Burak Demirag

Enhancement of tendon-bone healing of anterior cruciate ligament grafts by blockage of matrix metalloproteinases

BACKGROUND The use of soft-tissue grafts for anterior cruciate ligament reconstruction delays the healing process. This delay may be due to biochemical and/or biomechanical insults. We hypothesized that the blocking effect of alpha2-macroglobulin on synovial matrix metalloproteinase activity may enhance the healing of tendon graft in a bone tunnel. METHODS The study was performed on twenty-eight healthy, skeletally mature New Zealand White rabbits. Each rabbit underwent bilateral anterior cruciate ligament reconstruction with use of the ipsilateral semitendinosus tendon. Alpha-2-macroglobulin (alpha2-macroglobulin) was injected into the knee joint in one limb, and the contralateral limb served as a control. The rabbits were killed two weeks (fourteen rabbits) or five weeks (fourteen rabbits) after the operative procedures. The presence of matrix metalloproteinases in synovial fluid, and the blocking effect of alpha2-macroglobulin on them, were determined with enzymatic assays. Healing between the tendon and the bone tunnel was assessed morphologically by determining the presence of fibrovascular tissue and collagen fibers. Healing also was assessed quantitatively by measuring the ultimate load to failure of the reconstructed complex. RESULTS There was an increase in matrix metalloproteinases in the control group; in contrast, there was a decrease in the study group (p < 0.05). In the control specimens, the fibrovascular tissue at the bone-tendon interface had developed into dense connective tissue with poor vascularization. In the treated specimens, the bone tunnel had more areas of denser connective-tissue ingrowth. The interface tissue was more mature and contained numerous perpendicular collagen bundles (Sharpey fibers). The ultimate load to failure was significantly greater in the alpha2-macroglobulin-treated specimens than in the untreated controls at both two and five weeks. CONCLUSIONS The present study demonstrated that alpha2-macroglobulin blockade of matrix metalloproteinases can enhance bone-tendon healing. This effect of alpha2-macroglobulin could occur through its effect solely on collagenase or on a subset of matrix metalloproteinases that are present at the healing interface.

The pathophysiology of Osgood-Schlatter disease: a magnetic resonance investigation.

Osgood–Schlatter disease (OSD) is a well-described clinical condition, although its origin remains controversial. Mechanical, growth or traumatic factors are suggested as causes of this lesion. Thirty-five patients were included in this study. Twenty of them had OSD (study group) and the remaining 15 adolescents constituted the control group. Magnetic resonance imaging of the knees was performed in all patients. The distance between the distal pole of the patella and the proximal margin of patellar tendon attachment to the tibial apophysis (A), the distance between the distal pole of the patella and the tibial tubercle epiphysis (B), the distance between the proximal margin of the patellar tendon attachment to the tibia and the tibial tubercle epiphysis (C) and the distance between the knee joint level and the tibial tubercle epiphysis (D) were measured. The ratio of the distance between the distal pole of the patella and the proximal margin of the patellar tendon attachment to the tibia to the distance between the distal pole of the patella and the tibial tubercle epiphysis (A : B) was lower in the study group. The ratio of the distance between the proximal margin of the patellar tendon attachment point to the tibia and the tibial tubercle epiphysis to the distance between the knee joint level and the tibial tubercle epiphysis (C : D) was higher in the control group. We conclude that if the patellar tendon attaches more proximally and in a broader area to the tibia, this might probably cause OSD.

The Effect of Alpha-2 Macroglobulin on the Healing of Ruptured Anterior Cruciate Ligament in Rabbits

To investigate the effect of modification of biological environmental conditions, one of the factors influencing the healing of anterior cruciate ligament rupture, we performed experimental anterior cruciate ligament ruptures on New Zealand rabbits. After experimental rupture, intra-articular alpha-2 macroglobulin was injected into the knees of the rabbits in the experiment group to prevent structural changes resulting from the enzymatic reactions in the ruptured anterior cruciate ligament. At the end of 10th day of the experiment, we observed that the anterior cruciate ligaments in the experiment group had retained their prerupture brightness and volume when compared with the control group in which intra-articular alpha-2 macroglobulin had not been injected. We also noted that the anterior cruciate ligaments in the experiment group had not retracted or swollen, the incision sites were regular and clean, and they did not show any signs of degeneration. In the histological examination, the anterior cruciate ligaments in the control groups showed disruption of the collagen network and a significant diminution in number of fibroblasts and fibrocytes (p <. 001). At the end of this study, we concluded that the necessary conditions for the healing and repair of ruptured anterior cruciate ligament could exist if the enzymatic and biological environments were under control.

