MRI study of medial meniscus degeneration of osteoarthritic knees with or without posterior root tear.

PURPOSE: The purpose of this study was to compare the medial meniscus (MM) degeneration, meniscus extrusion, and tibial joint inclination by using MRI to consider the pathogenesis of posterior root tear (PRT) in medial-type knee osteoarthritis (KOA) both with and without medial meniscus posterior root tear (MMPRT). METHODS: This study used open MRI with flexion sagittal view and included 324 medial-type osteoarthritic knees with a Kellegren-Lawrence grade of 2 or less. Following the exclusion process, 151 knees were selected for MRI analysis. MM degeneration grading was performed according to Jerosch by 5 degrees of 0-4 in four different portions from anterior to posterior. MM medial extrusion (MMME), MM posterior extrusion (MMPE), medial tibial medial slope (MTMS), and medial tibial posterior slope (MTPS) were measured according to previous studies. RESULTS: MM degeneration in the anterior portion to MCL averaged 1.72 ± 0.67 in the PRT group (n = 48) and 1.40 ± 0.78 in the non-PRT group (n = 103). The degeneration grade was statistically higher in the PRT group than in the non-PRT group (p = 0.050). There was no difference in MM degeneration in the other three portions. MMME averaged 4.02 ± 1.12 mm in the PRT group and 3.11 ± 1.11 mm in the non-PRT group. MMPE averaged 4.22 ± 0.87 mm in the PRT group and 2.83 ± 1.12 mm in the non-PRT group. Both MMME and MMPE in the PRT group were statistically larger than those in the non-PRT group (p < 0.001). There was no difference in MTMS between the two groups. MTPS averaged 6.34 ± 2.25° in the PRT group and 5.28 ± 2.23° in the non-PRT group. The MTPS of the PRT group was statistically larger than that of the non-PRT group (p = 0.007). CONCLUSION: The severity of MM degeneration, extrusion of MM, and degree of tibial slope were compared between medial-type KOA with and without PRT using an open MRI. MM degeneration was more severe anteriorly in the PRT group. The PRT group showed larger MMME and MMPE with greater MTPS. LEVEL OF EVIDENCE: III. Retrospective cohort study.

The kinematic analysis of female subjects after double-bundle anterior cruciate ligament reconstruction during single-leg squatting.

BACKGROUND: The kinematic characteristics of female anterior cruciate ligament (ACL)-injured subjects were recognized in our previous study using an electromagnetic device comparing both female control groups and male ACL-injured subjects during single-leg squatting. OBJECTIVE: To assess the kinematic characteristics of female subjects after double-bundle ACL reconstruction during single-leg squatting. METHODS: Three-dimensional motion analysis was performed for single-leg squatting in female subjects after ACL reconstruction. We evaluated the relative angles between the pelvis, thigh, and lower leg using an electromagnetic device during single-leg squatting in 28 female subjects with ACL reconstruction. All patients included in this study restored their sports performance level to 90 % or higher. RESULTS: Comparing the involved leg to the uninjured leg of female subjects after ACL reconstruction, the involved leg demonstrated significantly more hip adduction and less knee varus than the uninjured leg. Comparing the anterior cruciate ligament-reconstructed female subjects to the healthy female controls, the involved leg after ACL reconstruction demonstrated significantly less hip flexion, more hip external rotation, more hip adduction, and more knee flexion than the dominant leg of the control group. CONCLUSION: This kinematic study exhibited kinematic characteristics of ACL-reconstructed knees of female subjects. Double-bundle anterior cruciate ligament reconstruction could not quite restore the normal kinematics of female-involved legs compared with both uninjured legs of female subjects and healthy female controls. In future studies, restoring the correct alignment of ACL reconstructed knee during single-leg squatting would be expected to reduce ACL re-injury and to assist a safe return to sport activities.

High-flex posterior cruciate-retaining vs posterior cruciate-substituting designs in simultaneous bilateral total knee arthroplasty: a prospective, randomized study.

