Hajime Yamanaka

Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in rheumatoid synovium

In vitro, membrane-type matrix metalloproteinases (MT-MMP) are known to activate the zymogen of MMP-2 (proMMP-2, progelatinase A), which is one of the key MMP in joint destruction in rheumatoid arthritis. In the present study, we examined the production and activation of proMMP-2, and the expression of MT1-MMP, MT2-MMP, and MT3-MMP, their correlation with proMMP-2 activation, and their localization in rheumatoid synovial tissue. Using sandwich enzyme immunoassay and gelatin zymography techniques, proMMP-2 production levels and activation ratios were found to be significantly higher in rheumatoid synovium compared with normal synovium (p < 0.01). Quantitative RT-PCR analyses demonstrated that MT1-MMP and MT3-MMP were expressed in all rheumatoid synovial tissue (30 of 30 cases), but that the mean expression level of MT1-MMP was approximately 11-fold higher than MT3-MMP. Significant correlation was found between the mRNA expression level of MT1-MMP and the activation ratio of proMMP-2 (p < 0.01). In situ hybridization indicated that the hyperplastic lining cells of rheumatoid synovium expressed MT1-MMP. Immunohistochemistry demonstrated that MT1-MMP was co-localized with MMP-2 and with a tissue inhibitor of metalloproteinase-2, and was mainly located in the rheumatoid synovial lining cells. In situ zymography of rheumatoid synovium showed gelatinolytic activity, predominantly in the lining cell layer. This activity was blocked when incubated with BB94, a specific MMP inhibitor. These results demonstrate that MT1-MMP plays an important role in the activation of proMMP-2 in the rheumatoid synovial lining cell layer, and suggest that its activity may be involved in the cartilage destruction of rheumatoid arthritis.

The diagnosis of double-crush lesion in the L5 lumbar nerve using diffusion tensor imaging

BACKGROUND CONTEXT A double-crush lesion is a condition in which the lumbar nerve is compressed both medially and laterally in the spinal canal, where diagnosis can be very difficult, and is a factor leading to poor surgical success rates. PURPOSE Diffusion tensor imaging (DTI) was used to determine DTI parameter fractional anisotropy (FA) values and apparent diffusion coefficient (ADC) in both intraspinal column lesions alone and in double-crush lesions. STUDY DESIGN This study used a prospective study. PATIENT SAMPLE Of the 56 cases (mean age: 72.2 years) that underwent laminectomy for lumbar spinal stenosis at our clinic between April 2013 to March, 2015, 10 cases with L5 radiculopathy caused by L4-L5 stenosis (Intraspinal stenosis group (Group I); mean age: 74.7 years), and 5 cases with persistent symptoms caused by L5 foraminal stenosis despite L4-L5 decompression surgery (Double-crush group (Group D); mean age: 77.6 years) were targeted. One patient in Group D was diagnosed through microendoscopic intrapedicular partial pediculotomy and the remaining four cases by nerve root infiltration. Five healthy cases (mean age: 54 years) were studied as controls. OUTCOME MEASURES Intraspinal zone (Iz), nerve root (N), and extraforaminal zone (Ez) were established as the regions of interest, and the L5 nerve FA and ADC values were determined on the affected side. METHODS Diffusion tensor imaging was performed prospectively by 1.5T magnetic resonance imaging before surgery, and DTI parameters of L5 nerve were evaluated in all patients and healthy volunteers. Student t test was used for group comparisons, and a p<.05 was considered statistically significant. RESULTS Fractional anisotropy values (Iz, N, Ez) were 0.415, 0.448, and 0.517, respectively, increasing as sites became more distal. Group I values were 0.335, 0.393, and 0.484, and Group D values were 0.296, 0.367, and 0.360. Compared with the healthy volunteers, Group D had significantly lower Iz (p<.05) and Ez (p<.001) values, while Group I had significantly lower Iz (p<.05) values. In Group D, Ez FA values were significantly lower (p<.001) than in Group I. Apparent diffusion coefficient values (Iz, N, Ez) in the healthy control group were 1.270 mm2/s, 1.151 mm2/s, and 0.937 mm2/s with values decreasing as sites grew distal. In Group I, the ADC values were 1.406 mm2/s, 1.184 mm2/s, and 1.001 mm2/s, while in Group D they were 1.551 mm2/s, 1.412 mm2/s, and 1.329 mm2/s. Compared with the healthy volunteers, Iz (p<.05) and Ez (p<.05) values were significantly higher in Group D. The N (p<.01) and Ez (p<.001) ADC values were significantly higher in Group D than in Group I. CONCLUSIONS Depending on where the nerve was compressed, changes in DTI parameters revealed nerve damage (low FA values and increased ADC) in the intraspinal canal in the Intraspinal Group, and over a widespread area in the Double-crush Group spanning the medial to lateral spinal canal. Our research suggests that in cases where double crush is suspected before surgery, failed back surgery syndrome may be prevented by evaluating DTI images.

