研究者詳細 - 松本　守雄

論文 - 松本　守雄

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Differentiation of spinal giant cell tumors from chordomas by using a scoring system

Tsuji Takashi, Chiba Kazuhiro, Watanabe Kota, Ishii Ken, Nakamura Masaya, Nishiwaki Yuji, Matsumoto Morio

European Journal of Orthopaedic Surgery and Traumatology 1 - 6 2016年07月

ISSN 1633-8065

Introduction: Few reports have compared the clinical features and imaging characteristics of giant cell tumor and chordoma of the spine. The aim of the present study was to investigate whether the two types of tumors could be differentially diagnosed, by comparing clinical characteristics as well as magnetic resonance imaging (MRI) or computed tomography (CT) findings and then scoring the characteristic findings. Methods: A total of 18 patients were retrospectively assessed. To elucidate the characteristic findings, we investigated the following 10 items: age at diagnosis, sex, and site of occurrence; for MRI findings, the pattern of tumor expansion, T1-weighted images, T2-weighted images, septal structure, and cystic changes; and for CT findings, calcification or residual bone fragments and incomplete bone shells. Then, we developed a unique scoring system and investigated whether the two tumors could be differentiated by this scoring system. Results: Six items, including, age, site of occurrence, tumor expansion pattern, T2-weighted images, septal structure, and incomplete bone shells, were significantly different between giant cell tumor and chordoma patients. By using newly developed scoring system, the mean scores of 0.9 ± 0.6 (range 0–2) for giant cell tumor and 4.8 ± 1.5 (range 3–6) for chordoma patients were significantly different (P <0.001), thereby allowing the differential diagnosis by setting the cutoff value to three. Conclusions: We found that the six items were useful for differentially diagnosing giant cell tumor and chordoma. These results indicate that it may be possible to distinguish the two types of tumor by scoring these items.

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Adamantinoma of the distal femur diagnosed 5 years after initial surgery

Cao Kai, Susa Michiro, Watanabe Itsuo, Nishimoto Kazumasa, Horiuchi Keisuke, Sasaki Aya, Hayashi Yuichiro, Emoto Katsura, Kameyama Kaori, Nakamura Masaya, Matsumoto Morio, Morioka Hideo

Journal of Medical Case Reports 10 （ 1 ） 2016年06月

ISSN 1752-1947

Background: Adamantinoma arising in the femur is extremely rare. We report a case of an adamantinoma occurring in the right medial femoral condyle that was diagnosed 5 years after the primary surgery. Case presentation: A 74-year-old Asian woman first complained of right knee pain without any cause. Radiographs demonstrated a 4×4.5 cm osteolytic lesion in her medial femoral condyle. Magnetic resonance imaging revealed a lesion which showed low signal on both T1 and T2-weighted image, and enhanced signal with gadolinium contrast administration. She underwent a wide resection of the lesion and was reconstructed with a tumor endoprosthesis. On histological examination, the tumor showed clusters of spindle-shaped and squamoid epithelial cells among the fibrous stroma. Adamantinoma was considered, however, the diagnosis was inconclusive due to the unusual localization and her age. Moreover, it was difficult to exclude metastatic carcinoma. Five years later, she was diagnosed with an abnormal shadow occupying the upper lobe of her right lung in a routine physical examination. She subsequently underwent a resection of the lung mass which histologically showed proliferation of spindle-shaped and squamoid epithelial cells. The histological similarity of the lung tumor and the femoral tumor led to the diagnosis of adamantinoma arising in her right medial femoral condyle with metastasis to the upper lobe of her right lung. Conclusion: In this case report, we report the clinical, radiographic, and histological features of an adamantinoma arising in the distal femur with a review of the literature.

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Smad2/3 proteins are required for immobilization-induced skeletal muscle atrophy

Tando Toshimi, Hirayama Akiyoshi, Furukawa Mitsuru, Sato Yuiko, Kobayashi Tami, Funayama Atsushi, Kanaji Arihiko, Hao Wu, Watanabe Ryuichi, Morita Mayu, Oike Takatsugu, Miyamoto Kana, Soga Tomoyoshi, Nomura Masatoshi, Yoshimura Akihiko, Tomita Masaru, Matsumoto Morio, Nakamura Masaya, Toyama Yoshiaki, Miyamoto Takeshi

Journal of Biological Chemistry 291 （ 23 ） 12184 - 12194 2016年06月

ISSN 0021-9258

Skeletal muscle atrophy promotes muscle weakness, limiting activities of daily living. However, mechanisms underlying atrophy remain unclear. Here, we show that skeletal muscle immobilization elevates Smad2/3 protein but not mRNA levels in muscle, promoting atrophy. Furthermore, we demonstrate that myostatin, which negatively regulates muscle hypertrophy, is dispensable for denervation-induced muscle atrophy and Smad2/3 protein accumulation. Moreover, muscle-specific Smad2/3-deficient mice exhibited significant resistance to denervation-induced muscle atrophy. In addition, expression of the atrogenes Atrogin-1 and MuRF1, which underlie muscle atrophy, did not increase in muscles of Smad2/3-deficient mice following denervation. We also demonstrate that serum starvation promotes Smad2/3 protein accumulation in C2C12 myogenic cells, an in vitro muscle atrophy model, an effect inhibited by IGF1 treatment. In vivo, we observed IGF1 receptor deactivation in immobilized muscle, even in the presence of normal levels of circulating IGF1. Denervation-induced muscle atrophy was accompanied by reduced glucose intake and elevated levels of branched-chain amino acids, effects that were Smad2/3-dependent. Thus, muscle immobilization attenuates IGF1 signals at the receptor rather than the ligand level, leading to Smad2/3 protein accumulation, muscle atrophy, and accompanying metabolic changes.

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Geographic and ethnic variations in radiographic disability thresholds

Ames Christopher, Gammal Isaac, Matsumoto Morio, Hosogane Naobumi, Smith Justin S., Protopsaltis Themistocles, Yamato Yu, Matsuyama Yukihiro, Taneichi Hiroshi, Lafage Renaud, Ferrero Emmanuelle, Schwab Frank J., Lafage Virginie

Neurosurgery 78 （ 6 ） 793 - 800 2016年06月

ISSN 0148-396X

BACKGROUND: Thresholds for spinal pelvic parameters in adult spinal deformity (ASD) were previously defined in North American patients and are commonly used to guide surgical planning. However, it is unclear whether these same threshold parameters can be more widely applied in other geographic regions and in other ethnicities. OBJECTIVE: To evaluate the variation in the radiographic disability thresholds between North American and Japanese ASD populations and to adjust sagittal modifier thresholds accordingly. METHODS: Retrospective case series of 717 patients with ASD who had baseline radiographs and Oswestry Disability Index (ODI) from North America (n 518) and Japan (n 199) were studied. Patients were compared at baseline for ODI, ODI offset from age- and ethnic-specific values (ODIni), and radiographic parameters. RESULTS: Significant differences in classification were observed: A greater proportion of Japanese patients had marked pelvic tilt deformity, whereas a greater proportion of US patients had marked SVA deformity; no difference in the pelvic incidence-lumbar lordosis mismatch sagittal modifier was observed. Health-related quality-of-life scores also differed, with a greater ODI raw value observed in the US patients but similar ODIni scores between cohorts. Stratifying ODIni scores by sagittal modifier grades revealed similar disability scores corresponding to the 0 to + thresholds for pelvic tilt, pelvic incidence-lumbar lordosis mismatch, and sagittal vertical axis across ethnicities. Finally, linear regression analysis demonstrated that compared with US patients, Japanese patients had a lower estimated ODI corresponding to established thresholds of radiographic deformity. CONCLUSION: Our findings demonstrate significant variability in health-related quality-of-life measures and radiographic parameters between North American and Japanese patients, supporting the need for population-adjusted sagittal modifiers to more accurately classify deformity.

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Pseudoarthrosis of the ilium after periacetabular osteotomy that was treated by cemented total hip arthroplasty

Kanaji Arihiko, Nishiwaki Toru, Oya Akihito, Maehara Kazuyuki, Maehara Hideki, Oishi Teruyo, Yamada Harumoto, Suda Yasunori, Nakamura Masaya, Matsumoto Morio

Journal of Medical Case Reports 10 （ 1 ） 2016年05月

ISSN 1752-1947

Background: Preserving the hip joint to delay arthroplasty for patients with acetabular dysplasia-associated early-stage osteoarthritis has become more common, and several surgical procedures have demonstrated pain relief and improved hip joint function. Periacetabular osteotomy, one of the joint-preserving surgical procedures of the hip, provides favorable outcomes, although there are no reports of total hip arthroplasty being used to treat pseudoarthrosis of the periacetabular osteotomy segment. Therefore, we report a case of pseudoarthrosis in the osteotomy segment after periacetabular osteotomy. The patient was treated using modified total hip arthroplasty and achieved a favorable short-term outcome. Case presentation: A 62-year-old Japanese woman was diagnosed with bilateral acetabular dysplasia at the age of 50 years, and underwent right and left periacetabular osteotomy at the ages of 52 and 55 years, respectively. When she was 61-years old, she experienced repeated episodes of left coxalgia during walking, with increasing pain at rest, and subsequently visited our department. Plain radiography and computed tomography of her left hip joint confirmed pseudoarthrosis of the periacetabular osteotomy segment. In addition, narrowing of her left hip joint space was observed, which indicated advanced osteoarthritis of the hip. Therefore, she underwent left total hip arthroplasty when she was 62-years old. During the surgery, fibrous fusion of the periacetabular osteotomy segment was confirmed via fluoroscopy, although no abnormal mobility was observed. Thus, the osteotomy segment was fixed with one absorbable screw and two bone pegs (which were prepared using allogeneic bone), and the acetabular cup was fixed using cement. Her postoperative course was generally favorable and bone fusion of the periacetabular osteotomy segment was confirmed at 3 years and 6 months after surgery. Her modified Harris hip score was 43 before the surgery and had improved to 90 at the final follow-up. Conclusions: Modified total hip arthroplasty was successfully used to treat osteoarthritis of the hip and pseudoarthrosis of the periacetabular osteotomy segment. This procedure achieved pseudoarthrosis region bone fusion and a favorable postoperative outcome.

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Potential Involvement of Obesity-associated Chronic Inflammation in the Pathogenesis of Idiopathic Spinal Epidural Lipomatosis

Fujita Nobuyuki, Hosogane Naobumi, Hikata Tomohiro, Iwanami Akio, Watanabe Kota, Shiono Yuta, Okada Eijiro, Ishikawa Masayuki, Tsuji Takashi, Shimoda Masayuki, Horiuchi Keisuke, Nakamura Masaya, Matsumoto Morio, Ishii Ken

Spine 2016年04月

ISSN 0362-2436

STUDY DESIGN.: Multicenter case–control study. OBJECTIVE.: To characterize the pathogenesis of idiopathic spinal epidural lipomatosis (SEL). SUMMARY OF BACKGROUND DATA.: SEL is often associated with the history of steroid use or endocrine disorders; however, the pathogenesis of idiopathic SEL remains poorly understood. METHODS.: Sixteen patients who underwent lumbar decompression surgery due to severe idiopathic SEL were included in the study (L group, 15 males and 1 female; mean age, 71.5 years). Fifteen patients without SEL, who underwent decompression surgery for lumbar canal stenosis, were selected as controls (C group, 14 males and 1 female; mean age, 70.3 years). The following parameters were analyzed in these two groups: body mass index (BMI), medical history, histology, the size of adipocytes in the epidural fat (EF) tissues, and the expression level of the transcripts for adiponectin, leptin, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8. RESULTS.: The mean BMI of the L group was significantly higher than that of the C group (29.1 vs. 25.2?kg/m, P?=?0.006), and there was a significant correlation between BMI and the width of EF in both groups. The average adipocyte size in the EF was significantly larger in the L group than in the C group (2846.8 vs. 1699.0?μm, P?=?0.017). Furthermore, the expression levels of the transcripts for TNF-α and IL-1β in the L group were significantly higher than those in the C group [2.59-fold increase (P?=?0.023) and 2.60-fold increase (P?=?0.015), respectively]. CONCLUSION.: Our data suggest that the pathogenesis of idiopathic SEL is associated with obesity. In addition, the increased expression of two major inflammatory cytokines in the EF in the L group may indicate that SEL is causally related to chronic inflammation.Level of Evidence: 3

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Generation of heterozygous fibrillin-1 mutant cloned pigs from genome-edited foetal fibroblasts

Umeyama Kazuhiro, Watanabe Kota, Watanabe Masahito, Horiuchi Keisuke, Nakano Kazuaki, Kitashiro Masateru, Matsunari Hitomi, Kimura Tokuhiro, Arima Yoshimi, Sampetrean Oltea, Nagaya Masaki, Saito Masahiro, Saya Hideyuki, Kosaki Kenjiro, Nagashima Hiroshi, Matsumoto Morio

Scientific Reports 6 2016年04月

Marfan syndrome (MFS) is an autosomal dominant genetic disease caused by abnormal formation of the extracellular matrix with an incidence of 1 in 3, 000 to 5, 000. Patients with Marfan syndrome experience poor quality of life caused by skeletal disorders such as scoliosis, and they are at high risk of sudden death from cardiovascular impairment. Suitable animal models of MFS are essential for conquering this intractable disease. In particular, studies employing pig models will likely provide valuable information that can be extrapolated to humans because of the physiological and anatomical similarities between the two species. Here we describe the generation of heterozygous fibrillin-1 (FBN1) mutant cloned pigs (+/Glu433AsnfsX98) using genome editing and somatic cell nuclear transfer technologies. The FBN1 mutant pigs exhibited phenotypes resembling those of humans with MFS, such as scoliosis, pectus excavatum, delayed mineralization of the epiphysis and disrupted structure of elastic fibres of the aortic medial tissue. These findings indicate the value of FBN1 mutant pigs as a model for understanding the pathogenesis of MFS and for developing treatments.

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A novel hydroxyapatite film coated with ionic silver via inositol hexaphosphate chelation prevents implant-associated infection

Funao Haruki, Nagai Shigenori, Sasaki Aya, Hoshikawa Tomoyuki, Tsuji Takashi, Okada Yasunori, Koyasu Shigeo, Toyama Yoshiaki, Nakamura Masaya, Aizawa Mamoru, Matsumoto Morio, Ishii Ken

Scientific Reports 6 2016年03月

Various silver-coated implants have been developed to prevent implant-associated infections, and have shown dramatic effects in vitro. However, the in vivo results have been inconsistent. Recent in vitro studies showed that silver exerts antibacterial activity by mediating the generation of reactive oxygen species in the presence of oxygen. To maintain its antibacterial activity in vivo, the silver should remain in an ionic state and be stably bound to the implant surface. Here, we developed a novel bacteria-resistant hydroxyapatite film in which ionic silver is immobilized via inositol hexaphosphate chelation using a low-heat immersion process. This bacteria-resistant coating demonstrated significant antibacterial activity both in vitro and in vivo. In a murine bioluminescent osteomyelitis model, no bacteria were detectable 21 days after inoculation with S. aureus and placement of this implant. Serum interleukin-6 was elevated in the acute phase in this model, but it was significantly lower in the ionic-silver group than the control group on day 2. Serum C-reactive protein remained significantly higher in the control group than the ionic-silver group on day 14. Because this coating is produced by a low-heat immersion process, it can be applied to complex structures of various materials, to provide significant protection against implant-associated infections.

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Subcutaneous flexor tendon rupture in patients with rheumatoid arthritis

Funahashi Takuya, Suzuki Taku, Iwamoto Takuji, Shizu Kanae, Matsumura Noboru, Ochi Kensuke, Ikari Katsunori, Sato Kazuki, Nakamura Masaya, Matsumoto Morio, Momohara Shigeki, Suzuki Katsuji, Yamada Harumoto

Modern Rheumatology 1 - 4 2016年03月

ISSN 1439-7595

Objective: We examined the clinical features and functional outcomes of surgically repaired subcutaneous flexor tendon ruptures in patients with rheumatoid arthritis (RA). Methods: This retrospective study included 41 fingers of 24 RA patients who underwent surgical treatment for flexor tendon ruptures. Evaluations performed at the time of presentation following rupture were C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and disease activity score in 28 joints (DAS28)-ESR, as well as Larsen grading for carpal bone destruction. The ruptured tendon and postoperative active range of motion (ROM) of digits were also examined. Results: The mean CRP was 2.4 mg/dl, ESR was 52 mm/h, and the DAS28-ESR was 4.5. Carpal bone destruction according to Larsen grade IV–V was observed in 18/24 patients. Affected digits were most commonly the thumb (12) and the ring and little fingers (9 each). Tendon ruptures were most common in the carpal tunnel in zone IV. The mean postoperative finger ROM (flexion/extension) was 38°/2° for the interphalangeal (IP) joint of the thumb and 23°/−2° for the distal interphalangeal joint of the other four fingers. Conclusions: Patients with flexor tendon ruptures present with high disease activity and advanced bone destruction. It is important to reduce the risk of progressive bone destruction and subsequent tendon rupture via tight control of disease activity.

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Comparison of surgical treatments for triple extensor tendon ruptures in rheumatoid hands

Suzuki Taku, Iwamoto Takuji, Ikegami Hiroyasu, Sakuma Yu, Ikari Katsunori, Matsumura Noboru, Ochi Kensuke, Sato Kazuki, Nakamura Masaya, Matsumoto Morio, Momohara Shigeki

Modern Rheumatology 26 （ 2 ） 206 - 210 2016年03月

ISSN 1439-7595

Objective. This retrospective study was designed to evaluate the outcomes of four different surgical reconstructions for extensor tendon ruptures in ulnar three fingers in 48 patients with rheumatoid arthritis. Methods. The following four techniques were performed; palmaris longus tendon grafting (PL group; n = 9), extensor indicis proprius (EIP) tendon transfers (EIP group; n = 8), end-to-side transfers with tension-reduced early mobilization (End-to-side group; n = 16), and a combination of end-to-side and EIP transfers (Combination group; n = 15). Loss of extension was evaluated to determine the mean postoperative range of motion of the metacarpophalangeal (MP) joint and clinical outcomes were categorized using modified Geldmacher criteria. Results. Combination group demonstrated the best mean MP joint extension (- 3°), followed by End-to-side group (- 12°), EIP group (- 16°), and PL group (- 21°). Combination group yielded the best clinical outcomes with all cases showing good results. Conclusions. The combination of end-to-side and EIP transfer was an effective surgical reconstruction procedure for triple fingers extension loss.

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Hif1α is required for osteoclast activation and bone loss in male osteoporosis

Tando Toshimi, Sato Yuiko, Miyamoto Kana, Morita Mayu, Kobayashi Tami, Funayama Atsushi, Kanaji Arihiko, Hao Wu, Watanabe Ryuichi, Oike Takatsugu, Nakamura Masaya, Matsumoto Morio, Toyama Yoshiaki, Miyamoto Takeshi

Biochemical and Biophysical Research Communications 470 （ 2 ） 391 - 396 2016年02月

ISSN 0006-291X

The number of osteoporosis patients is increasing not only in women but in men. Male osteoporosis occurs due to aging or androgen depletion therapies, leading to fractures. However, molecular mechanisms underlying male osteoporosis remain unidentified. Here, we show that hypoxia inducible factor 1 alpha (Hif1α) is required for development of testosterone deficiency-induced male osteoporosis. We found that in mice Hif1α protein accumulates in osteoclasts following orchidectomy (ORX) in vivo. In vitro, Hif1α protein accumulated in osteoclasts cultured in hypoxic conditions, but Hif1α protein rather than mRNA levels were suppressed by testosterone treatment, even in hypoxia. Administration of a Hif1α inhibitor to ORX mice abrogated testosterone deficiency-induced osteoclast activation and bone loss but did not alter osteoclast activities or bone phenotypes in sham-operated, testosterone-sufficient animals. We conclude that Hif1α protein accumulation due to testosterone-deficiency promotes development of male osteoporosis. Thus Hif1α protein could be targeted to inhibit pathologically-activated osteoclasts under testosterone-deficient conditions to treat male osteoporosis patients.

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Reliability analysis of spino-pelvic parameters in adult spinal deformity

Chen Rui Qiang, Hosogane Naobumi, Watanabe Kota, Funao Haruki, Okada Eijiro, Fujita Nobuyuki, Hikata Tomohiro, Iwanami Akio, Tsuji Takashi, Ishii Ken, Abe Takayuki, Toyama Yoshiaki, Nakamura Masaya, Matsumoto Morio

Spine 41 （ 4 ） 320 - 327 2016年02月

ISSN 0362-2436

Study Design. Retrospective study. Objective. To examine the reliabilities of sagittal spino-pelvic alignment measurements using whole spine-pelvic and local pelvic radiographs and to determine whether spinal deformity affects these reliabilities. Summary of Background Data. Sagittal spino-pelvic alignment is important in adult spinal deformity patients (ASD). Spino-pelvic parameters are closely related to health-related quality of life and indispensable for surgical planning. However, few studies have focused on the reliability of these measurements. Methods. Three spino-pelvic parameters, pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) were measured in 2 patient groups: 33 adult scoliosis (AS) and 33 nondeformity (ND) patients, using whole spine-pelvic lateral radiographs (whole spine radiographs) and local pelvic lateral radiographs (local pelvic radiographs), by 5 experienced spine surgeons. Intra- and interobserver reliabilities for each procedure were evaluated by intraclass correlation coefficients (ICC). The interobserver reliability differences between the 2 procedures were statistically evaluated. The difference between the largest and smallest measurements among the 5 observers was also evaluated in the AS and ND groups. Results. Measurement of the 3 parameters using whole spine or local pelvic radiographs showed good to excellent intraobserver reliability (range of ICC: 0.820-0.935). The interobserver reliabilities of PI and PT from local pelvic radiographs were significantly higher than those from whole spine radiographs (P

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Calculation of the target lumbar lordosis angle for restoring an optimal pelvic tilt in elderly patients with adult spinal deformity

Yamato Yu, Hasegawa Tomohiko, Kobayashi Sho, Yasuda Tatsuya, Togawa Daisuke, Arima Hideyuki, Oe Shin, Iida Takahiro, Matsumura Akira, Hosogane Naobumi, Matsumoto Morio, Matsuyama Yukihiro

Spine 41 （ 4 ） E211 - E217 2016年02月

ISSN 0362-2436

Study Design. This investigation consisted of a cross-sectional study and a retrospective multicenter case series. Objective. This investigation sought to identify the ideal lumbar lordosis (LL) angle for restoring an optimal pelvic tilt (PT) in patients with adult spinal deformity (ASD). Summary of Background Data. To achieve successful corrective fusion in ASD patients with sagittal imbalance, it is essential to correct the sagittal spinal alignment and obtain a suitable pelvic inclination. We determined the LL angle that would restore the optimal PT following ASD surgery. Methods. The cross-sectional study included 184 elderly volunteers (mean age 64 years) with an Oswestry Disability Index score less than 20%. The relationship between PT or LL and the pelvic incidence (PI) in normal individuals was investigated. The second study included 116 ASD patients (mean age 66 years) who underwent thoracolumbar corrective fusion at 1 of 4 spine centers. The postoperative PT values were calculated using the parameters measured. On the basis of these studies, an ideal LL angle was determined. Results. In the cross-sectional study, the linear regression equation for the optimal PT as a function of PI was "optimal PT=0.47×PI-7.5." In the second study, the postoperative PT was determined as a function of PI and corrected LL, using the equation "postoperative PT=0.7×PI-0.5×corrected LL+8.1." The target LL angle was determined by mathematically equalizing the PTs of these 2 equations: "target LL=0.45×PI+31.8." Conclusion. The ideal LL angle can be determined using the equation "LL=0.45×PI+31.8," which can be used as a reference during surgical planning in ASD cases.

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Grafted Human iPS Cell-Derived Oligodendrocyte Precursor Cells Contribute to Robust Remyelination of Demyelinated Axons after Spinal Cord Injury

Kawabata Soya, Takano Morito, Numasawa-Kuroiwa Yuko, Itakura Go, Kobayashi Yoshiomi, Nishiyama Yuichiro, Sugai Keiko, Nishimura Soraya, Iwai Hiroki, Isoda Miho, Shibata Shinsuke, Kohyama Jun, Iwanami Akio, Toyama Yoshiaki, Matsumoto Morio, Nakamura Masaya, Okano Hideyuki

Stem Cell Reports 6 （ 1 ） 1 - 8 2016年01月

ISSN 2213-6711

Murine- and human-induced pluripotent stem cell-derived neural stem/progenitor cells (iPSC-NS/PCs) promote functional recovery following transplantation into the injured spinal cord in rodents and primates. Although remyelination of spared demyelinated axons is a critical mechanism in the regeneration of the injured spinal cord, human iPSC-NS/PCs predominantly differentiate into neurons both in vitro and in vivo. We therefore took advantage of our recently developed protocol to obtain human-induced pluripotent stem cell-derived oligodendrocyte precursor cell-enriched neural stem/progenitor cells and report the benefits of transplanting these cells in a spinal cord injury (SCI) model. We describe how this approach contributes to the robust remyelination of demyelinated axons and facilitates functional recovery after SCI.

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Vitamin D deficiency with high intact PTH levels is more common in younger than in older women

Miyamoto Takeshi, Katsuyama Eri, Kanagawa Hiroya, Fujie Atsuhiro, Miyamoto Hiroya, Yoshida Shigeyuki, Mori Tomoaki, Miyamoto Kana, Sato Yuiko, Kobayashi Tami, Nakamura Masaya, Matsumoto Morio, Nishiwaki Yuji, Hirose Hiroshi, Kanda Takeshi, Saito Ikuo, Toyama Yoshiaki

Keio Journal of Medicine 65 （ 2 ） 33 - 38 2016年

ISSN 0022-9717

Low serum 25-hydroxyvitamin D (25(OH)D) levels are implicated as a risk factor for hip and spine fractures. Studies of the relation between 25(OH)D levels and fractures have primarily involved elderly osteoporosis patients or patients with fractures; however, the serum 25(OH)D and parathyroid hormone (PTH) status in younger adult populations remains largely unknown. We evaluated serum 25(OH)D and intact PTH levels in 411 women aged 39–64 years who were not receiving medication for osteoporosis or other bone diseases. Serum 25(OH)D levels were positively correlated with age (P = 0.019), whereas intact PTH levels were inversely correlated with 25(OH)D levels (P <0.001). Thus, low vitamin D levels with high intact PTH levels were more common in younger than in older women. Our data show that serum 25(OH)D insufficiency could be a more serious concern in the younger population than had been previously anticipated. Because serum 25(OH)D insufficiency is reportedly a risk factor for hip and spine fracture, the number of fracture patients could increase in the future, suggesting that we may need to correct the serum vitamin D/intact PTH status to prevent future osteoporosis.

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Generation and characterization of a novel shoulder contracture mouse model

Oki Satoshi, Shirasawa Hideyuki, Yoda Masaki, Matsumura Noboru, Tohmonda Takahide, Yuasa Kazuki, Nakamura Masaya, Matsumoto Morio, Horiuchi Keisuke

Journal of Orthopaedic Research 33 （ 11 ） 1732 - 1738 2015年11月

ISSN 0736-0266

Frozen shoulder is a relatively common disorder that leads to severe pain and stiffness in the shoulder joint. Although this disorder is self-limiting in nature, the symptoms often persist for years, resulting in severe disability. Recent studies using human specimens and animal models have shown distinct changes in the gene expression patterns in frozen shoulder tissue, indicating that novel therapeutic intervention could be achieved by controlling the genes that are potentially involved in the development of frozen shoulder. To achieve this goal, it is imperative to develop a reliable animal joint contracture model in which gene expression can be manipulated by gene targeting and transgenic technologies. Here, we describe a novel shoulder contracture mouse model. We found that this model mimics the clinical presentation of human frozen shoulder and recapitulates the changes in the gene expression pattern and the histology of frozen shoulder and joint contracture in humans and other larger animal models. The model is highly reproducible, without any major complications. Therefore, the present model may serve as a useful tool for investigating frozen shoulder etiology and for identifying its potential target genes.

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A Novel Percutaneous Guide Wire (S-Wire) for Percutaneous Pedicle Screw Insertion

Ishii Ken, Kaneko Yasuhito, Funao Haruki, Ishihara Shinichi, Shinohara Akira, Nakanishi Kazuo, Hikata Tomohiro, Fujita Nobuyuki, Iwanami Akio, Hosogane Naobumi, Watanabe Kota, Nagura Takeo, Nakamura Masaya, Toyama Yoshiaki, Matsumoto Morio

Surgical Innovation 22 （ 5 ） 469 - 473 2015年10月

ISSN 1553-3506

Purpose. Minimally invasive spine stabilization (MISt) procedures, including MIS-transforaminal lumbar interbody fusion (MIS-TLIF), rely on precise placement of percutaneous pedicle screws (PPS). Serious intraoperative complications associated with PPS placement include great vessel and bowel injuries due to the guide-wire's anterior migration and penetration through the anterior aspect of the vertebral body. To address this issue, we developed a novel percutaneous guide wire (S-wire) and compared the biomechanical characteristics of S-wire and conventional wire in cadaveric spines, and to evaluate the S-wire's efficacy and safety in a clinical trial. Methods. The S-wire is hollow, with braided wires extending at one tip. We compared the push-out and penetration forces of the S-wire and conventional wire in fresh cadaveric lumbar spines, from L1 to L5. Results. Push-out forces caused the braided tip of the S-wire to bend or spread, and thus to resist anterior migration. The mean push-out forces for the S-wire and conventional wire were 15.5 ± 1.9 and 5.7 ± 0.8 N, respectively (P <.0001); the mean penetration forces were 69.1 ± 4.2 and 37.1± 4.8 N, respectively (P <.0005). There was no wire breakage or anterior-wall penetration in a clinical trial of 922 S-wires; interestingly, the pull-out force increased in 780 (84.6%) S-wires after placement. Conclusions. The mean push-out and penetration forces for the S-wire were approximately 3 and 2 times greater than those of conventional wire, respectively. The S-wire effectively prevented guide-wire anterior migration and penetration of the anterior vertebral-body wall. The S-wire device should effectively improve the safety of MISt procedures, including MIS-TLIF and percutaneous kyphoplasty in selected patient with osteoporosis.

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Effects of femoral bone tunnel characteristics on graft-bending angle in double-bundle anterior cruciate ligament reconstruction

Niki Yasuo, Nagai Katsuya, Harato Kengo, Suda Yasunori, Nakamura Masaya, Matsumoto Morio

Knee Surgery, Sports Traumatology, Arthroscopy 2015年08月

ISSN 0942-2056

Purpose: Bone tunnel creation techniques influence the 3-dimensional (3D) position of bone tunnels and graft-bending angle in anterior cruciate ligament (ACL) reconstruction. This study assessed graft-bending angle and 3D characteristics of femoral bone tunnels and compared them between outside-in (OI) and transportal (TP) techniques. Methods: Participants comprised 64 patients who underwent anatomic double-bundle ACL reconstruction, allocated to OI and TP groups (n = 32 each). The graft orientation plane exhibiting the largest graft-bending angle at the femoral tunnel aperture with the knee in extension was reconstructed from CT data using 3D imaging software. In this plane, graft-bending angle was compared between the OI and TP techniques. Results: Although positionings of the intra-articular apertures of the femoral and tibial bone tunnels were similar, several spatial parameters of bone tunnels differed between techniques. Graft-bending angles of both anteromedial and posterolateral bundles were significantly more acute with the OI technique than with the TP technique. On coronal-plane CT, angle of the bone tunnel axis relative to the distal condylar axis correlated negatively with graft-bending angle, while in the axial plane, angle of the bone tunnel axis relative to the posterior condylar axis correlated positively with graft-bending angle. Lysholm score, pivot shift test, and anteroposterior laxity at >2.5-year follow-up demonstrated no significant differences between techniques. Discussion: Different bone tunnel directions in OI and TP techniques substantially affected graft-bending angle, despite similar positionings of the intra-articular apertures. Graft-bending angle with the OI technique was acute, but risk of posterior blowout of the lateral femoral condyle was decreased. Surgeons should create the femoral tunnel while considering an obtuse graft-bending angle without increasing the risk of posterior blowout. Level of evidence: III.

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Comparison of surgical treatments for triple extensor tendon ruptures in rheumatoid hands

Suzuki Taku, Iwamoto Takuji, Ikegami Hiroyasu, Sakuma Y., Ikari Katsunori, Matsumura Noboru, Ochi Kensuke, Sato Kazuki, Nakamura Masaya, Matsumoto Morio, Momohara Shigeki

Modern Rheumatology 2015年08月

ISSN 1439-7595

Objective. This retrospective study was designed to evaluate the outcomes of four different surgical reconstructions for extensor tendon ruptures in ulnar three fingers in 48 patients with rheumatoid arthritis. Methods. The following four techniques were performed; palmaris longus tendon grafting (PL group; n = 9), extensor indicis proprius (EIP) tendon transfers (EIP group; n = 8), end-to-side transfers with tension-reduced early mobilization (End-to-side group; n = 16), and a combination of end-to-side and EIP transfers (Combination group; n = 15). Loss of extension was evaluated to determine the mean postoperative range of motion of the metacarpophalangeal (MP) joint and clinical outcomes were categorized using modified Geldmacher criteria. Results. Combination group demonstrated the best mean MP joint extension (− 3°), followed by End-to-side group (− 12°), EIP group (− 16°), and PL group (− 21°). Combination group yielded the best clinical outcomes with all cases showing good results. Conclusions. The combination of end-to-side and EIP transfer was an effective surgical reconstruction procedure for triple fingers extension loss.

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IRE1α/XBP1-mediated branch of the unfolded protein response regulates osteoclastogenesis

Tohmonda Takahide, Yoda Masaki, Iwawaki Takao, Matsumoto Morio, Nakamura Masaya, Mikoshiba Katsuhiko, Toyama Yoshiaki, Horiuchi Keisuke

Journal of Clinical Investigation 125 （ 8 ） 3269 - 3279 2015年08月

ISSN 0021-9738

The unfolded protein response (UPR) is a cellular adaptive mechanism that is activated in response to the accumulation of unfolded proteins in the endoplasmic reticulum. The inositol-requiring protein-1α/X-box-binding protein-mediated (IRE1α/ XBP1-mediated) branch of the UPR is highly conserved and has also been shown to regulate various cell-fate decisions. Herein, we have demonstrated a crucial role for the IREα/XBP1-mediated arm of the UPR in osteoclast differentiation. Using murine models, we found that the conditional abrogation of IRE1α in bone marrow cells increases bone mass as the result of defective osteoclastic bone resorption. In osteoclast precursors, IRE1α was transiently activated during osteoclastogenesis, and suppression of the IRE1α/XBP1 pathway in these cells substantially inhibited the formation of multinucleated osteoclasts in vitro. We determined that XBP1 directly binds the promoter and induces transcription of the gene encoding the master regulator of osteoclastogenesis nuclear factor of activated T cells cytoplasmic 1 (NFATc1). Moreover, activation of IRE1α was partially dependent on Ca2+ oscillation mediated by inositol 1,4,5-trisphosphate receptors 2 and 3 (ITPR2 and ITPR3) in the endoplasmic reticulum, as pharmacological inhibition or deletion of these receptors markedly decreased Xbp1 mRNA processing. The present study thus reveals an intracellular pathway that integrates the UPR and osteoclast differentiation through activation of the IRE1α/XBP1 pathway.

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Methotrexate inhibits osteoclastogenesis by decreasing RANKL-induced calcium influx into osteoclast progenitors

Kanagawa Hiroya, Masuyama Ritsuko, Morita Mayu, Sato Yuiko, Niki Yasuo, Kobayashi Tami, Katsuyama Eri, Fujie Atsuhiro, Hao Wu, Tando Toshimi, Watanabe Ryuichi, Miyamoto Kana, Morioka Hideo, Matsumoto Morio, Toyama Yoshiaki, Saya Hideyuki, Miyamoto Takeshi

Journal of Bone and Mineral Metabolism 2015年07月

ISSN 0914-8779

The increasing number of osteoporosis patients is a pressing issue worldwide. Osteoporosis frequently causes fragility fractures, limiting activities of daily life and increasing mortality. Many osteoporosis patients take numerous medicines due to other health issues; thus, it would be preferable if a single medicine could ameliorate osteoporosis and other conditions. Here, we screened 96 randomly selected drugs targeting various diseases for their ability to inhibit differentiation of osteoclasts, which play a pivotal role in development of osteoporosis, and identified methotrexate (MTX), as a potential inhibitor. MTX is currently used to treat sarcomas or leukemic malignancies or auto-inflammatory diseases such as rheumatoid arthritis (RA) through its anti-proliferative and immunosuppressive activities; however, a direct effect on osteoclast differentiation has not been shown. Here, we report that osteoclast formation and expression of osteoclastic genes such as NFATc1 and DC-STAMP, which are induced by the cytokine RANKL, are significantly inhibited by MTX. We found that RANKL-dependent calcium (Ca) influx into osteoclast progenitors was significantly inhibited by MTX. RA patients often develop osteoporosis, and osteoclasts are reportedly required for joint destruction; thus, MTX treatment could have a beneficial effect on RA patients exhibiting high osteoclast activity by preventing both osteoporosis and joint destruction.