Evaluation of intra-articular collagenase, TIMP-1, and TNF-α levels before and after anterior cruciate ligament reconstruction

OBJECTIVES We investigated intra-articular levels of collagenase, which presumably promotes bone-tendon healing, and collagenase mediators involved in its production (tumor necrosis factor-alpha, TNF-alpha) and inhibition (TIMP-1 enzyme) in patients following anterior cruciate ligament (ACL) reconstruction. METHODS The study included 16 patients (15 males, 1 female; mean age 27 years; range 17 to 40 years) who underwent arthrocentesis due to effusion that developed following reconstruction of isolated ACL injuries. Intra-articular levels of collagenase, TNF-alpha, and TIMP-1 were measured using appropriate activity assay and immunoassay kits in synovial fluid samples obtained intraoperatively and during arthrocentesis. The mean time from ACL injury to surgical repair was 21+/-10 months (range 1 to 72 months). Arthrocentesis was performed in a mean of 18 hours (range 12 to 36 hours) following ACL repair. RESULTS Measurements in synovial fluid samples obtained intra- and postoperatively yielded 1.49+/-0.06 ng/ml and 1.45+/-0.05 ng/ml for collagenase, 12+/-5 ng/ml and 22+/-9.5 ng/ml for TIMP-1, and 10.4+/-7.1 pr/ml and 14.11+/-6.1 pr/ml for TNF-alpha, respectively. Postoperative changes in the levels of collagenase (p=0.098) and TNF-alpha (p=0.069) were not significant, whereas increase in the TIMP-1 level was significant (p=0.026). CONCLUSION This study showed elevated levels of TNF-alpha, collagenase, and TIMP-1 due to the presence of ruptured ACL. Our findings showed how these levels changed in the acute postoperative period.

Effects of adding epinephrine plus fentanyl to low-dose lidocaine for spinal anesthesia in outpatient knee arthroscopy

Background:  This study investigated whether addition of 15 µg epinephrine plus 25 µg fentanyl to lidocaine spinal anesthesia for outpatient knee arthroscopy makes it possible to use a subanesthetic lidocaine dose. The aim was to assess the quality of anesthesia and the suitability of this protocol for outpatient knee arthroscopy.

Symptomatic infrapatellar plica

The purpose of this retrospective clinical study was to assess the clinical outcomes of a group of patients who underwent arthroscopic infrapatellar plica (IPP) excision, to determine whether the IPP was symptomatic or not, and the symptoms or signs in the patient’s clinical presentation and correlations between arthroscopic findings and the patient’s clinical presentation. We studied all patients undergoing arthroscopic resection of symptomatic IPP without other intraarticular abnormality at our department from February 1996 to April 2001. Fourteen patients with isolated IPP and with regular follow-up intervals were included. Arthroscopy findings, preoperative magnetic resonance imaging (MRI) findings, and clinical presentation were correlated. The mean duration of follow-up was 36 months with a range of 24–60 months. The IPP was found to be in a fenestra pattern in seven patients, separate (cordlike) pattern in five patients, and vertical septum pattern in two patients. IPP in all patients was excised with a powered instrument. Excellent and good results were obtained in 12 (89%) patients. Two patients had poor results. All patients had been documented as having pain; popping, or snapping with flexion and extension; giving way; and swelling. There was no correlation between IPP type and MRI findings with being symptomatic (p>0.05). It was found that IPP type was not a prognostic factor (p>0.05). IPP should be considered as a possible cause of knee pain when MRI imaging exhibits no other internal derangement.RésuméLe but de cette étude clinique rétrospective était d’évaluer les résultats cliniques d’un groupe de patients qui ont subi l’excision arthroscopique de la plica infrapatellaire (IPP) et pour déterminer, que l’IPP ait été symptomatique ou non, les symptômes du tableau clinique du patient et les corrélations entre les constatations arthroscopiques et le tableau clinique. Nous avons étudié tous les patients subissant la résection arthroscopique du plica infrapatellaire symptomatique sans autre anomalie intra-articulaire à notre département à partir de février 1996 à avril 2001. Quatorze patients avec IPP isolée et présentant des intervalles réguliers de suivi ont été inclus dans l’étude. Les constatations arthroscopiques, les données pré-opératoires de l’IRM et le tableau clinique ont été corrélés. La durée moyenne du suivi était de 36 mois avec des extrêmes de 24 à 60 mois. L’IPP s’est présentée dans le type fénestré chez sept patients, dans le type séparé (comme une corde) chez cinq patients et dans le type de septum vertical chez deux patients. L’IPP a été excisée au moteur chez tous les patients. Deux patients ont été évalués comme excellent résultat, 10 patients comme bon et deux patients en tant que résultats faibles. Pour tous les patients on a documenté la douleur à la pression, au saut en flexion et en extension, à la marche et en recherche d’épanchement. Il n’y avait aucune corrélation entre le type d’IPP et les données de l’IRM (p>0.05). On a constaté que le type d’IPP n’était pas un facteur pronostique. Le plica infrapatellaire devrait être considérée comme cause potentielle de douleur de genou avec possibilité de mise en évidence par IRM et en l’absence de tout autre dérangement interne du genou.

