[Guidelines for RA therapies].
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Publications and source records attributed to Takahiro Ochi.
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We have developed a four-dimensional (4D) model of the lower extremities after total hip arthroplasty in patients. The model can aid in preventing complications such as dislocation and wearing of the sliding surface. The skeletal structure and implant alignment were obtained from CT data. We applied registration method using CAD data to estimate accurate implant alignment from scattered CT data. The reconstructed three-dimensional (3D) skeletal model was combined with motion capture data that were acquired by an optical tracking system. We displayed the patient's skeletal movement and analyzed several parameters that relate to complications. The patient's skeletal model was superimposed onto video footage that was taken by a synchronized and calibrated digital video camera. For validation of the measurement error in this system, we used open MRI to evaluate the relative movement between skin markers and bones. This system visually represents not only the 3D anatomical structure, but also 4D dynamic functions that include the time sequential transitions of components and their positions. The open MRI results indicated that the average error in hip angle was within 5 degrees for each static posture. This system enables clinicians to analyze patient's motions on the basis of individual differences. We found that our system was an effective tool in providing precise guidance of daily postoperative motions that was individualized for each patient. This system will be applicable for surgical planning, assessment of postoperative activities, and the development of new surgical techniques, materials, and prosthetic designs.
Registration is a critical and important process in maintaining the accuracy of CT-based image-guided surgery. The aim of this study was to evaluate the effects of the area of intraoperative data sampling and number of sampling points on the accuracy of surface-based registration in a CT-based spinal-navigation system, using an optical three-dimensional localizer. A cadaveric dry-bone phantom of the lumbar spine was used. To evaluate registration accuracy, three alumina ceramic balls were attached to the anterior and lateral aspects of the vertebral body. CT images of the phantom were obtained (1-mm slice thickness, at1-mm intervals) using a helical CT scanner. Twenty surface points were digitized from five zones defined on the basis of anatomical classification on the posterior aspects of the target vertebra. A total of 20 sets of sampling data were obtained. Evaluation of registration accuracy accounted for positional and rotational errors. Of the five zones, the area that was the largest and easiest to expose surgically and to digitize surface points was the lamina. The lamina was defined as standard zone. On this zone, the effect of the number of sampling points on the positional and rotational accuracy of registration was evaluated. And the effects of the additional area selected for intraoperative data sampling on the registration accuracy were evaluated. Using 20 surface points on the posterior side of the lamina, positional error was 0.96 mm +/- 0.24 mm root-mean-square (RMS) and rotational error was 0.91 degrees +/- 0.38 degrees RMS. The use of 20 surface points on the lamina usually allows surgeons to carry out sufficiently accurate registration to conduct computer-aided spine surgery. In the case of severe spondylosis, however, it might be difficult to digitize the surface points from the lamina, due to a hypertrophic facet joint or the deformity of the lamina and noisy sampling data. In such cases, registration accuracy can be improved by combining use of the 20 surface points on the lamina with surface points on other zones, such as on the both sides of the spinous process.
Biochemical experiments have shown that Smad6 and Smad ubiquitin regulatory factor 1 (Smurf1) block the signal transduction of bone morphogenetic proteins (BMPs). However, their in vivo functions are largely unknown. Here, we generated transgenic mice overexpressing Smad6 in chondrocytes. Smad6 transgenic mice showed postnatal dwarfism with osteopenia and inhibition of Smad1/5/8 phosphorylation in chondrocytes. Endochondral ossification during development in these mice was associated with almost normal chondrocyte proliferation, significantly delayed chondrocyte hypertrophy, and thin trabecular bone. The reduced population of hypertrophic chondrocytes after birth seemed to be related to impaired bone growth and formation. Organ culture of cartilage rudiments showed that chondrocyte hypertrophy induced by BMP2 was inhibited in cartilage prepared from Smad6 transgenic mice. We then generated transgenic mice overexpressing Smurf1 in chondrocytes. Abnormalities were undetectable in Smurf1 transgenic mice. Mating Smad6 and Smurf1 transgenic mice produced double-transgenic pups with more delayed endochondral ossification than Smad6 transgenic mice. These results provided evidence that Smurf1 supports Smad6 function in vivo.
