumours and metastases of the spine : cavity/coblation surgery and vertebroplasty/kyphoplasty]. / Tumoren und Metastasen an der Wirbelsäule : Cavity/Coblation-Operation und Vertebro-/Kyphoplastie.

BACKGROUND: Radical surgery for metastases in the spine is in many cases not possible, includingthe higher risk of surgery in older patients with co-morbidities. The aims of treatment are: minimally invasive and maximally effective tumour removal, fracture position, stabilization, pain reduction, and improved quality of life. The specific features and problems of diagnosis and treatment using the cavity/coblation method, , the surgical technique, and the results of the treatment of 250 patients with spinal tumours/metastases are presented. MATERIALS AND METHODS: Tumour resection is carried out by plasma field, via percutaneous trans-/extrapedicular access, followed by kyphoplasty. Clinical and radiological follow-up was carried out postoperatively, including data on pain reduction and improvement of quality of life. RESULTS: Within 6 years (March 2008t February 2014) a total of 250 patients, or 812 spines were treated. In 59 cases dorsal percutaneous instrumentation and straightening were carried out. Minimal blood loss and a very low complication rate were recorded. After surgery, significant pain reduction, satisfaction, early mobilization, and improvement in quality of life were demonstrated in all patients. Immediate radio- and chemotherapy could be carried out. In 38 cases cement escaped laterally into the intervertebral space, but this had no clinical relevance. 188 patients have since died because of tumour manifestations. CONCLUSIONS: The cavity/coblation method has been demonstrated to be a safe, minimally invasive procedure, with good short- and long-term results and lower complication rates. A comprehensive diagnostic, including tumour staging, the correct indication, and prognosis estimation, is important.

[Minimally invasive treatment of tumours and metastases in the spine by plasma field therapy (cavity coblation) and vertebro-/kyphoplasty with and without additional dorsal percutaneous instrumentation]. / Minimalinvasive Therapie der Tumoren und Metastasen der Wirbelsäule durch Plasmafeldtherapie (Cavity Coblation) und Vertebro-/Kyphoplastie mit und ohne zusätzliche dorsale perkutane Instrumentation.

BACKGROUND: Realisation of a major operation of tumours/metastases in the backbone is in many cases not possible, above all in older multimorbid patients with higher OP risks. So it is important to proceed here so minimally invasive as possible, but at least actually to reduce above all pain for the patient and the danger of other fractures and deformations and to improve thereby the quality of life. The modern method of the percutaneous cavity coblation by plasma field has been known for a short time and has been used by us for 5.5 years successfully. The aim of this work is to present the specific features of the methodology, problems, OP technology, results of the treatment of more than 218 patients with spine tumours/metastases. PATIENTS/MATERIAL AND METHODS: Old and young patients with spinal tumours (painful large haemangiomas) and metastases were treated. The Cavity SpineWand device (ArthroCare) provides a space in the tumour by patented coblation technology (coblation = controlled ablation, based on plasma-provided high-frequency energy) and can be used with additional procedures such as, for example, cement injection for vertebral stabilisation - kypho-/vertebroplasty. Access to the backbone occurs percutaneously and transpedicularly, in some cases extrapedicularly. By the removal of tumour tissue not only space for the cement replenishment is achieved, but also complete destruction/vaporisation of the tumour cells. Recurrence risk, fracture danger and compression of the neural structures are clearly reduced thereby. RESULTS: Within the 5.5 years (03/2008-09/2013) we treated 218 patients (144 f., 74 m., age 31-92 years) with spinal tumours and backbone metastases with this method. In 59 cases it was carried out in addition to dorsal percutaneous instrumentation and erection. RESULTS of clinical and radiological evaluations were assessed at 2 and 14 days as well as at 3, 6, 12, 24, 36, 48 and 60 months post-surgery (but not for control with all patients on account of the shorter method application time). A clear pain reduction and with it satisfaction and quality of life improvement were seen for all patients. In several cases treatment was combined with chemotherapy or radiotherapy by which also tumour cell growth or recurrence could be clearly diminished. Patients could be mobilised quickly after surgery, blood loss was minimal, further oncological treatment could be initiated immediately. Especially for haemangiomas in one or several levels with massive bleeding tendency and danger of cement embolism, these risk factors were clearly minimised by ablation and coagulating the tumour vessels. COMPLICATIONS: in 29 cases with especially large osteolytic defects slight cement escape was observed paravertebrally (forwards, lateral and in the intervertebral disc field), without clinical relevance, an intervention was not necessary. 65 patients (43 f., 22 m.) died due to tumour intoxication. CONCLUSION: The percutaneous cavity coblation method for the treatment of tumours and metastases in the spine represents a sure, minimally invasive procedure for patients as demonstrated by short-term and long-term results. Due to the percutaneous, minimally invasive access, the OP risks, especially blood loss and OP times are clearly low and shorter. This new method is as yet only available in a few medical centres in Germany as well as in other countries but at the moment it is being used successfully and from our point of view has a promising future.