The superiority between the posterior cruciate-retaining and the posterior cruciate-substituting designs still remains controversial. We performed a prospective, randomized control study for evaluation of the superiority of these designs. This study investigated 58 knees in 29 patients with simultaneous bilateral total knee arthroplasty, in which the high-flex CR design was randomly implanted in one knee and the high-flex PS design was implanted in the other knee. The follow-up duration averaged 5.0 years, with a minimum duration of 3 years. Postoperatively, Knee Score and pain points in Knee Score resulted in no significant differences between the 2 designs. However, postoperative arc of range of motion, patient satisfaction, and posterior knee pain at passive flexion in the PS design were significantly superior to that of the CR design.

[Articular cartilage regeneration with synovial mesenchymal stem cells].

Cell transplantation has shown to be a promising strategy to repair cartilage defects. Mesenchymal stem cells derived from synovium have been shown to be a superior cell source for cartilage regeneration to those from other mesenchymal tissues due to their higher rates of colony formation, proliferation potential with autologous serum, and in vitro/vivo chondrogenic potentials. We have found that approximately 60% of synovial mesenchymal stem cells placed on cartilage defects adhered to the defect within 10 min, and the addition of magnesium enhanced this percentage further, which resulted in better cartilage regeneration. Based upon several basic research studies performed in our lab, we have begun the transplantation of synovial stem cells arthroscopically in a clinical study for the treatment of cartilage defects. To date, no adverse events have been reported in the study. Regeneration of cartilage, reduction in defect size and an improvement of symptoms have been obtained in most patients over the last 3 years.

Radiographic description of femoral tunnel placement expressed as intercondylar clock time in double-bundle anterior cruciate ligament reconstruction.

PURPOSE: The purpose of this study was to propose an objective description of femoral tunnel position expressed as time of the intercondylar clock in ACL reconstruction using a simple radiograph for the sake of objective discussion and technical improvement. The reproducibility of the method was evaluated in double-bundle (DB) reconstructions. METHODS: The first series of 54 knees in 54 patients who underwent primary "isometric" DB ACL reconstructions from 1995 to 2002 were randomly picked up. The second series of 48 knees in 48 patients with primary "anatomic" DB ACL reconstructions during 2007 were assessed as a recent femoral tunnel position with the same method. All DB reconstructions of ACL with the anteromedial (AM) and posterolateral (PL) bundles were performed with an arthroscopically assisted trans-tibial technique. The o'clock description of femoral tunnel placement was expressed using a weight-bearing posterior-anterior view at 45° of flexion (45° W/B PA view) of the knee. Assessment was undertaken with radiographs 1 year postoperatively. RESULTS: The o'clock descriptions of femoral tunnel placement resulted in noon 40 min (standard deviation (SD): 10 min) for the AM bundle and one o'clock 40 min (SD: 20 min) for the PL bundle on average in the "isometric" reconstruction. In the "anatomic" reconstruction, the time descriptions of femoral tunnel placement were one o'clock 20 min (SD: 10 min) for the AM bundle and two o'clock 20 min (SD: 20 min) for the PL bundle on average. With the intra-examiner reproducibility assessment in the "anatomic" reconstruction, the differences between first and second assessments averaged 10 min (SD: 7 min) for femoral tunnel placement of the AM bundle and 12 min (SD: 9 min) of the PL bundle. Regarding the inter-examiner reproducibility, the differences between two examiners averaged 9 min (SD: 6 min) for femoral tunnel placement of the AM bundle and 14 min (SD: 9 min) of the PL bundle. CONCLUSION: This simple radiographic assessment is reproducible and reliable for clinical use, and useful for the evaluation of ACL reconstructive procedures.

Hip acetabular dysplasia and joint laxity of female anterior cruciate ligament-injured patients.