Clinical results of Hi-tech Knee II total knee arthroplasty in patients with rheumatoid athritis: 5- to 12-year follow-up

BackgroundTotal knee arthroplasty (TKA) is a common form of treatment to relieve pain and improve function in cases of rheumatoid arthritis (RA). Good clinical outcomes have been reported with a variety of TKA prostheses. The cementless Hi-Tech Knee II cruciate-retaining (CR)-type prosthesis, which has 6 fins at the anterior of the femoral component, posterior cruciate ligament (PCL) retention, flat-on-flat surface component geometry, all-polyethylene patella, strong initial fixation by the center screw of the tibial base plate, 10 layers of titanium alloy fiber mesh, and direct compression molded ultra high molecular weight polyethylene (UHMWPE), is appropriate for TKA in the Japanese knee.The present study was performed to evaluate the clinical results of primary TKA in RA using the cementless Hi-Tech Knee II CR-type prosthesis.Materials and methodsWe performed 32 consecutive primary TKAs using cementless Hi-Tech Knee II CR-type prosthesis in 31 RA patients. The average follow-up period was 8 years 3 months. Clinical evaluations were performed according to the American Knee Society (KS) system, knee score, function score, radiographic evaluation, and complications.ResultsThe mean postoperative maximum flexion angle was 115.6°, and the KS knee score and function score improved to 88 and 70 after surgery, respectively. Complications, such as infection, occurred in 1 patient and revision surgery was performed. There were no cases of loosening in this cohort, and prosthesis survival rate was 96.9% at 12 years postoperatively.ConclusionThese results suggest that TKA using the cementless Hi-Tech Knee II CR-type prosthesis is a very effective form of treatment in RA patients at 5 to 12 years postoperatively. Further long-term follow-up studies are required to determine the ultimate utility of this type of prosthesis.

Total Knee Arthroplasty in a Patient with Bilateral Congenital Dislocation of the Patella Treated with a Different Method in Each Knee

We have operated total knee arthroplasty in a patient with bilateral congenital dislocation of the patella treated with a different method in each knee.

Discrimination between Lumbar Intraspinal Stenosis and Foraminal Stenosis using Diffusion Tensor Imaging Parameters: Preliminary Results

Study Design Retrospective observational study. Purpose To examine fractional anisotropy (FA) values and apparent diffusion coefficient (ADC) values of damaged nerves to discriminate between lumbar intraspinal stenosis (IS) and foraminal stenosis (FS) using diffusion tensor imaging (DTI) Overview of Literature It is important in the selection of surgical procedure to discriminate between lumbar IS and FS, but such discrimination is difficult. Methods There were 9 cases of IS, 7 cases of FS, and 5 healthy controls. The regions of interest were established in the lumbar intraspinal zone (Iz), nerve root (N), and extraforaminal zone (Ez). The FA and ADC values were measured on the affected and unaffected sides of the nerves. The FA ratio and the ADC ratio were calculated as the affected side/unaffected side ×100 (%). Results In the Ez, the FA value was significantly lower in FS than in IS (p<0.01). FA ratio was significantly lower in FS than in IS for the Ez (p<0.01). In the Iz, the ADC value was significantly higher in IS than FS (p<0.01). ADC ratio was significantly higher in FS than in IS for the N and Ez (p<0.05). For the Ez, receiver operating characteristic analysis of parameters revealed that the FA values showed a higher accuracy for the diagnosis of FS than the ADC values, and the FA value cut-off value was 0.42 (sensitivity: 85.7%, false positive: 11.1%) and the FA ratio cut-off value was 83.9% (sensitivity: 85.7%, false positive: 22.2%). Conclusions The low FA value in the extraforaminal zone suggests the presence of foraminal stenosis. When the FA value and FA ratio cut-off value were established as 0.42 and 83.9%, respectively, the accuracy was high for the diagnosis of foraminal stenosis. It may be possible to use DTI parameters to help in the discrimination between IS and FS.