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Hyperglycemia promotes Schwann cell de-differentiation and de-myelination via sorbitol accumulation and Igf1 protein down-regulation

Hao Wu, Tashiro Syoichi, Hasegawa Tomoka, Sato Yuiko, Kobayashi Tami, Tando Toshimi, Katsuyama Eri, Fujie Atsuhiro, Watanabe Ryuichi, Morita Mayu, Miyamoto Kana, Morioka Hideo, Nakamura Masaya, Matsumoto Morio, Amizuka Norio, Toyama Yoshiaki, Miyamoto Takeshi

Journal of Biological Chemistry 290 （ 28 ） 17106 - 17115 2015年07月

ISSN 0021-9258

Diabetes mellitus (DM) is frequently accompanied by complications, such as peripheral nerve neuropathy. Schwann cells play a pivotal role in regulating peripheral nerve function and conduction velocity; however, changes in Schwann cell differentiation status in DM are not fully understood. Here, we report that Schwann cells de-differentiate into immature cells under hyperglycemic conditions as a result of sorbitol accumulation and decreased Igf1 expression in those cells. We found that dedifferentiated Schwann cells could be re-differentiated in vitro into mature cells by treatment with an aldose reductase inhibitor, to reduce sorbitol levels, or with vitaminD<inf>3</inf>, to elevate Igf1 expression. In vivo DM models exhibited significantly reduced nerve function and conduction, Schwann cell de-differentiation, peripheral nerve de-myelination,andall conditionsweresignificantly rescued by aldose reductase inhibitor or vitamin D<inf>3</inf> administration. These findings reveal mechanisms underlying pathological changes in Schwann cells seen in DM and suggest ways to treat neurological conditions associated with this condition.

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Synergistic antiproliferative effect of imatinib and adriamycin in platelet-derived growth factor receptor-expressing osteosarcoma cells

Yamaguchi Sayaka I., Ueki Arisa, Sugihara Eiji, Onishi Nobuyuki, Yaguchi Tomonori, Kawakami Yutaka, Horiuchi Keisuke, Morioka Hideo, Matsumoto Morio, Nakamura Masaya, Muto Akihiro, Toyama Yoshiaki, Saya Hideyuki, Shimizu Takatsune

Cancer Science 106 （ 7 ） 875 - 882 2015年07月

ISSN 1347-9032

Osteosarcoma (OS) is the most frequent primary solid malignant tumor of bone. Its prognosis remains poor in the substantial proportion of patients who do not respond to chemotherapy and novel therapeutic options are therefore needed. We previously established a mouse model that mimics the aggressive behavior of human OS. Enzyme-linked immunosorbent assay-based screening of such mouse tumor lysates identified platelet-derived growth factor-BB (PDGF-BB) as an abundant soluble factor, the gene for which was expressed dominantly in surrounding non-malignant cells of the tumor, whereas that for the cognate receptor (PDGF receptor β) was highly expressed in OS cells. Platelet-derived growth factor-BB induced activation of both MEK-ERK and phosphatidylinositol 3-kinase-protein kinase B signaling pathways and promoted survival in OS cells deprived of serum, and these effects were blocked by the PDGF receptor inhibitor imatinib. However, these actions of PDGF-BB and imatinib were mostly masked in the presence of serum. Whereas imatinib alone did not manifest an antitumor effect in mice harboring OS tumors, combined treatment with imatinib and adriamycin exerted a synergistic antiproliferative effect on OS cells in vivo. These results suggest that treatment of OS with imatinib is effective only when cell survival is dependent on PDGF signaling or when imatinib is combined with another therapeutic intervention that renders the tumor cells susceptible to imatinib action, such as by inducing cellular stress.

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Breast carcinoma metastasis to meningioma in the thoracic spine

Okada Eijiro, Nakamura Masaya, Koshida Yoshitomo, Mukai Kiyoshi, Toyama Yoshiaki, Matsumoto Morio

Journal of Spinal Cord Medicine 38 （ 2 ） 231 - 235 2015年03月

ISSN 1079-0268

Context: Systemic metastasis to a primary tumor of the central nervous system is uncommon. Breast carcinomas metastasizing to a possibly preexisting meningioma in the spine are reported very rarely. Study design: Case report. Findings: A 69-year-old female was referred to us with progressive gait disturbance. She had undergone a total mastectomy for carcinoma of the right breast 11 years previously. A magnetic resonance imaging of the thoracic spine showed an intra- and extradural spinal cord tumor. The patient underwent resection of the tumor via laminectomy from T2 to T4. After the operation, the patient's neurological status improved significantly, and she was able to walk without assistance. Histological examination showed the tumor to be a fibrous-type meningioma within a metastatic breast cancer tumor. The patient underwent 40 Gy radiation treatment for local control of the tumor. However, the tumor recurred locally 7 months after the surgery. The patient died of carcinomatous pleurisy 13 months after the surgery. Conclusion: This case illustrates that a primary meningioma in the thoracic spine can be a recipient of breast cancer metastasis, which may alter the treatment strategy.

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Bcl6 promotes osteoblastogenesis through stat1 inhibition

Fujie Atsuhiro, Funayama Atsushi, Miyauchi Yoshiteru, Sato Yuiko, Kobayashi Tami, Kanagawa Hiroya, Katsuyama Eri, Hao Wu, Tando Toshimi, Watanabe Ryuichi, Morita Mayu, Miyamoto Kana, Kanaji Arihiko, Morioka Hideo, Matsumoto Morio, Toyama Yoshiaki, Miyamoto Takeshi

Biochemical and Biophysical Research Communications 457 （ 3 ） 451 - 456 2015年02月

ISSN 0006-291X

Bone mass is tightly controlled by a balance between osteoclast and osteoblast activities. Although these cell types mature via different pathways, some factors reportedly regulate differentiation of both. Here, in a search for factors governing osteoblastogenesis but also expressed in osteoclasts to control both cell types by one molecule, we identified B cell lymphoma 6 (Bcl6) as one of those factors and show that it promotes osteoblast differentiation. Bcl6 was previously shown to negatively regulate osteoclastogenesis. We report that lack of Bcl6 results in significant inhibition of osteoblastogensis in vivo and in vitro and in defects in secondary ossification center formation in vivo. Signal transducer and activator of transcription 1 (Stat1) reportedly attenuates osteoblast differentiation by inhibiting nuclear translocation of runt-related transcription factor 2 (Runx2), which is essential for osteoblast differentiation. We found that lack of Bcl6 resulted in signifi cant elevation of Stat1 mRNA and protein expression in osteoblasts and showed that Stat1 is a direct target of Bcl6 using a chromatin immune-precipitation assay. Mice lacking both Bcl6 and Stat1 (DKO) exhibited significant rescue of bone mass and osteoblastic parameters as well as partial rescue of secondary ossification center formation compared with Bcl6-de ficient mice in vivo. Altered osteoblastogenesis in Bcl6-defi cient cells was also restored in DKO in vitro. Thus, Bcl6 plays crucial roles in regulating both osteoblast activation and osteoclast inhibition.

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ADAM17 regulates IL-1 signaling by selectively releasing IL-1 receptor type 2 from the cell surface

Uchikawa Shinichi, Yoda Masaki, Tohmonda Takahide, Kanaji Arihiko, Matsumoto Morio, Toyama Yoshiaki, Horiuchi Keisuke

Cytokine 71 （ 2 ） 238 - 245 2015年02月

ISSN 1043-4666

Interleukin (IL)-1 is one of the most evolutionarily conserved cytokines and plays an essential role in the regulation of innate immunity. IL-1 binds to two different receptors, IL-1R1 and IL-1R2, which share approximately 28% amino acid homology. IL-1R1 contains a cytoplasmic domain and is capable of transducing cellular signals; by contrast, IL-1R2 lacks a functional cytoplasmic domain and serves as a decoy receptor for IL-1. Interestingly, IL-1R2 is proteolytically cleaved and also functions as a soluble receptor that blocks IL-1 activity. In the present study, we examined the shedding properties of IL-1R2 and demonstrate that ADAM17 is de facto the major sheddase for IL-1R2 and that introducing a mutation into the juxta-membrane domain of IL-1R2 significantly desensitizes IL-1R2 to proteolytic cleavage. IL-1R1 was almost insensitive to ADAM17-dependent cleavage; however, the replacement of the juxta-membrane domain of IL-R1 with that of IL-1R2 significantly increased the sensitivity of IL-1R1 to shedding. Furthermore, we demonstrate that ADAM17 indirectly enhances IL-1 signaling in a cell-autonomous manner by selectively cleaving IL-1R2. Taken together, the data collected in the present study indicate that ADAM17 affects sensitivity to IL-1 by changing the balance between IL-1R1 and the decoy receptor IL-1R2.

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Effects of Reduction Osteotomy on Gap Balancing During Total Knee Arthroplasty for Severe Varus Deformity

Niki Yasuo, Harato Kengo, Nagai Katsuya, Suda Yasunori, Nakamura Masaya, Matsumoto Morio

Journal of Arthroplasty 2015年01月

ISSN 0883-5403

This study aimed to assess the effects of down-sizing and lateralizing of the tibial component (reduction osteotomy) on gap balancing in TKA, and the clinical feasibility of an uncemented modular trabecular metal tibial tray in this technique. Reduction osteotomy was performed for 39 knees of 36 patients with knee OA with a mean tibiofemoral angle of 21° varus. In 20 knees, appropriate gap balance was achieved by release of the deep medial collateral ligament alone. Flexion gap imbalance could be reduced by approximately 1.7° and 2.8° for 4-mm osteotomy and 8-mm osteotomy, respectively. Within the first postoperative year, clinically-stable tibial component subsidence was observed in 9 knees, but it was not progressive, and the clinical results were excellent at a mean follow-up of 3.3years.

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The paravertebral muscle and psoas for the maintenance of global spinal alignment in patient with degenerative lumbar scoliosis

Yagi Mitsuru, Hosogane Naobumi, Watanabe Kota, Asazuma Takashi, Matsumoto Morio

Spine Journal 2015年01月

ISSN 1529-9430

Background context: Various factors are reported to affect the spinal alignment in degenerative lumbar scoliosis (DLS). Although trunk muscles also appear to affect spinal alignment, the role of the trunk muscles is not yet clear. Purpose: The aim was to elucidate the role of the multifidus (MF) and psoas (PS) in maintaining global spinal alignment in patients with DLS. Study design: This was a multicenter retrospective matched cohort study. Patient sample: Surgically treated 60 paired DLS and lumbar spinal stenosis (LSS) female (120 patients), matched for age and body mass index (BMI; DLS age 68.0±6.8 vs. LSS 67.1±8.9 years; BMI 21.6±3.3 vs. 23.2±3.8 kg/m2), were included and were followed for at least 2 years. Outcome measures: Spinal alignment, muscle area, and volume were measured from radiographs, magnetic resonance images (MRIs), and whole-body dual-energy X-ray absorptiometry (DXA) scans. Muscle strength was measured by grip power and peak expiratory flow (PEF). Methods: As a surrogate of muscle area, we obtained the cross-sectional area (CSA) at the L5-S level from preoperative MRIs. Results: The MF and PS CSAs were significantly smaller in the DLS group than in the LSS group (MF 477.7±192.5 vs. 779.8±248.6 mm2, p<.01; PS 692.3±201.2 vs. 943.4±272.4 mm2, p=.002), whereas percentage of difference between the right and left sides was significantly larger in the DLS group (MF 18.4±30.6 vs. 2.4±3.3%, p<.01; PS 14.4±15.8 vs. 2.1±2.2%, p<.01). In the extremities, there were no significant differences in the left- or right-side lean composition and grip strength or PEF tests between the groups. Correlation coefficient tests showed moderate correlations between the MF average CSA (avCSA) and global spinal alignment and spinopelvic alignment (pelvic incidence-lumbar lordosis; R=-0.37, -0.38) in the DLS group. The MF avCSA was correlated with the postoperative progression of kyphosis at the unfused thoracic vertebrae in the DLS group (R=0.34). Conclusions: The CSAs of the MF and PS were significantly smaller in the DLS group. Whole-body DXA showed no significant difference in the lean composition between the groups. There were significant correlations in the DLS patients between the MF CSA and sagittal spinal alignment. These findings suggest the causal relationship between muscles and global spine alignment.

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Interleukin-1 receptor-associated kinase-4 (IRAK4) promotes inflammatory osteolysis by activating osteoclasts and inhibiting formation of foreign body giant cells

Katsuyama Eri, Miyamoto Hiroya, Kobayashi Tami, Sato Yuiko, Hao Wu, Kanagawa Hiroya, Fujie Atsuhiro, Tando Toshimi, Watanabe Ryuichi, Morita Mayu, Miyamoto Kana, Niki Yasuo, Morioka Hideo, Matsumoto Morio, Toyama Yoshiaki, Miyamoto Takeshi

Journal of Biological Chemistry 290 （ 2 ） 716 - 726 2015年01月

ISSN 0021-9258

Formation of foreign body giant cells (FBGCs) occurs following implantation of medical devices such as artificial joints and is implicated in implant failure associated with inflammation or microbial infection. Two major macrophage subpopulations, M1 and M2, play different roles in inflammation and wound healing, respectively. Therefore, M1/M2 polarization is crucial for the development of various inflammation-related diseases. Here, we show that FBGCs do not resorb bone but rather express M2 macrophage-like wound healing and inflammation-terminating molecules in vitro. We also found that FBGC formation was significantly inhibited by inflammatory cytokines or infection mimetics in vitro . Interleukin-1 receptor-associated kinase-4 (IRAK4) deficiency did not alter osteoclast formation in vitro, and IRAK4-deficient mice showed normal bone mineral density in vivo. However, IRAK4-deficient mice were protected from excessive osteoclastogenesis induced by IL-1β in vitro or by LPS, an infection mimetic of Gram-negative bacteria, in vivo. Furthermore, IRAK4 deficiency restored FBGC formation and expression of M2 macrophage markers inhibited by inflammatory cytokines in vitro or by LPS in vivo. Our results demonstrate that osteoclasts and FBGCs are reciprocally regulated and identify IRAK4 as a potential therapeutic target to inhibit stimulated osteoclastogenesis and rescue inhibited FBGC formation under inflammatory and infectious conditions without altering physiological bone resorption.

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Coronal plane spinal malalignment and Parkinson's disease

Choi Hong June, Smith Justin S., Shaffrey Christopher I., Lafage Virginie C., Schwab Frank J., Ames Christopher P., Matsumoto Morio, Baik Jong Sam, Ha Yoon

Spine Journal 15 （ 1 ） 115 - 121 2015年01月

ISSN 1529-9430

Background context Parkinson's disease (PD) is a progressive degenerative disorder of the central nervous system. Patients with PD often present with abnormal posturing.Purpose To investigate coronal plane deformities in patients with PD, and to evaluate the correlation between clinical features, coronal parameters related to spine alignment, and disease severity.Study design A cross-sectional study.Patient sample Eighty-nine patients with PD and 89 controls were included.Outcome measures A medical history was collected from the medical records.Methods This study was a prospective assessment of consecutive patients with PD. Clinical and demographic parameters were collected from medical records and outpatient interviews. Full-length standing anteroposterior and lateral spine radiographs were used to assess the spinal parameters. The threshold for scoliosis was set at a 10° Cobb angle, and the curve type was classified using Schwab classification.Results A total of 178 patients (89 in PD and 89 in control groups) were included. Scoliosis was identified in 27 patients (30%) and 22 controls (p=.502). However, coronal imbalance was more common in patients with PD than in controls (11 vs. 0 patients, p=.001). Scoliosis was more common in women than in men (male:female=8:19, p=.04). Back pain was more common in patients with scoliosis than in those without scoliosis (14 of 27 vs. 17 of 62, p=.036). Schwab Type IV (thoracolumbar major) was the most common type of scoliosis in patients with PD and Type V (lumbar major) was the most common type in controls. With adjustment for patient age and gender, multiple linear regression analysis revealed that severity of PD (Unified Parkinson's Disease Rating Scale, p=.037) and magnitude of global coronal malalignment (p=.003) were associated with the scoliosis Cobb angle (p=.037, B=0.139). Direction of scoliosis and side of global coronal malalignment were not significantly correlated with the laterality of predominant PD symptoms (p>.05).Conclusions Global coronal malalignment is more prevalent in patients with PD than in controls. Greater severity of PD was significantly associated with greater magnitude of scoliosis Cobb angle, even after adjusting for the effects of patient age and gender. However, direction of scoliosis and side of global coronal malalignment were not significantly associated with the dominant laterality of PD symptoms.

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Antibacterial polyetheretherketone implants immobilized with silver ions based on chelate-bonding ability of inositol phosphate

Kakinuma H., Ishii K., Ishihama H., Honda M., Toyama Y., Matsumoto M., Aizawa M.

Journal of Biomedical Materials Research - Part A 103 （ 1 ） 57 - 64 2015年01月

ISSN 1549-3296

We developed a novel antibacterial implant by forming a hydroxyapatite (HAp) film on polyetheretherketone (PEEK) substrate, and then immobilizing silver ions (Ag⁺) on the HAp film based on the chelate-bonding ability of inositol phosphate (IP6). First, the PEEK surface was modified by immersion into concentrated sulfuric acid for 10 min. HAp film was formed on the acid-treated PEEK via the soft-solution process using simulated body fluid (SBF), urea, and urease. After HAp coating, specimens were immersed into IP6 solution, and followed by immersion into silver nitrite solution at concentrations of 0, 0.5, 1, 5 or 10 mM. Ag⁺ ions were immobilized on the resulting HAp film due to the chelate-bonding ability of IP6. On cell-culture tests under indirect conditions by Transwell®, MC3T3-E1 cells on the specimens derived from the 0.5 and 1 mM Ag⁺ solutions showed high relative growth when compared with controls. Furthermore, on evaluation of antibacterial activity in halo test, elution of Ag⁺ ions from Ag⁺-immobilized HAp film inhibited bacterial growth. Therefore, the above-mentioned results demonstrated that specimens had both biocompatibility and strong antibacterial activity. The present coating therefore provides bone bonding ability to the implant surface and prevents the formation of biofilms in the early postoperative period.

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Posterior correction and fusion surgery using pedicle-screw constructs for Lenke type 5c adolescent idiopathic scoliosis

Okada Eijiro, Watanabe Kota, Pang Long, Ogura Yoji, Takahashi Yohei, Hosogane Naobumi, Toyama Yoshiaki, Matsumoto Morio

Spine 40 （ 1 ） 25 - 30 2015年01月

ISSN 0362-2436

STUDY DESIGN.: A retrospective case series.OBJECTIVE.: To assess whether a short fusion strategy is applicable when treating adolescent idiopathic scoliosis with Lenke type 5C curve by posterior correction and fusion surgery using pedicle-screw constructs.SUMMARY OF BACKGROUND DATA.: Previous studies have discussed the selection of the lower instrumented vertebra to best preserve motion segments and obtain coronal balance. However, reports evaluating the selection of the upper instrumented vertebra when treating Lenke type 5C curves are not available.METHODS.: We evaluated 29 patients who were treated surgically for adolescent idiopathic scoliosis with Lenke type 5C curve (mean age, 16.8 ± 4.7 yr; range, 10-29 yr). The mean follow-up period was 28.0 ± 6.3 months (range, 24-48 mo). We compared radiographical parameters and clinical outcomes between patients with an upper instrumented vertebra at the end vertebra (EV) (n = 10) and those treated by short fusion (S group), with a upper instrumented vertebra 1-level caudal to the EV (n = 19 patients).RESULTS.: In the EV group, a preoperative mean Cobb angle of 50°± 15° was corrected to 8°± 7°, which was maintained at the final follow-up (7°± 1°). In the S group, a mean preoperative Cobb angle of 47°± 4° was corrected to 8°± 5°, but this increased significantly to 12°± 7° at final follow-up (P = 0.033). The mean correction rate at final follow-up was significantly lower in the S group (72%) than in the EV group (86%) (P = 0.027). Coronal and sagittal balance, thoracic kyphosis, lumbar lordosis, L4 tilt, and clinical outcomes evaluated by Scoliosis Research Society patient questionnaire-22 were equivalent between the 2 groups.CONCLUSION.: Scoliosis Research Society patient questionnaire-22 scores and radiographical parameters other than the correction rate were equivalent between the 2 groups. A short fusion strategy, in which the upper instrumented vertebra is 1-level caudal to the upper EV, is applicable to posterior correction and fusion surgery with pedicle-screw constructs for Lenke type 5C curves.

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In vivo evaluation of chelate-Setting cement fabricated from hydroxyapatite including bone minerals using a rabbit's tibia model

Aizawa Mamoru, Chibu Yuki, Nagata Kohei, Konishi Toshiisa, Ishii Ken, Funao Haruki, Toyama Yoshiaki, Matsumoto Morio, Honda Michiyo

402 - 407 2015年

Hydroxyapatite (HAp) is one of components of bone and teeth, and has an osteoconductivity. Thus, the HAp has been used as biomaterials for bone graftings. We have succeeded in development of the novel chelate-setting calcium-phosphate cement (CPC) using pure HAp particles surface-modified with inositol phosphate (IP6). While, biological apatite presented in bone and teeth of mammals contains various ions: Na<inf>+</inf>, K<inf>+</inf>, Mg<inf>2+</inf>, C1<inf>-</inf>", F" and C0<inf>3</inf><inf>2-</inf>", in addition to Ca<inf>2+</inf> and P0<inf>4</inf> ions. In this work, in order to create the chelate-setting CPC with enhanced osteoconductivity, the above-mentioned biological apatite powder (hereafter, bone HAp), instead of pure HAp, was used as a starting powder for fabrication of the chelate-setting cement. The biocompatibility of the resulting chelate-setting bone HAp cement (hereafter, IP6-bone HAp cement) was examined using a rabbit's tibia model. When the living reaction to hard tissue was histologically examined after 4 weeks implantation, we could observe that newly-formed bone directly bonded to the surface of the specimen. The newly-formed bone was also present around the cement specimen. The amounts of newly-formed bone around IP6-bone HAp cement was about 1.5 times those around IP6-pure HAp cement without bone minerals. The above findings demonstrate that the present IP6-bone HAp cements are one of the promising candidates as novel CPC with enhanced osteoconductivity.

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Japanese orthopaedic association back pain evaluation questionnaire (JOABPEQ) as an outcome measure for patients with low back pain

Hashizume Hiroshi, Konno Shin Ichi, Takeshita Katsushi, Fukui Mitsuru, Takahashi Kazuhisa, Chiba Kazuhiro, Miyamoto Masabumi, Matsumoto Morio, Kasai Yuichi, Kanamori Masahiko, Matsunaga Shunji, Hosono Noboru, Kanchiku Tsukasa, Taneichi Hiroshi, Tanaka Nobuhiro, Kanayama Masahiro, Shimizu Takachika, Kawakami Mamoru

Journal of Orthopaedic Science 20 （ 2 ） 264 - 280 2015年

ISSN 0949-2658

Background: In 2007, the Japanese orthopaedic association back pain evaluation questionnaire (JOABPEQ) was established to overcome the limitations of the original JOA scoring system developed in 1986. Although this new self-administered questionnaire is a more accurate outcome measure for evaluating patients with low back pain, physicians were unable to as certain the exact status of a patient at a single time point because of a lack of reference values. This study aimed to establish the reference values of JOABPEQ in different age and gender groups using data obtained from healthy volunteers. Methods: This study was conducted in 21 university hospitals and affiliated hospitals from October 2012 to July 2013. The JOABPEQ includes 25 questions that yield five domains to evaluate individuals with low back pain from five different perspectives. A total of 1,456 healthy volunteers (719 men, 737 women; age range, 20–89 years) answered the questionnaire. The differences in scores according to age and gender were examined by non-parametric tests. Results: The JOABPEQ scores significantly decreased with age in the domains of lumbar spine dysfunction, gait disturbance, and social life dysfunction. In these three domains, the median scores approached the 100 possible points in individuals aged 20–70 for both genders. However, the median scores for lumbar spine dysfunction and social life dysfunction decreased to 83.0 and 65.0–78.0 points, respectively, in individuals in their 80 s and 70–80 s, respectively; and the scores for gait disturbance decreased to 93.0 and 71.0 points for males and females in their 80 s. Overall, the median scores for pain-related and psychological disorders were 100 and 60.0–72.0 points, respectively. Conclusion: The reference values for JOABPEQ according to age and gender were established herein. Patients with low back pain should be evaluated with this new self-administered questionnaire taking these reference values into account.

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A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females

Sharma Swarkar, Londono Douglas, Eckalbar Walter L., Gao Xiaochong, Zhang Dongping, Mauldin Kristen, Kou Ikuyo, Takahashi Atsushi, Matsumoto Morio, Kamiya Nobuhiro, Murphy Karl K., Cornelia Reuel, Herring John A., Burns Dennis, Ahituv Nadav, Ikegawa Shiro, Gordon Derek, Wise Carol A., Karol L., Rathjen K., Sucato D., Birch J., Johnston C., Richards B. S., Mildrant T., Talwakar V., Iwinski H., Muchow R., Tassone J. C., Liu X. C., Shindell R., Schrader W., Eberson C., Lapinsky A., Loder R., Davey J., Hosogane Naobumi, Ogura Yoji, Takahashi Yohei, Miyake Atushi, Watanabe Kota, Chiba Kazuhiro, Toyama Yoshiaki, Kono Katsuki, Kawakami Noriaki, Tsuji Taichi, Uno Koki, Suzuki Teppei, Ito Manabu, Sudo Hideki, Minami Shohei, Kotani Toshiaki, Yanagida Haruhisa, Taneichi Hiroshi, Yonezawa Ikuho, Kaneko Kazuo

Nature Communications 6 2015年

Idiopathic scoliosis (IS) is a common paediatric musculoskeletal disease that displays a strong female bias. By performing a genome-wide association study (GWAS) of 3,102 individuals, we identify significant associations with 20p11.22 SNPs for females (P=6.89 × 10 ^-9) but not males (P=0.71). This association with IS is also found in independent female cohorts from the United States of America and Japan (overall P=2.15 × 10 -10, OR=1.30 (rs6137473)). Unexpectedly, the 20p11.22 IS risk alleles were previously associated with protection from early-onset alopecia, another sexually dimorphic condition. The 174-kb associated locus is distal to PAX1, which encodes paired box 1, a transcription factor involved in spine development. We identify a sequence in the associated locus with enhancer activity in zebrafish somitic muscle and spinal cord, an activity that is abolished by IS-associated SNPs. We thus identify a sexually dimorphic IS susceptibility locus, and propose the first functionally defined candidate mutations in an enhancer that may regulate expression in specific spinal cells.

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Neural stem/progenitor cell-laden microfibers promote transplant survival in a mouse transected spinal cord injury model

Sugai Keiko, Nishimura Soraya, Kato-Negishi Midori, Onoe Hiroaki, Iwanaga Shintaroh, Toyama Yoshiaki, Matsumoto Morio, Takeuchi Shoji, Okano Hideyuki, Nakamura Masaya

Journal of Neuroscience Research 2015年

ISSN 0360-4012

Previous studies have demonstrated that transplantation of neural stem/progenitor cells (NS/PCs) into the lesioned spinal cord can promote functional recovery following incomplete spinal cord injury (SCI) in animal models. However, this strategy is insufficient following complete SCI because of the gap at the lesion epicenter. To obtain functional recovery in a mouse model of complete SCI, this study uses a novel collagen-based microfiber as a scaffold for engrafted NS/PCs. We hypothesized that the NS/PC-microfiber combination would facilitate lesion closure as well as transplant survival in the transected spinal cord. NS/PCs were seeded inside the novel microfibers, where they maintained their capacity to differentiate and proliferate. After transplantation, the stumps of the transected spinal cord were successfully bridged by the NS/PC-laden microfibers. Moreover, the transplanted cells migrated into the host spinal cord and differentiated into three neural lineages (astrocytes, neurons, and oligodendrocytes). However, the NS/PC-laden scaffold could not achieve a neural connection between the rostral end of the injury and the intact caudal area of the spinal cord, nor could it achieve recovery of motor function. To obtain optimal functional recovery, a microfiber design with a modified composition may be useful. Furthermore, combinatorial therapy with rehabilitation and/or medications should also be considered for practical success of biomaterial/cell transplantation-based approaches to regenerative medicine.

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The vitamin D analogue ED71 but not 1,25(OH)₂D₃ targets HIF1α protein in osteoclasts

Sato Yuiko, Miyauchi Yoshiteru, Yoshida Shigeyuki, Morita Mayu, Kobayashi Tami, Kanagawa Hiroya, Katsuyama Eri, Fujie Atsuhiro, Hao Wu, Tando Toshimi, Watanabe Ryuichi, Miyamoto Kana, Morioka Hideo, Matsumoto Morio, Toyama Yoshiaki, Miyamoto Takeshi

PLoS ONE 9 （ 11 ） 2014年11月

Although both an active form of the vitamin D metabolite, 1,25(OH)₂D₃, and the vitamin D analogue, ED71 have been used to treat osteoporosis, anti-bone resorbing activity is reportedly seen only in ED71-but not in 1,25(OH)₂D₃ -treated patients. In addition, how ED71 inhibits osteoclast activity in patients has not been fully characterized. Recently, HIF1α expression in osteoclasts was demonstrated to be required for development of post-menopausal osteoporosis. Here we show that ED71 but not 1,25(OH)₂D₃, suppress HIF1α protein expression in osteoclasts in vitro. We found that 1,25(OH)₂D₃ or ED71 function in osteoclasts requires the vitamin D receptor (VDR). ED71 was significantly less effective in inhibiting M-CSF and RANKL-stimulated osteoclastogenesis than was 1,25(OH)₂D₃ in vitro. Downregulation of c-Fos protein and induction of Ifnβ mRNA in osteoclasts, both of which reportedly block osteoclastogenesis induced by 1,25(OH)₂D₃ in vitro, were both significantly higher following treatment with 1,25(OH)₂D₃ than with ED71. Thus, suppression of HIF1α protein activity in osteoclasts in vitro, which is more efficiently achieved by ED71 rather than by 1,25(OH)₂D₃, could be a reliable read-out in either developing or screening reagents targeting osteoporosis.

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Postoperative shoulder imbalance in Lenke Type 1A adolescent idiopathic scoliosis and related factors

Matsumoto Morio, Watanabe Kota, Kawakami Noriaki, Tsuji Taichi, Uno Koki, Suzuki Teppei, Ito Manabu, Yanagida Haruhisa, Minami Shohei, Akazawa Tsutomu

BMC Musculoskeletal Disorders 366 2014年11月

Backgrounds: The purpose of this study was to investigate the occurrence and factors associated with postoperative shoulder imbalance (PSI) in Lenke type 1A curve. Methods: This study included 106 patients with Lenke Type 1A curve who were followed up more than two years after posterior correction surgery. Pedicle screw (PS) constructs were used in 84 patients, and hybrid constructs in 22. The upper instrumented vertebra was rostral to the upper-end vertebra (UEV) in 70 patients, at UEV in 26, and below UEV in 10. The clavicle angle and T1 tilt angle were measured as PSI indicators, and correlations between radiographic parameters of shoulder balance and other radiographic parameters and associations between PSI and clinical parameters were investigated. For statistical analyses, paired and unpaired t-tests were used. Results: The mean Cobb angles of the main and proximal thoracic curves were 54.6 ± 9.5 and 26.7 ± 7.9 degrees before surgery, 14.5 ± 7.5, and 14.9 ± 7.1 at follow-up. Clavicle angle and T1 tilt angle were -2.9 ± 2.8 and -2.6 ± 6.3 before surgery, 2.4 ± 2.8 and 4.4 ± 4.3 immediately after surgery, and 1.8 ± 2.1 and 3.4 ± 5.5 at follow-up. Twenty patients developed distal adding-on. Clavicle angle at follow-up correlated weakly but significantly with preoperative clavicle angle (r = 0.34, p = 0.001) and with the correction rates of the main thoracic curve (r = 0.34, p = 0.001); it correlated negatively with the proximal curve spontaneous correction rate (r = -0.21, p = 0.034). The clavicle angle at follow-up was significantly larger in patients with PS-only constructs (PS 2.1 degrees vs. hybrid 0.9, p = 0.02), and tended to be smaller in patients with distal adding-on (adding-on 1.1 vs. non adding-on 2.0, p = 0.09). Conclusions: PSI was more common with better correction of the main curve (using PS constructs), in patients with a larger preoperative clavicle angle, and with a larger and more rigid proximal curve. Distal adding-on may compensate for PSI.

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Massive hemothorax caused by Gelpi retractor during posterior correction surgery for adolescent idiopathic scoliosis

Pang Long, Watanabe Kota, Toyama Yoshiaki, Matsumoto Morio

Scoliosis 9 （ 1 ） 2014年10月

Background context: Gelpi retractors are used in surgery because they can reduce paravertebral muscle damage during retraction. No pleural injuries associated with their use in posterior spine surgery have been reported. Purpose: To describe a patient who suffered a massive postoperative hemothorax caused by a Gelpi retractor used during posterior correction surgery for adolescent idiopathic scoliosis (AIS). Study design: Case report. Methods: A case report of a rare hemothorax complication due to a Gelpi retractor is reported. The relevant literature was reviewed. Results: A 12-year-old girl with Lenke type 2 AIS, with curves of 60° at T2-7 and 75° at T7-L1, underwent posterior correction and fusion surgery using a segmental pedicle screw construct placed between T2 and L2. Although the patient's vital signs were stable during and soon after the surgery, a chest x-ray taken one day later revealed a massive left hemothorax. Her hemoglobin concentration was decreased to 5.5g/dl, and SpO<inf>2</inf> remained as low as 92% even with oxygen administration. Thoracoscopy revealed subpleural hemorrhaging at several points in the left upper intercostal area (T3-6), and a penetration of the pleura between the left 4th and 5th ribs. Active bleeding had already stopped. The tip of the Gelpi retractor appeared to have penetrated the pleura. A chest tube was placed in the patient to treat the hemothorax. Conclusions: A pleural injury by the Gelpi retractor was determined to be the cause of the hemothorax in this case. The patient's prominent thoracic hump may have increased the risk of such an injury because the tip of a Gelpi retractor might easily have become stuck in the intercostal space rather than the paravertebral muscles.

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Pulmonary function recovery demonstrated by ventilation-perfusion scan after posterior vertebral column resection for severe adolescent idiopathic scoliosis

Fujii Takeshi, Watanabe Kota, Toyama Yoshiaki, Matsumoto Morio

Spine 39 （ 19 ） 2014年09月

ISSN 0362-2436

Study Design. Case report. Objective. To describe a case in which a patient regained pulmonary function, assessed by ventilation-perfusion scans, after undergoing posterior vertebral column resection (VCR) to correct severe adolescent idiopathic scoliosis (AIS) with associated pulmonary dysfunction. Summary of Background Data. Pulmonary improvement after corrective surgery for AIS has been reported. Ventilation-perfusion scans are useful for assessing pulmonary function. However, these scans have not been used to examine the recovery of pulmonary function after VCR for severe AIS with pulmonary dysfunction. Methods. A patient was described in whom ventilation-perfusion scans were used to examine improvements in impaired air ventilation and blood perfusion after VCR surgery for severe AIS. The relevant literature was reviewed. Results. An 18-year-old male came to Keio University Hospital with exertional dyspnea associated with severe AIS. Radiographs showed severe scoliosis of 91° at T6-T12, and hypokyphosis of 6° at T5-T12. Computed tomographic scans showed narrowing of the thoracic cage on the convex side of the main thoracic curve, with the vertebral bodies at the apex of the curve obstructing the right main bronchus. Pulmonary function tests revealed a percent vital capacity of 44% and percent forced expiratory volume in 1 second of 76%. A ventilation-perfusion scan showed decreased air ventilation and blood perfusion in the right lung. The patient underwent posterior correction surgery, which used segmental pedicle screws with a VCR at T9. The scoliosis was corrected to 28°, and the kyphosis to 14°. Postoperative computed tomographic scans showed expansion of the right main bronchus. A ventilation-perfusion scan conducted 1 year after surgery showed clear improvement in both ventilation and blood perfusion in the right lung. The patient's forced expiratory volume in 1 second had increased to 91%. Conclusion. This is the first report in which ventilation-perfusion scans were used to examine improvements in impaired air ventilation and blood perfusion after VCR surgery in a patient with severe AIS. © 2014, Lippincott Williams & Wilkins.

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TNFα promotes osteosarcoma progression by maintaining tumor cells in an undifferentiated state

Mori T., Sato Y., Miyamoto K., Kobayashi T., Shimizu T., Kanagawa H., Katsuyama E., Fujie A., Hao W., Tando T., Iwasaki R., Kawana H., Morioka H., Matsumoto M., Saya H., Toyama Y., Miyamoto T.

Oncogene 33 （ 33 ） 4236 - 4241 2014年08月

ISSN 0950-9232

Chronic inflammation is frequently associated with tumorigenesis in elderly people. By contrast, young people without chronic inflammation often develop tumors considered independent of chronic inflammation but driven instead by mutations. Thus, whether inflammation has a significant role in tumor progression in tumors driven by mutations remains largely unknown. Here we show that TNFα is required for the tumorigenesis of osteosarcoma, the most common tumor in children and adolescents. We show that transplantation of AX osteosarcoma cells, which harbor mutations driving c-Myc overexpression and Ink4a-deficiency, in wild-type mice promotes lethal tumorigenesis accompanied by ectopic bone formation and multiple metastases, phenotypes seen in osteosarcoma patients. Such tumorigenesis was completely abrogated in TNFα-deficient mice. AX cells have the capacity to undergo osteoblastic differentiation; however, that activity was significantly inhibited by TNFα treatment, suggesting that TNFα maintains AX cells in an undifferentiated state. TNFα inhibition of AX cell osteoblastic differentiation occurred through ERK activation, and a pharmacological TNFα inhibitor effectively inhibited both AX cell tumorigenesis and increased osteoblastic gene expression and increased survival of tumor-bearing mice. Lethal tumorigenesis of AX cells was also abrogated in IL-1α/IL-1β doubly deficient mice. We found that both TNFα and IL-1 maintained AX cells in an undifferentiated state via ERK activation. Thus, inflammatory cytokines are required to promote tumorigenesis even in mutation-induced tumors, and TNFα/IL-1 and ERK may represent therapeutic targets for osteosarcoma. © 2014 Macmillan Publishers Limited.