The purpose of this study was to clarify differences in tendon graft-to-bone tunnel healing between bone-attached tendon grafts with interference-screw fixation and bone-free tendon grafts with extra-articular suture fixation. In 42 Japanese White rabbits, anterior half replacement of the medial collateral ligament was performed using half of the ipsilateral patellar tendon. At the femoral attachment, the bone-plug-attached graft was fixed with an interference screw (group A). The bone-plug-free graft was fixed by the extra-articular suture fixation technique with sutures tied over a button (group B). Biomechanical and histological evaluations were performed at 2, 4 and 8 weeks postoperatively. In biomechanical evaluation, at 2 or 4 weeks 27 of 28 specimens (96%) were pulled out from the femoral tunnel, while one 4-week specimen and all four 8-week specimens failed at the graft's mid-substance. At 2 weeks, the maximum failure load was 25+/-10 N and 24+/-6 N for group A and group B respectively (mean+/-SD). At 4 weeks, the maximum failure load was 42+/-17 N and 35+/-15 N respectively. There were no significant differences in maximum pullout failure load between the groups at 2 or 4 weeks postoperatively. (P=0.887 at 2 weeks and P=0.339 at 4 weeks using ANOVA measurement). Histologically, the bone-attached grafts showed partial bone-to-bone union at the graft-bone tunnel interface at 4 weeks, and complete bony union at 8 weeks. The bone-free grafts exhibited newly formed Sharpey-like collagen fibers at 4 weeks, and strong connection by mature granulation tissue at 8 weeks. Graft-to-bone tunnel healing of bone-attached graft with screw fixation and bone-free graft with extra-articular suture fixation are comparable in terms of biomechanical evaluation during the early postoperative periods.
OBJECTIVE: To examine the capacity of bone marrow CD34+ cells to generate endothelial cells, in order to assess the role of bone marrow in neovascularization in the synovium of rheumatoid arthritis (RA). METHODS: CD34+ cells purified from the bone marrow of 13 patients with active RA and 9 control subjects (7 osteoarthritis [OA] patients and 2 healthy individuals) were cultured in the presence of stem cell factor (10 ng/ml) and granulocyte-macrophage colony-stimulating factor (1 ng/ml). After 18 days of incubation, the generation of endothelial cells was assessed by flow cytometry. The generation of endothelial cells was compared with the degree of vascularization in the synovial tissues and with the microvessel densities in the synovium, as determined by microscopy. The expression of vascular endothelial growth factor receptor 2/kinase insert domain receptor (KDR) messenger RNA (mRNA) in CD34+ cells was examined by quantitative reverse transcription-polymerase chain reaction. RESULTS: The generation of CD14+ cells from bone marrow-derived CD34+ cells from RA patients was comparable to that from control subjects. However, the generation of von Willebrand factor (vWF)-positive cells and CD31+/vWF+ cells from RA bone marrow-derived CD34+ cells was significantly higher than that from control subjects (P = 0.004 and P = 0.030, respectively). The generation of vWF+ cells from bone marrow CD34+ cells correlated significantly with the microvessel densities in the synovial tissues (r = 0.569, P = 0.021). Finally, RA bone marrow CD34+ cells expressed KDR mRNA at higher levels than OA bone marrow CD34+ cells. CONCLUSION: These results indicate that RA bone marrow CD34+ cells have enhanced capacities to differentiate into endothelial cells in relation to synovial vascularization. The data therefore suggest that bone marrow CD34+ cells might contribute to synovial neovascularization by supplying endothelial precursor cells and, thus, play an important role in the pathogenesis of RA.