An economic analysis of aseptic revision hip arthroplasty: calculation of partial hospital costs in relation to reimbursement.

INTRODUCTION: Aseptic loosening is one of the most common intermediate and long-term complications after total hip replacement (THR). These complications cause suffering and require expensive revision surgery. Little concrete data on direct costs are available from the hospital's, moreover operating department's perspective. We here provide a detailed analysis of the costs of THR revision and relate them to reimbursement underlying the German diagnosis-related groups (DRG) system. MATERIALS AND METHODS: Major cost parameters were identified using for orientation the cost matrix of the German Institute for Hospital Reimbursement (InEK GmbH). We then retrospectively analysed the major direct costs of aseptic revision THR in terms of contribution margins I and II. The analysis included a total of 114 patients who underwent aseptic revision from 1 January 2009 to 31 March 2012. Data were retrieved from the hospital information system and patient records. All costs of surgery, diagnostic tests, and other treatments were calculated as purchase prices in EUR. The comparative analysis of direct costs and reimbursements was done for DRG I46A and I46B from the hospital's, especially treating department's rather than the society or healthcare insurance's perspective. RESULTS: The average direct cost incurred by the hospital for a THR revision was 4,380.0. The largest share was accounted for surgical costs (62.7 % of total). Implant and staff costs were identified as the most important factors that can be influenced. The proportion of the daily contribution margin that was left to cover the hospital's indirect cost decreased with the relative cost weight of the DRG to which a patient was assigned. CONCLUSION: Our study for the first time provides a detailed analysis of the major direct case costs of THR revision for aseptic loosening from the provider's perspective. Our findings suggest that these revision operations could be performed cost-beneficially by the operating unit. From an economic perspective, cases with higher cost weights are more favorable for a hospital. These results need to be confirmed in multicenter studies.

[Sledge versus bicondylar surface treatment in the endoprosthetic therapy for unicompartmental knee arthrtitis--a comparative cost analysis]. / Kostenvergleichskalkulation der Schlitten- vs. bikondylären Oberflächenversorgung am Kniegelenk.

BACKGROUND: The G-DRG system reimburses sledge endoprosthetic implantations (UKA) at a much lower rate than surface replacements (TKA), at significantly different cost weights (CW). Therefore, when only G-DRG payments are considered, the complete endoprosthesis implantation produces higher gains. An orientation on these revenues alone, however, does not provide the basis for an economically sound decision-making process. The aim of this study is to present a comparison of the variable costs of the two procedures. MATERIAL AND METHODS: The mean cost and performance data of 28 Endo-Model UKA implantations and of 85 NexGen CR TKA replacements were compared with each other in 2007. RESULTS: From the perspective of the hospital, when the correct medical indication is present, UKA treatment is of greater economic advantage. In this way the total unit contribution margin can be improved, and although the relative weighting is comparatively low, the costs are significantly lower than in a comparative analysis of the TKA. CONCLUSION: For the desired maximisation of the unit contribution margin, assuming that it is the proper medical indication, the recommendation for the hospital would be implantation of the UKA. Considered from the economic perspective of gains and costs, the assumption that a TKA would be advantageous could not be confirmed in the present study.