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Risk factors for proximal junctional kyphosis associated with dual-rod growing-rod surgery for early-onset scoliosis

Watanabe Kota, Uno Koki, Suzuki Teppei, Kawakami Noriaki, Tsuji Taichi, Yanagida Haruhisa, Ito Manabu, Hirano Toru, Yamazaki Ken, Minami Shohei, Taneichi Hiroshi, Imagama Shiro, Takeshita Katsushi, Yamamoto Takuya, Matsumoto Morio

Journal of Spinal Disorders and Techniques 2014年07月

ISSN 1536-0652

STUDY DESIGN: A retrospective, multicenter study. OBJECTIVE: To identify risk factors for proximal junctional kyphosis (PJK) when treating early-onset scoliosis (EOS) with dual-rod growing-rod (GR) procedure. SUMMARY OF BACKGROUND DATA: The risk factors for PJK associated with GR treatment for EOS have not been adequately studied. METHODS: We evaluated clinical and radiographic results from 88 patients with EOS who underwent dual-rod GR surgery in 12 spine centers in Japan. The mean age at the time of the initial surgery was 6.5±2.2 years (range, 1.5-9.8{medium shade}y), and the mean follow-up period was 3.9±2.6 years (range, 2.0-12.0{medium shade}y). Risk factors for PJK were analyzed by binomial multiple logistic regression analysis. The potential factors analyzed were gender, etiology, age, the number of rod-lengthening procedures, coronal and sagittal parameters on radiographs, the type of foundation (pedicle screws or hooks), the uppermost level of the proximal foundation, and the lowermost level of the distal foundation. RESULTS: PJK developed in 23 patients (26%); in 19 of these, the proximal foundation became dislodged following PJK. Binomial multiple logistic regression analysis identified the following significant independent risk factors for PJK: a lower instrumented vertebra (LIV) at or cranial to L3 (odds ratio; OR, 3.32), a proximal thoracic scoliosis of 40° or more (OR, 2.95), and a main thoracic kyphosis of 60° or more (OR, 5.08). CONCLUSIONS: The significant independent risk factors for PJK during dual-rod GR treatment for EOS were an LIV at or cranial to L3, a proximal thoracic scoliosis of 40° or more, and a main thoracic kyphosis of 60° or more.

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Major complications and sequelae after total en bloc spondylectomy for malignant spinal tumors

Matsumoto Morio, Hikata Tomohiro, Iwanami Akio, Hosogane Naobumi, Watanabe Kota, Ishii Ken, Nakamura Masaya, Toyama Yoshiaki

Neurosurgery Quarterly 2014年07月

ISSN 1050-6438

This retrospective study looked at 33 consecutive patients with malignant, aggressive tumors in the thoracic and lumbar spine who underwent TES (24 men and 9 women; mean age 49.9 years; mean follow-up 3.6 years; 14 primary tumors and 19 metastatic tumors). TES was performed by a posterior-only approach in 15 patients and by a combined anterior and posterior approach in 18 patients. We classified complications as intraoperative, early (within 1 month after surgery), or late (>1 month after surgery), and examined the relationships between major complications and potentially related factors. Ten died of disease at 22.3 months after TES. Local recurrence was observed in 8 patients (24%) at an average of 15.4 months. Thirty-one major complications occurred in 24 patients (72.7%). There were 3 intraoperative, 17 early, and 11 late complications. Intraoperative complications included injury to the segmental artery, to the aorta, and to the spinal cord in 1 patient each. Early complications included prolonged chest tube drainage, cerebrospinal fluid leakage, and monoplegia due to the severing of nerve roots in 3 patients each, and pulmonary embolism, recurrent nerve palsy, pneumonia, endplate fracture, implant dislodgement, gastric ulcer, and ileus in 1 patient each. Late complications included implant failures in 8 patients and infection in 3 patients. Major complications were significantly associated with major blood loss (P=0.047). TES was frequently associated with major intraoperative, early, and late postoperative complications; most complications were managed successfully.

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Sagittal spinopelvic malalignment in parkinson disease

Oh Jae Keun, Smith Justin S., Shaffrey Christopher I., Lafage Virginie, Schwab Frank, Ames Christopher P., Matsumoto Morio, Baik Jong Sam, Ha Yoon

Spine 39 （ 14 ） 2014年06月

ISSN 0362-2436

STUDY DESIGN.: Prospective study. OBJECTIVE.: Our objectives were to evaluate the prevalence of sagittal spinopelvic malalignment in a consecutive series of patients with Parkinson disease (PD) and to identify factors associated with sagittal spinopelvic deformity in this population. SUMMARY OF BACKGROUND DATA.: PD is a degenerative neurological condition characterized by tremor, rigidity, bradykinesia, and loss of postural reflexes. The prevalence of spinal deformity in PD is higher than that of age-matched adults without PD. METHODS.: This study was a prospective assessment of consecutive patients with PD presenting to a neurology clinic during 12 months. Inclusion criteria included age more than 21 years and diagnosis of PD. Age- and sex-matched control group was selected from patients with cervical spondylosis. Clinical and demographic factors were collected including Unified Parkinson Disease Rating Scale score and Hoehn and Yahr stage. Full-length standing spine radiographs were assessed. Patients were grouped into either low C7 sagittal vertical axis (SVA) (<5 cm) or high C7 SVA (≥5 cm) and into matched (≤10°) or mismatched (>10°) pelvic incidence (PI)-lumbar lordosis. RESULTS.: Eighty-nine patients met criteria (41 males/48 females), including 52 with low C7 SVA and 37 with high C7 SVA. Significantly higher prevalence of high C7 SVA was found in PD (41.6 vs. 16.8%; P < 0.001). The high C7 SVA group was significantly older (72.4 vs. 65.1 yr; P < 0.001) and had a higher proportion of females (68% vs. 44%; P = 0.034), greater severity of PD based on Hoehn and Yahr stage (1.89 vs. 1.37; P < 0.001) and Unified Parkinson Disease Rating Scale (30.5 vs. 17.2; P = 0.002. Unified Parkinson Disease Rating Scale significantly correlated with C7 SVA (r = 0.474). Compared with the matched (≤10°) PI-lumbar lordosis group, the mismatch PI-lumbar lordosis group had higher C7 SVA, higher PI, higher pelvic tilt, lower lumbar lordosis, and lower thoracic kyphosis (P ≤ 0.003). CONCLUSION.: Patients with PD have a high prevalence of sagittal spinopelvic malalignment than control group patients. Greater severity of PD is associated with sagittal spinopelvic malalignment. © 2014 Lippincott Williams & Wilkins.

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Association of postoperative shoulder balance with adding-on in lenke type ii adolescent idiopathic scoliosis

Cao Kai, Watanabe Kota, Hosogane Naobumi, Toyama Yoshiaki, Yonezawa Ikuho, Machida Masafumi, Yagi Mitsuru, Kaneko Shinjiro, Kawakami Noriaki, Tsuji Taichi, Matsumoto Morio

Spine 39 （ 12 ） 2014年05月

ISSN 0362-2436

STUDY DESIGN.: A retrospective, multicenter study. OBJECTIVE.: To investigate the relationship between postoperative shoulder balance and adding-on in Lenke type 2 adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA.: Postoperative shoulder imbalance (PSI) and adding-on are the main postoperative complications occurring at the proximal to upper instrumented vertebra and the distal to the lower instrumental vertebra (LIV), respectively. Inadequate selection of LIV in the selective thoracic fusion surgery may result in postoperative distal adding-on. It remains unclear whether postoperative shoulder balance is associated with postoperative adding-on. METHODS.: Preoperative, postoperative, and 2-year follow-up radiographs of 142 consecutive patients with Lenke type 2 curves who underwent posterior-fusion surgery were analyzed. The patients were grouped into PSI positive and negative at follow-up. Radiographical and categorical factors between patients with and without PSI were compared. The relationship between the radiographical shoulder height and the parameters of adding-on were analyzed. RESULTS.: PSI occurred in 23 patients (16.2%) and distal adding-on was recognized in 20 patients (14.1%) at final follow-up. The occurrence of adding-on was significantly lower in the shoulder imbalance group at follow-up (P < 0.01). There was no shoulder imbalance occurring in the patients with distal adding-on at final follow-up (P < 0.01). Correlation analysis showed that the radiographical shoulder height was positively correlated with the change in the angulation of the first disc below LIV (r = 0.228, P ≤ 0.01) and negatively correlated with the deviation change of the LIV+1 at follow-up (r =-0.254, P ≤ 0.01). CONCLUSION.: The postoperative shoulder balance and postoperative distal adding-on were weakly but significantly associated with each other, and both shoulder imbalance and adding-on need to be prevented in Lenke type 2 curves. Copyright © 2014 Lippincott Williams &Wilkins.

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Factors affecting the postoperative progression of thoracic kyphosis in surgically treated adult patients with lumbar degenerative scoliosis

Yagi Mitsuru, Hosogane Naobumi, Okada Eijiro, Watanabe Kota, Machida Masafumi, Tezuka Masaki, Matsumoto Morio, Asazuma Takashi

Spine 39 （ 8 ） E521 - E528 2014年04月

ISSN 0362-2436

STUDY DESIGN: A retrospective case series of patients treated surgically for degenerative lumbar scoliosis (DLS).OBJECTIVE: To determine incidence and risk factors of progressive global thoracic kyphosis (pGTK) after surgery for DLS.SUMMARY OF BACKGROUND DATA: Sagittal balance affects the surgical treatment of spinal deformity in adults. Little is known about the loss of sagittal balance due to pGTK, or about the risk factors for pGTK, after surgery for DLS.METHODS: We reviewed records from a multicenter database of adults with DLS, treated with posterior spinal fusion. Inclusion required an age of 50 years or more at the time of surgery, an upper instrumented vertebra at T9 and below, more than 5 fused segments, and at least 2 years of follow-up. We included 73 patients with a mean age of 68.3 years (range, 51-77 yr) and a mean follow-up period of 3.6 years (range, 2-11 yr). Independent risk factors for pGTK were identified by logistic regression analysis.RESULTS: Significant pGTK, defined as an increase in thoracic kyphosis of more than 10° from before surgery to the time of final follow-up, was observed in 41% of the patients. Loss of the sagittal vertical axis was larger in patients with pGTK than without (4.7 vs. 1.5 cm; P = 0.02). Risk analysis showed larger lumbar lordosis correction in patients with pGTK. Multivariate logistic regression analysis identified an age greater than 75 (odds ratio, 5.53; P = 0.02, 95% confidence interval [1.4-22.4]) and sacropelvic fusion (odds ratio = 2.66, P = 0.02, 95% confidence interval [1.5-11.1]) as independent risk factors for pGTK.CONCLUSION: The pGTK incidence after surgery for DLS was 41%. Age, sacropelvic fusion, and a larger sagittal correction were identified as pGTK risk factors. Long-term follow-up will provide more data on the clinical impact of pGTK in elderly patients.3.

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Surgeons' exposure to radiation in single- and multi- level minimally invasive transforaminal lumbar interbody fusion; a prospective study

Funao Haruki, Ishii Ken, Momoshima Suketaka, Iwanami Akio, Hosogane Naobumi, Watanabe Kota, Nakamura Masaya, Toyama Yoshiaki, Matsumoto Morio

PLoS ONE 9 （ 4 ） 2014年04月

Although minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has widely been developed in patients with lumbar diseases, surgeons risk exposure to fluoroscopic radiation. However, to date, there is no studies quantifying the effective dose during MIS-TLIF procedure, and the radiation dose distribution is still unclear. In this study, the surgeons' radiation doses at 5 places on the bodies were measured and the effective doses were assessed during 31 consecutive 1- to 3-level MIS-TLIF surgeries. The operating surgeon, assisting surgeon, and radiological technologist wore thermoluminescent dosimeter on the unshielded thyroid, chest, genitals, right middle finger, and on the chest beneath a lead apron. The doses at the lens and the effective doses were also calculated. Mean fluoroscopy times were 38.7, 53.1, and 58.5 seconds for 1, 2, or 3 fusion levels, respectively. The operating surgeon's mean exposures at the lens, thyroid, chest, genitals, finger, and the chest beneath the shield, respectively, were 0.07, 0.07, 0.09, 0.14, 0.32, and 0.05 mSv in 1-level MIS-TLIF; 0.07, 0.08, 0.09, 0.18, 0.34, and 0.05 mSv in 2-level; 0.08, 0.09, 0.14, 0.15, 0.36, and 0.06 mSv in 3-level; and 0.07, 0.08, 0.10, 0.15, 0.33, and 0.05 mSv in all cases. Mean dose at the operating surgeon's right finger was significantly higher than other measurements parts (P,0.001). The operating surgeon's effective doses (0.06, 0.06, and 0.07 mSv for 1, 2, and 3 fusion levels) were low, and didn't differ significantly from those of the assisting surgeon or radiological technologist. Revision MIS-TLIF was not associated with higher surgeons' radiation doses compared to primary MIS-TLIF. There were significantly higher surgeons' radiation doses in over-weight than in normal-weight patients. The surgeons' radiation exposure during MIS-TLIF was within the safe level by the International Commission on Radiological Protection's guidelines. The accumulated radiation exposure, especially to surgeon's hands, should be carefully monitored. © 2014 Funao et al.

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Mycobacterium tuberculosis promotes arthritis development through toll-like receptor 2

Kanagawa Hiroya, Niki Yasuo, Kobayashi Tami, Sato Yuiko, Katsuyama Eri, Fujie Atsuhiro, Hao Wu, Miyamoto Kana, Tando Toshimi, Watanabe Ryuichi, Morita Mayu, Morioka Hideo, Matsumoto Morio, Toyama Yoshiaki, Miyamoto Takeshi

Journal of Bone and Mineral Metabolism 2014年03月

ISSN 0914-8779

Rheumatoid arthritis (RA) is a multifactorial disease caused by genetic and environmental factors: however, precise molecular mechanisms underlying its pathogenesis remain largely unknown. Treatment of RA patients with disease-modifying biological agents occasionally promotes Mycobacterium tuberculosis infection or recurrence of M. tuberculosis, although how infection promotes arthritis has not been characterized. Here, we found that arthritis phenotypes in a collagen-induced mouse model were evident only when killed M. tuberculosis was co-administered. Treatment of cultured macrophages with killed M. tuberculosis promoted production of IL-6, a major inflammatory cytokine in RA patients, while similar treatment of TLR2-deficient macrophages failed to induce IL-6 expression. Arthritis scores, joint destruction, and serum IL-6 levels were all significantly ameliorated in TLR2-deficient compared with wild-type mice, even in animals treated with killed M. tuberculosis. These results suggest that M. tuberculosis infection enhances arthritis development and that TLR2 could serve as a therapeutic target for some forms of the disease. © 2014 The Japanese Society for Bone and Mineral Research and Springer Japan.

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Selection of lower instrumented vertebra in treating lenke type 2A adolescent idiopathic scoliosis

Cao Kai, Watanabe Kota, Kawakami Noriaki, Tsuji Taichi, Hosogane Naobumi, Yonezawa Ikuho, Machida Masafumi, Yagi Mitsuru, Kaneko Shinjiro, Toyama Yoshiaki, Matsumoto Morio

Spine 39 （ 4 ） 2014年02月

ISSN 0362-2436

STUDY DESIGN.: A retrospective, observational, and multicenter study. OBJECTIVE.: To identify the ideal lower instrumented vertebra (LIV) to prevent distal adding-on after surgical correction of Lenke type 2A curve. SUMMARY OF BACKGROUND DATA.: LIV level may affect the risk of postsurgical adding-on. The choice of the last touching vertebra (LTV) - the most caudal vertebra of the main thoracic curve that touches the central sacral vertical line when standing - as an appropriate LIV has been validated for Lenke type 1A but not type 2A curve. METHODS.: Radiographs obtained before, immediately after, and 2 years after surgery were evaluated for 116 consecutive patients who underwent posterior thoracic fusion surgery for Lenke type 2A curve. The LIV was proximal to the LTV in 18 patients (PLTV), distal in 43 (DLTV), and at the LTV in 55 (ALTV). Significant independent factors associated with adding-on were analyzed first by univariate analysis, and then by stepwise logistic regression analysis. RESULTS.: Distal adding-on was present in 16 patients (13.8%) at follow-up: 9 PLTV (50.0%), 3 DLTV (7.0%), and 4 ALTV (7.3%). Adding-on was significantly more common in the PLTV group. One PLTV-group patient required revision surgery to treat adding-on. Univariate analysis identified the following significant factors associated with adding-on: the T2-T5 kyphosis angle and shoulder height before, immediately after, and 2 years after surgery; the lumbar Cobb angle at the 2-year follow-up; the 2-year postoperative lumbar curve correction rate; and the difference between the LIV and the end vertebra, neutral vertebra, and LTV levels. Significant independent risk factors identified by stepwise logistic regression analysis included the clavicle angle at follow-up, the correction rate of the lumbar curve immediately after surgery, and the difference between the LIV and LTV levels. CONCLUSION.: A LIV at or distal to the LTV may prevent postoperative adding-on in Lenke type 2A curve. © 2014 Lippincott Williams and Wilkins.

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Quantification of the spatial strain distribution of scoliosis using a thin-plate spline method

Kiriyama Yoshimori, Watanabe Kota, Matsumoto Morio, Toyama Yoshiaki, Nagura Takeo

Journal of Biomechanics 47 （ 1 ） 302 - 307 2014年01月

ISSN 0021-9290

The objective of this study was to quantify the three-dimensional spatial strain distribution of a scoliotic spine by nonhomogeneous transformation without using a statistically averaged reference spine. The shape of the scoliotic spine was determined from computed tomography images from a female patient with adolescent idiopathic scoliosis. The shape of the scoliotic spine was enclosed in a rectangular grid, and symmetrized using a thin-plate spline method according to the node positions of the grid. The node positions of the grid were determined by numerical optimization to satisfy symmetry. The obtained symmetric spinal shape was enclosed within a new rectangular grid and distorted back to the original scoliotic shape using a thin-plate spline method. The distorted grid was compared to the rectangular grid that surrounded the symmetrical spine. Cobb's angle was reduced from 35° in the scoliotic spine to 7° in the symmetrized spine, and the scoliotic shape was almost fully symmetrized. The scoliotic spine showed a complex Green-Lagrange strain distribution in three dimensions. The vertical and transverse compressive/tensile strains in the frontal plane were consistent with the major scoliotic deformation. The compressive, tensile and shear strains on the convex side of the apical vertebra were opposite to those on the concave side. These results indicate that the proposed method can be used to quantify the three-dimensional spatial strain distribution of a scoliotic spine, and may be useful in quantifying the deformity of scoliosis. © 2013 Elsevier Ltd.

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Pediatric myxopapillary ependymoma treated with subtotal resection and radiation therapy

Shirasawa H., Ishii K., Iwanami A., Mikami S., Toyama Y., Matsumoto M., Nakamura M.

Spinal Cord 52 （ SUPPL. 2 ） 2014年

ISSN 1362-4393

Study design:Case report and review of the literature.Objectives: Myxopapillary ependymoma (MPE) is a relatively rare glioma that develops from the spinal part of the filum terminale, usually in adulthood. While it is generally benign, MPE can disseminate intraspinally, and this malignant behavior requires a multidisciplinary response with surgery and radiotherapy. We report here a case of MPE occurring in the lumbosacral spine area of an 8-year-old boy.Setting:Japan, Tokyo.Methods:We report here a case of MPE, treated with subtotal surgical resection followed by craniospinal irradiation (CSI), in an 8-year-old boy. The patient was referred to our hospital with a 6-month history of severe pain in the lower back and legs, paralysis of the legs and dysuria. Magnetic resonance imaging images showed a large tumor that filled the entire spinal canal below L1. After subtotal resection of the tumor, the pathological findings established a diagnosis of MPE. Since the tumor had perforated its capsule, increasing the risk of intraspinal dissemination, the patient underwent radiotherapy and CSI after surgery.Results:Magnetic resonance images obtained 3 years after the surgery did not show any recurrence of MPE.Conclusion:Although tumor resection followed by CSI can be considered an effective strategy for treating a child with MPE, long-term follow-up is necessary to ensure early detection of any local recurrence or dissemination of the tumor, or of post-radiotherapy scoliosis. © 2014 International Spinal Cord Society All rights reserved.

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Response

Matsumoto Morio

Journal of Neurosurgery: Spine 20 （ 5 ） 596 2014年

ISSN 1547-5654

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An outcome measure for patients with cervical myelopathy

Tanaka Nobuhiro, Konno Shin Ichi, Takeshita Katsushi, Fukui Mitsuru, Takahashi Kazuhisa, Chiba Kazuhiro, Miyamoto Masabumi, Matsumoto Morio, Kasai Yuichi, Kanamori Masahiko, Matsunaga Shunji, Hosono Noboru, Kanchiku Tsukasa, Taneichi Hiroshi, Hashizume Hiroshi, Kanayama Masahiro, Shimizu Takachika, Kawakami Mamoru

Journal of Orthopaedic Science 19 （ 1 ） 33 - 48 2014年

ISSN 0949-2658

Background: An outcome measure to evaluate the neurological function of patients with cervical myelopathy was proposed by the Japanese Orthopaedic Association (JOA score) and has been widely used in Japan. However, the JOA score does not include patients' satisfaction, disability, handicaps, or general health, which can be affected by cervical myelopathy. In 2007, a new outcome measure, the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), which is a self-administered questionnaire, was developed. However, the influence of age and gender on the scores has not been fully examined. The purpose of this study was to establish the standard value of the JOACMEQ by age using healthy volunteers. Methods: This study was conducted in 23 university hospitals and their affiliated hospitals from September to December 2011. The questionnaire included 24 questions for evaluation of physical function of the cervical spine and spinal cord. A total of 1,629 healthy volunteers were recruited for the study. The ages ranged from 20 to 89 years old. Results: The volunteers comprised 798 men and 831 women. In the elderly healthy volunteers, the JOACMEQ scores decreased with age. In general, the scores for cervical spine function and upper/lower extremity function were retained up to the 60s, then decreased in the 70s and 80s. The scores for quality of life were retained up to the 70s; however, the score for bladder function was retained up to the 40s, then declined with age from the 50s to 80s. Conclusion: The standard values of the JOACMEQ by age were established. Differences in the scores were found among different generations. Patients with cervical myelopathy should be evaluated with this new self-administered questionnaire taking into account the standard values according to different ages. © The Japanese Orthopaedic Association 2013.

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A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups

Londono Douglas, Kou Ikuyo, Johnson Todd A., Sharma Swarkar, Ogura Yoji, Tsunoda Tatsuhiko, Takahashi Atsushi, Matsumoto Morio, Herring John A., Lam Tsz Ping, Wang Xingyan, Tam Elisa M S, Song You Qiang, Fan Yan Hui, Chan Danny, Cheah Kathryn S E, Qiu Xusheng, Jiang Hua, Huang Dongsheng, Su Peiqiang, Sham Pak, Cheung Kenneth M C, Luk Keith D K, Gordon Derek, Qiu Yong, Cheng Jack, Tang Nelson, Ikegawa Shiro, Wise Carol A.

Journal of Medical Genetics 51 （ 6 ） 401 - 406 2014年

ISSN 0022-2593

Background: Adolescent idiopathic scoliosis (AIS) is a common rotational deformity of the spine that presents in children worldwide, yet its etiology is poorly understood. Recent genome-wide association studies (GWAS) have identified a few candidate risk loci. One locus near the chromosome 10q24.31 LBX1 gene (OMIM #604255) was originally identified by a GWAS of Japanese subjects and replicated in additional Asian populations. To extend this result, and to create larger AIS cohorts for the purpose of large-scale meta-analyses in multiple ethnicities, we formed a collaborative group called the International Consortium for Scoliosis Genetics (ICSG). Methods: Here, we report the first ICSG study, a metaanalysis of the LBX1 locus in six Asian and three non- Asian cohorts. Results: We find significant evidence for association of this locus with AIS susceptibility in all nine cohorts. Results for seven cohorts containing both genders yielded P=1.22-10-43 for rs11190870, and P=2.94-10-48 for females in all nine cohorts. Comparing the regional haplotype structures for three populations, we refined the boundaries of association to a ̃25 kb block encompassing the LBX1 gene. The LBX1 protein, a homeobox transcription factor that is orthologous to the Drosophila ladybird late gene, is involved in proper migration of muscle precursor cells, specification of cardiac neural crest cells, and neuronal determination in developing neural tubes. Conclusions: Our results firmly establish the LBX1 region as the first major susceptibility locus for AIS in Asian and non-Hispanic white groups, and provide a platform for larger studies in additional ancestral groups.

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Dumbbell mesenchymal chondrosarcoma

Iida Tsuyoshi, Nakamura Masaya, Tsuji Osahiko, Iwanami Akio, Mikami Shuji, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Journal of Orthopaedic Science 19 （ 1 ） 190 - 193 2014年

ISSN 0949-2658

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A novel mouse model of soft-tissue infection using bioluminescence imaging allows noninvasive, real-time monitoring of bacterial growth

Yoshioka Kenji, Ishii Ken, Kuramoto Tetsuya, Nagai Shigenori, Funao Haruki, Ishihama Hiroko, Shiono Yuta, Sasaki Aya, Aizawa Mamoru, Okada Yasunori, Koyasu Shigeo, Toyama Yoshiaki, Matsumoto Morio

PLoS ONE 9 （ 9 ） 2014年

Musculoskeletal infections, including surgical-site and implant-associated infections, often cause progressive inflammation and destroy areas of the soft tissue. Treating infections, especially those caused by multi-antibiotic resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) remains a challenge. Although there are a few animal models that enable the quantitative evaluation of infection in soft tissues, these models are not always reproducible or sustainable. Here, we successfully established a real-time, in vivo, quantitative mouse model of soft-tissue infection in the superficial gluteus muscle (SGM) using bioluminescence imaging. A bioluminescent strain of MRSA was inoculated into the SGM of BALB/c adult male mice, followed by sequential measurement of bacterial photon intensity and serological and histological analyses of the mice. The mean photon intensity in the mice peaked immediately after inoculation and remained stable until day 28. The serum levels of interleukin-6, interleukin-1 and C-reactive protein at 12 hours after inoculation were significantly higher than those prior to inoculation, and the C-reactive protein remained significantly elevated until day 21. Histological analyses showed marked neutrophil infiltration and abscesses containing necrotic and fibrous tissues in the SGM. With this SGM mouse model, we successfully visualized and quantified stable bacterial growth over an extended period of time with bioluminescence imaging, which allowed us to monitor the process of infection without euthanizing the experimental animals. This model is applicable to in vivo evaluations of the long-term efficacy of novel antibiotics or antibacterial implants.

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Postoperative behavior of thoracolumbar/lumbar curve and coronal balance after posterior thoracic fusion for Lenke 1C and 2C adolescent idiopathic scoliosis

Ishikawa Masayuki, Cao Kai, Pang Long, Watanabe Kota, Yagi Mitsuru, Hosogane Naobumi, Machida Masafumi, Shiono Yuta, Nishiyama Makoto, Fukui Yasuyuki, Matsumoto Morio

Journal of Orthopaedic Science 20 （ 1 ） 31 - 37 2014年

ISSN 0949-2658

Methods: Twenty-four Lenke 1C and 2C AIS patients who underwent posterior thoracic fusion were included. The mean age of patients was 15.7 years old at time of surgery. Constructs used for surgery in all cases were pedicle screw constructs ending at L3 or above. Radiographic measurements were performed on Cobb angles of the main thoracic and TLL curves and coronal balance. Factors related to final Cobb angle of TLL curve and postoperative change of coronal balance were investigated.Results: Mean Cobb angles for main thoracic and TLL curves were 59.0° and 43.9° preoperatively, and were corrected to 21.5° and 22.0° at final follow-up, respectively. Mean coronal balance was −5.6 mm preoperatively and was corrected to −14.6 mm at final follow-up. Final Cobb angle of TLL curve was significantly correlated with immediate postoperative Cobb angle of main thoracic curve and tilt of lowest instrumented vertebra (LIV). Postoperative change of coronal balance was significantly correlated with selection of LIV relative to stable vertebra.Conclusion: Spontaneous correction of TLL curve occurred consistently by correcting the main thoracic curve and making the LIV more horizontal after posterior thoracic fusion for Lenke 1C and 2C AIS. The more distal fixation to stable vertebra resulted in coronal balance shifting more to the left postoperatively.Background: Controversy still exists around surgical strategies for Lenke type 1C and 2C curves with primary thoracic and compensatory lumbar curves in adolescent idiopathic scoliosis (AIS). The benefit of selective thoracic fusion (STF) for these curve types is spontaneous lumbar curve correction while saving more mobile lumbar segments. However, a risk of postoperative coronal decompensation after STF has also been reported. This multicenter retrospective study was conducted to evaluate postoperative behavior of thoracolumbar/lumbar (TLL) curve and coronal balance after posterior thoracic fusion for Lenke 1C and 2C AIS.

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Updates on surgical treatments for pediatric scoliosis

Matsumoto Morio, Watanabe Kota, Hosogane Naobumi, Toyama Yoshiaki

Journal of Orthopaedic Science 19 （ 1 ） 6 - 14 2014年

ISSN 0949-2658

Scoliosis in children poses serious problems including respiratory problems, trunk imbalance, and depression, as well as detracting from the child's appearance. Scoliosis can also contribute to back pain later in life. Advanced surgical techniques allow for good correction and maintenance of progressive curves, and growth-sparing treatments are now available for patients with early-onset scoliosis (EOS). Posterior corrective surgeries using pedicle screw (PS) constructs, which allow curves to be corrected in three dimensions, has become the most popular surgical treatment for scoliosis. Several navigation systems and probes have been developed to aid in accurate PS placement. For thoracolumbar and lumbar curves, anterior surgery remains the method of choice. Growth-sparing techniques for treating EOS include growing rods, the Shilla method, anterior stapling, and vertical expandable prosthetic titanium rib, which was originally designed to treat thoracic insufficiency syndrome. However, these advanced surgical techniques do not always offer a perfect solution for pediatric scoliosis, and they are associated with complications such as infections and problems with instrumentation. Surgeons have developed several techniques in efforts to address these complications. We here review historic and recent advances in the surgical treatment of scoliosis in children, the problems associated with various techniques, and the challenges that remain to be overcome. Scoliosis can affect a child's appearance, hamper respiratory function and trunk balance, lead to depression, and cause back pain later in life. Moderate scoliotic curves are usually treated conservatively using a brace, but a curve that continues to progress despite treatment requires corrective surgery, either with or without fusion. Recent advances in surgical techniques have made it possible to obtain good correction and maintenance of progressive curves, and several growth-sparing techniques are now available for treating patients with early-onset scoliosis (EOS). However, these advanced surgical techniques do not provide a perfect solution for pediatric scoliosis, and some are associated with suboptimal clinical outcomes. In this article, we review recent technical advances and problems associated with the surgical treatment of scoliosis in children, both from a historic perspective and with a view to the future. © The Japanese Orthopaedic Association 2013.

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High preoperative hemoglobin A1c is a risk factor for surgical site infection after posterior thoracic and lumbar spinal instrumentation surgery

Hikata Tomohiro, Iwanami Akio, Hosogane Naobumi, Watanabe Kota, Ishii Ken, Nakamura Masaya, Kamata Michihiro, Toyama Yoshiaki, Matsumoto Morio

Journal of Orthopaedic Science 19 （ 2 ） 223 - 228 2014年

ISSN 0949-2658

Background: Diabetes mellitus (DM) is reported to be a risk factor for surgical site infection (SSI), which is a serious complication after spinal surgery. The effect of DM on SSI after instrumented spinal surgery remains to be clarified. The aim was to elucidate perioperative risk factors for infection at the surgical site after posterior thoracic and lumbar spinal arthrodesis with instrumentation in patients with DM. Methods: Consecutive patients who underwent posterior instrumented thoracic and lumbar spinal arthrodesis during the years 2005-2011, who could be followed for at least 1 year after surgery, were included. These included 36 patients with DM (19 males and 17 females; mean age 64.3 years). The patients' medical records were retrospectively reviewed to determine the SSI rate. The characteristics of the DM patients were examined in detail, including the levels of serum glucose and HbA1c, which indicate the level of diabetes control. Results: Patients with DM had a higher rate of SSI (6 of 36 patients, 16.7 %) than patients without DM (10 of 309 patients, 3.2 %). Although the perioperative serum glucose level did not differ between DM patients that did or did not develop SSI, the preoperative HbA1c value was significantly higher in the patients who developed SSI (7.6 %) than in those who did not (6.9 %). SSI developed in 0.0 % of the patients with controlled diabetes (HbA1c <7.0 %) and in 35.3 % of the patients with uncontrolled diabetes (HbA1c ≥7.0 %). Conclusions: DM patients whose blood glucose levels were poorly controlled before surgery were at high risk for SSI. To prevent SSI in DM patients, we recommend lowering the HbA1c to <7.0 % before performing surgery. © 2013 The Japanese Orthopaedic Association.

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New classification system for ossification of the posterior longitudinal ligament using CT images

Kawaguchi Yoshiharu, Matsumoto Morio, Iwasaki Motoki, Izumi Tomohiro, Okawa Atsushi, Matsunaga Shunji, Chiba Kazuhiro, Tsuji Takashi, Yamazaki Masashi, Fujimori Takahito, Yoshii Toshitaka, Toyama Yoshiaki

Journal of Orthopaedic Science 19 （ 4 ） 530 - 536 2014年

ISSN 0949-2658

Background: Ossification of the posterior longitudinal ligament (OPLL) is most frequently seen in the cervical spine. The types of cervical OPLL are classified into continuous, mixed, segmental, and other based on plain lateral X-ray. Computed tomography (CT) imaging is often used in clinical practice for evaluating ossified lesions as it can detect their precise location, size, and shape. However, to date, no CT classification of OPLL lesions has been proposed. Methods: One hundred and forty-four patients diagnosed with cervical OPLL by plain radiograph were included in this study. Sagittal and axial CT images of the cervical spine were obtained. We propose three classification systems: A, B, and axial. Classification A comprises two lesion types: bridge and nonbridge. Classification B requires examiners to describe all vertebral and intervertebral levels where OPLL exits in the cervical spine. Axial classification comprises central and lateral lesions identified on axial CT images. Seven observers evaluated CT images using this classification system, and intra- and interrater reliability were examined. Results: Averaged Fleiss' kappa coefficient of interrater agreement was 0.43 ± 0.26 among the seven observers, averaged intrarater reliability for the existence of OPLL was 72.4 ± 8.8 % [95 % confidence interval (CI) 67.5-76.8]. Fifty-four patients (37.5 %) had the bridge type and 90 the nonbridge type according to Classification A; 102 (70.8 %) had central and 42 (29.2 %) lateral OPLL in the axial classification. Four representative cases defined according to the three classification types are reported here. Conclusion: Subcommittee members of the Investigation Committee on the Ossification of the Spinal Ligaments of the Japanese Ministry of Public Health and Welfare propose three new classification systems of cervical OPLL based on CT imaging: A, B, and axial. © 2014 The Japanese Orthopaedic Association.

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C1 posterior arch screw as an auxiliary anchor in posterior reconstruction for atlantoaxial dislocation associated with type II odontoid fracture

Nagoshi Narihito, Suda Kota, Morita Tomonori, Matsumoto Satoko, Iimoto Seiji, Yasui Keigo, Komatsu Miki, Kobayashi Yosuke, Minami Akio, Toyama Yoshiaki, Matsumoto Morio, Nakamura Masaya

SpringerPlus 3 （ 1 ） 2014年

Introduction: Although pedicle or lateral mass screws are usually chosen to fix atlantoaxial (C1-C2) instability, there is an increased risk for vertebral artery (VA) injury when used in patients with bone or arterial anomalies or osteoporotic bone. Here we report the C1 posterior arch screw as a new technique for upper cervical fixation.Case description: A 90-year-old man complained of upper cervical pain after falling in his house. The initial computed tomography (CT) scan showed C1-C2 posterior dislocation with a type II odontoid fracture. The patient underwent C2 fracture reduction and posterior C1-C2 fixation. On the right side of C1, because lateral mass screw placement could cause injury to the dominant VA considering a risk in oldest-old osteoporotic patients, a posterior arch screw was chosen instead as an auxiliary anchor. An intralaminar screw was placed on the right side of C2 because a high-riding VA was observed. A lateral mass screw and a pars interarticularis screw were placed on the left side of C1 and C2, respectively. Ten months later, the odontoid fracture had healed, with normal anatomical alignment. Although the patient experienced slight weakness when spreading his bilateral fingers, his overall condition was good.Discussion and evaluation: We have presented a novel technique using C1 posterior arch screws for the fixation of a C1-C2 dislocation. Such a screw is an alternative to the C1 lateral mass screw in patients who are at risk for a VA injury because of anomalous bone and arterial structures or poor bone quality.Conclusions: Although there have been few comparable studies, and the long-term outcome is unknown, fixation with a posterior arch screw could be a beneficial choice for surgeries involving the upper cervical region.