Assessment of Clinical Symptoms in Lumbar Foraminal Stenosis Using the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire

Objective It is important to develop an easy means of diagnosing lumbar foraminal stenosis (LFS) in a general practice setting. We investigated the use of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) to diagnose LFS in symptomatic patients. Methods Subjects included 13 cases (mean age, 72 years) with LFS, and 30 cases (mean age, 73 years) with lumbar spinal canal stenosis (LSCS) involving one intervertebral disc. The visual analogue scale score for low back pain and leg pain, the JOABPEQ were evaluated. Results Those with LFS had a significantly lower JOA score (p<0.001), while JOABPEQ scores (p<0.05) for lumbar dysfunction and social functioning impairment (p<0.01) were both significantly lower than the scores in LSCS. The following JOABPEQ questionnaire items (LFS vs. LSCS, p-value) for difficulties in: sleeping (53.8% vs. 16.6%, p<0.05), getting up from a chair (53.8% vs. 6.6%, p<0.001), turning over (76.9% vs. 40%, p<0.05), and putting on socks (76.9% vs. 26.6%, p<0.01) such as pain during rest, and signs of intermittent claudication more than 15 minutes (61.5% vs. 26.6%, p<0.05) were all significantly more common with LFS than LSCS. Conclusion Results suggest that of the items in the JOABPEQ, if pain during rest or intermittent claudication is noted, LFS should be kept in mind as a cause during subsequent diagnosis and treatment. LFS may be easily diagnosed from LSCS using this established patient-based assessment method.

Diagnosis of Lumbar Foraminal Stenosis using Diffusion Tensor Imaging

Diagnosis of lumbar foraminal stenosis remains difficult. Here, we report on a case in which bilateral lumbar foraminal stenosis was difficult to diagnose, and in which diffusion tensor imaging (DTI) was useful. The patient was a 52-year-old woman with low back pain and pain in both legs that was dominant on the right. Right lumbosacral nerve compression due to a massive uterine myoma was apparent, but the leg pain continued after a myomectomy was performed. No abnormalities were observed during nerve conduction studies. Computed tomography and magnetic resonance imaging indicated bilateral L5 lumbar foraminal stenosis. DTI imaging was done. The extraforaminal values were decreased and tractography was interrupted in the foraminal region. Bilateral L5 vertebral foraminal stenosis was treated by transforaminal lumbar interbody fusion and the pain in both legs disappeared. The case indicates the value of DTI for diagnosing vertebral foraminal stenosis.

Recent advances in magnetic resonance neuroimaging of lumbar nerve to clinical applications: A review of clinical studies utilizing Dffusion Tensor Imaging and Diffusion-weighted magnetic resonance neurography

Much progress has been made in neuroimaging with Magnetic Resonance neurography and Diffusion Tensor Imaging (DTI) owing to higher magnetic fields and improvements in pulse sequence technology. Reports on lumbar nerve DTI have also increased considerably. Many studies have shown that the use of DTI in lumbar nerve lesions, such as lumbar foraminal stenosis and lumbar disc herniation, makes it possible to capture images of interruptions of tractography at stenotic sties, enabling the diagnosis of stenosis. DTI can also reveal significant decreases in fractional anisotropy (FA) with significant increases in apparent diffusion coefficient (ADC) values in compression lesions. FA values have higher accuracy than ADC values. Furthermore, strong correlations exist between FA values and indications of neurological severity, including the Japanese Orthopedic Association (JOA) score, the Oswestry Disability Index (ODI), and the Roland-Morris Disability Questionnaire (RDQ) in patients with lumbar disc herniation-induced radiculopathy. Most lumbar DTI has become 3T; 3T MRI has made it possible to take high-resolution DTI measurements in a short period of time. However, increased motion artifacts in the magnetic susceptibility effect lead to signal irregularities and image distortion. In the future, high-resolution DTI with reduced field-of-view may become useful in clinical applications, since visualization of nerve lesions and quantification of DTI parameters could allow more accurate diagnoses of lumbar nerve dysfunctions. Future translational studies will be necessary to successfully bring MR neuroimaging of lumbar nerve into clinical use.