[2010 Love Parade in Duisburg: clinical experiences in planning and treatment]. / Loveparade 2010 Duisburg - klinische Erfahrungen in Vorbereitung und Versorgung.

BACKGROUND: Tragic incidents at the 2010 Love Parade attracted significant public attention. As the frequency of similar events increases, more hospitals and practitioners will face the necessities of planning and response to unforeseeable occurrences. Obligatory guidelines for physicians do not exist, so that essential aspects are repeatedly discussed for each new event. This paper summarizes the experience of hospitals and emergency departments and draws conclusions, allowing recommendations for reasonable proposals for hospitals and practitioners. METHODS AND MATERIAL: A structured analysis of data concerning planning, patient flow and injury statistics led to a profile determining personnel, rooms and material which have to be provided by the hospitals. In a consensus conference afterwards and personal interviews with clinical coordinators the preparation of hospitals was evaluated to separate reasonable from needless efforts. RESULTS: We describe various measures concerning staff, logistics and rooms from the viewpoint of actual application. Reasonable measures for preparation and management of mass panic are analysed and described in detail. Problems are explained and solutions discussed. The result is a qualitative catalogue, which supports the organization of future events. CONCLUSION: Knowledge and reflection on the experience of the 2010 Love Parade optimizes local emergency guidelines and planning for similar events. A coordinated cooperation of all involved is essential.

[Relevance of different sequences in MRI-detected subchondral bone damage of the knee joint and possible therapeutic options]. / Relevanz unterschiedlicher MRI-Sequenzen bei subchondralen Verletzungen des Kniegelenkes und mögliche therapeutische Konsequenzen.

With the advent of magnetic resonance imaging (MRI) after knee injuries interest has focussed on the clinical relevance of different concomitant osseous damage. Different MRI- sequences reveal varying characteristics of such lesions. Prospective data of 69 patients with MRI-detected sub-acute subchondral fractures or bone bruises according to the classification of Mink was recorded. Function, symptoms (Noyes) and activity (Tegner) were assessed at the time of first MRI and 7,4 months later including a follow-up MRI using T 2-weighted fat saturated (fs) fast-spin-echo-sequences (FSE), T 1-weighted spin echo (SE) sequences, Proton-density-weighted spin echo-sequences (SE) and T 2-weighted (fs) gradient-echo-sequences. The patients were divided in 4 groups: patients with subchondral fracture and patients with pure bone bruise subdivided in patients with and without intraarticular knee lesions. Bone bruises were diagnosed in 44 cases, subchondral fractures in 25 patients. Patients without intra-articular pathology had significantly poorer function at the time of MRI with subchondral fractures, but not in the sub-group with intra-articular damage. Symptoms were not significantly different in both groups at this time. At 7,4 months both sub-groups with fractures had a lower level of function compared to patients with bone bruises, activity score and symptoms showed poorer results in the group without intraarticular lesion (p = 0,01 for all scores). T 1- weighted spin echo (SE) sequences revealed to be the most important tool to differentiate the various lesions. Hints for a modification of rehabilitation avoiding axial forces in case of subchondral fractures might be the use of isokinetics using open kinetic chain instead of closed kinetic chain or orthosis with relief of the affected compartment.

Tibial wedge osteotomy for osteochondral transplantation in talar lesions.

Between 1999 and 2002, 16 patients with osteochondral lesions on the central and posterior talar dome underwent osteochondral autografting. A new approach with temporary removal and replacement of a tibial bone block from the anterior tibial plafond was adopted. Inclusion criteria were joint stability, an age between 18 and 50 years, and osteochondral lesions stages 3 and 4 according to the radiological classification of Loomer, for which previous arthroscopic treatment was not successful. All patients underwent clinical and MRI evaluation after 12, 35 and 59 months. The AOFAS Ankle Hindfoot score improved significantly between the preoperative period and 1 year (p < 0.001), between 1 and 3 years (p < 0.001), but not between 3 and 5 years postoperative (p = 0.37). The score was independent from patients gender (p = 0.44) and age. The Spearman coefficient of correlation between clinical outcome and defect size was - 0.79 (p = 0.01), indicating that patients with small lesions had the best results. Control radiographs and MRIs showed no reduced joint space and good integration of the tibial bone block without incongruency. Osteochondral grafting with temporary removal of a tibial bone block is a successful technique with good midterm results in osteochondral talar lesions for which arthroscopic excision, curettage and drilling has failed.

Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases.

Previous findings have suggested that class IIa histone deacetylases (HDACs) (HDAC4, -5, -7, and -9) are inactive on acetylated substrates, thus differing from class I and IIb enzymes. Here, we present evidence supporting this view and demonstrate that class IIa HDACs are very inefficient enzymes on standard substrates. We identified HDAC inhibitors unable to bind recombinant human HDAC4 while showing inhibition in a typical HDAC4 enzymatic assay, suggesting that the observed activity rather reflects the involvement of endogenous copurified class I HDACs. Moreover, an HDAC4 catalytic domain purified from bacteria was 1,000-fold less active than class I HDACs on standard substrates. A catalytic Tyr is conserved in all HDACs except for vertebrate class IIa enzymes where it is replaced by His. Given the high structural conservation of HDAC active sites, we predicted the class IIa His-Nepsilon2 to be too far away to functionally substitute the class I Tyr-OH in catalysis. Consistently, a Tyr-to-His mutation in class I HDACs severely reduced their activity. More importantly, a His-976-Tyr mutation in HDAC4 produced an enzyme with a catalytic efficiency 1,000-fold higher than WT, and this "gain of function phenotype" could be extended to HDAC5 and -7. We also identified trifluoroacetyl-lysine as a class IIa-specific substrate in vitro. Hence, vertebrate class IIa HDACs may have evolved to maintain low basal activities on acetyl-lysines and to efficiently process restricted sets of specific, still undiscovered natural substrates.

Regression and correlation analysis of preoperative versus intraoperative assessment of axes during navigated total knee arthroplasty.

OBJECTIVE: Modern computer assisted surgery (CAS) systems allow accurate positioning of the implants in navigated Total Knee Arthroplasty (TKA). However, when an operation is performed with a navigation system, it is important to know if the anatomical situation of the knee is reflected equally in both the preoperative image (e.g., CT) and the intraoperative navigation setup. In this study, we compared the preoperative anatomical situation to the virtual intraoperative situation of the navigation setup. MATERIAL AND METHODS: We analyzed 24 navigated operations. Intraoperatively, the condylar twist angle (CTA) was documented with the navigation system by measuring the angle between the transepicondylar axis (TEA) and posterior condyle axis (PCA). This data was compared with the preoperative data from the CT scan. RESULTS: Statistical analysis revealed that there was no correlation between the pre- and intraoperative data (r = 0.095). CONCLUSIONS: Statistically, there is no possibility of collecting the same angles and axes when using the two different methods (CT and navigation) on the same knee. It is not possible to copy the preoperative anatomical situation exactly with the virtual intraoperative data. Reasons for this include systematic errors, as well as inter- and intraobserver errors in both methods.

Subchondral bone trauma causes cartilage matrix degeneration: an immunohistochemical analysis in a canine model.