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Surgeons' exposure to radiation in single- and multi-level minimally invasive transforaminal lumbar interbody fusion; a prospective study

Funao Haruki, Ishii Ken, Momoshima Suketaka, Iwanami Akio, Hosogane Naobumi, Watanabe Kota, Nakamura Masaya, Toyama Yoshiaki, Matsumoto Morio

PLoS ONE 9 （ 4 ） e95233 2014年

Although minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has widely been developed in patients with lumbar diseases, surgeons risk exposure to fluoroscopic radiation. However, to date, there is no studies quantifying the effective dose during MIS-TLIF procedure, and the radiation dose distribution is still unclear. In this study, the surgeons' radiation doses at 5 places on the bodies were measured and the effective doses were assessed during 31 consecutive 1- to 3-level MIS-TLIF surgeries. The operating surgeon, assisting surgeon, and radiological technologist wore thermoluminescent dosimeter on the unshielded thyroid, chest, genitals, right middle finger, and on the chest beneath a lead apron. The doses at the lens and the effective doses were also calculated. Mean fluoroscopy times were 38.7, 53.1, and 58.5 seconds for 1, 2, or 3 fusion levels, respectively. The operating surgeon's mean exposures at the lens, thyroid, chest, genitals, finger, and the chest beneath the shield, respectively, were 0.07, 0.07, 0.09, 0.14, 0.32, and 0.05 mSv in 1-level MIS-TLIF; 0.07, 0.08, 0.09, 0.18, 0.34, and 0.05 mSv in 2-level; 0.08, 0.09, 0.14, 0.15, 0.36, and 0.06 mSv in 3-level; and 0.07, 0.08, 0.10, 0.15, 0.33, and 0.05 mSv in all cases. Mean dose at the operating surgeon's right finger was significantly higher than other measurements parts (P<0.001). The operating surgeon's effective doses (0.06, 0.06, and 0.07 mSv for 1, 2, and 3 fusion levels) were low, and didn't differ significantly from those of the assisting surgeon or radiological technologist. Revision MIS-TLIF was not associated with higher surgeons' radiation doses compared to primary MIS-TLIF. There were significantly higher surgeons' radiation doses in over-weight than in normal-weight patients. The surgeons' radiation exposure during MIS-TLIF was within the safe level by the International Commission on Radiological Protection's guidelines. The accumulated radiation exposure, especially to surgeon's hands, should be carefully monitored.

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In vitro and in vivo antimicrobial properties of silver-containing hydroxyapatite prepared via ultrasonic spray pyrolysis route

Honda Michiyo, Kawanobe Yusuke, Ishii Ken, Konishi Toshiisa, Mizumoto Minori, Kanzawa Nobuyuki, Matsumoto Morio, Aizawa Mamoru

Materials Science and Engineering C 33 （ 8 ） 5008 - 5018 2013年12月

ISSN 0928-4931

Hydroxyapatite (HAp), with its high biocompatibility and osteoconductivity, readily absorbs proteins, amino acids and other substances, which in turn favor the adsorption and colonization of bacteria. To prevent bacterial growth and biofilm formation on HAp discs, silver-containing (1-20 mol%) HAp (Ag-HAp) powders were synthesized using an ultrasonic spray pyrolysis (USSP) technique. The X-ray diffraction (XRD) peaks were very broad, indicating low crystallinity, and this induced the release of Ag⁺ ions from Ag-HAp powders. In addition, a gradual increase in Ca²⁺ ion release was observed. These results suggest that dissolution of Ca²⁺ ion in Ag-HAp triggered the release of Ag⁺ ions. The antimicrobial efficacy of Ag-HAp disc was tested against Staphylococcus aureus. Samples with Ag contents of more than 5 mol%were found to be highly effective against bacterial colonization and biofilm formation in vitro. In vivo antibacterial tests using bioluminescent strains also showed reductions in the viability of bacteria with Ag-HAp (5 mol%) discs. Biocompatibility tests using a modified Transwell® insert method showed that Ag-HAp (5 mol%) discs have negative effects on osteoblast proliferation. These results indicate that Ag-HAp (5 mol%) has effective antibacterial activity and good biocompatibility both in vitro and in vivo together with good biocompatibility, thus confirming its utility as a bactericidal material. © 2013 Elsevier B.V. All rights reserved.

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FOXC2 mutations in familial and sporadic spinal extradural arachnoid cyst

Ogura Yoji, Yabuki Shoji, Iida Aritoshi, Kou Ikuyo, Nakajima Masahiro, Kano Hiroki, Shiina Masaaki, Kikuchi Shinichi, Toyama Yoshiaki, Ogata Kazuhiro, Nakamura Masaya, Matsumoto Morio, Ikegawa Shiro

PLoS ONE 8 （ 11 ） 2013年11月

Spinal extradural arachnoid cyst (SEDAC) is a cyst in the spinal canal that protrudes into the epidural space from a defect in the dura mater. Most cases are sporadic; however, three familial SEDAC cases have been reported, suggesting genetic etiological factors. All familial cases are associated with lymphedema-distichiasis syndrome (LDS), whose causal gene is FOXC2. However, FOXC2 mutation analysis has been performed in only 1 family, and no mutation analysis has been performed on sporadic (non-familial) SEDACs. We recruited 17 SEDAC subjects consisting of 2 familial and 7 sporadic cases and examined FOXC2 mutations by Sanger sequencing and structural abnormalities by TaqMan copy number assay. We identified 2 novel FOXC2 mutations in 2 familial cases. Incomplete LDS penetrance was noted in both families. Four subjects presented with SEDACs only. Thus, SEDAC caused by the heterozygous FOXC2 loss-of-function mutation should be considered a feature of LDS, although it often manifests as the sole symptom. Seven sporadic SEDAC subjects had no FOXC2 mutations, no symptoms of LDS, and showed differing clinical characteristics from those who had FOXC2 mutations, suggesting that other gene(s) besides FOXC2 are likely to be involved in SEDAC. © 2013 Ogura et al.

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Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant

Song You Qiang, Karasugi Tatsuki, Cheung Kenneth M C, Chiba Kazuhiro, Ho Daniel W H, Miyake Atsushi, Kao Patrick Y P, Sze Kit Ling, Yee Anita, Takahashi Atsushi, Kawaguchi Yoshiharu, Mikami Yasuo, Matsumoto Morio, Togawa Daisuke, Kanayama Masahiro, Shi Dongquan, Dai Jin, Jiang Qing, Wu Chengai, Tian Wei, Wang Na, Leong John C Y, Luk Keith D K, Yip Shea Ping, Cherny Stacey S., Wang Junwen, Mundlos Stefan, Kelempisioti Anthi, Eskola Pasi J., Männikkö Minna, Mäkelä Pirkka, Karppinen Jaro, Järvelin Marjo Riitta, O'Reilly Paul F., Kubo Michiaki, Kimura Tomoatsu, Kubo Toshikazu, Toyama Yoshiaki, Mizuta Hiroshi, Cheah Kathryn S E, Tsunoda Tatsuhiko, Sham Pak Chung, Ikegawa Shiro, Chan Danny

Journal of Clinical Investigation 123 （ 11 ） 4909 - 4917 2013年11月

ISSN 0021-9738

Lumbar disc degeneration (LDD) is associated with both genetic and environmental factors and affects many people worldwide. A hallmark of LDD is loss of proteoglycan and water content in the nucleus pulposus of intervertebral discs. While some genetic determinants have been reported, the etiology of LDD is largely unknown. Here we report the findings from linkage and association studies on a total of 32,642 subjects consisting of 4,043 LDD cases and 28,599 control subjects. We identified carbohydrate sulfotransferase 3 (CHST3), an enzyme that catalyzes proteoglycan sulfation, as a susceptibility gene for LDD. The strongest genome-wide linkage peak encompassed CHST3 from a Southern Chinese family-based data set, while a genome-wide association was observed at rs4148941 in the gene in a meta-analysis using multiethnic population cohorts. rs4148941 lies within a potential microRNA-513a-5p (miR-513a-5p) binding site. Interaction between miR-513a-5p and mRNA transcribed from the susceptibility allele (A allele) of rs4148941 was enhanced in vitro compared with transcripts from other alleles. Additionally, expression of CHST3 mRNA was significantly reduced in the intervertebral disc cells of human subjects carrying the A allele of rs4148941. Together, our data provide new insights into the etiology of LDD, implicating an interplay between genetic risk factors and miRNA.

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A rare case of dumbbell meningioma of the upper cervical spinal cord

Ozaki Masahiro, Nakamura Masaya, Tsuji Osahiko, Iwanami Akio, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Journal of Orthopaedic Science 18 （ 6 ） 1042 - 1045 2013年11月

ISSN 0949-2658

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Spinal coronal profiles and proximal femur bone mineral density in adolescent idiopathic scoliosis

Chen Rui Qiang, Watanabe Kota, Hosogane Naobumi, Hikata Tomohiro, Iwanami Akio, Ishii Ken, Nakamura Masaya, Toyama Yoshiaki, Matsumoto Morio

European Spine Journal 22 （ 11 ） 2433 - 2437 2013年11月

ISSN 0940-6719

Purpose: Although the occurrence and progression of AIS has been linked to low bone mineral density (BMD), the relationships between spinal curvature and bilateral differences in proximal femur BMD are controversial. Few correlation studies have stratified patients by curve type. The purpose of this study was to evaluate the relationships between spinal coronal profile and bilateral differences in proximal femur BMD in patients with adolescent idiopathic scoliosis (AIS). Methods: This study included 67 patients with AIS who underwent posterior correction and fusion surgery between January 2009 and October 2011. The mean age at the time of surgery was 17.4 ± 4.1 years. Bilateral proximal femur BMD was measured before surgery by dual-energy X-ray absorptiometry. We compared the proximal femur BMDs by determining the bilateral BMD ratio (left proximal femur BMD divided by that of the right). We evaluated correlations between coronal parameters, obtained from preoperative radiographs, and the BMD ratio using Pearson's correlation analysis. Results: Patients with Lenke type 1 curve (48; all with a right convex curve) had a mean bilateral proximal femur BMD ratio of 1.00 ± 0.04. Patients with Lenke type 5 curve (19; all with a left convex curve) had a mean bilateral proximal femur BMD ratio of 0.94 ± 0.04, indicating that the BMD in the proximal femur on the right side (concave) was greater than that in the left (convex). Coronal balance was significantly correlated with the BMD ratio in both the Lenke type 1 and type 5 groups, with a correlation coefficient of 0.46 and 0.50, respectively. Conclusions: The bilateral proximal femur BMD ratio was significantly correlated with the coronal balance in AIS patients. When the C7 plumb line was shifted toward one side, the BMD was greater in the contralateral proximal femur. © 2013 Springer-Verlag Berlin Heidelberg.

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HIF1? is required for osteoclast activation by estrogen deficiency in postmenopausal osteoporosis

Miyauchi Yoshiteru, Sato Yuiko, Kobayashi Tami, Yoshida Shigeyuki, Mori Tomoaki, Kanagawa Hiroya, Katsuyama Eri, Fujie Atsuhiro, Hao Wu, Miyamoto Kana, Tando Toshimi, Morioka Hideo, Matsumoto Morio, Chambon Pierre, Johnson Randall S., Kato Shigeaki, Toyama Yoshiaki, Miyamoto Takeshi

Proceedings of the National Academy of Sciences of the United States of America 110 （ 41 ） 16568 - 16573 2013年10月

ISSN 0027-8424

In women, estrogen deficiency after menopause frequently accelerates osteoclastic bone resorption, leading to osteoporosis, the most common skeletal disorder. However, mechanisms underlying osteoporosis resulting from estrogen deficiency remain largely unknown. Here we show that in bone-resorbing osteoclasts, estrogendependent destabilization of hypoxia-inducible factor 1 alpha (HIF1?), which is unstable in the presence of oxygen, plays a pivotal role in promoting bone loss in estrogen-deficient conditions. In vitro, HIF1? was destabilized by estrogen treatment even in hypoxic conditions, and estrogen loss in ovariectomized (Ovx) mice stabilized HIF1? in osteoclasts and promoted their activation and subsequent bone loss in vivo. Osteoclast-specific HIF1? inactivation antagonized bone loss in Ovx mice and osteoclast-specific estrogen receptor alpha deficient mice, both models of estrogen-deficient osteoporosis. Oral administration of a HIF1? inhibitor protected Ovx mice from osteoclast activation and bone loss. Thus, HIF1? represents a promising therapeutic target in osteoporosis.

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Identification of a Susceptibility Locus for Severe Adolescent Idiopathic Scoliosis on Chromosome 17q24.3

Miyake Atsushi, Kou Ikuyo, Takahashi Yohei, Johnson Todd A., Ogura Yoji, Dai Jin, Qiu Xusheng, Takahashi Atsushi, Jiang Hua, Yan Huang, Kono Katsuki, Kawakami Noriaki, Uno Koki, Ito Manabu, Minami Shohei, Yanagida Haruhisa, Taneichi Hiroshi, Hosono Naoya, Tsuji Taichi, Suzuki Teppei, Sudo Hideki, Kotani Toshiaki, Yonezawa Ikuho, Kubo Michiaki, Tsunoda Tatsuhiko, Watanabe Kota, Chiba Kazuhiro, Toyama Yoshiaki, Qiu Yong, Matsumoto Morio, Ikegawa Shiro

PLoS ONE 8 （ 9 ） 2013年09月

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, affecting around 2% of adolescents worldwide. Genetic factors play an important role in its etiology. Using a genome-wide association study (GWAS), we recently identified novel AIS susceptibility loci on chromosomes 10q24.31 and 6q24.1. To identify more AIS susceptibility loci relating to its severity and progression, we performed GWAS by limiting the case subjects to those with severe AIS. Through a two-stage association study using a total of ∼12,000 Japanese subjects, we identified a common variant, rs12946942 that showed a significant association with severe AIS in the recessive model (P = 4.00×10^-8, odds ratio [OR] = 2.05). Its association was replicated in a Chinese population (combined P = 6.43×10^-12, OR = 2.21). rs12946942 is on chromosome 17q24.3 near the genes SOX9 and KCNJ2, which when mutated cause scoliosis phenotypes. Our findings will offer new insight into the etiology and progression of AIS. © 2013 Miyake et al.

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Risk factors for lumbar disc degeneration in High School American Football Players

Nagashima Masaki, Abe Hitoshi, Amaya Kenji, Matsumoto Hideo, Yanaihara Hisashi, Nishiwaki Yuji, Toyama Yoshiaki, Matsumoto Morio

American Journal of Sports Medicine 41 （ 9 ） 2059 - 2064 2013年09月

ISSN 0363-5465

Background: Several risk factors have been proposed for intervertebral disc degeneration (DD) among adolescent athletes. However, the causes of DD are not well understood, and there have been few prospective studies evaluating DD in adolescents. Purpose: To identify risk factors for DD among adolescent American football (AF) players. Study Design: Cohort study (prevalence); Level of evidence, 2. Methods: This study investigated the relationships between the progression of DD and the following factors: lumbar spine abnormalities on baseline radiographs, body mass index, AF position played (lineman or other), and length of playing career (2 full competitive AF seasons or<2 seasons). Included were 192 students who joined a top-ranked high school AF team from 2004 to 2008. Of these, 160 played for 2 full competitive AF seasons. The remaining 32 players, who stopped before completing 2 seasons, were used as a control group. Baseline radiographs and lumbar magnetic resonance imaging (MRI) scans were obtained when the players enrolled in the AF team in May, and follow-up lumbar MRI scans were obtained 2 years later at the end of their second academic year in March. Disc degeneration was measured by the signal intensity of the nucleus pulposus, and its progression was evaluated by multiple regression analysis of decreases in signal intensity. Also analyzed was the relationship between DD and low back pain (LBP). Results: The mean decrease in signal intensity of the nucleus pulposus was 4.30% ± 11.63% in players who completed 2 AF seasons and 1.41% ± 10.03% in those who did not (P = .12). Mean visual analog scale scores for LBP at follow-up were significantly higher (P = .001) in players who had played for 2 full seasons (2.67 ± 2.81) than in those with a shorter career (0.99 ± 1.61). Decreases in signal intensity of the nucleus pulposus after 2 years of playing AF related significantly to playing a lineman position (partial regression coefficient, 3.47%), the presence of Schmorl nodes (partial regression coefficient, 3.58%), and disc herniation (partial regression coefficient, 4.09%). Conclusion: Significant risk factors for DD progression in high school AF players included playing a lineman position, the presence of Schmorl nodes, and disc herniation. Continuing to play AF through 2 years of high school was a risk factor for the onset of LBP. © 2013 The Author(s).

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Nondura-based clear cell meningioma of the cauda equina in an adult

Kobayashi Yoshiomi, Nakamura Masaya, Tsuji Osahiko, Iwanami Akio, Ishii Ken, Watanabe Kota, Hosogane Naobumi, Tsuji Takashi, Kameyama Kaori, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Journal of Orthopaedic Science 18 （ 5 ） 861 - 865 2013年09月

ISSN 0949-2658

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Optimal treatment for Spinal Cord Injury associated with cervical canal Stenosis (OSCIS)

Chikuda Hirotaka, Ohtsu Hiroshi, Ogata Toru, Sugita Shurei, Sumitani Masahiko, Koyama Yurie, Matsumoto Morio, Toyama Yoshiaki

Trials 14 （ 1 ） 2013年08月

Background: The optimal management of acute cervical spinal cord injury (SCI) associated with preexisting canal stenosis remains to be established. The objective of this study is to examine whether early surgical decompression (within 24 hours after admission) would result in greater improvement in motor function compared with delayed surgery (later than two weeks) in cervical SCI patients presenting with canal stenosis, but without bony injury.Methods/design: OSCIS is a randomized, controlled, parallel-group, assessor-blinded, multicenter trial. We will recruit 100 cervical SCI patients who are admitted within 48 hours of injury (aged 20 to 79 years; without fractures or dislocations; American Spinal Injury Association (ASIA) grade C; preexisting spinal canal stenosis). Patients will be enrolled from 36 participating hospitals across Japan and randomly allocated in a 1:1 ratio to either early surgical decompression (within 24 hours after admission) or delayed surgery following at least two weeks of conservative treatment. The primary outcomes include: 1) the change from baseline to one year in the ASIA motor score; 2) the total score of the Spinal Cord Independence Measure and 3) the proportion of patients who are able to walk without human assistance. The secondary outcomes are: 1) the health-related quality of life as measured by the Medical Outcomes Study Short Form 36 and the EuroQol 5 Dimension; 2) the Neuropathic Pain Symptom Inventory and 3) the walking status as evaluated with the Walking Index for Spinal Cord Injury II. The analysis will be on an intention-to-treat basis. The primary analysis will be a comparison of the primary and secondary outcomes one year after the injury.Discussion: The results of this study will provide evidence of the potential benefit of early surgical decompression compared to the current 'watch and wait' strategy. © 2013 Chikuda et al.; licensee BioMed Central Ltd.

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A replication study for association of 53 single nucleotide polymorphisms in a scoliosis prognostic test with progression of adolescent idiopathic scoliosis in Japanese

Ogura Yoji, Takahashi Yohei, Kou Ikuyo, Nakajima Masahiro, Kono Katsuki, Kawakami Noriaki, Uno Koki, Ito Manabu, Minami Shohei, Yanagida Haruhisa, Taneichi Hiroshi, Yonezawa Ikuho, Tsuji Taichi, Suzuki Teppei, Sudo Hideki, Kotani Toshiaki, Watanabe Kota, Chiba Kazuhiro, Toyama Yoshiaki, Matsumoto Morio, Ikegawa Shiro

Spine 38 （ 16 ） 1375 - 1379 2013年07月

ISSN 0362-2436

STUDY DESIGN.: A genetic association study of single nucleotide polymorphisms (SNPs) previously reported to be associated with curve progression of adolescent idiopathic scoliosis (AIS). OBJECTIVE.: To determine whether the association of 53 SNPs with curve progression reported in white patients with AIS are replicated in Japanese patients with AIS. SUMMARY OF BACKGROUND DATA.: Predicting curve progression is important in clinical practice of AIS. The progression of AIS is reported to be associated with a number of genes. Associations with 53 SNPs have been reported, and the SNPs are used for a progression test in white patients with AIS; however, there has been no replication study for their association. METHODS.: We recruited 2117 patients with AIS with 10 or more (Cobb angle) of scoliosis curves. They were divided into progression and nonprogression groups according to their Cobb angle. We defined the progression of the curve as Cobb angle more than 50 for skeletally mature subjects and more than 40 for immature patients, subjects. We defined the nonprogression of the curve as Cobb angle 50 or less only for skeletally mature subjects. Of the 2117 patients, 1714 patients with AIS were allocated to either the progression or nonprogression group. We evaluated the association of 53 SNPs with curve progression by comparing risk allele frequencies between the 2 groups. RESULTS.: We evaluated the progression (N = 600) and nonprogression (N = 1114) subjects. Their risk allele frequencies were not different significantly. We found no replication of the association on AIS curve progression in any of the SNPs. CONCLUSION.: The associations of the 53 SNPs with progression of AIS curve are not definite. Large-scale association studies based on appropriate criteria for progression would be necessary to identify SNPs associated with the curve progression. Copyright © 2013 Lippincott Williams & Wilkins.

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Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis

Kou Ikuyo, Takahashi Yohei, Johnson Todd A., Takahashi Atsushi, Guo Long, Dai Jin, Qiu Xusheng, Sharma Swarkar, Takimoto Aki, Ogura Yoji, Jiang Hua, Yan Huang, Kono Katsuki, Kawakami Noriaki, Uno Koki, Ito Manabu, Minami Shohei, Yanagida Haruhisa, Taneichi Hiroshi, Hosono Naoya, Tsuji Taichi, Suzuki Teppei, Sudo Hideki, Kotani Toshiaki, Yonezawa Ikuho, Londono Douglas, Gordon Derek, Herring John A., Watanabe Kota, Chiba Kazuhiro, Kamatani Naoyuki, Jiang Qing, Hiraki Yuji, Kubo Michiaki, Toyama Yoshiaki, Tsunoda Tatsuhiko, Wise Carol A., Qiu Yong, Shukunami Chisa, Matsumoto Morio, Ikegawa Shiro

Nature Genetics 45 （ 6 ） 676 - 679 2013年06月

ISSN 1061-4036

Adolescent idiopathic scoliosis (AIS) is the most common pediatric skeletal disease. We previously reported a locus on chromosome 10q24.31 associated with AIS susceptibility in Japanese using a genome-wide association study (GWAS) consisting of 1,033 cases and 1,473 controls. To identify additional AIS-associated loci, we expanded the study by adding X-chromosome SNPs in the GWAS and increasing the size of the replication cohorts. Through a stepwise association study including 1,819 cases and 25,939 controls, we identified a new susceptibility locus on chromosome 6q24.1 in Japanese (P = 2.25 × 10 ^-10; odds ratio (OR) = 1.28). The most significantly associated SNP, rs6570507, was in GPR126 (encoding G protein-coupled receptor 126). Its association was replicated in Han Chinese and European-ancestry populations (combined P = 1.27 × 10^-14; OR = 1.27). GPR126 was highly expressed in cartilage, and the knockdown of gpr126 in zebrafish caused delayed ossification of the developing spine. Our results should provide insights into the etiology and pathogenesis of AIS. © 2013 Nature America, Inc. All rights reserved.

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Total en bloc spondylectomy for spinal metastasis of differentiated thyroid cancers

Matsumoto Morio, Tsuji Takashi, Iwanami Akio, Watanabe Kota, Hosogane Naobumi, Ishii Ken, Nakamura Masaya, Morioka Hideo, Toyama Yoshiaki

Journal of Spinal Disorders and Techniques 26 （ 4 ） 2013年06月

ISSN 1536-0652

Study Design: A retrospective case series. Objective: To evaluate the long-term effectiveness and problems of total en bloc spondylectomy (TES) for treating metastatic thyroid cancer of the spine. Summary of Background Data: Although TES is indicated for low-grade malignant spinal tumors, its efficacy in treating thyroid cancer metastases in the spine is uncertain. Methods: This study followed 8 patients who underwent TES for spinal metastasis of thyroid cancer (5 males, 3 females; mean age, 55.3 y; mean follow-up period, 6.4 y), 6 with follicular carcinomas and 2 with papillary carcinomas. In 6 patients without a marked paravertebral tumor extension, TES was performed using a posterior approach. Two patients had prominent anterior or anterolateral tumor extension into the thoracic and retroperitoneal cavities, and a combined anterior and posterior approach was used. We evaluated the patients' clinical symptoms, operative procedures, complications, and prognoses. Results: Before surgery, the patients' neurological status was evaluated by the Frankel classification (grade C, 4 patients; grade D, 1 patient; grade E, 3 patients) and Tokuhashi scores (9, 1 patient; 11, 2 patients; 13 and 14, 1 patient each; 15, 3 patients). One year after surgery, all the patients had improved by at least a Frankel grade, and 4 patients classified as grade C before surgery had become ambulatory. At the final follow-up (average of 6.4 y), 5 patients had a grade E Frankel classification and 1 had grade D, but 2 patients had suffered neurological deterioration, because of tumor recurrence, at the same level as the TES in one patient and at an adjacent level in the other. At follow-up, all patients were alive; 5 showed no evidence of disease. Two patients experienced rod breakage, at 2.8 and at 3.3 years after TES, and 1 patient suffered an endplate fracture 6 months after TES; this patient developed a late infection, 7 years after TES. Conclusions: TES was effective in controlling spinal thyroid cancer metastasis locally and in preserving the ability to walk. However, instrumentation failure and other late complications arose during the patients' long survival times after TES. Copyright © 2012 by Lippincott Williams & Wilkins.

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Modic changes of the cervical spine in patients with whiplash injury

Matsumoto Morio, Ichihara Daisuke, Okada Eijiro, Toyama Yoshiaki, Fujiwara Hirokazu, Momoshima Suketaka, Nishiwaki Yuji, Takahata Takeshi

Injury 44 （ 6 ） 819 - 824 2013年06月

ISSN 0020-1383

Introduction: There are few studies on Modic changes of the cervical spine in patients suffering from whiplash. This study compared Modic changes seen in whiplash patients 10 years after the injury with those observed in asymptomatic volunteers. Methods: This is a follow-up study of 133 patients who suffered whiplash injuries in 1994-1996 and underwent MRI with a superconductive imager (63 men, 70 women, mean age 49.6 ± 15.3 years, mean follow-up 11.4 years). In addition, 223 healthy volunteers who underwent MRI during the same period were included as controls (123 men, 100 women, mean age 50.5 ± 15.0 years, mean follow-up 11.6 years). All participants underwent follow-up MRI. We examined all participants for Modic changes, and investigated relationships between Modic changes and clinical symptoms or potentially related factors. Results: Modic changes were observed in 4 patients (3%) and at 7 intervertebral levels in the initial study, and in 17 patients (12.8%) and at 30 intervertebral levels at the follow-up. Modic Type 2 changes were the most prevalent in the whiplash patients in both the initial and follow-up studies. There was no significant difference in the percentage of whiplash patients versus control subjects with positive Modic changes, either at the initial study or at follow-up. Modic changes were not related to clinical symptoms present at follow-up, but were associated with preexisting disc degeneration. There was no association between Modic changes and the details of the car accident that caused the injury. Conclusions: While Modic changes became more common in whiplash patients in the 10-year period after the accident, they occurred with a similar frequency in control subjects. We did not find any association between Modic changes and the nature of the car accident in which the whiplash occurred. Modic changes found in whiplash patients may be a result of the physiological ageing process rather than pathological findings relating to the whiplash injury. © 2012 Elsevier Ltd.

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Postoperative distal adding-on and related factors in Lenke type 1A curve

Matsumoto Morio, Watanabe Kota, Hosogane Naobumi, Kawakami Noriaki, Tsuji Taichi, Uno Koki, Suzuki Teppei, Ito Manabu, Yanagida Haruhisa, Yamaguchi Toru, Minami Shohei, Akazawa Tsutomu

Spine 38 （ 9 ） 737 - 744 2013年04月

ISSN 0362-2436

Study Design: A retrospective, multicenter study. Objective: To investigate the occurrence of and factors related to postoperative adding-on in Lenke type 1A curve. Summary of Background Data: Although several studies have investigated factors associated with adding-on in Lenke type 1A curve, these factors have not been elucidated in a large study population. Methods: This study included 112 patients who were followed more than 2 years after undergoing selective posterior thoracic fusion surgery for Lenke Type 1A curve (8 males, 104 females; mean age at surgery, 16.1 yr; mean follow-up, 3.6 yr). The lower instrumented vertebra (LIV) was T12 in 22 patients, L1 in 55, L2 in 32, and L3 in 3. Distal to the main thoracic curve, the end vertebra, neutral vertebra, stable vertebra (SV), and the last vertebra touching the central sacral vertical line (last touching vertebra, LTV) were determined. The occurrence and factors associated with distal adding-on were investigated. Results: The mean Cobb angle and apical translation of the main thoracic curve were 54.6 ° ± 9.6 ° and 53.1 ± 20.4 mm before surgery, and 14.2 ± 7.4 and 16.2 ± 12.7 at follow-up, respectively. Distal adding-on was observed in 21 patients (18.8%) at follow-up. Univariate analyses identifi ed several factors signifi cantly associated with adding-on, including the preoperative proximal thoracic curve, the apical translation of the main thoracic curve, Miyanji's subclassifi cation, the postsurgical proximal and main thoracic curves, the postsurgical apical translation of the main thoracic curve, the correction rate of the main thoracic curve and the clavicle angle immediately after surgery and at follow-up, and the difference in levels between the LIV and the end vertebra, neutral vertebra, LTV, and stable vertebra. Logistic regression analysis showed that the apical translation of the main thoracic curve immediately after surgery (apical translation > 25 mm, odds ratio: 10.7, 95% confi dence interval: 3.1-37.0, P = 0.001) and the difference in levels between LIV and LTV (LIV-LTV) (LIV-LTV < 0, odds ratio: 6.7, 95% confi dence interval: 1.9-23.9, P = 0.003) were signifi cantly associated with adding-on. Conclusion: Since the residual apical translation of the main thoracic curve and the lowest instrumented vertebra more cranial to the last touching vertebra were signifi cantly associated with addingon, surgeons may need to obtain the maximum reduction of the apical translation of the main thoracic curve and to extend the LIV at least to the LTV to avoid postoperative adding-on. Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

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Risk factors for complications associated with growing-rod surgery for early-onset scoliosis

Watanabe Kota, Uno Koki, Suzuki Teppei, Kawakami Noriaki, Tsuji Taichi, Yanagida Haruhisa, Ito Manabu, Hirano Toru, Yamazaki Ken, Minami Shohei, Kotani Toshiaki, Taneichi Hiroshi, Imagama Shiro, Takeshita Katsushi, Yamamoto Takuya, Matsumoto Morio

Spine 38 （ 8 ） 2013年04月

ISSN 0362-2436

STUDY DESIGN.: A retrospective multicenter study. OBJECTIVE.: To identify risk factors for postoperative complications associated with growing-rod (GR) surgery for early-onset scoliosis (EOS). SUMMARY OF BACKGROUND DATA.: Results and complications of GR surgery for EOS have not been adequately studied. METHODS.: We evaluated clinical and radiographical results from 88 patients with EOS who underwent GR surgery in 12 spine centers in Japan. The mean age at the time of initial surgery was 6.5 ± 2.2 years (range, 1.5-9.8 yr) and the mean follow-up period was 3.9 ± 2.6 years (range, 2.0-12.0 yr). Risk factors for postoperative complications were analyzed using binomial multiple logistic regression analysis. We considered the potential factors of sex, age, number of rod-lengthening procedures, whether a pedicle screw foundation was used, the uppermost level of the proximal foundation and lowermost level of the distal foundation, Cobb angles of the proximal thoracic, main thoracic, and lumbar curves, and the kyphosis angles in the proximal, main thoracic, thoracolumbar, and lumbar spine. Kaplan-Meier analysis was used to determine the complication-free survival rate of GR surgery as a function of the number of surgical procedures. RESULTS.: Complications affected 50 of the patients (57%) and were associated with 119 of 538 surgical procedures, with 86 implant-related failures (72%), 19 infections (16%), 3 neurological impairments (3%), and 11 other complications. The most frequent implant-related failure was dislodged implant (71%) and 95% of the dislodgements occurred at the proximal foundation. Kaplan-Meier analysis demonstrated a linear decrease in complication-free rates as the number of rod-lengthening procedures increased. Binomial multiple logistic regression analysis found the following significant independent risk factors: 6 or more rod-lengthening procedures (odds ratio [OR], 6.534), an increase of every 20 in the proximal thoracic Cobb angle (OR, 3.091), and an increase of every 25 in the lumbar lordosis angle (OR, 2.607) in the preoperative condition. CONCLUSION.: Increases in the upper thoracic scoliotic curve, thoracic kyphosis, and number of rod-lengthening procedures are positively associated with an increased risk of complications after GR surgery for EOS.Level of Evidence: 4 © 2013, Lippincott Williams & Wilkins.

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A replication study for association of 5 single nucleotide polymorphisms with curve progression of adolescent idiopathic scoliosis in japanese patients

Spine 38 （ 7 ） 571 - 575 2013年04月

ISSN 0362-2436

STUDY DESIGN.: A genetic association study of single nucleotide polymorphisms (SNPs) previously reported to be associated with curve progression of adolescent idiopathic scoliosis (AIS). OBJECTIVE.: To determine whether the association of 5 SNPs with curve progression reported in Chinese with AIS are replicated in Japanese patients with AIS. SUMMARY OF BACKGROUND DATA.: AIS is a common spinal deformity and has a strong genetic predisposition. Predicting curve progression is important in clinical practice. The progression of AIS is reported to be associated with a number of genes. Associations with neurotrophin 3, G protein-coupled estrogen receptor, and tissue inhibitor of metalloproteinase 2 have been reported in Han Chinese with AIS; however, there has been no replication study for them. METHODS.: We recruited 2117 patients with AIS with a Cobb angle of 10 or greater of scoliosis curves. They were grouped into progression and nonprogression groups according to their scoliosis curves. Patients whose scoliotic curves were 40 or greater were included in the progression group, and those whose scoliotic curves were less than 30 and had reached skeletal maturation in the nonprogression group. We evaluated the association of 5 SNPs (rs11063714 in neurotrophin 3, rs3808351, rs10269151, and rs4266553 in G protein-coupled estrogen receptor, and rs8179090 in tissue inhibitor of metalloproteinase 2 with curve progression by comparing risk allele frequencies between the 2 groups and the mean Cobb angle for each genotype. RESULTS.: We evaluated the progression (N = 880) and nonprogression (N = 492) subjects, and their risk allele frequencies were not significantly different. The mean Cobb angle for each genotype also did not have statistical difference. We found no replication of the association on AIS curve progression in any of the SNPs. CONCLUSION.: The associations of the 5 SNPs with progression of AIS curve are not definite. Large-scale association studies based on appropriate criteria for progression would be necessary to identify SNPs associated with the curve progression. © 2013, Lippincott Williams & Wilkins.

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Short fusion strategy for lenke type 1 thoracic curve using pedicle screw fixation

Matsumoto Morio, Watanabe Kota, Ogura Yoji, Okada Eijiro, Hosogane Naobumi, Chiba Kazuhiro, Toyama Yoshiaki

Journal of Spinal Disorders and Techniques 26 （ 2 ） 93 - 97 2013年04月

ISSN 1536-0652

STUDY DESIGN: A retrospective case-control study OBJECTIVE: Short fusion using pedicle screws (PSs) with an attempt to attain maximum correction of the main thoracic curve was conducted for patients with a Lenke type 1 curve, to prevent postoperative left shoulder elevation. The outcomes were compared with those of conventional surgery. SUMMARY OF BACKGROUND DATA: Excessive correction of the main thoracic curve by PSs causes problematic left shoulder elevation even in a Lenke type 1 curve. METHODS: Thirty-eight patients (3 male, 35 female, mean age 16.2 years, mean follow-up 24 mo) with Lenke type 1 curve underwent posterior corrective surgery using PSs. The upper instrumented vertebra was 1 level below the end vertebra in 14 patients (short, S group), and it was at the end vertebra in 24 patients (conventional, C group). There was no difference in the preoperative Cobb angle (51.8 vs. 58.0) or curve flexibility (49.7 vs. 46.1) between the 2 groups. Radiographic results, perioperative data, and scoliosis research society 22 scores were compared between the 2 groups. RESULTS: The postoperative Cobb angle of the main curve after surgery was 13.2±5.7 degrees in the S group and 10.6±7.3 degrees in the C group (not significant). The clavicle angle was -2.1±2.8 degrees versus -2.7±2.6 degrees before surgery (not significant), and 0.8±2.3 versus 3.8±2.4 after surgery (P<0.05). The number of fused vertebrae, mean surgical time, and estimated blood loss were significantly lower in the S group than in the C group. The scoliosis research society 22 score at follow-up was not different between the 2 groups. CONCLUSIONS: The short fusion strategy for a Lenke type 1 curve can produce equivalent correction of the main curve and clinical outcomes to conventional fusion strategy with less surgical time and blood loss, while maintaining better shoulder balance. Copyright © 2012 by Lippincott Williams & Wilkins.