BACKGROUND: It has been noted that some female anterior cruciate ligament-injured patients have complaints of both coxalgia and joint laxity. HYPOTHESIS: Female anterior cruciate ligament-injured patients tend to have both acetabular dysplasia and generalized joint laxity. STUDY DESIGN: Cohort study (prevalence); Level of evidence, 2. METHODS: Hip radiographs of 100 female anterior cruciate ligament-injured patients and 40 female athletes without any hip joint complaints or history of anterior cruciate ligament injury were evaluated by measuring their center-edge angle (CEA). In addition, generalized joint laxity tests using 8 items were performed for anterior cruciate ligament-injured patients. Anterior-posterior (A-P) tibiofemoral translation of the uninjured knee was measured using a KT-1000 knee arthrometer to evaluate joint laxity under anesthesia before anterior cruciate ligament reconstruction. RESULTS: The average (± standard deviation) CEA of female anterior cruciate ligament-injured patients was 25.5° ± 5.3° (uninjured side) and 25.8° ± 4.8° (injured side), and that of the control group was 28.2° ± 4.2° (right side) and 29.2° ± 5.7° (left side), both P < .05. Among the 100 patients with anterior cruciate ligament tears, both the generalized joint laxity score and A-P tibiofemoral translation of the group with acetabular dysplasia (CEA of <25°, n = 37) were significantly greater than that of the normal group (CEA of ≥25°, n = 63). There was a negative correlation between the CEA of female anterior cruciate ligament-injured patients and both the generalized joint laxity score and A-P tibiofemoral translation. CONCLUSION: The CEA of female anterior cruciate ligament-injured patients was significantly smaller than that of the control group. Statstical analysis showed a moderate negative correlation between the CEA and generalized joint laxity score. Female athletes with an anterior cruciate ligament injury had an increased prevalence of acetabular dysplasia and generalized joint laxity.

Revision anterior cruciate ligament reconstruction by double-bundle technique using multi-strand semitendinosus tendon.

PURPOSE: The purpose of the study was to compare the outcome of revision anterior cruciate ligament (ACL) reconstruction by the double-bundle (DB) technique using multi-strand semitendinosus tendon with that of primary reconstruction by use of the same technique. METHODS: The study included 21 patients who underwent revision ACL reconstruction (mean follow-up, 40 months) with the semitendinosus tendon DB technique between 1995 and 2006 and 86 unilateral primary DB ACL reconstructions (mean follow-up, 33 months) between 2000 and 2004. The outcome of both groups was compared based on differences between operated and unoperated limbs and modified International Knee Documentation Committee grades. Both the overall and sports-related subjective scores were evaluated between the 2 groups. RESULTS: The KT measurements (MEDmetric, San Diego, CA) averaged 1.7 mm (SD, 1.8 mm) in the revision group and 1.5 mm (SD, 1.6 mm) in the primary group. There was no significant difference in KT measurements between the 2 groups. The Lachman test was negative in 83% of revision cases and 87% of primary cases; the anterior drawer test was negative in 83% and 91%, respectively, and the pivot-shift test was negative in 78% and 90%, respectively. There was a tendency for a positive pivot-shift test in the revision group being higher. The Lysholm score and subjective recovery score were significantly lower in the revision group. CONCLUSIONS: The semitendinosus tendon DB revision procedure provided range of motion and anterior stability comparable to those after primary DB surgery and a comparable return to athletic activities. However, the patients tended to have positive pivot-shift test results. The revision cases were also inferior in terms of the general evaluation of recovery of knee condition. The outcome scores were lower overall in the revision group. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Discrimination of types of venous emboli using Doppler ultrasound.

BACKGROUND: Many studies have identified features of the emboli traveling in the arterial system by Doppler ultrasound, and estimated their composition and size for anticipation of cerebral infarct. Another concern is features of the emboli in the venous system for anticipation of pulmonary embolism (PE). The objective is to prove that the emboli in the venous system can be discriminated by Doppler ultrasound in animal study and to assess whether PE can be predicted by using this technique in clinical case. METHODS: Animal study--lard oil, thrombus, or bone marrow was injected to the femoral veins in pigs. High intensity transient signals were transhepatically identified at the inferior vena cava using Doppler ultrasound. Intensity volume (dB) and frequency shift (Hz) of each signal were obtained. The cutoff values at which thrombi, fat emboli, and marrow emboli could be discriminated were calculated by receiver-operating characteristic curves analysis. Human study--Subjects were 47 patients who underwent total knee arthroplasty. On postoperative day 0 and 1, High intensity transient signals were identified at the affected common femoral vein using Doppler ultrasound. Contrast computed tomography was done, and the patients were divided into two groups according to the presence of PE. The two groups were distinguished by intensity volume (dB) and frequency shift (Hz) of each signal and calculated the sensitivity and specificity. The statistics analysis was done as in animal study. RESULTS: Animal study--Thrombus and bone marrow could be discriminated from lard oil well at frequency shift of 208 Hz and 196 Hz (with sensitivity of 86.9, 85.7%, and specificity of 82.3%, 91.8%, respectively). Human study--The sensitivity and specificity were 76.7 and 75.0% to discriminate patients with and without PE at frequency shift of 208 Hz. CONCLUSIONS: Our animal study results indicated that emboli could be identified and discriminated in the venous system. Clinical study informed that the frequency shift (208 Hz) of the Doppler signal was the best parameter to discriminate PE with and without PE in patients with total knee arthroplasty.