UNLABELLED: Joint instability was believed to be the main cause of osteoarthritis following non-fracture articular trauma. However, sudden high impact load through articular cartilage onto subchondral bone may also cause osteoarthritic changes. OBJECTIVE: We asked whether early osteoarthritic changes following transarticular impact may be depicted using immunofluorescence on unfixed cryosections to contribute to a more detailed understanding of degenerative processes of joint impaction. DESIGN: Transarticular impacts were applied to patellofemoral joints of 12 skeletally mature beagle dogs (age: 15-16 months) using a drop tower. Biopsies of impact areas were sampled after 6 months and processed for standard light microscopy on formalin-fixed sections and for immunofluorescence for collagen type I (col I), type II (col II) and aggrecan (AC) on unfixed cryosections. Gross morphology and immunofluorescence on cryosections were documented using a semi-quantitative scaling system, compared to healthy controls and to standard light microscopy. RESULTS: Four biopsies showed almost entirely fibrocartilaginous morphology, four appeared to be of preserved hyaline morphology with only minor signs of fibrocartilaginous remodelling and four showed preserved hyaline appearance. We found decrease in col II and AC expression in highly degenerative specimens as well as increase of col I expression. Increased col I expression in the pericellular matrix could even be depicted in specimens with intact hyaline morphology. DISCUSSION/CONCLUSION: Observations suggest that joint impaction causes early osteoarthritic changes after 6 months. Collagen network disruption seems to lead to AC loss, although other researchers found isolated AC loss without denaturation of col II using immunofluorescence in formalin-fixed specimens. This is the first study on effects of transarticular impact using immunofluorescence on unfixed cryosections.

Subchondral and trabecular bone remodeling in canine experimental osteoarthritis.

INTRODUCTION: We wanted to test the hypothesis that quality changes occur in early-stage arthritic subchondral cancellous bone after acute subchondral damage. So far, not much attention has been paid to changes of the subchondral bone after traumatic subchondral lesions. MATERIALS AND METHODS: With an established animal model, we produced pure subchondral damage without initial affection of the articular cartilage in 12 Beagle dogs under MRI and histological control. We utilized bone histomorphometry to evaluate bone turnover, its structure and the articular cartilage 6 months after the initial damage. RESULTS: On follow-up, bone remodelling was indicated, e.g. by a significant increase in the trabecular bone volume and thickness, osteoblast number and osteoid surface and a decrease in the trabecular number in all 12 samples. Several other parameters showed a tendency, e.g. osteoblast surface and osteoclast number. Cartilage analysis showed degenerative changes in ten of 12 samples that had not shown any evidence of damage during the initial examination. DISCUSSION: Our investigation indicates a significant deterioration in the architecture of the cancellous bone with degenerative changes of the overlying articular cartilage after subchondral lesions, which change the mechanical properties.

Comparison of total and partial traumatic tears of the subscapularis tendon.

We treated surgically 16 shoulders with an isolated traumatic rupture of the subscapularis tendon over a six-year period. Nine patients had a total and seven a partial tear of the subscapularis tendon. Repair was undertaken through a small deltopectoral groove approach. The mean Constant score improved in total tears from 38.7 to 89.3 points (p = 0.003) and in partial tears from 50.7 to 87.9 points (p = 0.008). The total tears were significantly more improved by surgery than the partial tears (p = 0.001). The delay between trauma and surgery was inversely proportional to the improvement in the Constant score suggesting that early diagnosis and surgical repair improves outcome.

An experimental canine model for subchondral lesions of the knee joint.

Aim of the study was to create an animal model for the investigation of the role of subchondral bone damage without initial cartilage lesion in the pathogenesis of osteoarthritis, the mechanical properties of the joints as well as its role in cartilage metabolism. Therefore, after cadaver studies an animal model was created to apply a transarticular load to the femoro-patellar joint under reproducible conditions and produce a pure subchondral damage without affecting the articular cartilage. Following the cadaver studies a first group of four dogs was impacted to identify forces to produce isolated subchondral fractures in the femoral condyle. Then a second group of 12 dogs knee joints was impacted under identical conditions with forces of approximately 2100 N to produce similar subchondral fractures without cartilage damage in one joint under MRI control: T1-weighted SE-sequences. T2-weighted TSE, fat suppressed TIRM-sequences and 3D-FLASH fat saturated sequences. FLASH 3D-sequences revealed intact cartilage after impact in all cases and TIRM-sequences showed subchondral fractures representing bleeding, microfractures and fragmented bone trabecules. Turbo spin echo sequences and T1-weighted images revealed other intact intraarticular structures such as ligaments and menisci. The proposed experimental animal model is suitable to investigate the effect of pure subchondral damage on the articular cartilage and on means of treatment of cartilage defects without surgical intervention and without initial cartilage damage.