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Curve progression after decompression surgery in patients with mild degenerative scoliosis

Hosogane Naobumi, Watanabe Kota, Kono Hitoshi, Saito Masashi, Toyama Yoshiaki, Matsumoto Morio

Journal of Neurosurgery: Spine 18 （ 4 ） 321 - 326 2013年04月

ISSN 1547-5654

Object. The authors undertook this study to evaluate curve progression, risk factors for curve progression, and outcomes after decompression surgery in patients with degenerative lumbar scoliosis with minimal to moderate curvature. Methods. Of 852 patients with lumbar canal stenosis treated by posterior decompression surgery, 50 patients had a lumbar curve greater than 10° at final follow-up. These patients were divided into 2 groups according to curve progression during the follow-up period: the P group (11 patients), with a curve progression of more than 5°, and the NP group (39 patients), with a curve progression of 5° or less. The authors compared preoperative parameters in these 2 groups to elucidate risk factors associated with curve progression and other surgical outcomes. Results. The average lumbar curve progression in the total group of 50 patients was 3.4° ± 3.9° (range -2.0° to 22.0°). In the P group the average curve progression was 8.5°, and in the NP group it was 2.0°. Multivariate logistic regression analysis showed no significant association between curve progression and any of the potential risk factors evaluated (including curve magnitude, decompression method, and degenerative intervertebral disc changes). Spur formation, evaluated with the Nathan classification at the concave side of the curve, tended to be greater in the P group, although the difference was not statistically significant. There was no significant difference in revision surgery rate, and none of the patients required arthrodesis due to curve progression. Clinical outcomes, evaluated with the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire and the Scoliosis Research Society 22-question questionnaire, were also similar in the 2 groups. Conclusions. Surgical outcomes did not deteriorate in the P group. While curve progression after decompression surgery could not be predicted from the preoperative factors considered, spur formation at the concave side of the curve may be a candidate factor. The results of this study indicate that spinal fixation to halt deformity progression is not always necessary if the patient's pathological condition derives mainly from canal stenosis. Copyright © 1944-2012 American Association of Neurological Surgeons.

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Response

Hosogane Naobumi, Watanabe Kota, Kono Hitoshi, Saito Masashi, Toyama Yoshiaki, Matsumoto Morio

Journal of Neurosurgery: Spine 18 （ 4 ） 320 2013年04月

ISSN 1547-5654

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Tandem age-related lumbar and cervical intervertebral disc changes in asymptomatic subjects

Matsumoto Morio, Okada Eijiro, Toyama Yoshiaki, Fujiwara Hirokazu, Momoshima Suketaka, Takahata Takeshi

European Spine Journal 22 （ 4 ） 708 - 713 2013年04月

ISSN 0940-6719

Purpose To investigate the frequency of tandem lumbar and cervical intervertebral disc degeneration in asymptomatic subjects. Methods We evaluated magnetic resonance imaging (MRI) results from 94 volunteers (48 men and 46 women; mean age 48 years) for age-related intervertebral disc degeneration in the lumbar and cervical spine. Results MRI indicated degenerative changes in the lumbar spine in 79 subjects (84 %), with decreased disc signal intensity in 74.5 %, posterior disc protrusion in 78.7 %, anterior compression of the dura in 81.9 %, disc space narrowing in 21.3 %, and spinal canal stenosis in 12.8 %. These findings were more common in older subjects at caudal levels. MRI showed degenerative changes in both the lumbar and cervical spine in 78.7 % of the volunteers. Conclusions Degenerative findings in both the lumbar and cervical spine, suggesting tandem disc degeneration, was common in asymptomatic subjects. These results provide normative data for evaluating patients with degenerative lumbar and cervical disc diseases. © Springer-Verlag 2012.

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Curve progression. Response.

Hosogane Naobumi, Watanabe Kota, Kono Hitoshi, Saito Masashi, Toyama Yoshiaki, Matsumoto Morio

Journal of neurosurgery. Spine 18 （ 4 ） 320 2013年04月

ISSN 1547-5654

Novel chelate-setting calcium-phosphate cements fabricated with wet-synthesized hydroxyapatite powder

Konishi Toshiisa, Horiguchi Yukiko, Mizumoto Minori, Honda Michiyo, Oribe Kazuya, Morisue Hikaru, Ishii Ken, Toyama Yoshiaki, Matsumoto Morio, Aizawa Mamoru

Journal of Materials Science: Materials in Medicine 24 （ 3 ） 611 - 621 2013年03月

ISSN 0957-4530

The hydroxyapatite (HAp) powder preparation process was optimized to fabricate inositol phosphate-HAp (IP6-HAp) cement with enhanced mechanical properties. Starting HAp powders were synthesized via a wet chemical process. The effect of the powder preparation process on the morphology, crystallinity, median particle size, and specific surface area (SSA) of the cement powders was examined, together with the mechanical properties of the resulting cement specimens. The smallest crystallite and median particle sizes, and the highest SSA were obtained from ball-milling of as-synthesized HAp powder under wet conditions and then freeze-drying. IP6-HAp cement fabricated with this powder had a maximum compressive strength of 23.1 ± 2.1 MPa. In vivo histological studies using rabbit models revealed that the IP6-HAp cements were directly in contact with newly formed and host bones. Thus, the present chelate-setting HAp cement is promising for application as a novel paste-like artificial bone. © 2012 Springer Science+Business Media New York.

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Cervical intramedullary ependymoma masquerading as cervical spondylotic myelopathy on MRI analysis

Tsuji Osahiko, Nakamura Masaya, Fujiyoshi Kanehiro, Ishii Ken, Watanabe Kota, Hosogane Naobumi, Tsuji Takashi, Momoshima Suketaka, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Journal of Orthopaedic Science 18 （ 2 ） 355 - 358 2013年03月

ISSN 0949-2658

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Surgical correction of severe cervical kyphosis in patients with neurofibromatosis Type 1

Kawabata Soya, Watanabe Kota, Hosogane Naobumi, Ishii Ken, Nakamura Masaya, Toyama Yoshiaki, Matsumoto Morio

Journal of Neurosurgery: Spine 18 （ 3 ） 274 - 279 2013年03月

ISSN 1547-5654

Severe cervical kyphosis requiring surgical treatment is rare in patients with neurofibromatosis Type 1 (NF1). When it occurs, however, dystrophic changes in the vertebrae make surgical correction and fusion of the deformity extremely difficult. The authors report on 3 cases of severe cervical kyphosis associated with NF1 that were successfully treated with combined anterior and posterior correction and fusion. All patients underwent halo-gravity traction for approximately 1 month prior to surgery to correct the deformity gradually. Posterior correction and fusion were performed with segmental spinal instrumentation consisting of lateral mass screws, lamina screws, pedicle screws, and polyethylene tape for sublaminar wiring. Anterior spinal fusion was performed using a fibula strut to induce solid bone fusion. All patients used a halo vest for postoperative external fixation. Preoperative CT scans showed dystrophic cervical spine changes, and MR images demonstrated extensive neurofibromas outside the cervical spine in all 3 patients. The preoperative kyphotic angles were as follows: Case 1, 140°; Case 2, 81°; and Case 3, 72°; after halo-gravity traction, the kyphosis angles improved to 50°, 55°, and 51°, respectively; and after surgery, they were 50°, 15°, and 27°, respectively. Solid bone union was observed in all patients at the latest follow-up. All three patients experienced postoperative complications consisting of superficial infection, severe pneumonia, and partial dislocation of the distal fibula graft after removing the halo vest, in one patient each. Although dystrophic cervical vertebral changes in these patients with NF1 complicated the correction of severe cervical kyphosis, the use of preoperative halo-gravity traction, a combination of spinal instrumentations, an anterior strut bone graft, and postoperative halo-vest fixation made it possible to correct the kyphosis, maintain the correction, and achieve solid bone fusion. © 2013 AANS.

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Minimally invasive endoscopic resection of a solitary bone cyst of the lumbar vertebrae

Matsubayashi Kohei, Tsuji Osahiko, Watanabe Kota, Hosogane Naobumi, Tsuji Takashi, Ishii Ken, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Neurosurgery Quarterly 23 （ 1 ） 66 - 69 2013年02月

ISSN 1050-6438

Solitary bone cysts of the lumbar vertebrae are extremely rare. We report a 20-year-old man, who presented with a 5-year history of persistent low back pain. Radiographic examination, magnetic resonance imaging, and subsequent computed tomography revealed a well-circumscribed osteolytic and cystic lesion at the right pedicle of the L3 vertebra. On the basis of the radiologic findings, a simple bone cyst was considered the most probable diagnosis. The patient underwent a minimally invasive operation with the assistance of an endoscope. The gross total curettage resection of the lesion including the cyst walls was accomplished, followed by a combined graft consisting of granulated β-tricalcium phosphate and autologous iliac crest cancellous bone. At the 1-year follow-up, the patient's symptoms were resolved, bone union at the lesion site had been achieved, and he had returned to his previous level of physical activity. Copyright © 2013 by Lippincott Williams & Wilkins.

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The IRE1α-XBP1 pathway positively regulates parathyroid hormone (PTH)/PTH-related peptide receptor expression and is involved in PTH-induced osteoclastogenesis

Tohmonda Takahide, Yoda Masaki, Mizuochi Hiroshi, Morioka Hideo, Matsumoto Morio, Urano Fumihiko, Toyama Yoshiaki, Horiuchi Keisuke

Journal of Biological Chemistry 288 （ 3 ） 1691 - 1695 2013年01月

ISSN 0021-9258

Background: XBP1 is a transcription factor that is activated by one of the ER stress sensors, IRE1. Results: XBP1 promotes the expression of PTH/PTH-related peptide receptor in osteoblasts and renders these cells responsive to PTH. Conclusion: The IRE1-XBP1 pathway indirectly regulates PTH-induced osteoclastogenesis. Significance: This study may be the first to reveal the potential link between ER stress sensors and the regulation of osteoclastogenesis. To address the "endoplasmic reticulum stress" triggered by the burden of protein synthesis, the unfolded protein response is induced during osteoblast differentiation. In this study, we show that the transcription of parathyroid hormone (PTH)/PTH-related peptide receptor (PTH1R) is regulated by one of the endoplasmic reticulum-stress mediators, the IRE1α-XBP1 pathway, in osteoblasts. We found that the increase in Pth1r transcription upon BMP2 treatment is significantly suppressed in mouse embryonic fibroblasts lacking IRE1α. As expected, gene silencing of Ire1α and Xbp1 resulted in a decrease in Pth1r transcripts in BMP2-treated embryonic fibroblasts. We identified two potential binding sites for XBP1 in the promoter region of Pth1r and found that XBP1 promotes the transcription of Pth1r by directly binding to those sites. Moreover, we confirmed that the gene silencing of Xbp1 suppresses PTH-induced Rankl expression in primary osteoblasts and thereby abolishes osteoclast formation in an in vitro model of osteoclastogenesis. Thus, the present study reveals potential involvement of the IRE1-XBP1 pathway in PTH-induced osteoclastogenesis through the regulation of PTH1R expression. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

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Systemic Overexpression of TNFα-converting Enzyme Does Not Lead to Enhanced Shedding Activity In Vivo

Yoda Masaki, Kimura Tokuhiro, Tohmonda Takahide, Morioka Hideo, Matsumoto Morio, Okada Yasunori, Toyama Yoshiaki, Horiuchi Keisuke

PLoS ONE 8 （ 1 ） 2013年01月

TNFα-converting enzyme (TACE/ADAM17) is a membrane-bound proteolytic enzyme with a diverse set of target molecules. Most importantly, TACE is indispensable for the release and activation of pro-TNFα and the ligands for epidermal growth factor receptor in vivo. Previous studies suggested that the overproduction of TACE is causally related to the pathogenesis of inflammatory diseases and cancers. To test this hypothesis, we generated a transgenic line in which the transcription of exogenous Tace is driven by a CAG promoter. The Tace-transgenic mice were viable and exhibited no overt defects, and the quantitative RT-PCR and Western blot analyses confirmed that the transgenically introduced Tace gene was highly expressed in all of the tissues examined. The Tace-transgenic mice were further crossed with Tace^-/+ mice to abrogate the endogenous TACE expression, and the Tace-transgenic mice lacking endogenous Tace gene were also viable without any apparent defects. Furthermore, there was no difference in the serum TNFα levels after lipopolysaccharide injection between the transgenic mice and control littermates. These observations indicate that TACE activity is not necessarily dependent on transcriptional regulation and that excess TACE does not necessarily result in aberrant proteolytic activity in vivo. © 2013 Yoda et al.

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Long-term surgical outcomes of cervical dumbbell neurinomas

Nakamura Masaya, Iwanami Akio, Tsuji Osahiko, Hosogane Naobumi, Watanabe Kota, Tsuji Takashi, Ishii Ken, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Journal of Orthopaedic Science 18 （ 1 ） 8 - 13 2013年01月

ISSN 0949-2658

Study design: Retrospective case series. Objective: To evaluate our treatment strategy for cervical dumbbell neurinoma. Summary of background data: In treating cervical dumbbell neurinoma, possible difficulties include reoperation due to recurrent tumor, denervation due to nerve root resection, and postoperative spinal deformity due to extensive bony removal. Methods: We reviewed 75 cases of cervical dumbbell neurinoma that were treated surgically between 1985 and 2006. Postoperative neurological deficits, effects of surgical margins on tumor recurrence, and surgical complications were investigated retrospectively. Results: Sensory and motor deficits due to resection of specific nerve roots appeared temporarily in 33 and 23 % of all cases, and persisted in 8 and 8 % at final evaluation, respectively. Total, subtotal, and partial resection was performed in 57, 13, and 5 cases, respectively. The total resection rate was low in the tumors that had large extraforaminal components. Of the subtotally resected 13 cases, only two cases of high tumor-growth rate required re-operation or showed tumor growth. Among the five partially resected cases, re-operation was necessary in two cases 13 and 15 years later because of aggravated neurological symptoms due to tumor growth. Two patients who underwent C2 laminectomy developed kyphosis, and three patients who underwent facet joint resection and curettage of vertebral body lesions developed scoliosis. Conclusion: Total resection should be attempted for cervical dumbbell tumors. In cases where total resection was potentially of high risk, however, subtotal resection (within the capsule) was found to be a practical choice yielding favorable long-term outcome when the tumor growth rate (MIB-1 index) was low. © 2012 The Japanese Orthopaedic Association.

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A genome-wide sib-pair linkage analysis of Ossification of the posterior longitudinal ligament of the spine

Karasugi Tatsuki, Nakajima Masahiro, Ikari Katsunori, Tsuji Takashi, Matsumoto Morio, Chiba Kazuhiro, Uchida Kenzo, Kawaguchi Yoshiharu, Mizuta Hiroshi, Ogata Naoshi, Iwasaki Motoki, Maeda Shingo, Numasawa Takuya, Abumi Kuniyoshi, Kato Tsuyoshi, Ozawa Hiroshi, Taguchi Toshihiko, Kaito Takashi, Neo Masashi, Yamazaki Masashi, Tadokoro Nobuaki, Yoshida Munehito, Nakahara Shinnosuke, Endo Kenji, Imagama Shiro, Demura Satoru, Sato Kimiaki, Seichi Atsushi, Ichimura Shoichi, Watanabe Masahiko, Watanabe Kei, Nakamura Yutaka, Mori Kanji, Baba Hisatoshi, Toyama Yoshiaki, Ikegawa Shiro

Journal of Bone and Mineral Metabolism 31 （ 2 ） 136 - 143 2013年

ISSN 0914-8779

Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common musculoskeletal disease among people after middle age. The OPLL presents with serious neurological abnormalities due to compression of the spinal cord and nerve roots. The OPLL is caused by genetic and environment factors; however, its etiology and pathogenesis still remain to be elucidated. To determine the susceptibility loci for OPLL, we performed a genome-wide linkage study using 214 affected sib-pairs of Japanese. In stratification analyses for definite cervical OPLL, we found loci with suggestive linkage on 1p21, 2p22-2p24, 7q22, 16q24 and 20p12. Fine mapping using additional markers detected the highest non-parametric linkage score (3.43, P = 0.00027) at D20S894 on chromosome 20p12 in a subgroup that had no complication of diabetes mellitus. Our result would shed a new light on genetic aspects of OPLL. © The Japanese Society for Bone and Mineral Research and Springer Japan 2012.

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Fabrication of novel biodegradable α-tricalcium phosphate cement set by chelating capability of inositol phosphate and its biocompatibility

Konishi Toshiisa, Mizumoto Minori, Honda Michiyo, Horiguchi Yukiko, Oribe Kazuya, Morisue Hikaru, Ishii Ken, Toyama Yoshiaki, Matsumoto Morio, Aizawa Mamoru

Journal of Nanomaterials 2013 2013年

ISSN 1687-4110

Biodegradable α-tricalcium phosphate (α-TCP) cement based on the chelate-setting mechanism of inositol phosphate (IP6) was developed. This paper examined the effect of the milling time of α-TCP powder on the material properties of the cement. In addition, biocompatibility of the result cement in vitro using osteoblasts and in vivo using rabbit models will be studied as well. The α-TCP powders were ballmilled using ZrO₂ beads in pure water for various durations up to 270 minutes, with a single-phase α-TCP obtained at ballmilling for 120 minutes. The resulting cement was mostly composed of α-TCP phase, and the compressive strength of the cement was 8.5±1.1 MPa, which suggested that the cements set with keeping the crystallite phase of starting cement powder. The cell-culture test indicated that the resulting cements were biocompatible materials. In vivo studies showed that the newly formed bones increased with milling time at a slight distance from the cement specimens and grew mature at 24 weeks, and the surface of the cement was resorbed by tartrate-resistant acid phosphatase-(TRAP-)positive osteoclast-like cells until 24 weeks of implantation. The present α-TCP cement is promising for application as a novel paste-like artificial bone with biodegradability and osteoconductivity. © 2013 Toshiisa Konishi et al.

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Metastasis of intracranial meningeal hemangiopericytoma to thoracic spine 17 years after surgical excision

Fukuda Yoshitsugu, Watanabe Kota, Toyama Yoshiaki, Mikami Shuji, Matsumoto Morio

Journal of Orthopaedic Science 1 - 5 2013年

ISSN 0949-2658

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Recurrence of lumbar disc herniation after microendoscopic discectomy

Matsumoto Morio, Watanabe Kota, Hosogane Naobumi, Tsuji Takashi, Ishii Ken, Nakamura Masaya, Chiba Kazuhiro, Toyama Yoshiaki

Journal of Neurological Surgery, Part A: Central European Neurosurgery 74 （ 4 ） 222 - 227 2013年

ISSN 2193-6315

Background Although microendoscopic discectomy (MED) is a minimally invasive surgical method for lumbar disc herniation (LDH), early postoperative recurrence may outweigh that advantage. The purpose of the present study was to retrospectively investigate the recurrence rate after MED for LDH and to determine the risk factors for recurrence in patients treated by a single surgeon. Materials and Methods The study included 344 patients who underwent MED (213 males and 131 females; mean age, 39.3 years; age range, 11-82 years; mean follow-up, 3.6 years; follow-up range, 2.0-6.5 years). The clinical outcomes were evaluated using the Japanese Orthopedic Association Score for Low Back Pain (JOA score). Recurrence factors investigated by logistic regression analysis included age; sex; level, laterality, and classified type of LDH; occupation; sports activity; and learning curve of the surgeon. Results LDH recurrence was observed in 37 patients (10.8%). It was observed at the same level in the ipsilateral side as the original LDH in 30 patients, in the contralateral side in three patients, and at a level adjacent to the original level in four patients. The mean time interval between MED and the recurrence was 16.6 months (range, 0.5-52 months). Twenty patients (54.1%) developed recurrence within 1 year after MED. Twenty-two patients (59.5%) were treated by revision surgery (MED in 20 patients and microdiscectomy in two patients), and 15 patients (40.5%) were treated conservatively. The mean JOA score of all the patients was 14.7 ± 3.5 before surgery and 26.5 ± 2.2 at the final follow-up, yielding an average recovery rate of 82.3 ± 15.7%. The recovery rate was 83.1 ± 14.8% in patients without recurrence and 75.7 ± 20.4% in patients with recurrence (p = 0.006). By logistic regression analysis, we identified migration of LDH as a significant factor related to recurrence. The patients with caudal migration of LDH had recurrence more frequently (19.0%) than those with rostral migration (12.5%) or without migration (10.2%) (p = 0.04; odds ratio, 2.0; 95% confidence interval, 1.0-3.8). Conclusion The recurrence rate and reoperation rate for LDH after MED were comparable to those of conventional discectomy. More than half of the cases of recurrence occurred at an early postoperative phase, and patients with caudally migrated LDH experienced recurrence significantly more often than those with rostrally migrated or nonmigrated LDH. ©2013 Georg Thieme Verlag KG Stuttgart, New York.

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Acute respiratory failure due to hemothorax after posterior correction surgery for adolescent idiopathic scoliosis

Ogura Yoji, Watanabe Kota, Hosogane Naobumi, Toyama Yoshiaki, Matsumoto Morio

BMC Musculoskeletal Disorders 14 2013年

Background: Although posterior correction and fusion surgery using pedicle screws carries the risk of vascular injury, a massive postoperative hemothorax in a patient with adolescent idiopathic scoliosis (AIS) is quite rare. We here report a case of a 12-year-old girl with AIS who developed a massive postoperative hemothorax. Case presentation. The patient had a double thoracic curve with Cobb angles of 63° at T2-7 and 54° at T7-12. Posterior correction and fusion surgery was performed using a segmental pedicle screw construct placed between T2 and T12. Although the patient's respiration was stable during the surgery, 20 minutes after removing the trachea tube, the patient's pulse oximetry oxygen saturation suddenly decreased to 80%. A contrast CT scan showed a massive left hemothorax, and a drainage tube was quickly inserted into the chest. The patient was re-intubated and a positive end-expiratory pressure of 5 cmH§ssub§2§esub§O applied, which successfully stopped the bleeding. The patient was extubated 4 days after surgery without incident. Based on contrast CT scans, it was suspected that the hemothorax was caused by damage to the intercostal arteries or branches during pedicle probing on the concave side of the upper thoracic curve. Extensive post-surgical blood tests, echograms, and CT and MRI radiographs did not detect coagulopathy, pulmonary or vascular malformation, or any other possible causative factors. Conclusion: This case underscores the potential risk of massive hemothorax related to thoracic pedicle screw placement, and illustrates that for this serious complication, respiratory management with positive airway pressure, along with a chest drainage tube, can be an effective treatment option. © 2013 Ogura et al.; licensee BioMed Central Ltd.

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Surgical correction of severe kyphoscoliosis resulting in a neurological complication in Marshall-Smith syndrome

Cao Kai, Watanabe Kota, Hosogane Naobumi, Toyama Yoshiaki, Matsumoto Morio

Journal of Orthopaedic Science 1 - 4 2013年

ISSN 0949-2658

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Comparative study on bioresorbability of chelate-setting cements with various calcium-phosphate phase using rabbit model

Konishi Toshiisa, Takahashi Shuhei, Mizumoto Minori, Honda Michiyo, Kida Koki, Horiguchi Yukiko, Oribe Kazuya, Ishii Ken, Morisue Hikaru, Toyama Yoshiaki, Matsumoto Morio, Aizawa Mamoru

167 - 172 2013年

We have developed novel calcium-phosphate cements (CPCs) based on the chelate-setting mechanism of inositol phosphate (IP6) using hydroxyapatite (HAp), β-tricalcium phosphate (β-TCP) and α-TCP as starting materials. These cements (IP6-HAp, IP6-β-TCP and IP6-α-TCP cements) have different bioresorbability due to the chemical composition of starting materials. In the present study, biocompatibility and bioresorbability of the above three cements and commercially available cement (BiopexR-R) was histologically evaluated in vivo using rabbit model for 4, 8, and 24 weeks, in addition to their dissolution in vitro. The dissolution of these cements increased in the order of IP6-HAp, IP6-β-TCP and IP6-α-TCP cements. The newly-formed bones were directly in contact with both the IP6-HAp and BiopexR-R cement specimens. As for the IP6-β-TCP and IP6-α-TCP cements, newly-formed bones were formed time-dependently slightly apart from the cement specimens. Resorption rate for BiopexR-R, IP6-HAp, IP6-β-TCP, and IP6-α-TCP cements after 24 weeks implantation were of 7.2, 5.0, 13.7, and 16.2%, respectively, compared to original cements. The present chelate-setting cements with different bioresorbability are promising candidates for application as the novel CPCs. © (2013) Trans Tech Publications, Switzerland.

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Comparison of stainless steel and titanium alloy instruments in posterior correction and fusion surgery for adolescent idiopathic scoliosis-prospective cohort study with minimum 2-year follow-up

Okada Eijiro, Watanabe Kota, Hosogane Naobumi, Shiono Yuta, Takahashi Yohei, Nishiwaki Yuji, Chiba Kazuhiro, Toyama Yoshiaki, Matsumoto Morio

Journal of Medical and Biological Engineering 33 （ 3 ） 325 - 330 2013年

ISSN 1609-0985

This prospective study compares the radiographic and clinical results of posterior correction and fusion surgery for adolescent idiopathic scoliosis (AIS) using stainless steel and titanium alloy instruments. The subjects consisted of 65 AIS patients who underwent posterior correction and fusion surgeries using a 5.5-mm-diameter rod at a single institution. Of these, 27 patients were treated using stainless steel instruments (S group) and 38 were treated using titanium alloy instruments (T group). The mean age at the time of surgery was 14.4 ± 3.5 years. The radiographic findings, intra-operative time, estimated blood loss, perioperative complications, and SRS-22 (a patient questionnaire used in the clinical evaluation of idiopathic scoliosis outcomes) were examined. The mean preoperative Cobb angle of the major curve was 62.5 ± 17.2° in the S group and 57.8 ± 13.2° in the T group (p = 0.407). Postoperatively, the curves were corrected to 11.2 ± 10.5° and 10.3 ± 8.5° (p = 0.384), with mean correction rates of 83.4 ± 12.2% and 83.1 ± 11.6% (p = 0.940), respectively. At the final follow-up, although the mean correction loss was slightly larger in the S group (4.4 ± 5.2°) compared with that in the T group (2.3 ± 5.5°), the values were not significantly different (p = 0.118). The coronal balance and sagittal balance were also not significantly different between the two groups at the final follow-up. The function, pain, and mental health sub-scores and the total score for SRS-22 show a tendency for better outcomes in the T group; however, there were no significant differences between the two groups. Thus, there was no statistical difference in radiographical and clinical outcomes between AIS patients treated surgically using stainless steel instruments and those treated using titanium alloy instruments.

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Morphometric analysis of the lumbar intervertebral foramen in patients with degenerative lumbar scoliosis by multidetector-row computed tomography

Kaneko Yasuhito, Matsumoto Morio, Takaishi Hironari, Nishiwaki Yuji, Momoshima Suketaka, Toyama Yoshiaki

European Spine Journal 21 （ 12 ） 2594 - 2602 2012年12月

ISSN 0940-6719

Purpose: How the lumbar neural foramina are affected by segmental deformities in patients in whom degenerative lumbar scoliosis (DLS) is unknown. Here, we used multidetector-row computed tomography (MDCT) to measure the morphology of the foramina in three dimensions, which allowed us to elucidate the relationships between foraminal morphology and segmental deformities in DLS. Methods: In 77 DLS patients (mean age, 69.4) and 19 controls (mean age, 69), the foraminal height (FH), foraminal width (FW), posterior disc height (PDH), interval between the pedicle and superior articular process (P-SAP), and cross-sectional foraminal area (FA) were measured on reconstructed MDCT data, using image-editing software, at the entrance, minimum-area point, and exit of each foramen. The parameters of segmental deformity included the intervertebral wedging angle and anteroposterior and lateral translation rate, measured on radiographs, and the vertebral rotation angle, measured using reconstructed MDCT images. Results: The FH, PDH, P-SAP, and FA were smaller at lower lumbar levels and on the concave side of intervertebral wedging (p < 0.05). In the DLS patients, the FH, P-SAP, and FA were significantly smaller than for the control group at all three foraminal locations and every lumbar level (p < 0.05). Intervertebral wedging strongly decreased the FA of the concave side (p < 0.05). Anteroposterior translation caused the greatest reduction in P-SAP (p < 0.05). Vertebral rotation decreased the P-SAP and FA at the minimum-area point on the same side as the rotation (p < 0.05). Conclusion: The new analysis method proposed here is useful for understanding the pathomechanisms of foraminal stenosis in DLS patients. © 2012 Springer-Verlag.

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Transoral anterior approach using median mandibular splitting in upper spinal tumor extirpation

Hiromasa Kawana, Shin Kato, Seiji Asoda, Akihiko Koike, Ryotaro Iwasaki, Morio Matsumoto, Kota Watanebe, Yorihisa Imanishi, Kaoru Ogawa, Taneaki Nakagawa

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 114 （ 5 ） 2012年11月

ISSN 2212-4403

Objective: Transoral approach from the anterior direction is necessary if an upper spinal tumor is too big to extirpate via the posterior approach alone. To obtain a good anterior view of the surgical field, the mandible, tongue, and soft palate have to be split, and we developed a criterion to select the surgical strategy. Study Design: We indicated a decision-making process of splitting techniques and indications with actual cases and review of literatures. Result: Tumors were located from the level of C1 to the lower part of C3. Computerized tomography and magnetic resonance imaging were important to decide approaches. The orthopedic surgical team invited oral and maxillofacial surgeons team to assist in all transoral anterior approach cases. Conclusions: Vertical splitting of the mandible, incising the skin of the mental region, and splitting the middle of the tongue were combined according to the position of the spinal tumor. © 2012 Elsevier Inc. All rights reserved.

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A method for quantifying intervertebral disc signal intensity on T2-weighted imaging

Nagashima Masaki, Abe Hitoshi, Amaya Kenji, Matsumoto Hideo, Yanaihara Hisashi, Nishiwaki Yuji, Toyama Yoshiaki, Matsumoto Morio

Acta Radiologica 53 （ 9 ） 1059 - 1065 2012年11月

ISSN 0284-1851

Background: Quantification of intervertebral disc degeneration based on intensity of the nucleus pulposus in magnetic resonance imaging (MRI) often uses the mean intensity of the region of interest (ROI) within the nucleus pulposus. However, the location and size of ROI have varied in different reports, and none of the reported methods can be considered fully objective. Purpose: To develop a more objective method of establishing ROIs for quantitative evaluation of signal intensity in the nucleus pulposus using T2-weighted MRI. Material and Methods: A 1.5-T scanner was used to obtain T2-weighted mid-sagittal images. A total of 288 intervertebral discs from 48 patients (25 men, 23 women) were analyzed. Mean age was 47.4 years (range, 17-69 years). All discs were classified into five grades according to Pfirrmann et al. Discs in grades I and II were defined as bright discs, and discs in grades IV and V were defined as dark discs. Eight candidate methods of ROI determination were devised. The method offering the highest degree of discrimination between bright and dark discs was investigated among these eight methods. Results: The method with the greatest degree of discrimination was as follows. The quadrangle formed by anterior and posterior edges of the upper and lower end plates in contact with the intervertebral disc to be measured was defined as the intervertebral area. A shape similar to the intervertebral area but with one-quarter the area was drawn. The geometrical center of the shape was matched to the center of intensity, and this shape was then used as the ROI. Satisfactory validity and reproducibility were obtained using this method. Conclusion: The present method offers adequate discrimination and could be useful for longitudinal tracking of intervertebral disc degeneration with sufficient reproducibility.

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Comparative study of spinopelvic sagittal alignment between patients with and without degenerative spondylolisthesis

Funao Haruki, Tsuji Takashi, Hosogane Naobumi, Watanabe Kota, Ishii Ken, Nakamura Masaya, Chiba Kazuhiro, Toyama Yoshiaki, Matsumoto Morio

European Spine Journal 21 （ 11 ） 2181 - 2187 2012年11月

ISSN 0940-6719

Abstract Introduction To date, few studies have focused on spinopelvic sagittal alignment as a predisposing factor for the development of degenerative spondylolisthesis (DS). The objectives of this study were to compare differences in spinopelvic sagittal alignment between patients with or without DS and to elucidate factors related to spinopelvic sagittal alignment. Materials and methods A total of 100 patients with or without DS who underwent surgery for lumbar spinal canal stenosis were assessed in this study. Fifty patients with DS (DS group) and 50 age- and gender-matched patients without DS (non-DS group) were enrolled. Spinopelvic parameters including pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), L4 slope, L5 slope, thoracic kyphosis (TK), lumbar lordosis (LL) and sagittal balance were compared between the two groups. In the DS group, the percentage of vertebral slip (% slip) was also measured. Results Several spinopelvic parameters, PI, SS, L4 slope, L5 slope, TK and LL, in the DS group were significantly greater than those in the non-DS group, and PI had positive correlation with % slip (r = 0.35, p0.05). Degrees of correlations among spinopelvic parameters differed between the two groups. In the DS group, PI was more strongly correlated with SS (r = 0.82, p0.001) than with PT (r = 0.41, p0.01). In the non-DS group, PI was more strongly correlated with PT (r = 0.73, p0.001) than with SS (r = 0.38, p0.01). Conclusions Greater PI may lead to the development and the progression of vertebral slip. Different compensatory mechanisms may contribute to the maintenance of spinopelvic sagittal alignment in DS and non-DS patients. © 2012 Springer-Verlag.

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Increase in spinal longitudinal length by correction surgery for adolescent idiopathic scoliosis

Watanabe Kota, Hosogane Naobumi, Kawakami Noriaki, Tsuji Taichi, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

European Spine Journal 21 （ 10 ） 1920 - 1925 2012年10月

ISSN 0940-6719

Purpose One of the downsides of spinal correction surgery for adolescent idiopathic scoliosis (AIS) is the cessation of spinal longitudinal growth within the fused levels in growing children. However, the surgery itself has the potential to increase spinal longitudinal length by correcting the curvature. The purpose of this study was to evaluate the correlation between curve correction and increased spinal longitudinal length by corrective surgery for AIS. Methods This study included 208 consecutive patients (14 male, 194 female) with AIS who underwent posterior or anterior correction and fusion surgeries. Mean age at the time of surgery was 15.7 ± 3.3 years (range 10-20 years). Patients with hyperkyphosis of more than 40° were excluded. All patients had main curves in the thoracic spine (Lenke type 1 or 2). Forty-three patients underwent anterior spinal correction and fusion (ASF) and 164 underwent posterior spinal correction and fusion (PSF). The mean preoperative height was 154.7 ± 6.9 cm (range 133-173 cm). Pre and postoperative PA standing X-ray films were used to measure the Cobb angle and spinal length between the end vertebrae of the main thoracic curve, and between T1 and L5. The patients were divided into ASF and PSF groups, within which correlations between the Cobb angle correction and spinal length increase were evaluated. Results In the ASF group, the mean preoperative Cobb angle of the main thoracic curve was 54.9 ± 8.3° (range 41-83°) and it was corrected to 19.7 ± 9.5° (range 0-47°) with a mean correction of 35.2 ± 11.1° (range 10-74°) after surgery. The mean increase in the length of the main thoracic curve was 1.5 ± 4.6 mm (range -8 to 13 mm), and the mean increase in T1-L5 length was 16.6 ± 7.7 mm (range -3 to 51 mm). Significant correlation between the correction of the Cobb angle and increase in T1-L5 length was observed, with a correlation coefficient of 0.44. In the PSF group, the mean preoperative Cobb angle of the main thoracic curve was 58.8 ± 11.6° (range 36-107°) and it was corrected to 17.1 ± 7.6° (range 10-49°), with a mean correction of 41.7 ± 10.2° (range 21-73°) after surgery. The mean increase in the length of the main thoracic curve was 14.0 ± 5.2 mm (range 0-42 mm), and the mean increase in T1-L5 length was 32.4 ± 10.8 mm (10-61 mm). Correlation between the correction of the Cobb angle and increase in T1-L5 length was high, with a correlation coefficient of 0.64. The increase in T1-L5 length could be calculated by the following formula based on linear regression analysis: increase in T1-L5 length (mm) = correction of the Cobb angle (8) 9 0.77. Conclusion Spinal longitudinal length was significantly increased after surgery in both the ASF and PSF groups. Correction of the Cobb angle and increase in T1-L5 length were highly correlated with each other, especially in the PSF group. © Springer-Verlag 2012.

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An essential role for STAT6-STAT1 protein signaling in promoting macrophage cell-cell fusion

Miyamoto Hiroya, Katsuyama Eri, Miyauchi Yoshiteru, Hoshi Hiroko, Miyamoto Kana, Sato Yuiko, Kobayashi Tami, Iwasaki Ryotaro, Yoshida Shigeyuki, Mori Tomoaki, Kanagawa Hiroya, Fujie Atsuhiro, Hao Wu, Morioka Hideo, Matsumoto Morio, Toyama Yoshiaki, Miyamoto Takeshi

Journal of Biological Chemistry 287 （ 39 ） 32479 - 32484 2012年09月

ISSN 0021-9258

Macrophage lineage cells such as osteoclasts and foreign body giant cells (FBGCs) form multinuclear cells by cell-cell fusion of mononuclear cells. Recently, we reported that two seven-transmembrane molecules, osteoclast stimulatory transmembrane protein (OC-STAMP) and dendritic cell-specific transmembrane protein (DC-STAMP), were essential for osteoclast and FBGC cell-cell fusion in vivo and in vitro. However, signaling required to regulate FBGC fusion remained largely unknown. Here, we show that signal transducer and activator of transcription 1 (STAT1) deficiency in macrophages enhanced cell-cell fusion and elevated DC-STAMP expression in FBGCs. By contrast, lack of STAT6 increased STAT1 activation, significantly inhibiting cell-cell fusion and decreasing OC-STAMP and DC-STAMP expression in IL-4-induced FBGCs. Furthermore, either STAT1 loss or co-expression of OC-STAMP/DC-STAMP was sufficient to induce cell-cell fusion of FBGCs without IL-4. We conclude that the STAT6-STAT1 axis regulates OC-STAMP and DC-STAMP expression and governs fusogenic mechanisms in FBGCs. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

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Aldehyde-stress resulting from Aldh2 mutation promotes osteoporosis due to impaired osteoblastogenesis

Hoshi Hiroko, Hao Wu, Fujita Yoshinari, Funayama Atsushi, Miyauchi Yoshiteru, Hashimoto Kazuaki, Miyamoto Kana, Iwasaki Ryotaro, Sato Yuiko, Kobayashi Tami, Miyamoto Hiroya, Yoshida Shigeyuki, Mori Tomoaki, Kanagawa Hiroya, Katsuyama Eri, Fujie Atsuhiro, Kitagawa Kyoko, Nakayama Keiichi I., Kawamoto Toshihiro, Sano Motoaki, Fukuda Keiichi, Ohsawa Ikuroh, Ohta Shigeo, Morioka Hideo, Matsumoto Morio, Chiba Kazuhiro, Toyama Yoshiaki, Miyamoto Takeshi

Journal of Bone and Mineral Research 27 （ 9 ） 2015 - 2023 2012年09月

ISSN 0884-0431

Osteoporosis is a complex disease with various causes, such as estrogen loss, genetics, and aging. Here we show that a dominant-negative form of aldehyde dehydrogenase 2 (ALDH2) protein, ALDH2*2, which is produced by a single nucleotide polymorphism (rs671), promotes osteoporosis due to impaired osteoblastogenesis. Aldh2 plays a role in alcohol-detoxification by acetaldehyde-detoxification; however, transgenic mice expressing Aldh2*2 (Aldh2*2 Tg) exhibited severe osteoporosis with increased levels of blood acetaldehyde without alcohol consumption, indicating that Aldh2 regulates physiological bone homeostasis. Wild-type osteoblast differentiation was severely inhibited by exogenous acetaldehyde, and osteoblastic markers such as osteocalcin, runx2, and osterix expression, or phosphorylation of Smad1,5,8 induced by bone morphogenetic protein 2 (BMP2) was strongly altered by acetaldehyde. Acetaldehyde treatment also inhibits proliferation and induces apoptosis in osteoblasts. The Aldh2*2 transgene or acetaldehyde treatment induced accumulation of the lipid-oxidant 4-hydroxy-2-nonenal (4HNE) and expression of peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor that promotes adipogenesis and inhibits osteoblastogenesis. Antioxidant treatment inhibited acetaldehyde-induced proliferation-loss, apoptosis, and PPARγ expression and restored osteoblastogenesis inhibited by acetaldehyde. Treatment with a PPARγ inhibitor also restored acetaldehyde-mediated osteoblastogenesis inhibition. These results provide new insight into regulation of osteoporosis in a subset of individuals with ALDH2*2 and in alcoholic patients and suggest a novel strategy to promote bone formation in such osteopenic diseases. © 2012 American Society for Bone and Mineral Research.