Total knee arthroplasty for rheumatoid arthritis patients with large tibial condyle defects

Purpose. To review clinical results of total knee arthroplasty (TKA) in rheumatoid arthritis (RA) patients with large bone defects of the tibial condyle. Methods. Records of 33 knees in 27 women and 3 men aged 44 to 80 (mean, 63.6) years who underwent primary TKA for RA with large tibial bone defects were reviewed. 16 knees had peripheral defects extending to the bone cortex, whereas 17 knees had central defects that did not extend to the bone cortex. The femorotibial angle (FTA) was <170° in 15 knees, 170° to 180° in 3 knees, and >180° in 15 knees. The mean duration of RA was 13.5 (range, 3–35) years. In 14 knees with severe bone defects, bone grafts (harvested from articular surfaces of knee bones and fixed without screws or Kirschner wires) and/or metal wedges (for peripheral defects) were used to fill the defects. Clinical outcome was assessed pre- and post-operatively using Knee Society scores. Results. The mean follow-up duration was 6.3 (range, 2.3–13.2) years. The mean depth of tibial bone defects was 11.2 (range, 1–25) mm, whereas the mean width ratio of the bone defects was 36.5% (range, 16.4–76.9%). Mean extension and flexion (range of motion) improved from −12.5° and 113.4° to −5.1° and 115.6°, respectively. The mean Knee Society knee score improved from 35 (range, 21–59) to 85 (range, 49–95), whereas the mean Knee Society function score improved from 30 (range, 25–53) to 80 (range, 44–97) [p<0.001, Wilcoxon signed rank test]. The cruciate retention prosthesis was used in 6 knees; the posterior stabilised prosthesis was used in 27 knees; and the constrained condylar knee prosthesis was used in 3 knees. No patient had any infection or implant loosening. Conclusion. TKA achieved favourable outcome for RA patients with large tibial bone defects. The type of prosthesis used and the use of bone grafts and/or metal wedges were based on the depth and width ratio of the bone defects.

Influence of Skeletal Muscle Mass and Spinal Alignment on Surgical Outcomes for Lumbar Spinal Stenosis

Study Design Retrospective observational study. Purpose We considered the relationship between spinal alignment and skeletal muscle mass on clinical outcomes following a surgery for lumbar spinal stenosis (LSS). Overview of Literature There are no reports of preoperative factors predicting residual low back pain following surgery for LSS. Methods Our target population included 34 women (mean age, 74.4 years) who underwent surgery for LSS. Prior to and 6 months after the surgery, systemic bone mineral density and lean soft tissue mass were measured using dual-energy X-ray absorptiometry. Skeletal muscle mass index (SMI) was calculated as the sum of the arm and leg lean mass in kilograms divided by height in meters squared. The spinal alignment was also measured. Clinical outcomes were evaluated using the Japanese Orthopedic Association scoring system, leg and low back pain Visual Analog Scale, and Roland–Morris Disability Questionnaire (RDQ). Additionally, we examined the bone mineral density, skeletal muscle mass, and spinal alignment before and after the surgery. We used the Spearman correlation coefficient to examine the associations among clinical outcomes, preoperative muscle mass, and spinal alignment. Results Sarcopenia (SMI <5.46) was observed in nine subjects (26.5%). Compared with normal subjects (SMI >6.12), RDQ was significantly higher in subjects with sarcopenia (p =0.04). RDQ was significantly negatively correlated with SMI (r =−0.42, p <0.05). There was a significant positive correlation between postoperative RDQ and pelvic tilt (PT; r =0.41, p <0.05). SMI and PT were significantly negatively correlated (r =−0.39, r <0.05). Conclusions Good postoperative outcomes were negatively correlated with low preoperative appendicular muscle mass, suggesting that postoperative outcomes were inferior in cases of decreased appendicular muscle mass (sarcopenia). Posterior PT due to decreased limb muscle mass may contribute to postoperative back pain, showing that preoperatively reduced limb muscle mass and posterior PT are predictive factors in the persistence of postoperative low back pain.