Experimental autologous osteochondral plug transfer in the treatment of focal chondral defects: magnetic resonance imaging signs of technical success in sheep.

PURPOSE: To describe the magnetic resonance imaging (MRI) signs of technically successful osteochondral plug transfer and to correlate the findings with histology using the Mankin score. MATERIAL AND METHODS: The study was done in a prospective animal experiment: 11 adult black-head sheep underwent surgical treatment with osteochondral plug transfer of a knee joint. The animals were killed 6 months later and MRI of the joints was done immediately. MRI was applied with a 1.5T MR scanner using a spin-echo (SE) T1-weighted, turbo spin-echo (TSE) T2-weighted with spectral fat suppression and a fat-suppressed 3D-spoiled gradient echo (GRE) sequence (manufacturer's acronym: FLASH) (TR 50.0 ms, TE 11.0 ms, flip 35 degrees). After MRI, all knee joints were dissected and a biopsy of the plug and the adjacent cartilage was taken. Classification of the cartilage biopsies was carried out in accordance with a modified Mankin score. RESULTS: Cartilage repairs with a hypointense cartilage signal in the FLASH 3D sequence were correlated with poor histological results (lower Mankin score). Histologically, the regions of cartilage with a hypointense signal showed a fibrocartilage-like repair tissue. Hyaline cartilage with well-defined layers had the same signal intensity in the FLASH sequence relative to adjacent hyaline cartilage. There were two plugs with a surface defect, graded as Outerbridge grade 1 in MRI and histology. Both had a poor outcome in the histologic Mankin score. Grade 2-4 lesions were not observed in the MRI study nor in the histologic study. CONCLUSION: MRI is a useful non-invasive tool for evaluating the morphologic status of osteochondral plug transfers. A good postoperative result of the cartilage repair was found histologically if an isointense cartilage signal of the graft was documented in the FLASH 3D sequence, and the graft had good congruity with the articular surface without defects.

Photoshop-based image analysis of canine articular cartilage after subchondral damage.

INTRODUCTION: The validity of histopathological grading is a major problem in the assessment of articular cartilage. Calculating the cumulative strength of signal intensity of different stains gives information regarding the amount of proteoglycan, glycoproteins, etc. Using this system, we examined the medium-term effect of subchondral lesions on initially healthy articular cartilage. MATERIALS AND METHODS: After cadaver studies, an animal model was created to produce pure subchondral damage without affecting the articular cartilage in 12 beagle dogs under MRI control. Quantification of the different stains was provided using a Photoshop-based image analysis (pixel analysis) with the histogram command 6 months after subchondral trauma. RESULTS: FLASH 3D sequences revealed intact cartilage after impact in all cases. The best detection of subchondral fractures was achieved with fat-suppressed TIRM sequences. Semiquantitative image analysis showed changes in proteoglycan and glycoprotein quantities in 9 of 12 samples that had not shown any evidence of damage during the initial examination. Correlation analysis showed a loss of the physiological distribution of proteoglycans and glycoproteins in the different zones of articular cartilage. CONCLUSION: Currently available software programs can be applied for comparative analysis of histologic stains of hyaline cartilage. After subchondral fractures, significant changes in the cartilage itself occur after 6 months.

Hepatitis C virus proteins as targets for drug development: the role of bioinformatics and modelling.

Hepatitis C virus (HCV), a member of the Flaviviridae family, has been recognised to be responsible for both parenterally transmitted and sporadic non-A and non-B hepatitis affecting 1-3% of the world population. HCV is a positive stranded RNA virus encoding a single polyprotein which contains at least ten unique structural and non-structural proteins. Amongst these the structural protein E2 has been of special interest for vaccine development and the serine protease NS3, which is responsible for cleavage of the polyprotein, for the development of small molecule inhibitors. We will focus on the contribution of computational techniques and the use of structural information for the design and discovery of novel therapeutic agents for these targets. Both drug discovery and vaccine design efforts will be discussed taking into account also the problem of emerging resistance.