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Conditional inactivation of Blimp1 in adult mice promotes increased bone mass

Miyauchi Yoshiteru, Miyamoto Hiroya, Yoshidas Shigeyuki, Mori Tomoaki, Kanagawa Hiroya, Katsuyama Eri, Fujie Atsuhiro, Hao Wu, Hoshi Hiroko, Miyamoto Kana, Sato Yuiko, Kobayashi Tami, Akiyama Haruhiko, Morioka Hideo, Matsumoto Morio, Toyama Yoshiaki, Miyamoto Takeshi

Journal of Biological Chemistry 287 （ 34 ） 28508 - 28517 2012年08月

ISSN 0021-9258

Bone resorption, which is regulated by osteoclasts, is excessively activated in bone destructive diseases such as osteoporosis. Thus, controlling osteoclasts would be an effective strategy to prevent pathological bone loss. Although several transcription factors that regulate osteoclast differentiation and function could serve as molecular targets to inhibit osteoclast formation, those factors have not yet been characterized using a loss of function approach in adults. Here we report such a study showing that inactivation of B-lymphocyte induced maturation protein 1 (Blimp1) in adult mice increases bone mass by suppressing osteoclast formation. Using an ex vivo assay, we show that osteoclast differentiation is significantly inhibited by Blimp1 inactivation at an early stage of osteoclastogenesis. Conditional inactivation of Blimp1 inhibited osteoclast formation and increased bone mass in both male and female adult mice. Bone resorption parameters were significantly reduced by Blimp1 inactivation in vivo. Blimp1 reportedly regulates immune cell differentiation and function, but we detected no immune cell failure following Blimp1 inactivation. These data suggest that Blimp1 is a potential target to promote increased bone mass and prevent osteoclastogenesis. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

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Serum cartilage metabolites as biomarkers of degenerative lumbar scoliosis

Hosogane Naobumi, Watanabe Kota, Tsuji Takashi, Miyamoto Takeshi, Ishii Ken, Niki Yasuo, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Journal of Orthopaedic Research 30 （ 8 ） 1249 - 1253 2012年08月

ISSN 0736-0266

Several biomarkers have been used to evaluate osteoarthritis of the limb joints. Here we evaluated the use of serum cartilage metabolites as biomarkers for degenerative lumbar scoliosis (DLS). Fifty-two DLS patients with Cobb angle>10° were compared with 19 control patients. Serum levels of hyaluronic acid (HA), keratan sulfate (KS), cartilage oligomeric matrix protein (COMP), collagen type II cleavage (C2C), and procollagen type II C-propeptide (CPII) were measured. Serum levels of KS (DLS 1.20±0.44μg/ml vs. control 0.98±0.33μg/ml), CPII (DLS 1905.1±948.2ng/ml vs. control 1223.6±884.4ng/ml), and C2C (DLS 219.1±59.2ng/ml vs. control 177.7±71.7ng/ml) were significantly higher in DLS. There were no significant differences in the levels of HA or COMP. There was a significant positive correlation between the Cobb angle and CPII in DLS. This is the first study to evaluate the cartilage biomarkers in DLS. The results suggest DLS patients have higher levels of type II collagen synthesis and degradation, indicated by elevated serum CPII and C2C, respectively. As type II collagen is a major component of collagens in the nucleus pulposus and facet joint cartilages, its enhanced turnover may be related to the development and progression of DLS. Copyright © 2012 Orthopaedic Research Society.

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Surgical treatment of spinal extradural arachnoid cysts in the thoracolumbar spine

Funao Haruki, Nakamura Masaya, Hosogane Naobumi, Watanabe Kota, Tsuji Takashi, Ishii Ken, Kamata Michihiro, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Neurosurgery 71 （ 2 ） 278 - 284 2012年08月

ISSN 0148-396X

BACKGROUND: Because an idiopathic spinal extradural arachnoid cyst (SEAC) is rare, its optimal surgical treatment remains controversial. OBJECTIVE: To evaluate the results of surgical treatments for SEACs and to clarify features of the disease associated with poor outcomes. METHODS: Twelve patients with SEACs who underwent surgery at our hospital between 1988 and 2008 were examined retrospectively. The mean follow-up period was 4.7 years. Total resection of the cyst was performed in 7 patients and closure of the dural defect without cyst resection in 5 patients. Surgical outcomes were evaluated with regard to the duration of symptoms, the size of the cyst, and the surgical procedure used. RESULTS: Neurological recovery was observed in all patients, and there was no recurrence. Poor outcomes were observed in patients with a long duration of symptoms (>1 year, P < .01) and large cyst size (>5 vertebrae, P < .05). The surgical procedure had no significant association with the postoperative neurological recovery. However, there was a significant difference in the degree of the mean postoperative kyphotic angle between the patients treated by total resection of the cyst (9.7 degrees) and those treated by closure of the dural defect without cyst resection through selective laminectomy (2.2 degrees) (P < .01). CONCLUSION: There was no significant difference in postoperative neurological recovery between the 2 surgical procedures. However, closure of the dural defect without cyst resection was less invasive, preventing postoperative kyphotic deformity of the thoracolumbar spine. Copyright © 2012 by the Congress of Neurological Surgeons.

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Clinical significance of diffusion tensor tractography as a predictor of functional recovery after laminoplasty in patients with cervical compressive myelopathy

Nakamura Masaya, Fujiyoshi Kanehiro, Tsuji Osahiko, Konomi Tsunehiko, Hosogane Naobumi, Watanabe Kota, Tsuji Takashi, Ishii Ken, Momoshima Suketaka, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Journal of Neurosurgery: Spine 17 （ 2 ） 147 - 152 2012年08月

ISSN 1547-5654

Object. This study was conducted to determine whether postoperative changes in the fractional anisotropy (FA) value and diffusion tensor imaging of the cervical spinal cord can predict functional outcome for patients with cervical compressive myelopathy (CCM). Methods. Twenty patients with CCM were treated by laminoplasty from 2008 to 2009. Both T2-weighted MRI and diffusion tensor imaging were performed before and after surgery. The FA values were analyzed and fiber tracking was performed. The fiber tract (FT) ratio was calculated according to the following formula: (number of fibers at the compressed level)/(number of fibers at the C-2 level) x 100%. The Japanese Orthopaedic Association scoring system for cervical myelopathy was used to determine pre- and postoperative neurological status of the patients, and the Hirabayashi method was used to calculate the recovery rate. Results. There was no significant difference in recovery rates between patients with and those without intramedullary high signal intensity on preoperative T2-weighted images. Substantial differences in FA value among spinal cord, bone, and CSF made it difficult to obtain a precise FA value for the compressed spinal cord. There was a significant correlation between the preoperative FT ratio and the recovery rate (p = 0.0006). A poor outcome (recovery rate < 40%) could be anticipated for CCM patients with preoperative FT ratios below 60%. Conclusions. The preoperative FT ratio correlated significantly with the recovery rates in CCM patients. Preoperative diffusion tensor tractography can be a new prognostic predictor for neurological recovery in CCM patients after laminoplasty.

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Impact of lamina closure on long-term outcomes of open-door laminoplasty in patients with cervical myelopathy

Matsumoto Morio, Watanabe Kota, Hosogane Naobumi, Tsuji Takashi, Ishii Ken, Nakamura Masaya, Chiba Kazuhiro, Toyama Yoshiaki

Spine 37 （ 15 ） 1288 - 1291 2012年07月

ISSN 0362-2436

Study Design: A prospective follow-up study. Objective: To elucidate the impact of lamina closure on long-term outcomes after open-door laminoplasty. Summary of Background Data: In a previous study, we did not find significant associations between lamina closure and short-term outcomes. Methods: Of the original cohort of 82 patients who underwent open-door laminoplasty, 69 were included in this study (52 men, 17 women; mean age, 60.9 yr; mean follow-up, 6.2 yr; 56 with spondylosis or disc herniation, 13 with ossification of posterior longitudinal ligament). Lamina closure was previously observed in 23 of these patients (closure group) but not in 46 (nonclosure group). The Japanese Orthopaedic Association (JOA) scores and Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire were recorded. Results: The JOA score was 9.9 ± 3.2 in the closure group and 11.2 ± 2.3 in the nonclosure group before surgery (P = 0.1), 13.8 ± 2.3 and 13.8 ± 2.2 at 1.8 years (P = 0.99), and 13.6 ± 2.2 and 14.2 ± 2.7 at final follow-up (P = 0.29). The recovery rate of the JOA scores was 56.7 ± 30.0% and 46.7 ± 29.2% at 1.8 years (P = 0.22) and 51.0 ± 32.5 and 57.6 ± 31.1 at the final follow-up (P = 0.42). The subdomains assessed by the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire at follow-up were cervical spine function, 68.7 ± 27.5 in the closure group and 67.7 ± 30.0 in the nonclosure group (P = 0.93); upper extremity function, 78.6 ± 24.3 and 87.6 ± 15.4 (P = 0.40); lower extremity function, 69.9 ± 26.0 and 73.9 ± 22.5 (P = 0.68); bladder function, 74.6 ± 22.6 and 84.9 ± 29.2 (P = 0.18); and quality of life, 53.9 ± 25.3 and 56.2 ± 18.1 (P = 0.96). Conclusion: Lamina closure did not significantly impact the long-term surgical outcomes of laminoplasty for cervical myelopathy. Although not statistically significant, the recovery rate tended to decline in the closure group compared with the nonclosure group during the long-term follow-up period, and the utilization of a laminar retention device to prevent the laminar closure should be considered. Copyright © 2012 Lippincott Williams & Wilkins.

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Central neuropathic pain after surgical resection in patients with spinal intramedullary tumor

Nakamura Masaya, Tsuji Osahiko, Iwanami Akio, Tsuji Takashi, Ishii Ken, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Journal of Orthopaedic Science 17 （ 4 ） 352 - 357 2012年07月

ISSN 0949-2658

Study design Retrospective case series. Objective To examine central neuropathic pain after surgical resection of intramedullary spinal cord tumor (IMSCT). Summary of background data Because of the rarity of IMSCT, there is little information about postoperative neuropathic pain after surgical resection. Methods Eighty-five of 105 patients treated surgically for IMSCT at our hospital between 2000 and 2008 completed the Neuropathic Pain Symptom Inventory (NPSI) and the short form (SF)-36 health inventory. The NPSI score was analyzed against the tumor type and the postoperative Japanese Orthopaedic Association (JOA) score for neurological symptoms. Results The mean NPSI score of the patients was 13.5. The subscore for paresthesia/dysesthesia was significantly higher than the other subscores. Analysis of the NPSI scores by tumor type revealed no significant differences among patients with ependymoma, astrocytoma, and vascular tumors. The postoperative JOA score showed a weak negative correlation with the NPSI score in patients with thoracic spinal cord tumor, and no correlation in those with cervical tumor. In the 11 patients with hemangioblastoma, intense pain was reported at the level of the tumor, although postoperative paralysis was mild. All the postoperative SF-36 subscores of our study patients were significantly lower than the national average, and a significant negative correlation was observed between the SF-36 and the NPSI subscores. Conclusion Neuropathic pain after surgical resection reduces the QOL of patients with IMSCTs, and pain severity varies with the tumor's location and histological features, the severity of paralysis, and the location of pain relative to the tumor. © The Japanese Orthopaedic Association 2012.

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Osteoclast stimulatory transmembrane protein and dendritic cell-specific transmembrane protein cooperatively modulate cell-cell fusion to form osteoclasts and foreign body giant cells

Miyamoto Hiroya, Suzuki Takayuki, Miyauchi Yoshiteru, Iwasaki Ryotaro, Kobayashi Tami, Sato Yuiko, Miyamoto Kana, Hoshi Hiroko, Hashimoto Kazuaki, Yoshida Shigeyuki, Hao Wu, Mori Tomoaki, Kanagawa Hiroya, Katsuyama Eri, Fujie Atsuhiro, Morioka Hideo, Matsumoto Morio, Chiba Kazuhiro, Takeya Motohiro, Toyama Yoshiaki, Miyamoto Takeshi

Journal of Bone and Mineral Research 27 （ 6 ） 1289 - 1297 2012年06月

ISSN 0884-0431

Cell-cell fusion is a dynamic phenomenon promoting cytoskeletal reorganization and phenotypic changes. To characterize factors essential for fusion of macrophage lineage cells, we identified the multitransmembrane protein, osteoclast stimulatory transmembrane protein (OC-STAMP), and analyzed its function. OC-STAMP-deficient mice exhibited a complete lack of cell-cell fusion of osteoclasts and foreign body giant cells (FBGCs), both of which are macrophage-lineage multinuclear cells, although expression of dendritic cell specific transmembrane protein (DC-STAMP), which is also essential for osteoclast/FBGC fusion, was normal. Crossing OC-STAMP-overexpressing transgenic mice with OC-STAMP-deficient mice restored inhibited osteoclast and FBGC cell-cell fusion seen in OC-STAMP-deficient mice. Thus, fusogenic mechanisms in macrophage-lineage cells are regulated via OC-STAMP and DC-STAMP. Copyright © 2012 American Society for Bone and Mineral Research.

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Cross-sectional area of the posterior extensor muscles of the cervical spine in whiplash injury patients versus healthy volunteers - 10 year follow-up MR study

Matsumoto Morio, Ichihara Daisuke, Okada Eijiro, Chiba Kazuhiro, Toyama Yoshiaki, Fujiwara Hirokazu, Momoshima Suketaka, Nishiwaki Yuji, Takahata Takeshi

Injury 43 （ 6 ） 912 - 916 2012年06月

ISSN 0020-1383

Introduction: Long-term follow-up studies focusing on the posterior extensor muscles in patients suffering from whiplash injury are scarce. The purpose of this study was to elucidate the changes in the posterior extensor muscles 10 years after whiplash injury. Methods: Twenty-three patients who had suffered from whiplash injury in 1994-1996 and had undergone MRI using a 1.5-T superconductive imager participated in this follow-up study (13 males, 10 females, mean age 51.8 years, mean follow-up 11.5 years). In addition, 60 healthy volunteers who had undergone MRI in the same period were included as controls (36 males, 24 females, mean age 47.8 years, mean follow-up 11.1 years). All participants underwent follow-up MRI. The cross-sectional areas of the deep posterior muscles (CSA) including the multifidus, semispinalis cervicis, semispinalis capitis, and splenius capitis were digitally measured at C3-4, C4-5, and C5-6 using NIH image. The long-term changes in the CSA were compared between the two groups. In addition, correlations between the CSA and cervical spine-related symptoms were evaluated. Results: The mean total CSA per patient (the sum of the area from C3-4 to C5-6) was 4811.6 ± 878.4 mm ² in the whiplash patients and 4494.9 ± 1032.7 mm ² in the controls at the initial investigation (p = 0.20), and 5173.4 ± 946.1 mm ² and 4713.0 ± 1065.3 mm ² at the follow-up (p = 0.07). The mean change in CSA over time was 361.8 ± 804.9 mm ² in the whiplash patients and 218.1 ± 520.7 mm ² in the controls (p = 0.34). Ten whiplash patients (43.5%) had neck pain and 11 (47.8%) had shoulder stiffness. However, there was no difference in the change in CSA over time between the symptomatic and asymptomatic patients. Conclusions: There was no significant difference in the change in CSA between whiplash patients and healthy volunteers after a 10-year follow-up period. In both groups, the cross-sectional area slightly increased at follow-up. In addition, there was no association between the change in CSA and clinical symptoms such as neck and shoulder pain. These results suggest that whiplash injury is not associated with symptomatic atrophy of the posterior cervical muscles over the long term. © 2012 Elsevier Ltd. All rights reserved.

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Loss of apical vertebral derotation in adolescent idiopathic scoliosis

Cui Guanyu, Watanabe Kota, Nishiwaki Yuji, Hosogane Naobumi, Tsuji Takashi, Ishii Ken, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

European Spine Journal 21 （ 6 ） 1111 - 1120 2012年06月

ISSN 0940-6719

Purpose: The objective of this study was to evaluate 2 years post-surgical loss of three-dimensional correction in adolescent idiopathic scoliosis (AIS) patients using multi-planar reconstruction computed tomography (CT). Methods: Twenty-seven AIS patients treated by segmental pedicle screw (PS) constructs were included in this study. Correction in the axial plane was evaluated using the "relative apical vertebral rotation angle" (rAVR), defined as the difference between the axial rotation angles of the upper instrumented vertebra and the apical vertebra on reconstructed axial CT images. The Cobb angle of the main curve and apical vertebral translation was measured to evaluate the coronal correction. Thoracic kyphosis was also measured for the evaluation of sagittal profile. Measurements were performed before surgery, and 1 week and 2 years after surgery. The relationships between the correction losses and skeletal maturity, and variety of spinal constructs were also evaluated. Results: The mean preoperative Cobb angle of the major curve was 59.1° ± 11.2° before and 13.0° ± 7.2° immediately after surgery. Two years later, the mean Cobb angle had increased significantly, to 15.5° ± 7.8°, with a mean correction loss of 2.5° ± 1.5° (p<0.001). The mean preoperative rAVR of 28.5° ± 8.4° was corrected to 15.8° ± 7.8° after surgery. It had increased significantly to 18.5 ± 8.4 by 2 years after surgery, with a mean correction loss of 2.7° ± 1.0° (p<0.001). The mean correction losses for both the Cobb angle and rAVR were significantly greater in the skeletally immature patients. The significant correlations were recognized between the correction losses and the proportion of multi-axial screws, and the materials of constructs. Conclusions: Statistically significant loss of correction in the Cobb angle and apical vertebral axial rotation angle (AVR) were recognized 2 years after surgery using PS constructs. The correction losses, especially AVR, were more evident in the skeletally immature patients, and in patients treated with more multi-axial screws and with titanium constructs rather than with stainless constructs. © Springer-Verlag 2012.

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Radiographic analysis of the progression of congenital scoliosis with rib anomalies during the growth period

Kawakami Noriaki, Tsuji T., Yanagida H., Uno K., Matsumoto M., Watanabe K., Yamamoto T., Hirano T., Taneichi H., Yamazaki K., Fujiwara K.

ArgoSpine News and Journal 24 （ 1-2 ） 56 - 61 2012年06月

ISSN 1957-7729

Study design: Retrospective study. Objectives: To evaluate progression of various types of congenital scoliosis (CS) with rib anomalies (RA) during the various stages of the growth period, and to assess severity of progression in order to make a strategic planning of expansion thoracoplasty. Summary of background data: VEPTR is approved for the treatment of patients with TIS in more than 30 countries. However, there is no consensus on the surgical indications, or the age or time when VEPTR surgery should be performed. Furthermore, there is no study related to natural history of congenital scoliosis with rib anomalies except two reports that are not sufficient to indicate risk factors of progression during the growth period. Methods: Based on a survey of CS and RA via questionnaires, 70 patients (32 males and 38 females with an average age of 2. 6 years at the first visit.) matched the inclusion criteria: CS with RA, no procedures that could influence natural history during follow-up periods, repeated plain X-ray check-ups with at least two years interval during growth periods. Average follow-up (F/U) time was 5. 4 years (2-14). Plain X-ray images of 70 patients were divided into three age groups: infantile (0-5,6), juvenile (5-10,11), and adolescent (11,12-). Each X-ray image was evaluated in terms of laterality, range and type of RA, severity of scoliosis, type of CS, thoracic height ratio, SAL, and associated anomalies. Results: 54 of the 70 patients had unilateral rib anomalies. Rib anomalies included rib fusion in 52, mixed type (fusion and defect) in 8, rib proximity in 6, and rib defect in 4. Vertebral anomalies included formation failure in 1, segmentation failure in 16 and mixed type in 53. The magnitude of scoliosis was 46. 9° at the first visit and 65. 7° at the final F/U. Scoliosis progressed at the rate of 4. 6°/year in 70, 3. 6°/year in bilateral RA involvement and 4. 9°/year in unilateral. Scoliosis progressed with the rate of 4. 6°/year in 70, 3. 6°/year in bilateral RA involvement and 4. 9°/year in unilateral. Scoliosis progressed most severely during infantile period with the rate of 5. 0°/year, followed by adolescent of 3. 8°/year and juvenile of 2. 3°/year. Patients with rib defect or unilateral unsegmented bar showed higher progression rates (10. 7°/year and 7. 0°/year) during infantile period. According to the relationship between SAL and scoliosis, four grades in severity of progression (most severe, severe, moderate, mild) were set up with the cut-off value of 70%, 85% of SAL and 45°, 85° of scoliosis for making the strategic planning of ET. Those grades were significantly related with types and location of RA and types of vertebral anomalies. Conclusions: Progression of scoliosis was analysed in 70 patients with CS & RA. Congenital scoliosis with rib anomalies progressed most rapidly during the early infantile period (7. 8°/year), followed by the late infantile period (5. 0°/year), and the adolescent period (3. 8°/year). Progression of scoliosis in patients with CS and RA occurred in early phase of growth periods and significantly related with types and location of RA as well as type of vertebral anomalies. The results of this study surely suggest the timing of ET for the patients with CS and RA. © 2012 ARGOS and Springer-Verlag France.

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PDGFBB promotes PDGFRα-positive cell migration into artificial bone in vivo

Yoshida Shigeyuki, Iwasaki Ryotaro, Kawana Hiromasa, Miyauchi Yoshiteru, Hoshi Hiroko, Miyamoto Hiroya, Mori Tomoaki, Kanagawa Hiroya, Katsuyama Eri, Fujie Atsuhiro, Hao Wu, Kobayashi Tami, Sato Yuiko, Miyamoto Kana, Morioka Hideo, Matsumoto Morio, Chiba Kazuhiro, Toyama Yoshiaki, Nakagawa Taneaki, Miyamoto Takeshi

Biochemical and Biophysical Research Communications 421 （ 4 ） 785 - 789 2012年05月

ISSN 0006-291X

Bone defects caused by traumatic bone loss or tumor dissection are now treated with auto- or allo-bone graft, and also occasionally by artificial bone transplantation, particularly in the case of large bone defects. However, artificial bones often exhibit poor affinity to host bones followed by bony union failure. Thus therapies combining artificial bones with growth factors have been sought. Here we report that platelet derived growth factor bb (PDGFBB) promotes a significant increase in migration of PDGF receptor α (PDGFRα)-positive mesenchymal stem cells/pre-osteoblastic cells into artificial bone . in vivo. Growth factors such as transforming growth factor beta (TGFβ) and hepatocyte growth factor (HGF) reportedly inhibit osteoblast differentiation; however, PDGFBB did not exhibit such inhibitory effects and in fact stimulated osteoblast differentiation . in vitro, suggesting that combining artificial bones with PDGFBB treatment could promote host cell migration into artificial bones without inhibiting osteoblastogenesis. © 2012 Elsevier Inc.

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Long-term surgical outcomes of spinal meningiomas

Nakamura Masaya, Tsuji Osahiko, Fujiyoshi Kanehiro, Hosogane Naobumi, Watanabe Kota, Tsuji Takashi, Ishii Ken, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Spine 37 （ 10 ） 2012年05月

ISSN 0362-2436

STUDY DESIGN.: Retrospective case series. OBJECTIVE.: To evaluate the treatment strategies for spinal meningioma. SUMMARY OF BACKGROUND DATA.: Although previous studies have demonstrated favorable surgical outcomes for spinal meningioma, with a low incidence of tumor recurrence, few have examined long-term surgical outcomes. METHODS.: The influence of patient age, surgical margin status (Simpson grade), tumor location, and histological subtype on tumor recurrence were examined retrospectively. In addition, the resected dura mater from Simpson grade I cases was examined for invasive tumor cells and compared with the presence or absence of a dural tail sign on magnetic resonance image. RESULTS.: Complete resection (Simpson grades I and II) was performed in 62 patients. Among them, the tumor recurrence rate was 9.7%, all in patients who underwent grade II resection for ventral spinal lesions. The mean duration to reoperation in these patients was 12.2 ± 5.2 years. Of the 6 patients who underwent incomplete resection (Simpson grade III/IV), all required reoperation for tumor recurrence or regrowth, 5 years later on average. Patients younger than 50 years at the initial surgery had a significantly higher recurrence rate than those aged 50 years or older. Histologic examination of 43 dura mater specimens from Simpson grade I-resection patients revealed tumor cell invasion between the inner and outer layers in 15 patients. This invasion was noted in 8 (29%) of 28 patients who were negative for the dural tail sign on magnetic resonance image, and in 7 (47%) of 15 patients who showed a positive dural tail sign. The MIB-1 index reached about 10% for dumbbell-type meningiomas invading the vertebral body; these were associated with repeated recurrence and unfavorable prognosis. CONCLUSION.: Long-term follow-up after surgery for meningiomas indicated that Simpson grade I resection should be selected whenever practicable when treating younger patients or dumbbell-type meningiomas. Tumors recurred at 12 years, on average, in approximately 30% of patients who underwent grade II resection. Copyright © 2012 Lippincott Williams &Wilkins.

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A case of spontaneous spinal epidural hematoma that mimicked acute cerebral ischemic stroke and was treated by a recombinant tissue-type plasminogen activator

Okada Eijiro, Matsumoto Morio, Watanabe Kota, Yagi Mituru, Ninomiya Ken, Horiuchi Yukio, Toyama Yoshiaki

Neurosurgery Quarterly 22 （ 2 ） 99 - 101 2012年05月

ISSN 1050-6438

Summary: A healthy 49-year-old female complaining of progressive hemiplegia of the left side consulted the Emergency Department. Neurological examinations and non-contrast computed tomography of the brain showed no evidence of hemorrhage. Acute ischemic stroke was diagnosed, and intravenous recombinant tissue-type plasminogen activator was administered under the guidelines of the National Institute of Neurological Disorders. After starting the treatment, the patient developed progressive quadriplegia and pain in the back of her neck. Cervical magnetic resonance imaging showed a vast epidural hematoma. The patient underwent emergency decompression surgery and removal of the hematoma by spine surgeons. Intraoperative epidural bleeding was observed on the left side at the C3-C4 level. Postoperatively, the patient showed significant improvement, becoming neurologically intact and functional by the 14-month follow-up. Importantly, this case illustrates that a cervical epidural hematoma can present as hemiplegia, which can be misdiagnosed as a cerebrovascular accident in neurology emergency rooms. Copyright © 2012 by Lippincott Williams & Wilkins.

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Modic changes in the cervical spine

Matsumoto M., Okada E., Ichihara D., Chiba K., Toyama Y., Fujiwara H., Momoshima S., Nishiwaki Y., Takahata T.

Journal of Bone and Joint Surgery - Series B 94 B （ 5 ） 678 - 683 2012年05月

ISSN 0301-620X

We conducted a prospective follow-up MRI study of originally asymptomatic healthy subjects to clarify the development of Modic changes in the cervical spine over a ten-year period and to identify related factors. Previously, 497 asymptomatic healthy volunteers with no history of cervical trauma or surgery underwent MRI. Of these, 223 underwent a second MRI at a mean follow-up of 11.6 years (10 to 12.7). These 223 subjects comprised 133 men and 100 women with a mean age at second MRI of 50.5 years (23 to 83). Modic changes were classified as not present and types 1 to 3. Changes in Modic types over time and relationships between Modic changes and progression of degeneration of the disc or clinical symptoms were evaluated. A total of 31 subjects (13.9%) showed Modic changes at followup: type 1 in nine, type 2 in 18, type 3 in two, and types 1 and 2 in two. Modic changes at follow-up were significantly associated with numbness or pain in the arm, but not with neck pain or shoulder stiffness. Age (≥ 40 years), gender (male), and pre-existing disc degeneration were significantly associated with newly developed Modic changes. In the cervical spine over a ten-year period, type 2 Modic changes developed most frequently. Newly developed Modic changes were significantly associated with age, gender, and pre-existing disc degeneration. © 2012 British Editorial Society.

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SNP rs11190870 near LBX1 is associated with adolescent idiopathic scoliosis in southern Chinese

Fan Yan Hui, Song You Qiang, Chan Danny, Takahashi Yohei, Ikegawa Shiro, Matsumoto Morio, Kou Ikuyo, Cheah Kathryn S E, Sham Pak, Cheung Kenneth M C, Luk Keith D K

Journal of Human Genetics 57 （ 4 ） 244 - 246 2012年04月

ISSN 1434-5161

A study was conducted to validate the most significant single nucleotide polymorphism (SNP) from a genome-wide association study of Japanese adolescent idiopathic scoliosis (AIS) patients in an independent southern Chinese population. In total, 300 AIS patients fulfilled the clinical criteria and 788 controls with MRI scans of the spine were included in the replication study. We employed case-control analysis to study the association of SNP rs11190870 near LBX1 (ladybird homeobox 1) with AIS in a southern Chinese population. The results suggest that SNP rs11190870 is significantly associated with AIS (P=9.1 × 10^-10; odds ratio1.85; 95% confidence interval=1.52-2.25). The results of this study confirm that SNP rs11190870 is associated with AIS. © 2012 The Japan Society of Human Genetics All rights reserved.

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Morphologic evaluation of the thoracic vertebrae for safe free-hand pedicle screw placement in adolescent idiopathic scoliosis

Cui Guanyu, Watanabe Kota, Hosogane Naobumi, Tsuji Takashi, Ishii Ken, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro, Lenke Lawrence G., Matsumoto Morio

Surgical and Radiologic Anatomy 34 （ 3 ） 209 - 216 2012年04月

ISSN 0930-1038

Objective To evaluate the morphologic characteristics of the thoracic pedicle with regard to safe free-hand thoracic pedicle screw placement, based on multi-planar reconstruction CT images. Methods Thirty adolescent idiopathic scoliosis (AIS) patients who had undergone posterior corrective surgery for major thoracic curve were included in this study. Reconstructed CT axial images at each thoracic vertebra were used to measure: (1) the shortest distance from an entry point to the ventral cortex of the lamina (critical distance), and (2) the distance from the entry point to the tangent of the spinal canal at the medial wall of the pedicle (safe distance). The critical length was defined as the distance between the critical distance and the safe distance. The distance from the entry point to the medial wall breach site (breach distance) was measured on post-operative CT images. Results The mean critical distance was 9.3 ± 1.1 mm. The critical distance of vertebrae from different levels was relatively constant, between 8.1 and 10.1 mm. The mean safe distance was 15.2 ± 1.3 mm. The safe distance of vertebrae from different levels was also relatively constant, between 14.5 and 16 mm. The mean critical length was 5.9 ± 1.0 mm. The critical length of vertebrae between T3 and T12 was relatively constant, ranging from 5 to 6.5 mm. The mean breach distance was 12.3 ± 1.3 mm and the each breach always recognized between the critical distance and the safe distance. Conclusions The risk of pedicle medial wall perforation increases as the pedicle probe advances beyond the critical distance of 8-10 mm from the entry point, while it decreases entering into the safe distance at 14.5-16 mm. These parameters were relatively constant even in the most rotated vertebrae at T9 or those with the narrowest pedicle at T7 or T4. © Springer-Verlag 2011.

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Sterility of posterior elements of the spine in posterior correction surgery

Shiono Yuta, Watanabe Kota, Hosogane Naobumi, Tsuji Takashi, Ishii Ken, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Spine 37 （ 6 ） 523 - 526 2012年03月

ISSN 0362-2436

Study Design.: Prospective clinical series. Objective.: To investigate the sterility of the posterior elements of the spine during posterior correction surgery. Summary of Background Data.: Bacterial growth in the operating field is considered one of the causes of surgical-site infection. Methods.: A total of 80 consecutive patients (mean age = 19.5 years) who underwent posterior correction surgery for spinal deformities were included in the study. During surgery, specimens for bacterial culture were obtained by swabs from (1) the skin after cleansing using povidone-iodine scrub solution but before draping, (2) laminae immediately after exposure, (3) laminae immediately after screw placement, (4) laminae immediately before wound closure, (5) a small piece of bone obtained from the spinous process immediately after exposure and placed on a sterile dish during surgery as a control, kept covered, and (6) a similar sample as (5), kept uncovered. The culture was conducted on both blood agar and Gifu anaerobic medium agar plates. Results.: No patient developed surgical-site infection. The culture was positive in specimen (S) 1 in 25 patients (31.3%), S2 in 20 (25%), S3 in 25 (31.3%), S4 in 26 (32.5%), S5 in 6 (7.5%), and S6 in 7 (8.8%). Bacterial species included Propionibacterium acnes in 15 specimens, Propionibacterium species in 9, and others in 10. Of the 25 patients with a positive culture in S1 and 55 patients without, 22 (88%) and 26 (47.3%), respectively, demonstrated a positive culture in specimens obtained during surgery. Conclusion.: The culture was more frequently positive in specimens obtained immediately before wound closure than in those harvested immediately after exposure and isolated from the surgical field. The results suggest that bacterial contamination of the operating field may originate from the skin of the patient during surgery. © 2012 Lippincott Williams and Wilkins.

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Management of chronic atlantoaxial rotatory fixation

Ishii Ken, Toyama Yoshiaki, Nakamura Masaya, Chiba Kazuhiro, Matsumoto Morio

Spine 37 （ 5 ） 2012年03月

ISSN 0362-2436

Study Design: Retrospective case series of chronic atlantoaxial rotatory fixation (AARF) treated by a novel closed reduction method (remodeling therapy) and review of the literature. Objective: To describe clinical features of chronic AARF and the rationale of the remodeling therapy. Summary of Background Data: Treatment strategy for chronic recurrent AARF remains controversial. Posterior C1-C2 arthrodesis has been widely used for recurrent unstable AARFs after the closed reduction, and a variety of posterior fusion techniques have been advocated. In contrast, several investigators reported a chronic AARF case treated by a simple traction or closed reduction followed by cervical immobilization. Previously, we have found that a deformity of the superior C2 facet joint (C2 facet deformity) on three dimensional computed tomography (3D CT) reconstructions is a risk factor for recurrent subluxation. In addition, the remodeling of this C2 facet deformity by careful closed manipulation followed by halo fixation (remodeling therapy) could prevent the recurrence of subluxation. Methods: Twelve children with chronic AARF who sustained torticollis for an average of 4.4 months after the onset were referred to our clinic. The mean age at the initial visit was 7.8 years. All patients underwent the remodeling therapy as reported previously. Radiographic findings and clinical courses were retrospectively reviewed. Treatment methodology, pearls, and pitfalls of the remodeling therapy were discussed with review of the literature. Results: 3D CT images before reduction revealed persistent atlantoaxial subluxation and the C2 facet deformity in the dislocated side in all cases. Follow-up 3D CT scans demonstrated the remodeling of the C2 facet deformity at an average of 2.4 months after successful reduction of subluxation. Neither recurrence of symptoms nor subluxation was observed at a mean follow-up of 42 months in any case. The cervical range of motion was 73.9° at the dislocated and 83.5° at the contra-dislocated side from the midline. Conclusion: Chronic irreducible and recurrent unstable AARF should be initially managed by remodeling therapy using the facet deformity sign as a clinical index, if the C1 and C2 have not been osseously fused. Copyright © 2012 Lippincott Williams & Wilkins.