The matrix extracellular phosphoglycoprotein (MEPE) gene is highly expressed in tumors that cause oncogenic hypophosphatemic osteomalacia (OHO). MEPE is also known as one of the bone-tooth matrix proteins and is associated with bone mineralization. We developed a rabbit polyclonal antibody directed against recombinant human MEPE (rhMEPE) after cloning its cDNA from the cDNA library of a nasal tumor tissue causing OHO. Using this antibody, we analyzed the distribution of MEPE in human bones by immunohistochemistry. In bone specimens from normal subjects, MEPE was predominantly expressed by osteocytes and not by osteoblasts. In bone specimens from patients with osteomalacia, however, MEPE was focally expressed by deeply located osteocytes. We also compared the MEPE positivity of osteocytes in mineralized bone and non-mineralized osteoid obtained from patients with osteomalacia and osteoporosis. Among osteomalacia patients, MEPE positivity was seen in 87.5 +/- 8.6% of the osteocytes from mineralized bone compared with 7.8 +/- 6.4% of those from osteoid. Among osteoporosis patients, MEPE positivity was found in 95.3 +/- 0.5% of the osteocytes from mineralized bone compared with 4.9 +/- 5.7% of those from osteoid. MEPE was mainly expressed by osteocytes embedded in the matrix of mineralized bone from patients with osteomalacia or osteoporosis. Our data provide the first histological evidence that MEPE is predominantly expressed by osteocytes in human bone, with significant expression by osteocytes within mineralized bone.
The purpose of this study was to evaluate the clinical accuracy of femoral canal preparation using postoperative reconstructed computed tomography (CT) images of 75 consecutive total hip arthroplasties performed with a two-pin-based ROBODOC system. Intraoperatively, the robot milled the femoral canal according to the preoperative planning performed with preoperative CT data and the ROBODOC workstation. Postoperative CT data was obtained 1 month postoperatively. Anteroposterior and lateral synthetic radiographs and axial images were reconstructed from CT data on the workstation. The mean difference between the preoperative planning and the postoperative CT images was less than 5% in canal fill, less than 1 mm in gap, and less than 1 degrees in the mediolateral and anteroposterior alignment. Clinical femoral canal preparation using the ROBODOC system results in a high degree of accuracy.
We have developed a novel system of four-dimensional motion analysis after total hip arthroplasty (THA) that can aid in preventing dislocation by assessing safe range of motion for patients in several daily activities. This system uses skeletal structure data from CT and motion capture data from an infrared position sensor. A 3-D model reconstructed from CT data is combined with the motion capture data. Using this system, we analyzed hip motion when getting up from and sitting down in a chair or picking up an object while sitting in a chair in 17 patients (26 hips) who underwent THA. To assess the accuracy of this system's measurements, open MRI was used to evaluate positions of skin markers against bones in five healthy volunteers in various postures. No impingement between bones and/or implants was found in any subjects during any activities. However, mean angle at the point of maximum hip flexion was different for each patient. The open MRI results indicated that average error in hip angle of the present system was within 5 degrees for each static posture. The functional position of the pelvis during daily activities must be taken into account when assessing the real risk of dislocation. The present system enables dynamic analysis involving not only alignment of components and bones of each patient, but also individual differences in characteristics of daily motions. Further investigation using this system can help determine safe ranges of motion for preventing hip dislocation, improving the accuracy of individualized guidance for patients regarding postoperative activities.
The current study aimed to analyze kinematics during deep knee bending motion by subjects with fully congruent mobile-bearing total knee arthroplasties allowing axial rotation and anteroposterior (AP) gliding. Twelve subjects were implanted with Dual Bearing Knee prostheses (DBK, slot type: Finsbury Orthopaedics, Surrey, UK). These implants include a mobile-bearing insert that is fully congruent with the femoral component throughout flexion and allows axial rotation and limited AP translation. Sequential fluoroscopic images were taken in the sagittal plane during loaded knee bending motion. In vivo kinematics were analyzed using a two- to three-dimensional registration technique, which uses computer-assisted design models to reproduce the spatial position of femoral and tibial components from single-view fluoroscopic images. The average femoral component demonstrated 13.4 degrees external axial rotation for 0-120 degrees flexion. On average, the medial condyle moved anteriorly 6.2 mm for 0-100 degrees flexion, then posteriorly 4.0 mm for 100-120 degrees flexion. On average, the lateral condyle moved anteriorly 1.0 mm for 0-40 degrees flexion, then posteriorly 8.7 mm for 40-120 degrees flexion. The typical subject exhibited a lateral pivot pattern from extension to 60 degrees flexion and a central pivot pattern from 60 degrees to 100 degrees flexion, patterns that are not usually observed in normal knees. Subsequently from 100 degrees to 120 degrees flexion, a rollback pattern was reproduced in which bilateral condyles moved backward.