Ketoprofen absorption by muscle and tendon after topical or oral administration in patients undergoing anterior cruciate ligament reconstruction.

Topical ketoprofen patches are widely used in the treatment of musculoskeletal pain, but the pharmacokinetics of ketoprofen following topical application remain unclear. This open-label, single-dose pharmacokinetic study was designed to determine the concentrations of ketoprofen in the semitendinosus muscle/tendon and plasma after topical application or oral administration to patients scheduled for anterior cruciate ligament reconstruction. Two ketoprofen patches (20 mg each) were applied over the semitendinosus muscle/tendon for 1, 6, 14, or 20 h before surgery in 21 patients, while one sustained-release 150 mg ketoprofen capsule was administered to six patients 14 h before surgery. Ten untreated patients served as the control group. The main outcome measures were the semitendinosus muscle/tendon and plasma concentrations of ketoprofen at 1, 6, 14, and 20 h. Ketoprofen was detected in the semitendinosus muscle/tendon from about 1 h after topical application. The peak concentration was reached at 6 h, and it decreased gradually until 20 h, although the concentration at 20 h was still higher than that at 1 h. Unlike the tissue concentration, the plasma concentration of ketoprofen increased gradually after topical application. At 14 h, there was no significant difference of the tissue concentration between the topical and oral groups, although the plasma concentration was about 17-fold higher in the oral group than in the topical group. In conclusion, following topical application in a patch, ketoprofen shows rapid and sustained delivery to the underlying tissues without a significant increase of the plasma drug concentration.

Periodic knee injections of BMP-7 delay cartilage degeneration induced by excessive running in rats.

Strenuous running of rats enhances mechanical stress on the knee, thereby inducing degeneration of articular cartilage. Bone morphogenetic protein-7 (BMP-7) has an inhibitory effect on cartilage degeneration, suggesting its usefulness for human osteoarthritis patients. However, its mode of administration should be investigated. We examined whether weekly knee injections of BMP-7 delayed the progression of cartilage degeneration. Wistar rats were forced to run 30 km in 6 weeks on a rodent treadmill, and BMP-7 was injected weekly into the knee. Macroscopically and histologically, this strenuous running regimen induced cartilage degeneration. Weekly injections of 250 ng BMP-7 delayed the progression of cartilage degeneration. Immunohistochemically, in the control knee, type II collagen expression decreased, while BMP-7 expression in chondrocytes slightly increased. Interestingly, weekly injection of BMP-7 increased BMP-7 expression even 9 days after the final injection. Disulfate disaccharide keratan sulfate in serum transiently increased in the control group, while it remained at a low level in the BMP-7 group. Weekly BMP-7 injection increased BMP-7 expression in chondrocytes and its effect seemed to last more than 7 days. The effect of BMP-7 could be monitored by serum keratan sulfate concentration. Periodical injections of BMP-7 delayed progression of cartilage degeneration induced by excessive running in rats.

Human sclera maintains common characteristics with cartilage throughout evolution.