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Surgical treatment of ossification of the posterior longitudinal ligament and its outcomes

Matsumoto Morio, Chiba Kazuhiro, Toyama Yoshiaki

Spine 37 （ 5 ） 2012年03月

ISSN 0362-2436

Study Design: Review article. Objective: To discuss the history, indication, surgical outcomes, prognostic factors, and complications of laminoplasty for ossification of the posterior longitudinal ligament (OPLL) of the cervical spine. Summary of Background Data: OPLL usually requires surgery, which often involves indirect decompression by the posterior approach. Of the posterior procedures for OPLL, laminoplasty is the favored treatment. Here, we review the previously published literature on laminoplasty for OPLL. Methods: PubMed and previously published English and Japanese book chapters were searched for posterior procedures for treating OPLL. Results: There is a large body of literature on OPLL and its treatment. Based on a review of the literature, the history, indication, surgical outcomes, prognostic factors, and complications of laminoplasty for OPLL were examined. The results showed that long-term outcomes of both the open-door and double-door types of laminoplasty are favorable, although late neurological deterioration occurs in some patients. Preoperative kyphosis of the cervical spine and severe (>60%) compromise of the spinal canal by OPLL appear to be the limiting factors for the indication of laminoplasty. Complications of laminoplasty include segmental motor palsy, lamina closure, and axial symptoms. Conclusion: Laminoplasty is a feasible surgical option for OPLL if candidate patients are appropriately selected. Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

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Establishment of a real-time, quantitative, and reproducible mouse model of staphylococcus osteomyelitis using bioluminescence imaging

Funao Haruki, Ishii Ken, Nagai Shigenori, Sasaki Aya, Hoshikawa Tomoyuki, Aizawa Mamoru, Okada Yasunori, Chiba Kazuhiro, Koyasu Shigeo, Toyama Yoshiaki, Matsumoto Morio

Infection and Immunity 80 （ 2 ） 733 - 741 2012年02月

ISSN 0019-9567

Osteomyelitis remains a serious problem in the orthopedic field. There are only a few animal models in which the quantity and distribution of bacteria can be reproducibly traced. Here, we established a real-time quantitative mouse model of osteomyelitis using bioluminescence imaging (BLI) without sacrificing the animals. A bioluminescent strain of Staphylococcus aureus was inoculated into the femurs of mice. The bacterial photon intensity (PI) was then sequentially measured by BLI. Serological and histological analyses of the mice were performed. The mean PI peaked at 3 days, and stable signals were maintained for over 3 months after inoculation. The serum levels of interleukin-6, interleukin-1β, and C-reactive protein were significantly higher in the infected mice than in the control mice on day 7. The serum monocyte chemotactic protein 1 level was also significantly higher in the infected group at 12 h than in the control group. A significantly higher proportion of granulocytes was detected in the peripheral blood of the infected group after day 7. Additionally, both acute and chronic histological manifestations were observed in the infected group. This model is useful for elucidating the pathophysiology of both acute and chronic osteomyelitis and to assess the effects of novel antibiotics or antibacterial implants. © 2012, American Society for Microbiology.

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Spontaneous regression of soft disc herniation in patients with cervical myelopathy

Matsumoto Morio, Okada Eijiro, Watanabe Kota, Hosogane Naobumi, Tsuji Takashi, Ishii Ken, Nakamura Masaya, Chiba Kazuhiro, Toyama Yoshiaki

Neurosurgery Quarterly 22 （ 1 ） 7 - 11 2012年02月

ISSN 1050-6438

PURPOSE:: To describe patients with cervical myelopathy due to cervical disc herniation (CDH) who showed spontaneous regression, we conducted a retrospective study. METHODS:: A review of clinical records since 1990 identified 19 patients (12 male and 7 female; mean age, 42.4 y) with mild cervical myelopathy due to CDH who exhibited spontaneous CDH regression after conservative treatment. RESULTS:: The mean Japanese Orthopaedic Association scores were 13.7±1.4 before conservative treatment, 14.8±1.2 at 3 months, and 15.9±0.7 at final follow-up. On magnetic resonance imaging (MRI), the CDH regression was observed at 7.5 months on average. Intramedullary high-signal intensity was observed in 15 patients (78.9%) before treatment and 9 patients (47.4%) at follow-up. The mean area of the spinal cord was 58.4±8.3 mm before treatment and 62.4±9.7 mm at follow-up. CONCLUSIONS:: Spontaneous regression of the CDH in 19 patients with mild cervical myelopathy was observed, with improvements in neurological status and in intramedullary high-signal intensity on MRI. © 2012 by Lippincott Williams & Wilkins.

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Changes in the cross-sectional area of deep posterior extensor muscles of the cervical spine after anterior decompression and fusion

Matsumoto Morio, Okada Eijiro, Ichihara Daisuke, Watanabe Kota, Chiba Kazuhiro, Toyama Yoshiaki, Fujiwara Hirokazu, Momoshima Suketaka, Nishiwaki Yuji, Hashimoto Takeshi, Iwanami Akio, Ikegami Takeshi, Takahata Takeshi

European Spine Journal 21 （ 2 ） 304 - 308 2012年02月

ISSN 0940-6719

Purpose To evaluate changes in the transverse area of deep posterior muscles of the cervical spine 10 years after anterior cervical decompression and fusion (ACDF), in comparison with healthy volunteers. Methods Thirty-one patients (22 males, 9 females, mean age at follow-up 59.3 years, mean follow-up 12.1 years) who had undergone preoperativeMRI and non-instrumented ACDF within levels C3-4 to C5-6 were enrolled. 32 asymptomatic volunteers (17 males, 15 females; mean age, 54.7 years; mean follow-up, 11.7 years) who underwent MRI between 1993 and 1996 served as controls. Follow-up MRI was performed on both patients and control subjects, and the cross-sectional areas of deep posterior muscles were measured digitally at levels C3-4, 4-5, and 5-6. Results The mean total cross-sectional area in the ACDF and control groups was 4,693.6 ± 1,140.9 and 4,825.8 ± 1,048.2 mm ² in the first MR study (P = 0.63), and 4,616.7 ± 1,086.0 and 5,036.7 ± 1,105.6 mm ² at followup (P = 0.13). The total cross-sectional area in the ACDF group slightly decreased, while that in the control group increased (-77.1 ± 889.7 vs. 210.9 ± 622.0 mm ², P = 0.14). The mean change in the cross-sectional area had no significant correlation with clinical symptoms, including neck pain or JOA score. Conclusions ACDF patients did not show a marked decrease in the cross-sectional area of the deep posterior cervical muscles, but as compared with control subjects there was a slight decrease. A decrease in the cross-sectional area of these muscles after ACDF may not result in the axial symptoms as seen in patients treated by posterior surgery. © 2011 Springer-Verlag.

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Vertebral derotation in adolescent idiopathic scoliosis causes hypokyphosis of the thoracic spine

Watanabe Kota, Nakamura Takayuki, Iwanami Akio, Hosogane Naobumi, Tsuji Takashi, Ishii Ken, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

BMC Musculoskeletal Disorders 13 2012年

Background: The purpose of this study was to test the hypothesis that direct vertebral derotation by pedicle screws (PS) causes hypokyphosis of the thoracic spine in adolescent idiopathic scoliosis (AIS) patients, using computer simulation. Methods: Twenty AIS patients with Lenke type 1 or 2 who underwent posterior correction surgeries using PS were included in this study. Simulated corrections of each patients scoliosis, as determined by the preoperative CT scan data, were performed on segmented 3D models of the whole spine. Two types of simulated extreme correction were performed: 1) complete coronal correction only (C method) and 2) complete coronal correction with complete derotation of vertebral bodies (C + D method). The kyphosis angle (T5-T12) and vertebral rotation angle at the apex were measured before and after the simulated corrections. Results: The mean kyphosis angle after the C + D method was significantly smaller than that after the C method (2.7 ± 10.0° vs. 15.0 ± 7.1°, p<0.01). The mean preoperative apical rotation angle of 15.2 ± 5.5° was completely corrected after the C + D method (0°) and was unchanged after the C method (17.6 ± 4.2°). Conclusions: In the 3D simulation study, kyphosis was reduced after complete correction of the coronal and rotational deformity, but it was maintained after the coronal-only correction. These results proved the hypothesis that the vertebral derotation obtained by PS causes hypokyphosis of the thoracic spine. © 2012 Watanabe et al. licensee BioMed Central Ltd.

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Dual functions of cell-autonomous and non-cell-autonomous ADAM10 activity in granulopoiesis

Yoda Masaki, Kimura Tokuhiro, Tohmonda Takahide, Uchikawa Shinichi, Koba Takeshi, Takito Jiro, Morioka Hideo, Matsumoto Morio, Link Daniel C., Chiba Kazuhiro, Okada Yasunori, Toyama Yoshiaki, Horiuchi Keisuke

Blood 118 （ 26 ） 6939 - 6942 2011年12月

ISSN 0006-4971

Previous studies have revealed various extrinsic stimuli and factors involved in the regulation of hematopoiesis. Among these, Notch-mediated signaling has been suggested to be critically involved in this process. Herein, we show that conditional inactivation of ADAM10, a membrane-bound protease with a crucial role in Notch signaling (S2 cleavage), results in myeloproliferative disorder (MPD) highlighted by severe splenomegaly and increased populations of myeloid cells and hematopoietic stem cells. Reciprocal transfer of bone marrow cells between wild-type and ADAM10 mutant mice revealed that ADAM10 activity in both hematopoietic and nonhematopoietic cells is involved in the development of MPD. Notably, we found that MPD caused by lack of ADAM10 in nonhematopoietic cells was mediated by G-CSF, whereas MPD caused by ADAM10-deficient hematopoietic cells was not. Taken together, the present findings reveal previously undescribed nonredundant roles of cell-autonomous and non-cell-autonomous ADAM10 activity in the maintenance of hematopoiesis. © 2011 by The American Society of Hematology.

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A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis

Takahashi Yohei, Kou Ikuyo, Takahashi Atsushi, Johnson Todd A., Kono Katsuki, Kawakami Noriaki, Uno Koki, Ito Manabu, Minami Shohei, Yanagida Haruhisa, Taneichi Hiroshi, Tsuji Taichi, Suzuki Teppei, Sudo Hideki, Kotani Toshiaki, Watanabe Kota, Chiba Kazuhiro, Hosono Naoya, Kamatani Naoyuki, Tsunoda Tatsuhiko, Toyama Yoshiaki, Kubo Michiaki, Matsumoto Morio, Ikegawa Shiro

Nature Genetics 43 （ 12 ） 1237 - 1240 2011年12月

ISSN 1061-4036

Adolescent idiopathic scoliosis is a pediatric spinal deformity affecting 2-3% of school-age children worldwide. Genetic factors have been implicated in its etiology. Through a genome-wide association study (GWAS) and replication study involving a total of 1,376 Japanese females with adolescent idiopathic scoliosis and 11,297 female controls, we identified a locus at chromosome 10q24.31 associated with adolescent idiopathic scoliosis susceptibility. The most significant SNP (rs11190870; combined P = 1.24 × 10 ^-19; odds ratio (OR) = 1.56) is located near LBX1 (encoding ladybird homeobox 1). The identification of this susceptibility locus provides new insights into the pathogenesis of adolescent idiopathic scoliosis. © 2011 Nature America, Inc. All rights reserved.

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Matrix metalloproteinase 13 in the ligamentum flavum from lumbar spinal canal stenosis patients with and without diabetes mellitus

Cui Guanyu, Watanabe Kota, Miyauchi Yoshiteru, Hosogane Naobumi, Tsuji Takashi, Ishii Ken, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro, Miyamoto Takeshi, Matsumoto Morio

Journal of Orthopaedic Science 16 （ 6 ） 785 - 790 2011年11月

ISSN 0949-2658

Background: Lumbar spinal canal stenosis (LSCS) is one of the most common spinal disorders in the elderly, and ligamentum flavum (LF) hypertrophy is an important cause of LSCS. Matrix metalloproteinase 13 (MMP13) can degrade fibrillar collagens and elastic microfibrils, and is involved in inflammation and fibrosis. The purpose of this study was to compare the expression of MMP13 in the LF from LSCS patients with diabetes mellitus [DM (+)] with that in the LF from patients without DM [DM (-)] and to analyze the relationship among DM, MMP13 expression, and LF hypertrophy. Methods: LFs from 11 DM (+) and 24 DM (-) LSCS patients were analyzed in this study. Histology analysis using hematoxylin and eosin and Masson's trichrome stain was performed for each LF. The expression of MMP13 was analyzed by quantitative real-time PCR. The thickness of LF was measured by CT. Results: In the LF from DM (+) LSCS patients, the elastic fibers were more disorganized and had lower volumes than in the LF from DM (-) LSCS patients, while more fibrotic tissue was observed in the LF from DM (+) than from DM (-) LSCS patients. MMP13 expression was significantly higher in the LF from DM (+) LSCS patients (0.46 ± 0.61 vs. 0.05 ± 0.09, P = 0.002). The LF from the DM (+) LSCS patients was significantly thicker than that from the DM (-) LSCS patients (5.0 ± 0.9 vs. 3.1 ± 0.8 mm, P < 0.01), and the thickness was correlated with the expression of MMP13 (correlation coefficient = 0.43, P = 0.01, Pearson's correlation test). Conclusion: DM-related MMP13 expression can be one of the factors contributing to fibrosis and hypertrophy of the LF. Further research on the mechanism of this process may lead to new therapies for LF hypertrophy. © 2011 The Japanese Orthopaedic Association.

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Mechanism of osteoporosis in adolescent idiopathic scoliosis

Kono Hitoshi, MacHida Masafumi, Saito Masashi, Nishiwaki Yuji, Kato Hiroyuki, Hosogane Naobumi, Chiba Kazuhiro, Miyamoto Takeshi, Matsumoto Morio, Toyama Yoshiaki

Journal of Pineal Research 51 （ 4 ） 387 - 393 2011年11月

ISSN 0742-3098

To clarify the mechanism of osteoporosis in adolescent idiopathic scoliosis (AIS), we investigated radiological and histological changes in the cervical vertebrae of a chicken thoracic scoliosis model. Forty newly hatched broiler chicks were randomly divided into four equal groups: sham-operated chickens serving as control (CON), pinealectomized chickens (PNX), sham-operated (CON + MLT) and pinealectomized chickens (PNX + MLT) that received intraperitoneal administration of melatonin. Pinealectomy was performed at the age of 3 days, and the chickens were killed at 2 months of age. Postmortem X-rays were examined for the presence of scoliosis, and micro-computed tomography (micro-CT) images were taken to evaluate the microstructure of the cervical vertebrae. Histological specimens of the scanned cervical vertebra were prepared, and a midsagittal section was stained with hematoxylin and eosin and tartrate-resistant acid phosphatase to evaluate the numbers of osteoblasts and osteoclasts, respectively. Scoliosis developed at the thoracic spine in all chickens of the PNX and in two of the PNX + MLT group. Micro-CT data revealed that chickens in the PNX group had a greater degree of generalized osteoporosis compared with the other birds. The number of osteoblasts was significantly decreased in the PNX group, while no significant difference was observed among chickens in the numbers of osteoclasts. Our results suggest that melatonin deficiency reduces osteoblast proliferation and leads to the development of scoliosis and osteoporosis. The restoration of melatonin prevented the development of scoliosis and osteoporosis, indicating that melatonin levels may be crucial to the development of deformity and osteoporosis in AIS. © 2011 John Wiley & Sons A/S.

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Outcomes of fusion surgery for ossification of the posterior longitudinal ligament of the thoracic spine

Matsumoto Morio, Toyama Yoshiaki, Chikuda Hirotaka, Takeshita Katsushi, Kato Tsuyoshi, Shindo Shigeo, Abumi Kuniyoshi, Takahata Masahiko, Nohara Yutaka, Taneichi Hiroshi, Tomita Katsuro, Kawahara Norio, Imagama Shiro, Matsuyama Yukihiro, Yamazaki Masashi, Okawa Akihiko

Journal of Neurosurgery: Spine 15 （ 4 ） 380 - 385 2011年10月

ISSN 1547-5654

Object. The aim of this study was to evaluate the outcomes of fusion surgery in patients with ossification of the posterior longitudinal ligament in the thoracic spine (T-OPLL) and to identify factors significantly related to surgical outcomes. Methods. The study included 76 patients (34 men and 42 women with a mean age of 56.3 years) who underwent fusion surgery for T-OPLL at 7 spine centers during the 5-year period from 2003 to 2007. The authors evaluated the patient demographic data, underlying disease, preoperative comorbidities, history of spinal surgery, radiological findings, surgical methods, surgical outcomes, and complications. Surgical outcomes were assessed using the Japanese Orthopaedic Association (JOA) scale score for thoracic myelopathy (11 points) and the recovery rate. Results. The mean JOA scale score was 4.6 ± 2.1 points preoperatively and 7.7 ± 2.5 points at the time of the final follow-up examination, yielding a mean recovery rate of 45.4% ± 39.1%. The recovery rates by surgical method were 38.5% ± 37.8% for posterior decompression and fusion, 65.0% ± 35.6% for anterior decompression and fusion via an anterior approach, 28.8% ± 41.2% for anterior decompression via a posterior approach, and 57.5% ± 41.1% for circumferential decompression and fusion. The recovery rate was significantly higher in patients without diabetes mellitus (DM) than in those with DM. One or more complications were experienced by 31 patients (40.8%), including 20 patients with postoperative neurological deterioration, 7 with dural tears, 5 with epidural hematomas, 4 with respiratory complications, and 10 with other complications. Conclusions. The outcomes of fusion surgery for T-OPLL were favorable. The absence of DM correlated with better outcomes. However, a high rate of complications was associated with the fusion surgery.

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Cross-sectional area of posterior extensor muscles of the cervical spine in asymptomatic subjects

Okada Eijiro, Matsumoto Morio, Ichihara Daisuke, Chiba Kazuhiro, Toyama Yoshiaki, Fujiwara Hirokazu, Momoshima Suketaka, Nishiwaki Yuji, Takahata Takeshi

European Spine Journal 20 （ 9 ） 1567 - 1573 2011年09月

ISSN 0940-6719

There has been no prospective study on agerelated changes of the extensor muscles of the cervical spine in healthy subjects. This study was conducted to elucidate any association between the changes in cross-sectional area of the extensor muscles of the cervical spine on MRIs and cervical disc degeneration or the development of clinical symptoms. Sixty-two subjects who underwent MR imaging by a 1.5-Tesla machine between 1993 and 1996 as asymptomatic volunteers in a previous study were recruited again 10 years later for this follow-up study. The mean interval between the studies was 11.0 ± 0.7 years. The cross-sectional areas of the multifidus, semispinalis cervicis, semispinalis capitis, and splenius capitis at C3-C4, C4-C5, and C5-C6 intervertebral levels were measured on T2-weighted axial images using Image J 1.42. The mean cross-sectional areas of the deep extensor muscles were 1,396.8 ± 337.6 mm ² at the C3-C4 level, 1,514.7 ± 381.0 mm ² at the C4-C5 level, and 1,542.8 ± 373.5 mm2 at the C5-C6 level in the previous investigation. The cross-sectional areas were 1,498.7 ± 374.4 mm2 at the C3-C4 level, 1,569.9 ± 390.9 mm ² at the C4-C5 level, and 1,599.6 ± 364.3 mm ² at the 10-year follow-up. An increase in the cross-sectional area of the muscles was more frequently observed in subjects in their tens to thirties in the initial study, while a decrease was more frequently observed in those in their forties and older in the initial study. Disc degeneration was not correlated with a change in extensor muscle volume. Development of shoulder stiffness during follow-up was significantly negatively correlated with a change in the cross-sectional area of the deep extensor muscles. © Springer-Verlag 2011.

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Late instrumentation failure after total en bloc spondylectomy

Matsumoto Morio, Watanabe Kota, Tsuji Takashi, Ishii Ken, Nakamura Masaya, Chiba Kazuhiro, Toyama Yoshiaki

Journal of Neurosurgery: Spine 15 （ 3 ） 320 - 327 2011年09月

ISSN 1547-5654

Object. The object of this study was to investigate failures after spinal reconstruction following total en bloc spondylectomy (TES), related factors, and sequelae arising from such failures in patients with malignant spinal tumors. Methods. Fifteen patients (12 males and 3 females, with a mean age of 46.5 years) with malignant spinal tumors who underwent TES and survived for more than 1 year were included in this analysis (mean follow-up 41.5 months). Seven patients had primary tumors, including giant cell tumors in 4 patients, chordoma in 2, and Ewing sarcoma in 1. Eight patients had metastatic tumors, including thyroid cancer in 6 and renal cell cancer and malignant fibrous histiocytoma in 1 patient each. Seven patients without prominent paravertebral extension of the tumor were treated using a posterior approach alone, and 8 patients who exhibited prominent anterior or anterolateral extension of the tumors into the thoracic or abdominal cavity were treated using a combined anterior and posterior approach. Spinal reconstruction after tumor resection was performed using a combination of anterior structural support and posterior instrumentation. The relationship between instrumentation failure and clinical and radiographic factors, including age, sex, history of previous surgery, preoperative radiotherapy, tumor histology, tumor level, surgical approach, number of resected vertebrae, rod diameter, number of instrumented vertebrae, and cage subsidence, was investigated. Results. Six patients (40%) with spinal instrumentation failure were identified: rod breakage occurred in 3 patients, and breakage of both the rod and the cage, combined cage breakage and screw back-out, and endplate fracture arising from cage subsidence occurred in 1 patient each. All of these patients experienced acute or chronic back pain, but only 1 patient with a tumor recurrence experienced neurological deterioration upon instrumentation failure. Cage subsidence (≥ 5 mm), preoperative irradiation, and the number of instrumented vertebrae (≤ 4 vertebrae) were significantly related to late instrumentation failure. Conclusions. Late instrumentation failure was a frequent complication after TES. Although patients with instrumentation failure experienced back pain, the neurological sequelae were not catastrophic. For prevention, meticulous preparation of the graft site and a longer posterior fixation should be considered.

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Neurological complications of cervical laminoplasty for patients with ossification of the posterior longitudinal ligament - A multi-institutional retrospective study

Seichi Atsushi, Hoshino Yuichi, Kimura Atsushi, Nakahara Shinnosuke, Watanabe Masahiko, Kato Tsuyoshi, Ono Atsushi, Kotani Yoshihisa, Mitsukawa Mamoru, Ijiri Kosei, Kawahara Norio, Inami Satoshi, Chikuda Hirotaka, Takeshita Katsushi, Nakagawa Yukihiro, Taguchi Toshihiko, Yamazaki Masashi, Endo Kenji, Sakaura Hironobu, Uchida Kenzo, Kawaguchi Yoshiharu, Neo Masashi, Takahashi Masahito, Harimaya Katsumi, Hosoe Hideo, Imagama Shiro, Taniguchi Shinichiro, Ito Takui, Kaito Takashi, Chiba Kazuhiro, Matsumoto Morio, Toyama Yoshiaki

Spine 36 （ 15 ） 2011年07月

ISSN 0362-2436

STUDY DESIGN.: Retrospective multi-institutional study. OBJECTIVE.: To investigate the incidence of neurological deficits after cervical laminoplasty for ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA.: According to analysis of long-term results, laminoplasty for cervical OPLL has been reported as a safe and effective alternative procedure with few complications. However, perioperative neurological complication rates of laminoplasty for cervical OPLL have not been well described. METHODS.: Subjects comprised 581 patients (458 men and 123 women; mean age: 62 ± 10 years; range: 30-86 years) who had undergone laminoplasty for cervical OPLL at 27 institutions between 2005 and 2008. Continuous-type OPLL was seen in 114, segmental-type in 146, mixed-type in 265, local-type in 24, and not judged in 32 patients. Postoperative neurological complications within 2 weeks after laminoplasty were analyzed in detail. Cobb angle between C2 and C7 (C2/C7 angle), maximal thickness, and occupying rate of OPLL were investigated. Pre- and postoperative magnetic resonance imaging was performed on patients with postoperative neurological complications. RESULTS.: Open-door laminoplasty was conducted in 237, double-door laminoplasty in 311, and other types of laminoplasty in 33 patients. Deterioration of lower-extremity function occurred after laminoplasty in 18 patients (3.1%). Causes of deterioration were epidural hematoma in 3, spinal cord herniation through injured dura mater in 1, incomplete laminoplasty due to vertebral artery injury while making a trough in 1, and unidentified in 13 patients. Prevalence of unsatisfactory recovery not reaching preoperative level by 6-month follow-up was 7/581 (1.2%). Mean occupying rate of OPLL for patients with deteriorated lower-extremity function was 51.2 ± 13.6% (range, 21.0%-73.3%), significantly higher than the 42.3 ± 13.0% for patients without deterioration. OPLL thickness was also higher in patients with deterioration (mean, 6.6 ± 2.2 mm) than in those without deterioration (mean, 5.7 ± 2.0 mm). No significant difference in C2/C7 lordotic angle was seen between groups. CONCLUSION.: Although most neurological deterioration can be expected to recover to some extent, the frequency of short-term neurological complications was higher than the authors expected. Copyright © 2011 Lippincott Williams & Wilkins.

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Long-term surgical outcomes of idiopathic spinal cord herniation

Nakamura Masaya, Fujiyoshi Kanehiro, Tsuji Osahiko, Watanabe Kota, Tsuji Takashi, Ishii Ken, Matsumoto Morio, Toyama Yoshiaki, Chiba Kazuhiro

Journal of Orthopaedic Science 16 （ 4 ） 347 - 351 2011年07月

ISSN 0949-2658

Background: Because of the lack of long-term postoperative follow-up studies of idiopathic spinal cord herniation (ISCH), there is little information about the long-term effectiveness and complications of the dural defect enlargement in patients with ISCH. The purpose of this study is to determine the long-term effectiveness of this procedure. Methods: Sixteen patients with ISCH were treated surgically by enlargement of the dural defect. The patient's neurological status and surgical outcome were evaluated by the JOA scores for thoracic myelopathy and the recovery rate (mean follow-up period 9.6 years). Correlations between the surgical outcomes and patients' age and duration of disease were assessed retrospectively. The patients were also divided into two groups based on the location of the dural defect: the ventro-lateral (VL) group and the ventral (V) group. The difference in the duration of disease, preoperative JOA score, and the recovery rate were compared between the two groups. Results: There was no recurrence of ISCH after surgery. The mean recovery rate was 42.6%. There was a significant correlation between the patient's age and the recovery rate, and between the duration of disease and the recovery rate. The median recovery rate was significantly lower in the V group than in the VL group. There were no complications related to CSF leakage after surgery. Conclusions: Long-term surgical outcomes of enlargement of the dural defect for ISCH were stable and favorable without recurrences or any complications. This procedure should be considered for patients with ISCH before their neurological deficit worsens, especially for the patients in whom the dural defect is located at the ventral part of the dural canal. © 2011 The Author(s).

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Lack of association between adolescent idiopathic scoliosis and previously reported single nucleotide polymorphisms in MATN1, MTNR1B, TPH1, and IGF1 in a Japanese population

Takahashi Yohei, Matsumoto Morio, Karasugi Tatsuki, Watanabe Kota, Chiba Kazuhiro, Kawakami Noriaki, Tsuji Taichi, Uno Koki, Suzuki Teppei, Ito Manabu, Sudo Hideki, Minami Shohei, Kotani Toshiaki, Kono Katsuki, Yanagida Haruhisa, Taneichi Hiroshi, Takahashi Atsushi, Toyama Yoshiaki, Ikegawa Shiro

Journal of Orthopaedic Research 29 （ 7 ） 1055 - 1058 2011年07月

ISSN 0736-0266

Adolescent idiopathic scoliosis (AIS) is a spinal deformity most commonly arising in apparently healthy girls around puberty. AIS has a strong genetic predisposition. Several genetic associations between AIS and single nucleotide polymorphisms (SNPs) have been reported; common SNPs in the genes for matrilin 1 (MATN1), melatonin receptor 1B (MTNR1B), tryptophan hydroxylase 1 (TPH1), and insulin-like growth factor 1 (IGF1) are reported to be associated with AIS in Chinese. However, these associations have not been replicated so far. To confirm the associations, we compared these SNPs with AIS predisposition and curve severity in a population of Japanese females consisting of 798 AIS patients and 1,239 controls. All the subjects were genotyped using the PCR-based Invader assay. We found no association of any of the SNPs with AIS predisposition or curve severity. Considering the statistical power and sample size of the present study, we concluded that these SNPs are not associated with either AIS predisposition or curve severity in Japanese. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc.

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Replication study of the association between adolescent idiopathic scoliosis and two estrogen receptor genes

Journal of Orthopaedic Research 29 （ 6 ） 834 - 837 2011年06月

ISSN 0736-0266

Adolescent idiopathic scoliosis (AIS) is a common disorder with a strong genetic predisposition. Associations between AIS and common single nucleotide polymorphisms (SNPs) in estrogen receptor genes have been reported. rs9340799 in the gene for estrogen receptor α (ESR1) is reported to be associated with curve severity in Japanese and with AIS predisposition and curve severity in Chinese. In addition, rs1256120 in the gene for estrogen receptor β (ESR2) is reported to be associated with AIS predisposition and curve severity in Chinese. However, the sample sizes of these previous studies were small, and the associations of these SNPs have not been replicated. To examine the association between AIS and estrogen receptor genes, we investigated the association of rs9340799 and rs1256120 with AIS predisposition and curve severity using a large Japanese population, consisting of 798 AIS patients and 637 sex-matched controls. We found no association of either SNP with AIS predisposition or curve severity in the Japanese population. Considering the statistical power of the present study and the limitations of the previous reports, we conclude that the associations of rs9340799 and rs1256120 with AIS predisposition and curve severity are negative. © 2010 Orthopaedic Research Society Published by Wiley Periodicals, Inc.

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Primary primitive neuroectodermal tumor of the conus medullaris in an elderly patient

Shimosawa H., Matsumoto M., Yabe H., Mukai M., Toyama Y., Morioka H.

Case Reports in Oncology 4 （ 2 ） 267 - 274 2011年05月

Primary spinal primitive neuroectodermal tumors (PNETs) are very rare conditions. Most of these tumors occur in children and young adults. A 63-year-old man with a primary spinal PNET in the conus medullaris from the L1 to L2 level is presented in this report. The optimal treatment of primary spinal PNETs is yet unknown. Surgical resection, radiation therapy, and chemotherapy have been advocated for the treatment of spinal PNET based on PNETs at other sites. However, the outcome is very poor. There are a few reports of cases with long-term survival and no recurrence. In these patients, en bloc resections were performed. Copyright © 2011 S. Karger AG, Basel.

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A rare case of spinal dumbbell tanycytic ependymoma

Ishihama Hiroko, Nakamura Masaya, Funao Hiroki, Ishii Ken, Matsumoto Morio, Toyama Yoshiaki, Chiba Kazuhiro

Spine 36 （ 9 ） 2011年04月

ISSN 0362-2436

Study Design.: Case report. OBJECTIVE:: To report an extremely rare case of spinal dumbbell-type tanycyticependymoma. Summary of Background Data.: Only two previous cases of a dumbbell-type tanycyticependymoma in the spinal cordhave been reported. Methods.: A 40-year-old female presented with low back pain and numbness of the left leg. Magnetic resonance imaging revealed a dumbbell tumor at the Th10-11 level that compressed the spinal cord extensively. The diagnosis of extradural dumbell spinal tumor was made, and a total tumor excision was performed with a thoracic 10-11 laminectomy. Results.: After surgery, the patient's low back pain and numbness disappeared. Detailed immunohistological examinations confirmed the diagnosis of tanycyticependymoma. At 16 months, there was no evidence of tumor recurrence and no further treatment was needed. Conclusion.: A rare case of spinal dumbbell-type tanycyticependy-moma was presented. Detailed histologic examinations are essential to differentiate tanycyticependymoma from other tumors such as schwannoma and pilocyticastrocytoma. © 2011, Lippincott Williams & Wilkins.

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Kyphectomy for severe kyphosis with pyogenic spondylitis associated with myelomeningocele

Yoshioka Kenji, Watanabe Kota, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Scoliosis 6 （ 1 ） 2011年04月

A 32-year-old woman was referred to our hospital for a refractory ulcer on her back. She had a history of myelomeningocele with spina bifida that was treated surgically at birth. The ulcer was located at the apex of the kyphosis. An X-ray film revealed a kyphosis of 154° between L1 and 3 and a scoliosis of 60° between T11 and L5. Computed tomography, magnetic resonance imaging and laboratory data indicated the presence of a pyogenic spondylitis at L2/3. To correct the kyphosis and remove the infected vertebrae together with the skin ulcer, kyphectomy was performed. Pedicle screws were inserted from T8 to T12 and from L4 to S1. The dural sac was transected and ligated at L2, followed by total kyphectomy of the L1-L3 vertebrae. The spinal column was reconstructed by approximating the ventral wall of the T12 vertebral body and the cranial endplate of the L4 vertebra. Postoperatively, the kyphosis was corrected to 61° and the scoliosis was corrected to 22°. In the present case, we treated the skin ulcer and pyogenic spondylitis successfully by kyphectomy, thereby, preventing recurrence of the ulcer and infection, and simultaneously obtaining sufficient correction of the spinal deformity. © 2011 Yoshioka et al; licensee BioMed Central Ltd.

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Disc degeneration of cervical spine on MRI in patients with lumbar disc herniation

Okada Eijiro, Matsumoto Morio, Fujiwara Hirokazu, Toyama Yoshiaki

European Spine Journal 20 （ 4 ） 585 - 591 2011年04月

ISSN 0940-6719

An association between progression of cervical disc degeneration and that of lumbar disc degeneration has been considered to exist. To date, however, this association has not yet been adequately studied. Age-related changes in the cervical intervertebral discs were evaluated by magnetic resonance imaging (MRI) in patients with lumbar disc herniation, and compared with the MRI findings of healthy volunteers without lower back pain. The purpose of this study was to clarify whether the prevalence of asymptomatic cervical disc degeneration is higher in patients with lumbar disc herniation than in healthy volunteers. The study was conducted on 51 patients who were diagnosed as having lumbar disc herniation and underwent cervical spine MRI. The patients consisted of 34 males and 17 females ranging in age from 21-83 years (mean 46.9 ± 14.5 years) at the time of the study. The control group was composed of 113 healthy volunteers (70 males and 43 females) aged 24-77 years (mean 48.9 ± 14.7 years), without neck pain or low back pain. The percentage of subjects with degenerative changes in the cervical discs was 98.0% in the lumbar disc herniation group and 88.5% in the control group (p = 0.034). The presence of lumbar disc herniation was associated significantly with decrease in signal intensity of intervertebral disc and posterior disc protrusion in the cervical spine. None of the MRI findings was significantly associated with the gender, smoking, sports activities, or BMI. As compared to healthy volunteers, patients with lumbar disc herniation showed a higher prevalence of decrease in signal intensity of intervertebral disc and posterior disc protrusion on MRI of the cervical spine. The result of this study suggests that disc degeneration appears to be a systemic phenomenon. © Springer-Verlag 2010.

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Wedging of vertebral bodies at the thoracolumbar junction in asymptomatic healthy subjects on magnetic resonance imaging

Matsumoto Morio, Okada Eijiro, Kaneko Yasuhito, Ichihara Daisuke, Watanabe Kota, Chiba Kazuhiro, Toyama Yoshiaki, Fujiwara Hirokazu, Momoshima Suketaka, Nishiwaki Yuji, Hashimoto Takeshi, Takahata Takeshi

Surgical and Radiologic Anatomy 33 （ 3 ） 223 - 228 2011年04月

ISSN 0930-1038

Purpose: Wedging of the vertebral body on radiological examination is a valuable indicator of a vertebral compression fracture, although it can also be observed in subjects with no history of trauma. The purpose of this study was to elucidate the normative value of vertebral wedging at the thoracolumbar junction in asymptomatic healthy subjects for differential diagnosis of vertebral compression fractures using MRI. Methods: A total of 115 subjects without back pain at the time of the examination and without history of spinal trauma was included (68 males, 47 females, mean age 49.5 years). They underwent MRI of the thoracic and lumbar spine, and the ratio of anterior vertical height to posterior vertical height of the vertebral body (APR) was determined from T10 to L2 on T2 weighted sagittal images. Results: APR was 0.92 ± 0.08 at T10, 0.92 ± 0.08 at T11, 0.90 ± 0.06 at T12, 0.89 ± 0.06 at L1, and 0.90 ± 0.07 at L2, indicating that vertebral bodies at the thoracolumbar junction appear wedge-shaped rather than rectangular. Males, thinner subjects, smokers, and subjects with abnormalities of the endplates such as a Schmorl nodule had a significantly smaller APR than females, fatter subjects, non-smokers, and those without endplate abnormalities. Conclusion: The normative values of APR obtained in the present study can represent a valuable reference in the diagnosis of vertebral compression fracture to help prevent confusion with physiological vertebral wedging. © 2010 Springer-Verlag.

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Severe progressive scoliosis due to huge subcutaneous cavernous hemangioma

Ogura Yoji, Watanabe Kota, Hosogane Naobumi, Tsuji Takashi, Ishii Ken, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Scoliosis 6 （ 1 ） 2011年03月

Cavernous hemangioma consists mainly of congenital vascular malformations present before birth and gradually increasing in size with skeletal growth. A small number of patients with cavernous hemangioma develop scoliosis, and surgical treatment for the scoliosis in such cases has not been reported to date. Here we report a 12-year-old male patient with severe progressive scoliosis due to a huge subcutaneous cavernous hemangioma, who underwent posterior correction and fusion surgery. Upon referral to our department, radiographs revealed a scoliosis of 85° at T6-L1 and a kyphosis of 58° at T4-T10. CT and MR images revealed a huge hemangioma extending from the subcutaneous region to the paraspinal muscles and the retroperitoneal space and invading the spinal canal. Posterior correction and fusion surgery using pedicle screws between T2 and L3 were performed. Massive hemorrhage from the hemangioma occurred during the surgery, with intraoperative blood loss reaching 2800 ml. The scoliosis was corrected to 59°, and the kyphosis to 45° after surgery. Seven hours after surgery, the patient suffered from hypovolemic shock and disseminated intravascular coagulation due to postoperative hemorrhage from the hemangioma. The patient developed sensory and conduction aphasia caused by cerebral hypoxia during the shock on the day of the surgery. At present, two years after the surgery, although the patient has completely recovered from the aphasia. This case illustrates that, in correction surgery for scoliosis due to huge subcutaneous cavernous hemangioma, intraoperative and postoperative intensive care for hemodynamics should be performed, since massive hemorrhage can occur during the postoperative period as well as the intraoperative period.© 2011 Ogura et al; licensee BioMed Central Ltd.