The purposes of this study were to clarify the effects of rotation on two-dimensional measurement of lower limb alignment for knee osteotomy using a three-dimensional method and to determine whether this 3-D simulation method could help with planning of knee osteotomy. We developed computer software to calculate femorotibial angle (FTA) and hip-knee-ankle angle (HKA) and simulate knee osteotomy from a CT-based 3-D bone model of the lower limb. Lower limb rotation on anteroposterior long-standing radiographs was measured by superimposing the 3-D bone models. Changes in alignment with limb rotation were calculated using the software. FTA after virtual closed-wedged osteotomy was measured for a hypothetical case of a rotation error of the osteotomy plane in reattaching the proximal cutting surface to the distal cutting surface. For 31 varus knees in 20 patients with medial compartment arthritis, the mean rotation angle, relative to the epicondylar axis, with variable limb position was 7.4 +/- 3.9 degrees of internal rotation (mean +/- SD), ranging from 8 degrees of external rotation to 14 degrees of internal rotation; the mean changes in FTA and HKA were 3.5 +/- 2.2 degrees (range, 0.4-8.6) and 1.6 +/- 1.3 degrees (range, 0.2-4.9), respectively. The FTA "flexion angle" (lateral view alignment from neutral AP) and the absolute HKA "flexion angle" correlated with the change in FTA and HKA with limb rotation, respectively (FTA, R = 0.999; HKA, R = 0.993). The mean change in FTA after virtual closed-wedged osteotomy was 3.2 degrees for internal and external 10 degrees rotation errors in reattaching the osteotomy plane. Rotation may affect measurement of lower limb alignment for knee osteotomy, and 3-D methods are preferable for surgical planning.
BACKGROUND: Opening-wedge high tibial osteotomy by hemicallotasis for osteoarthritis in the medial compartment of the knee requires external fixation for a long time, until callus maturation is complete. The aim of this study was to determine if low-intensity pulsed ultrasound would accelerate callus maturation when applied after distraction to limbs treated with opening-wedge high tibial osteotomy by hemicallotasis. METHODS: Twenty-one patients with symmetric grades of osteoarthritis and similar degrees of varus deformity in the two knees underwent bilateral one-stage opening-wedge high tibial osteotomy by hemicallotasis. After completion of distraction, the bone mineral density of the distraction callus was measured. Then, one randomly selected limb was subjected to ultrasound treatment for twenty minutes daily until removal of the external fixator. The contralateral limb was left untreated to serve as the control. After four weeks of treatment, bone mineral density was measured again. RESULTS: During the four-week treatment period, the mean increase in callus bone mineral density was significantly greater in the ultrasound-treated tibiae (0.20 +/- 0.12 g/cm(2)) than in the control tibiae (0.13 +/- 0.10 g/cm(2)) (p = 0.02, unpaired t test). In eighteen patients the increase in the bone mineral density was greater in the ultrasound-treated limb than in the control limb, whereas in three patients the increase was greater in the control limb. CONCLUSIONS: We found that low-intensity pulsed ultrasound applied during the consolidation phase of distraction osteogenesis accelerates callus maturation after opening-wedge high tibial osteotomy by hemicallotasis in elderly patients.
Tumor-infiltrating lymphocytes (TIL) play a central role in cellular immunity against tumor. We have revealed the characteristics of TILs in terms of T-cell receptor (TCR) repertoire, T-cell clonality, and cytokine production. TCR repertoire analyses and CDR3 size spectratyping were performed using peripheral blood mononuclear cells (PBMCs) and tissue specimens of gastric or colorectal cancers surgically resected from 11 patients. The cytokine expression was measured by real-time quantitative polymerase chain reaction. TCR repertoires were similar among multiple tissue specimens from different sites of the same tumor. Similar peak patterns of CDR3 size spectratyping were observed among these tumor specimens, but not in normal tissues or PBMCs. In addition, identical peaks were detected in multiple specimens of the same tumor. The ratio of the levels of IFN-gamma to that of IL-4 is significantly higher for tumor lesions compared with PBMCs. These results suggested that a limited number of TILs locally expand in response to tumor antigens exiting within gastric or colorectal cancers and local predominant production of the T helper 1/T cytotoxic 1 type cytokine may affect the anti-tumor immune response of TILs.