BACKGROUND: The sclera maintains and protects the eye ball, which receives visual inputs. Although the sclera does not contribute significantly to visual perception, scleral diseases such as refractory scleritis, scleral perforation and pathological myopia are considered incurable or difficult to cure. The aim of this study is to identify characteristics of the human sclera as one of the connective tissues derived from the neural crest and mesoderm. METHODOLOGY/PRINCIPAL FINDINGS: We have demonstrated microarray data of cultured human infant scleral cells. Hierarchical clustering was performed to group scleral cells and other mesenchymal cells into subcategories. Hierarchical clustering analysis showed similarity between scleral cells and auricular cartilage-derived cells. Cultured micromasses of scleral cells exposed to TGF-betas and BMP2 produced an abundant matrix. The expression of cartilage-associated genes, such as Indian hedge hog, type X collagen, and MMP13, was up-regulated within 3 weeks in vitro. These results suggest that human 'sclera'-derived cells can be considered chondrocytes when cultured ex vivo. CONCLUSIONS/SIGNIFICANCE: Our present study shows a chondrogenic potential of human sclera. Interestingly, the sclera of certain vertebrates, such as birds and fish, is composed of hyaline cartilage. Although the human sclera is not a cartilaginous tissue, the human sclera maintains chondrogenic potential throughout evolution. In addition, our findings directly explain an enigma that the sclera and the joint cartilage are common targets of inflammatory cells in rheumatic arthritis. The present global gene expression database will contribute to the clarification of the pathogenesis of developmental diseases such as high myopia.

Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect.

INTRODUCTION: Current cell therapy for cartilage regeneration requires invasive procedures, periosteal coverage and scaffold use. We have developed a novel transplantation method with synovial mesenchymal stem cells (MSCs) to adhere to the cartilage defect. METHODS: For ex vivo analysis in rabbits, the cartilage defect was faced upward, filled with synovial MSC suspension, and held stationary for 2.5 to 15 minutes. The number of attached cells was examined. For in vivo analysis in rabbits, an autologous synovial MSC suspension was placed on the cartilage defect, and the position was maintained for 10 minutes to adhere the cells to the defect. For the control, either the same cell suspension was injected intra-articularly or the defects were left empty. The three groups were compared macroscopically and histologically. For ex vivo analysis in humans, in addition to the similar experiment in rabbits, the expression and effects of neutralizing antibodies for adhesion molecules were examined. RESULTS: Ex vivo analysis in rabbits demonstrated that the number of attached cells increased in a time-dependent manner, and more than 60% of cells attached within 10 minutes. The in vivo study showed that a large number of transplanted synovial MSCs attached to the defect at 1 day, and the cartilage defect improved at 24 weeks. The histological score was consistently better than the scores of the two control groups (same cell suspension injected intra-articularly or defects left empty) at 4, 12, and 24 weeks. Ex vivo analysis in humans provided similar results to those in rabbits. Intercellular adhesion molecule 1-positive cells increased between 1 minute and 10 minutes, and neutralizing antibodies for intercellular adhesion molecule 1, vascular cell adhesion molecule 1 and activated leukocyte-cell adhesion molecule inhibited the attachment. CONCLUSION: Placing MSC suspension on the cartilage defect for 10 minutes resulted in adherence of >60% of synovial MSCs to the defect, and promoted cartilage regeneration. This adherent method makes it possible to adhere MSCs with low invasion, without periosteal coverage, and without a scaffold.

Analysis of the chondrogenic potential of human synovial stem cells according to harvest site and culture parameters in knees with medial compartment osteoarthritis.

OBJECTIVE: Synovial mesenchymal stem cells (MSCs) are an attractive cell source for cartilage regeneration because of their high chondrogenic ability. In this study, we examined the synovium of patients with medial compartment knee osteoarthritis (OA) to determine the proportion of MSCs in relation to cellular compartmentalization, and to identify the culture parameters that could affect the chondrogenic potential of synovial MSCs. METHODS: Human synovium was collected from 4 different harvest sites in the knees of patients with medial compartment OA. Each synovial tissue sample was divided into 2 parts, one for histologic assessment and the other for analysis of the cell size, surface epitopes, and chondrogenic potential of colony-forming cells in vitro. RESULTS: The numbers of alpha-smooth muscle actin-positive vessels and CD31+ endothelial cells were higher in the medial outer region than in the other regions of OA synovial tissue. The numbers of these cells correlated with the number of colony-forming cells. In parallel with increasing duration of the preculture period, the size of the cells increased, while the chondrogenic potential decreased, and this was correlated with expression of CD90. CONCLUSION: Medial compartment knee OA demonstrates variability in the distribution of vessels, which results in a varying distribution of MSCs. The preculture period should be utilized to assess both the potential for expansion and the chondrogenic potential of MSCs.