Effect of low-dose irradiation on structural and mechanical properties of hyaline cartilage-like fibrocartilage

OBJECTIVE The aim of this study was to analyze the effect of low-dose irradiation on fibrous cartilage and to obtain a hyaline cartilage-like fibrocartilage (HCLF) with similar structural and mechanical properties to hyaline cartilage. METHODS An osteochondral defect was created in 40 knees of 20 rabbits. At the 7th postoperative day, a single knee of each rabbit was irradiated with a total dose of 5.0 Gy in 1.0 Gy fractions for 5 days (radiotherapy group), while the other knee was not irradiated (control group). Rabbits were then divided into four groups of 5 rabbits each. The first three groups were sacrificed at the 4th, 8th and the 12th postoperative weeks and cartilage defects were macroscopically and microscopically evaluated. The remaining group of 5 rabbits was sacrificed at the 12th week and biomechanical compression tests were performed on the cartilage defects. RESULTS There was no significant biomechanical difference between the radiotherapy and the control group (p=0.686). There was no significant macroscopic and microscopic difference between groups (p=0.300). Chondrocyte clustering was observed in the irradiated group. CONCLUSION Low-dose irradiation does not affect the mechanical properties of HCLF in vivo. However, structural changes such as chondrocyte clustering were observed.

Contribution of thin slice (1 mm) oblique coronal proton density-weighted MR images for assessment of anteromedial and posterolateral bundle damage in anterior cruciate ligament injuries.

PURPOSE To evaluate the diagnostic efficacy of using additional oblique coronal 1 mm proton density-weighted (PDW) MR imaging of the knee for detection and grading anterior cruciate ligament (ACL), anteromedial bundle (AMB) and posterolateral bundle (PLB) injuries. MATERIALS AND METHODS We prospectively assessed preoperative MR images of 50 patients (36 men, 14 women; age range, 18-62 years). First, we compared the diagnostic performance of routine sagittal (3 mm) and additional oblique coronal images (1 mm) for ACL tears. Then, we compared the tear types (AMB or PLB) and grade presumed from oblique coronal MR imaging with arthroscopy. RESULTS Arthroscopy revealed ACL tear in 24 (48%) patients. There was significant difference between sagittal images and arthroscopy results for ACL tear recognition (p<0.001). No significant difference was detected for oblique coronal images when compared with arthroscopy results (p=0.180). Sensitivity and specificity values for ACL tear diagnosis were 37.04% and 95.65% for sagittal images; 74.07% and 91.30% for oblique coronal images. There was no significant difference between arthroscopy and oblique coronal MR images in grading AMB and PLB injuries (p>0.05). CONCLUSION Addition of thin slice oblique coronal images to conventional sequences could better contribute to better verifying the presence of ACL tear and in determining its grade.

The effect of HIF stabilizer on distraction osteogenesis

OBJECTIVE The aim of this study was to investigate the effect of an orally applicable hypoxia-inducible factor (HIF) stabilizer on distraction osteogenesis (DO) in a rat model. METHODS The study included 24 Wistar albino rats undergoing osteotomy of the left tibia diaphysis. Rats were divided equally into experiment and control groups. Tibias were fixed using an external fixator. HIF stabilizer was administered to the experiment group. On the 5th postoperative day, distraction with increased rate (0.4 mm twice a day) was commenced and continued for 10 days. Histological and immunohistochemical evaluation was performed. RESULTS Vascular endothelial growth factor levels of the experiment group were higher than those of the control group (p<0.05). The experiment group had slightly better intramembranous ossification quality than the control group on both Day 16 and 30. Endochondral ossification rates were better in the experiment group on Day 16. CONCLUSION Vascular endothelial growth factor levels increased and stimulated angiogenesis in the presence of HIF pathway activation by oral administration of HIF stabilizer during DO. The biomechanical features of the distraction and angiogenesis should be coupled to achieve adequate bone homeostasis.