We reviewed 21 patients with rheumatoid arthritis who had a total ankle replacement between 1984 and 2000. The average follow-up was 72 (15-169) months. Clinical results were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) score. At the latest review, three ankles had been revised. Two ankles were excellent, seven good, three fair, and 12 poor. Eleven patients with 13 ankles had residual pain, with radiographs showing a high incidence of radiolucent lines. Migration of the tibial component was seen in 13 ankles and collapse of talus in nine. Although clinical results were poor, patient satisfaction was not.
To evaluate the gastrointestinal tolerability of nonsteroidal antiinflammatory drugs (NSAIDs) in osteoarthritis patients in Japan, a systematic review of Japanese randomized controlled trials was performed. This study consisted of double-blind, randomized, controlled clinical trials with 4-week NSAID treatment of osteoarthritis patients in Japan. The analysis included 4725 patients from 25 trials. On average the cumulative incidences of patients who had experienced any adverse reaction and any adverse digestive reaction were 14.3% [95% confidence interval (CI) 13.3%-15.3%] and 10.4% (95% CI 9.4%-11.4%), respectively. The cumulative incidence for the upper gastrointestinal (GI) symptoms such as abdominal pain, nausea/vomiting, and dyspepsia was estimated to be approximately 10.9%. When the risk of upper GI symptoms was compared between males and females, the summary odds ratio was 1.71 (95% CI 1.11-2.65). Comparing the risk of upper GI symptoms between patients 59 years of age and younger and those 60+ years old, the summary odds ratio was 1.07 (95% CI 0.75-1.52). Despite the incidence of adverse reactions varying across the drugs being used, there was an obvious increased risk of GI symptoms.
The purpose of this investigation is to evaluate the diagnostic ability of three-dimensional spoiled gradient-echo (3D SPGR) magnetic resonance (MR) imaging in cases of osteonecrosis of the femoral head (ONFH), and to determine the accuracy of 3D SPGR imaging in area and volume measurement of ONFH. T1-weighted spin-echo (SE) and 3D SPGR imaging were performed on 20 femoral heads obtained from patients with ONFH. After MR imaging, the femoral heads were cut parallel to the imaging plane and were evaluated histologically. Areas and volumes of necrotic lesions were measured with a computer program and the deviation between MR images and anatomical measurements was evaluated. A low signal intensity band on 3D SPGR MR images was observed in all femoral heads and corresponded histologically to repaired marrow with viable fibrous mesenchymal tissue. The area proximate to the low band area coincided with the necrotic region. Both area and volume measurements by T1-weighted SE and 3D SPGR images showed a strong correlation to histological measurements. The discrepancies between histological and imaging results were minimal in 3D SPGR imaging, especially at the anterior and posterior portions of the femoral head. Three-dimensional SPGR imaging provides more accurate measurements of the area and volume of a necrotic lesion than T1-weighted SE imaging.
We performed transesophageal echocardiography on 88 patients treated with cementless or hybrid total hip arthroplasty (THA). We observed a significantly higher frequency of severe embolic events among patients without cup holes during insertion of press-fit cups (46.0%) than in patients with holes (15.6%) (P<.005). During stem insertion, severe embolic events occurred in 61.5% of hybrid operations and 5.9% of cementless operations. PaO(2), systolic blood pressure, and arterial oxygen saturation decreased significantly in severe embolic events (P<.05). The results indicate that embolic events may occur during THA whether or not cement is used. Based on these findings, we make several recommendations for technique modifications during insertion of both femoral and acetabular components in THA.
Intraoperative pulmonary embolism occurs not only during cemented but also during cementless total hip arthroplasty (THA). We determined whether the ROBODOC femoral milling system can reduce intraoperative pulmonary embolism, by using of transesophageal echocardiography and hemodynamic monitoring. We did a prospective clinical trial with 71 patients (75 hips) who were divided into 2 groups: group 1, 46 patients (50 hips) who underwent cementless THA with preparation of the femoral canal using ROBODOC; group 2, 25 patients (25 hips) who underwent conventional cementless THA surgery in whom separate measurements were made during preparation of the femur, insertion of the stem and relocation of the hip. The incidence of severe embolic events was lower in group 1 than in group 2. Our findings suggest that the ROBODOC femoral milling system may reduce the risk of clinically significant pulmonary embolism during cementless THA.