Autologous synovial fluid enhances migration of mesenchymal stem cells from synovium of osteoarthritis patients in tissue culture system.

Synovial fluid from osteoarthritic knee contains mesenchymal stem cells (MSCs). One of the possible reservoirs of MSCs in synovial fluid is synovial tissue, and synovial fluid may induce mobilization of MSCs into synovial fluid in osteoarthritis patients. Here, we investigated whether synovial fluid expanded synovial MSCs in a tissue culture system. Human synovium and synovial fluid were obtained from osteoarthritis patients during total knee arthroplasties. In the tissue culture system, autologous synovial fluid expanded synovial cells statistically higher than alpha MEM + FBS, and the addition of TGF beta 3 to alpha MEM + FBS increased expansion to a similar level in all 11 donors. The addition of decorin or anti-TGFbeta neutralizing antibody to synovial fluid partially inhibited synovial cell expansion. In cell culture assay, synovial fluid proliferated synovial cells fewer than alpha MEM + FBS. The expanded synovial cells in synovial fluid retained multipotentiality and showed surface markers similar to those of MSCs. We demonstrated that autologous synovial fluid enhanced expansion of MSCs in tissue culture of synovium from osteoarthritis patients by promoting cell migration. This effect was partially affected by TGFbeta.

Exogenous synovial stem cells adhere to defect of meniscus and differentiate into cartilage cells.

The meniscus is semilunar fibrocartilage, and its injury causes dysfunction of the knee. We previously reported a high chondrogenic potential of synovial mesenchymal stem cells (MSCs). Here, we examined whether intra-articular injected synovial MSCs adhered to the defect of the meniscus, survived there, and differentiated into cartilage cells. MSCs were isolated from the synovium of GFP rats. Cylindrical defects were created in the menisci in wild rats, and GFP-positive synovial MSCs were injected into the knee. In the control group, 100 microl of PBS was injected into the contralateral knee. The menisci were analyzed after day 1, weeks 2, 4, 8, and 12. One day after injecting of 10(7) GFP-positive synovial MSCs, the meniscal defect was filled with the cells. The GFP-positive synovial MSCs expressed type II collagen, exhibited representative characteristics of chondrocytes by electron microscopy at 8 weeks, and could still be observed at 12 weeks. The histological score improved within 12 weeks but there were no statistical difference between the two groups at each period in this model. GFP mRNA expressions were not observed in distant organs at day 1. After intra-articular injection, synovial MSCs attached to the meniscal defect and differentiated into cartilage cells.

A retrospective study of the midterm outcome of two-bundle anterior cruciate ligament reconstruction using quadrupled semitendinosus tendon in comparison with one-bundle reconstruction.

PURPOSE: The objective of the study was to retrospectively compare the outcome of the first series of a 2-bundle anterior cruciate ligament reconstruction technique using quadrupled semitendinosus tendon with that of a 1-bundle reconstruction technique from 1992 through 1996. TYPE OF STUDY: Case-control study. METHODS: The 1-bundle group consisted of 56 patients with a follow-up period of 24 months or more (average, 46.5 months). The 2-bundle group consisted of 79 patients with a follow-up period of 24 months or more (average, 40.8 months). Manual knee laxity tests, anterior stability with KT-1000 (manual maximum), and knee extension and flexion strength by Cybex were evaluated using an average and standard deviation, and data were categorized according to the International Knee Documentation Committee (IKDC) classification. The Lysholm scale and the subjective recovery scale were also evaluated. RESULTS: A statistically greater number of patients in the 1-bundle group were positive (+ or ++) based on the Lachman test (34% in the 1-bundle group and 13% in the 2-bundle group). The average KT-1000 anterior laxity of 2.7 +/- 2.3 mm in the 1-bundle group was statistically greater than the 1.9 +/- 1.9 mm in the 2-bundle group, with a statistical power between 70% and 80%. The total Lysholm knee scale score was 93 points in both groups, and the subjective recovery score was equivalent, 82% in the 1-bundle group and 86% in the 2-bundle group, respectively. CONCLUSIONS: There was no statistical difference based on the IKDC, Lysholm, and subjective analysis. However, there was a statistical difference in the Lachman test, anterior drawer test, and KT-1000 measurements. LEVEL OF EVIDENCE: Level III.