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Surgical treatment for scoliosis in patients with Shprintzen-Goldberg syndrome

Watanabe Kota, Okada Eijiro, Kosaki Kenjiro, Tsuji Takashi, Ishii Ken, Nakamura Masaya, Chiba Kazuhiro, Toyama Yoshiaki, Matsumoto Morio

Journal of Pediatric Orthopaedics 31 （ 2 ） 186 - 193 2011年03月

ISSN 0271-6798

Background: Shprintzen-Goldberg syndrome (SGS) is characterized by craniosynostosis and marfanoid habitus. The clinical findings of SGS include neurological, cardiovascular, connective tissue, and skeletal abnormalities. Among these skeletal findings, developmental scoliosis is recognized in half of all patients with SGS. However, no earlier reports have described the surgical treatment of scoliosis associated with SGS. Methods: Four patients (2 boys and 2 girls; mean age at the time of surgery, 7.3±4.4 y) with SGS who underwent surgical treatment for progressive scoliosis were reviewed. The radiologic findings, operative findings, and perioperative complications were evaluated. Results: The mean preoperative Cobb angle was 102.8±16.9 degrees. The curve patterns were a double curve in 2 cases and a triple curve in 2 cases. Local kyphosis at the thoracolumbar area was recognized in all the cases with a mean kyphosis angle of 49±16 degrees. Growing rod procedures were performed in 2 patients, and posterior correction and fusion were performed in 2 patients. The mean correction rate was 45% in the patients who underwent the growing rod procedures at the time of growing rod placement and 51% in the patients who underwent posterior correction and fusion. Dislodgement of the proximal anchors occurred in 3 of the 4 patients. One patient developed pseudoarthrosis. Two patients developed deep wound infections, and implant removal was necessary in 1 patient. Conclusions: Surgical treatment for scoliosis in patients with SGS was associated with a high incidence of perioperative and postoperative complications including implant dislodgements and deep wound infections attributable to poor bone quality and a thin body habitus, which are characteristic clinical features of this syndrome. Careful preoperative surgical planning and postoperative care are critical for the surgical treatment of scoliosis associated with SGS, especially in infants requiring multiple surgeries. Level of evidence: Level IV. © 2011 by Lippincott Williams & Wilkins.

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Remodeling of C2 facet deformity prevents recurrent subluxation in patients with chronic atlantoaxial rotatory fixation

Ishii Ken, Matsumoto Morio, Momoshima Suketaka, Watanabe Kota, Tsuji Takashi, Takaishi Hironari, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro

Spine 36 （ 4 ） 2011年02月

ISSN 0362-2436

Study Design. A retrospective case series. Objective. To propose a novel treatment strategy for chronic atlantoaxial rotatory fixation (AARF). Summary Of Background Data. Treatment strategy for chronic or recurrent AARF remains controversial. We have previously reported that a deformity of the superior facet of the axis (C2 facet deformity), which is frequently observed in patients with chronic AARFs, is a risk factor for recurrent dislocation. In this article, we report seven consecutive cases of chronic AARF who underwent closed manipulation followed by external halo fixation and maintained good reduction with the remodeling of the C2 facet deformity. Methods. Seven girls with a chronic AARF who sustained torticollis for an average of 4.6 months after the onset were referred to our clinic. Closed manipulation by careful manipulation under general anesthesia followed by external immobilization with a halo vest was performed in all cases. Radiographic findings and clinical courses were retrospectively reviewed with approvals by the institutional review board. Results. Three-dimensional computed tomography images before reduction revealed persistent atlantoaxial subluxation and the C2 facet deformity in the dislocated side in all cases. Follow-up three-dimensional computed tomographic scans demonstrated the remodeling of the C2 facet deformity at an average of 2.8 months after successful reduction of subluxation. Subsequently, the halo vests were removed and gentle neck range of motion exercise was started in all cases. The normal cervical range of motion was obtained 2 weeks after the removal of halo vests in five cases, whereas the range of motion remained limited in two cases. At a mean follow-up of 17.4 months, neither symptoms nor recurrence of subluxation occurred in all cases. Conclusion. Chronic irreducible and recurrent unstable AARF can be managed successfully by careful closed manipulation followed by halo fixation, if the C1 and C2 have not been osseously fused. The remodeling of the C2 facet deformity detected on follow-up CT scans can be a useful radiographic parameter to determine the appropriate period of halo fixation in this new treatment strategy obviating the need for surgical intervention. Copyright © 2011 Lippincott Williams & Wilkins.

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Interpedicular graft using a titanium mesh cage in a patient with lumbar scoliosis associated with a congenital butterfly vertebra

Cui Guanyu, Watanabe Kota, Ishii Ken, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Journal of Neurosurgery: Spine 14 （ 2 ） 215 - 218 2011年02月

ISSN 1547-5654

A butterfly vertebra is a congenital anomaly often associated with a series of syndromic diseases and is often recognized incidentally without any presenting symptoms. The authors report the case of a 13-year-old girl with lumbar scoliosis and mild spondylolisthesis associated with a butterfly vertebra at L-6 causing radiculopathy. The L-5 and L-6 nerve roots were entrapped at the intervertebral foramina between L-5 and the butterfly vertebra (L-6) and between L-6 and S-1 in the concave side. To decompress and preserve the two nerve roots, correct the deformity, and obtain a solid bone fusion, surgery involving the thorough removal of the facet joints between L-5 and L-6 and between L-6 and S-1 in the concave side was performed, with a partial resection of the butterfly vertebra and the placement of a titanium mesh cage between the L-5 and S-1 pedicles dorsal to the nerve roots. Complete pain relief and correction of the deformity with solid bone fusion was obtained after a 2-year follow-up period.

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Reduced postoperative wound pain after lumbar spinous process-splitting laminectomy for lumbar canal stenosis

Watanabe Kota, Matsumoto Morio, Ikegami Takeshi, Nishiwaki Yuji, Tsuji Takashi, Ishii Ken, Ogawa Yuto, Takaishi Hironari, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro

Journal of Neurosurgery: Spine 14 （ 1 ） 51 - 58 2011年01月

ISSN 1547-5654

Object. To reduce intraoperative damage to the posterior supporting structures of the lumbar spine during decompressive surgery for lumbar canal stenosis (LCS), lumbar spinous process-splitting laminectomy (LSPSL or split laminectomy) was developed. This prospective, randomized, controlled study was conducted to clarify whether the split laminectomy decreases acute postoperative wound pain compared with conventional laminectomy. Methods. Forty-one patients with LCS were enrolled in this study. The patients were randomly assigned to either the LSPSL group (22 patients) or the conventional laminectomy group (19 patients). Questionnaires regarding wound pain (intensity, depth, and duration) and activities of daily living (ADL) were administered at postoperative days (PODs) 3 and 7. Additionally, the authors evaluated the pre- and postoperative serum levels of C-reactive protein and creatine phosphokinase, the amount of pain analgesics used during a 3-day postoperative period, and the muscle atrophy rate measured on 1-month postsurgical MR images. Results. Data obtained in patients in the LSPSL group and in 16 patients in the conventional laminectomy group were analyzed. The mean visual analog scale for wound pain on POD 7 was significantly lower in the LSPSL group (16 ± 17 mm vs 34 ± 31 mm, respectively; p = 0.04). The mean depth-of-pain scores on POD okinase level was significantly lower in the LSPSL group (126 ± 93 U/L) than in the other group (207 ± 150 U/L) (p = 0.02); on POD 7, the mean serum C-reactive protein level was significantly lower in the LSPSL group (1.1 ± 0.6 mg/dl) than in the conventional laminectomy group (1.9 ± 1.5 mg/dl) (p = 0.04). The number of pain analgesics taken during the 3-day postoperative period was lower in the LSPSL group than in the conventional laminectomy group (1.7 ± 1.3 tablets vs 2.3 ± 2.4 tablets, respectively; p = 0.22). The mean muscle atrophy rate was also significantly lower in the LSPSL group (24% ± 15% vs 43% ± 22%; p = 0.004). Conclusions. Lumbar spinous process-splitting laminectomy for the treatment of LCS reduced acute postoperative wound pain and prevented postoperative muscle atrophy compared with conventional laminectomy, possibly because of minimized damage to the paraspinal muscles.

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Central neuropathic pain after surgical resection in patients with spinal intramedullary tumor

Nakamura Masaya, Tsuji Osahiko, Hosogane Naobumi, Watanabe Kota, Tsuji Takashi, Ishii Ken, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio

Clinical Neurology 51 （ 11 ） 937 - 938 2011年

ISSN 0009-918X

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A novel pedicle channel classification describing osseous anatomy

Watanabe Kota, Lenke Lawrence G., Matsumoto Morio, Harimaya Katsumi, Kim Yongjung J., Hensley Marsha, Stobbs Georgia, Toyama Yoshiaki, Chiba Kazuhiro

Spine 35 （ 20 ） 1836 - 1842 2010年09月

ISSN 0362-2436

Study Design. Prospective clinical series. Objective. To determine how many thoracic scoliotic pedicles have cancellous versus cortical versus absent channels. Summary of Background Data. Although morphologic evaluations of thoracic pedicles have been well reported, the results do not practically reflect clinical findings during actual pedicle screw placement. We propose a novel pedicle channel classification describing the osseous anatomy encountered during pedicle probe insertion. Methods. We noted 4 pedicle types in 53 consecutive scoliosis patients. Type A: pedicle probe smoothly inserted without difficulty; the morphology is described as a "Large Cancellous Channel." Type B: pedicle probe inserted snugly with increased force; described as a "Small Cancellous Channel." Type C: pedicle probe cannot be manually pushed but must be tapped with a mallet down the pedicle into the body; described as a "Cortical Channel." Type D: pedicle probe cannot locate a channel thus necessitating a "juxtapedicular" screw position; described as a "Slit/Absent Channel." The average age at time of surgery was 23.4 ± 16.7 years. Diagnoses included idiopathic scoliosis (n = 38) and syndromic scoliosis (n = 15). The average main thoracic Cobb angle was 73° ± 26°. Evaluation of pedicle morphology of the 4 types was also performed in 21 consecutive cases of adolescent idiopathic scoliosis using preoperative computed tomography images. Results. A total of 1021 pedicles with screws placed were evaluated. The average percent per type was as follows: 61.0% type A; 29.2% type B, 6.8% type C, and 3.0% type D. On the convexity, 98.2% of pedicles were type A or B versus 81.5% on the concavity (P < 0.05). There were significant differences between adolescent versus adult idiopathic scoliosis (P = 0.007), and syndromic scoliosis versus adult idiopathic scoliosis (P = 0.017) regarding pedicle morphologic proportions. There was a significant tendency toward a decrease in the proportion of type A pedicles, an increase in the proportion of type B pedicles as the Cobb angle increased (P < 0.0001). Evaluation based on 312 thoracic pedicles in 21 consecutive adolescent idiopathic scoliosis patients using preoperative computed tomography axial images confirmed assumptions of the 4 pedicle types. Conclusion. We propose a classification for pedicle channels describing the osseous anatomy encountered during pedicle probe insertion. Based on the classification, surprisingly, we found during surgery that 90% of thoracic pedicles had a cancellous channel, whereas 7% had a cortical channel and only 3% had an absent channel. © 2010, Lippincott Williams & Wilkins.

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Prospective ten-year follow-up study comparing patients with whiplash-associated disorders and asymptomatic subjects using magnetic resonance imaging

Matsumoto Morio, Okada Eijiro, Ichihara Daisuke, Chiba Kazuhiro, Toyama Yoshiaki, Fujiwara Hirokazu, Momoshima Suketaka, Nishiwaki Yuji, Hashimoto Takeshi, Inoue Tomoo, Watanabe Masahiko, Takahata Takeshi

Spine 35 （ 18 ） 1684 - 1690 2010年08月

ISSN 0362-2436

Study Design: A prospective 10-year follow-up study of patients with whiplash-associated disorders (WAD) and asymptomatic volunteers. Objective: To clarify long-term impact of whiplash injury on patient's symptoms and on magnetic resonance imaging (MRI) findings of the cervical spine. Summary of background data: Long-term prognosis of WAD has not been fully elucidated. Methods: Between 1993 and 1996, we conducted cross-sectional comparative study of 508 acute WAD patients and 497 asymptomatic volunteers, all of whom underwent MRI of the cervical spine. For this follow-up study, 133 WAD patients and 223 control subjects were recruited again. All participants underwent follow-up MRI and physical examination, and answered to questionnaires regarding neck symptoms. Evaluation of MRI included decrease in signal intensity of discs, posterior disc protrusion, disc space narrowing, and foraminal stenosis using 2 to 4 numerical grades. Increase in the numerical grades by one or more was considered to be progression of degenerative changes. Results: Progression of decrease in signal intensity was observed in 109 WAD patients (82.0%), and 132 control subjects (59.2%), (age, sex adjusted odds ratio [OR]: 3.06), posterior disc protrusion in 101 (75.9%) and in 155 (69.5%) (OR = 1.46), disc space narrowing in 33 (24.8%) and in 59 (26.5%) (OR = 0.98), and foraminal stenosis in 6 (4.5%), and in 20 (9.0%) (OR = 0.52), respectively. Neck pain was observed in 34 WAD patients (25.6%) and 22 control subjects (9.9%) (P < 0.0001). There was no statistically significant correlation between neck pain and progression in each MR finding in either group. Conclusion: The results of this study suggest that, although some WAD patients are more likely to suffer from long-lasting neck pain, MRI findings cannot explain the symptoms. © 2010, Lippincott Williams & Wilkins.

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Ball tip technique for thoracic pedicle screw placement in patients with adolescent idiopathic scoliosis

Watanabe Kota, Matsumoto Morio, Takashi Tsuji Ken Ishii, Takaishi Hironari, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro

Journal of Neurosurgery: Spine 13 （ 2 ） 246 - 252 2010年08月

ISSN 1547-5654

Object. The aim in this study was to evaluate the efficacy of the ball tip technique in placing thoracic pedicle screws (TPSs), as compared with the conventional freehand technique, in both a cadaveric study and a clinical study of patients with adolescent idiopathic scoliosis. Although posterior spinal surgery using TPSs has been widely applied, these screws are associated with the potential risk of vascular, pulmonary, or neurological complications. To further enhance the accuracy and safety of TPS placement, the authors developed the ball tip technique. Methods. After creating an appropriate starting point for probe insertion, a specially designed ball tip probe consisting of a ball-shaped tip with a flexible metal shaft is used to make a guide hole into the pedicle. Holding the probe with the fingertips while using an appropriate amount of pressure or by tapping it gently and continuously with a hammer, one can safely insert the ball tip probe into the cancellous channel in the pedicle. In a cadaveric study, 5 spine fellows with similar levels of experience in placing TPSs applied the ball tip or the conventional technique to place screws in 5 cadavers with no spinal deformities. The incidence of misplaced screws was evaluated by dissecting the spines. In a clinical study, 40 patients with adolescent idiopathic scoliosis underwent posterior surgery with TPS placement via the ball tip or conventional technique (20 patients in each treatment group). The accuracy of the TPS placements was evaluated on postoperative axial CT scanning. Results. In the cadaveric study, 100 TPSs were evaluated, and the incidence of misplaced screws was 14% in the ball tip group and 34% in the conventional group (p = 0.0192). In the clinical study, 574 TPSs were evaluated. One hundred seventy-one intrapedicular screws (67%) were recognized in the conventional group and 288 (90%) in the ball tip group (p < 0.01). In the conventional and ball tip groups, the respective numbers of TPSs with a pedicle breach of ≤ 2 mm were 20 (8%) and 15 (5%), those with a pedicle breach of > 2 mm were 32 (13%) and 9 (3%; p < 0.01), and those located in the costovertebral joints were 32 (13%) and 7 (2%). Conclusions. In both cadaveric and clinical studies the ball tip technique enhanced the accuracy of TPS placement as compared with the conventional freehand technique. Thus, the ball tip technique is useful for the accurate and safe placement of TPSs in deformed spines.

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Risk factors for development of subaxial subluxations following atlantoaxial arthrodesis for atlantoaxial subluxations in rheumatoid arthritis

Ishii Ken, Matsumoto Morio, Takahashi Yuichiro, Okada Eijiro, Watanabe Kota, Tsuji Takashi, Takaishi Hironari, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro

Spine 35 （ 16 ） 1551 - 1555 2010年07月

ISSN 0362-2436

Study Design: Retrospective radiographic/imaging study. Objective: To evaluate preoperative and sequential postoperative radiographs following C1-C2 arthrodesis for atlantoaxial subluxation in patients with rheumatoid arthritis (RA) to determine risk factors for the development of subaxial subluxations (SAS). Summary of Background Data: The development of SAS has often been observed after C1-C2 arthrodesis. However, there have been no previous reports on the correlation between radiographic parameters and the incidence of postoperative SAS. Methods: The study group comprised of 58 patients with RA who underwent C1-C2 arthrodesis due to atlantoaxial subluxation. There were 5 men and 53 women with a mean age of 55.8 years. The mean follow-up period was 137 months. Nineteen patients with a postoperative SAS after C1-C2 arthrodesis were classified as the SAS+ group. Other 39 pat ents without a postoperative SAS were included in the SAS- group. Clinical outcomes and plain radiographs were reviewed retrospectively and compared between the 2 groups. Results: The difference between pre- and postoperative atlantoaxial (AA) angles in the SAS+ group was significantly greater than those in the SAS- group (P = 0.039). The C2-C7 angles changed significantly between pre- and postoperative periods in the SAS+ group (P = 0.039), but not in the SAS- group (P = 0.897). It was suggested that a large AA angle and a small C2-C7 angle observed at the early postoperative period were the risk factors for the development of SAS. We also demonstrated that a high incidence of the C3-C4 SAS resulted from excessive bone fusion at the C2-C3. Conclusion: Excessive correction of AA angle is likely to cause loss of cervical lordosis, resulting in the development of postoperative SAS. In addition, extensive bony union at C2-C3 following C1-C2 arthrodesis frequently leads to the development of extensive SAS at the C3-C4. © 2010, Lippincott Williams & Wilkins.

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GRIP1 enhances estrogen receptor α-dependent extracellular matrix gene expression in chondrogenic cells

Kato M., Takaishi H., Yoda M., Tohmonda T., Takito J., Fujita N., Hosogane N., Horiuchi K., Kimura T., Okada Y., Saito T., Kawaguchi H., Kikuchi T., Matsumoto M., Toyama Y., Chiba K.

Osteoarthritis and Cartilage 18 （ 7 ） 934 - 941 2010年07月

ISSN 1063-4584

Objective: The role of postmenopause on the pathogenesis of cartilage degeneration has been an open question. We assessed cartilage degeneration in estrogen receptor (ER)α null mice and examined the role of glucocorticoid receptor-interacting protein 1 (GRIP1) in the ERα-dependent transcription of a type II collagen gene (col2a1) with special reference to a crosstalk with the transforming growth factor (TGF)-β signaling pathway. Methods: The vertebral cartilaginous endplate from female ERα null mice was subjected to histological analyses. Col2a1 expression of primary chondrocytes (PCs) obtained from ERα null mice after 17β-estradiol (E₂) and TGF-β1 stimulation was examined by reverse transcription polymerase chain reaction (RT-PCR). Estrogen response element (ERE) or col2a1 promoter-enhancer luciferase reporter system was used to investigate the crosstalk among ERα, GRIP1, and MKK6. Col2a1 expression and glycosaminoglycan (GAG) content were measured in ATDC5 cells treated with GRIP1 small interfering RNA (siRNA). Results: ERα deficiency clearly accelerated impairment of the vertebral cartilaginous endplate. E₂ and TGF-β1 stimulation increased col2a1 expression in PC from wild-type mice, but not that from ERα null mice. The same stimulation increased the col2a1 promoter-enhancer reporter activity, and the elevated activity was decreased by dominant-negative ERα and p38 mitogen-activated protein kinase (MAPK) inhibitor. GRIP1 increased the E₂-dependent ERE activation in the presence of ERα and constitutive-active MKK6. GRIP1 siRNA repressed col2a1 expression and GAG production in ATDC5 cells. Conclusions: Crosstalks between ERα/GRIP1 and TGF-β/MKK6/p38 MAPK pathway have protective roles on cartilage metabolism via regulating the extracellular matrices expression. The finding may lead to the development of a novel therapeutic approach for cartilage degeneration. © 2010 Osteoarthritis Research Society International.

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Inhibition of STAT1 accelerates bone fracture healing

Tajima Kosuke, Takaishi Hironari, Takito Jiro, Tohmonda Takahide, Yoda Masaki, Ota Norikazu, Kosaki Naoto, Matsumoto Morio, Ikegami Hiroyasu, Nakamura Toshiyasu, Kimura Tokuhiro, Okada Yasunori, Horiuchi Keisuke, Chiba Kazuhiro, Toyama Yoshiaki

Journal of Orthopaedic Research 28 （ 7 ） 937 - 941 2010年07月

ISSN 0736-0266

Skeletal fracture healing involves a variety of cellular and molecular events; however, the mechanisms behind these processes are not fully understood. In the current study, we investigated the potential involvement of the signal transducer and activator of transcription 1 (STAT1), a critical regulator for both osteoclastogenesis and osteoblast differentiation, in skeletal fracture healing. Weused a fracture model and a cortical defect model in mice, and found that fracture callus remodeling and membranous ossification are highly accelerated in STAT1-deficient mice. Additionally, we found that STAT1 suppresses Osterix transcript levels and Osterix promoter activity in vitro, indicating the suppression of Osterix transcription as one of the mechanisms behind the inhibitory effect of STAT1 on osteoblast differentiation. Furthermore, we found that fludarabine, a potent STAT1 inhibitor, significantly increases bone formation in a heterotopic ossification model. These results reveal previously unknown functions of STAT1 in skeletal homeostasis and may have important clinical implications for the treatment of skeletal bone fracture. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

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Age-related changes of thoracic and cervical intervertebral discs in asymptomatic subjects

Matsumoto Morio, Okada Eijiro, Ichihara Daisuke, Watanabe Kota, Chiba Kazuhiro, Toyama Yoshiaki, Fujiwara Hirokazu, Momoshima Suketaka, Nishiwaki Yuji, Hashimoto Takeshi, Takahata Takeshi

Spine 35 （ 14 ） 1359 - 1364 2010年06月

ISSN 0362-2436

Study Design.: Magnetic resonance imaging (MRI) study on degeneration of the thoracic spine in asymptomatic subjects. Objective.: To investigate the incidence of degenerative MRI findings of the thoracic spine in asymptomatic subjects and to identify factors related to the degeneration of the thoracic discs. Summary of Background Data.: Studies on age-related degenerative changes of the thoracic spine are scarce. Methods.: Ninety-four asymptomatic Japanese volunteers (48 men and 46 women, mean age of 48.0 ± 13.4 years) underwent MRI of the thoracic and cervical spine and filled the questionnaire regarding life styles. The items evaluated on MRI using a numerical grading system were (1) decrease in the signal intensity of the intervertebral discs (DSI), (2) posterior disc protrusion (PDP), (3) anterior compression of the dural sac (ACD), and (4) disc space narrowing. Association between each degenerative MRI finding and several factors, including age, sex, smoking, sports, body mass index, and degeneration of cervical spine was investigated. Results.: Forty-four (46.8%) patients demonstrated positive degenerative MRI findings at 1 or more thoracic intervertebral levels. The percentage of the subjects with positive MRI findings was 37.2% in DSI, 30.9% in PDP, 29.8% in ACD, and 4.3% in disc space narrowing. The percentages of all MRI findings increased with aging. In 85 (90.4%) patients, degenerative MRI findings were positive in the cervical spine. DSI was significantly associated with age (odds ratio, 11.21, 95% confidence interval, 2.70-46.5), PDP with age (3.44, 1.02-16.61), smoking (4.94, 1.55-15.71) and presence of PDP in the cervical spine (4.25, 1.01-17.92), and ACD was associated with smoking (3.99, 1.28-12.44). Conclusion.: Degenerative changes in the thoracic spine on MRI was observed in approximately half of the asymptomatic subjects, whereas their incidences were less frequent than those in the cervical spine. Factors significantly associated with degenerative changes in the thoracic spine included age, smoking, and degeneration in the cervical spine. © 2010, Lippincott Williams & Wilkins.

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Complicated surgical resection of malignant tumors in the upper cervical spine after failed ion-beam radiation therapy

Matsumoto Morio, Watanabe Kota, Ishii Ken, Tsuji Takashi, Takaishi Hironari, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro, Imanishi Yorihisa, Kishi Kazuo, Kawana Hiromasa

Spine 35 （ 11 ） 2010年05月

ISSN 0362-2436

STUDY DESIGN.: Case report. OBJECTIVE.: To report 3 cases of malignant tumors in the upper cervical spine that were treated surgically by a combination of posterior tumor resection and stabilization and anterior tumor resection through a mandible-splitting approach after failed ion-beam radiation therapy. SUMMARY OF BACKGROUND DATA.: Few clinical reports have described in detail the postoperative complications associated with transoral surgical resection of tumors in the upper cervical spine after unsuccessful ion-beam radiation therapy. METHODS.: Three patients with malignant tumors in the upper cervical spine who had undergone ion-beam radiotherapy and experienced tumor recurrence were treated by a combination of posterior and anterior surgery through a mandible-splitting approach. One patient (patient 1, a 32-year-old man) had a hemangioendothelioma at the C2 and C3 level, whereas the other 2 patients (patient 2, a 66-year-old woman and patient 3, a 65-year-old man) had a chordoma at the C2 and C3 level. RESULTS.: The intralesional but macroscopic total resection of the tumors was achieved in all 3 patients. However, serious complications developed after surgery, including deep wound infection, cerebrospinal fluid leakage, and meningitis in patient 1, prolonged swallowing difficulty, subsidence of the strut graft, and recurrence in patient 2, and deep wound infection and discitis causing progressive paralysis in patient 3. All patients underwent salvage surgery, including debridement of the wound in patient 1, posterior reinforcement using instrumentation and posterior tumor resection for the recurrent tumor in patient 2, and anterior debridement of the wound with a pedicle flap using the pectoral major muscle in patient 3 to address these problems. Patients 1 and 3 had no signs of recurrence at the time of a follow-up examination. CONCLUSION.: Severe complications, mainly associated with the disturbance in healing of the retropharyngeal wall, were observed in all 3 patients. A preventive method, such as primary repair of the retropharyngeal wall using muscular/musculocutaneous flaps, should be considered for patients undergoing resection through a transoral approach after ion-beam irradiation. © 2010, Lippincott Williams & Wilkins.

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Receptor activator of NF-κB (RANK) ligand induces ectodomain shedding of RANK in murine RAW264.7 macrophages

Hakozaki Akihiro, Yoda Masaki, Tohmonda Takahide, Furukawa Mitsuru, Hikata Tomohiro, Uchikawa Shinichi, Takaishi Hironari, Matsumoto Morio, Chiba Kazuhiro, Horiuchi Keisuke, Toyama Yoshiaki

Journal of Immunology 184 （ 5 ） 2442 - 2448 2010年03月

ISSN 0022-1767

Osteoclastogenesis is a highly sophisticated process that involves a variety of membrane-bound proteins expressed in osteoblasts and osteoclast precursors. Over the past several years, proteolytic cleavage and release of the ectodomain of membrane-bound proteins, also referred to as ectodomain shedding, has emerged as an important posttranslational regulatory mechanism for modifying the function of cell surface proteins. In line with this notion, several membrane-bound molecules involved in osteoclastogenesis, including CSF-1R and receptor activator of NF-κB ligand (RANKL), are proteolytically cleaved and released from the cell surface. In this study, we investigated whether receptor activator of NF-κB (RANK), one of the most essential molecules in osteoclastogenesis, undergoes ectodomain shedding. The results showed that RANK is released in the form of a soluble monomeric protein and that TNF-α-converting enzyme is involved in this activity. We also identified potential cleavage sites in the juxtamembrane domain of RANK and found that rRANKL induces RANK shedding in a macrophage-like cell line RAW264.7 via TNFR-associated factor 6 and MAPK pathways. Furthermore, we found that RANKL-induced osteoclastogenesis is accelerated in TNF-α-converting enzyme-deficient osteoclast precursors. These observations suggest the potential involvement of ectodomain shedding in the regulation of RANK functions and may provide novel insights into the mechanisms of osteoclastogenesis. Copyright © 2010 by The American Association of Immunologists, Inc.

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Adjacent segment disease and degeneration after anterior cervical decompression and fusion

Matsumoto Morio, Okada Eijiro, Ichihara Daisuke, Watanabe Kota, Chiba Kazuhiro, Toyama Yoshiaki

Neurosurgery Quarterly 20 （ 1 ） 15 - 22 2010年03月

ISSN 1050-6438

Anterior cervical decompression and fusion (ACDF) is one of the standard surgical techniques for the treatment of cervical spinal disorders including degenerative diseases, trauma, infection, and tumor. However, the surgical outcomes of ACDF can be deteriorated by the development of adjacent segment degeneration or disease in the postoperative time course. In this article, the biomechanical background, incidence, risk factors, prevention, and management of this disorder are discussed. The incidence rate of adjacent segment degeneration or disease varies according to different reports. The risk factors are reported to be a level of fusion, the number of fusion levels, the preexistence of degenerative changes at the adjacent segments, and the alignment of the entire cervical spine and the fused segments. Although adjacent segment disease can be a sequel of the natural aging of the patients, a comparative study with control population revealed that patients who underwent ACDF had significantly higher incidence of disc degeneration at the adjacent segments than the control population. Adjacent segment diseases can be prevented by the use of motion preservation techniques including artificial disc replacement and decompression surgery without fusion. It can be managed by repeated ACDF, expansive laminoplasty, and artificial disc replacement, although the efficacies of these revision surgical procedures remain to be tested in the larger case series. © 2010 Lippincott Williams & Wilkins, Inc.

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The effect of timing in the administration of hepatocyte growth factor to modulate BMP-2-induced osteoblast differentiation

Kawasaki Toshiki, Niki Yasuo, Miyamoto Takeshi, Horiuchi Keisuke, Matsumoto Morio, Aizawa Mamoru, Toyama Yoshiaki

Biomaterials 31 （ 6 ） 1191 - 1198 2010年02月

ISSN 0142-9612

Development of bone morphogenetic protein (BMP) signaling modulators may provide useful therapeutic options for the treatment of large bony defects in clinical settings. Controversy remains over whether hepatocyte growth factor (HGF) is a positive or negative modulator of BMP-induced osteogenesis. This study analyzed osteogenic properties of HGF, particularly during BMP-2-induced bone formation. Using a mouse model of ectopic bone formation, HGF-impregnated gelatin sponges displayed significantly reduced bone formation induced by BMP-2, both radiologically and histologically. Abrogation of endogenous HGF production by knockdown of HGF mRNA resulted in upregulation of BMP-2-induced ALP activity for C2C12 myoblasts in vitro. In contrast, addition of exogenous HGF inhibited BMP-2-induced ALP activity and osteocalcin production by mouse embryonic fibroblasts (MEFs) through HGF-c-Met interactions. Inhibition of ALP activity by HGF was rescued by U0126, a MEK1/2 inhibitor, indicating that HGF suppresses the BMP-2-Smad axis via activation of ERK1/2. Importantly, treatment with HGF prior to administration of BMP-2 induced cellular proliferation of MEFs and did not influence subsequent osteoblast differentiation induced by BMP-2. The effects of HGF may differ according to the differentiation stage of mesenchymal stem cells, which would explain the inconsistencies seen in osteogenic properties of HGF in previous reports. The timing of HGF treatment is critical and should be carefully determined for successful induction of bone formation by BMPs. © 2009 Elsevier Ltd. All rights reserved.

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Anterior cervical decompression and fusion accelerates adjacent segment degeneration

Matsumoto Morio, Okada Eijiro, Ichihara Daisuke, Watanabe Kota, Chiba Kazuhiro, Toyama Yoshiaki, Fujiwara Hirokazu, Momoshima Suketaka, Nishiwaki Yuji, Iwanami Akio, Ikegami Takeshi, Takahata Takeshi, Hashimoto Takeshi

Spine 35 （ 1 ） 36 - 43 2010年01月

ISSN 0362-2436

Study Design. Prospective 10-year follow-up magnetic resonance imaging (MRI) study of patients who underwent anterior cervical decompression and fusion (ACDF) and healthy control subjects. Objective. To clarify the incidence of adjacent segment degeneration during 10 years after ACDF. Summary of Background Data. There have been few studies which investigated incidence of progression of degenerative changes at adjacent segments in patients treated by ACDF comparing with healthy subjects. Methods. Sixty-four patients who underwent ACDF (48 males, 16 females, mean age 47.3 years, mean follow-up 12.1 year) and 201 asymptomatic volunteers who underwent MRI in our previous study (113 males, 88 females, mean age; 41.1 year, mean follow-up; 11.7 years) were included in this study. The patients and control subjects underwent follow-up MRI in this study. Following MR findings were evaluated using a numerical grading system from C2-C3-C7-T1: (1) Decrease in signal intensity of disc (DSI), (2) Posterior disc protrusion (PDP), (3) Disc space narrowing, and (4) Foraminal stenosis. When an increase in at least one grade in any of the radiographic parameters was detected between the 2 time points, progression of disc degeneration was judged as present at the level of interest. Results. Progression of DSI was significantly more frequent in ACDF group than in control group at C4-C5, while progression of PDP was significantly more frequent in ACDF group than in control group at all levels except for C5-C6. Progression of disc space narrowing and foraminal stenosis was significantly more frequent in ACDF group at C3-C4 and at C6-C7, respectively. Conclusion. Although both ACDF patients and control subjects demonstrated progression of disc degeneration during 10 years, ACDF patients had significantly higher incidence of progression of disc degeneration at adjacent segments than control subjects, while progression of disc degeneration at adjacent segments was not always related to development of clinical symptoms. © 2009, Lippincott Williams & Wilkins.

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Posterior decompression surgery for extraforaminal entrapment of the fifth lumbar spinal nerve at the lumbosacral junction

Matsumoto Morio, Watanabe Kota, Ishii Ken, Tsuji Takashi, Takaishi Hironari, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro

Journal of Neurosurgery: Spine 12 （ 1 ） 72 - 81 2010年01月

ISSN 1547-5654

Object. In this paper, the authors' goal was to elucidate the clinical features and results of decompression surgery for extraforaminal stenosis at the lumbosacral junction. Methods. Twenty-eight patients with severe leg pain caused by extraforaminal stenosis at the lumbosacral junction (18 men and 10 women; mean age 68.2 ± 8.9 years) were treated by posterior decompression without fusion using a microendoscope in 19 patients and a surgical microscope or loupe in 9 patients. The decompression procedures consisted of partial resection of the sacral ala, the L-5 transverse process, and the L5-S1 facet joint along the L-5 spinal nerve. The following items were investigated: 1) preoperative neurological findings; 2) preoperative radiological findings, including plain radiographs, CT scans, selective radiculography of L-5; 3) surgical outcome as evaluated using the Japanese Orthopaedic Association scale for low-back pain (JOA score); and 4) need for revision surgery. Results. All patients presented with neurological deficits compatible with a diagnosis of L-5 radiculopathy such as weakness of the extensor hallucis longus muscle and sensory disturbance in the L-5 area together with neurogenic claudication. On plain radiographs, 21 patients (75%) and 17 patients (60.7%) exhibited lumbar scoliosis (? 5° ) and wedging of the L5-S1 intervertebral space (≥ 3 ^o ), respectively. The CT scans demonstrated marked osteophyte formation at the posterolateral margin of the L5-S1 vertebral bodies, and a selective L-5 nerve root block was effective in all patients. All patients reported pain relief immediately after surgery. The mean JOA scores were 11.3 ± 3.8 before surgery and 24.3 ± 3.4 at the time of the final follow-up examination; the recovery rate was 68.6 ± 16.5%. The mean estimated blood loss was 66.6 ± 98.6 ml, and the mean surgical time was 135.3 ± 46.5 minutes. No significant difference in the recovery rate of the JOA scores or in the surgical time and blood loss was observed between the 2 surgical approaches. Four patients underwent revision posterior interbody fusion for the recurrence of radicular pain as a result of intraforaminal stenosis in 3 patients and insufficient decompression of the extraforaminal area in the remaining patient at an average of 19.5 months after surgery. Conclusions. Extraforaminal stenosis at the lumbosacral junction is a rare but distinct pathological condition causing L-5 radiculopathy. Decompression surgery without fusion using a microendoscope or a surgical microscope/loupe is a feasible and less invasive surgical option for elderly patients with extraforaminal stenosis at the lumbosacral junction.

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Incidence of complications associated with spinal endoscopic surgery

Matsumoto Morio, Hasegawa Toru, Ito Manabu, Aizawa Toshimi, Konno Shinichi, Yamagata Masatsune, Ebara Sohei, Hachiya Yudo, Nakamura Hiroaki, Yagi Shoji, Sato Kimiaki, Dezawa Akira, Yoshida Muneto, Shinomiya Kenichi, Toyama Yoshiaki, Shimizu Katsuji, Nagata Kensei

Journal of Orthopaedic Science 15 （ 1 ） 92 - 96 2010年01月

ISSN 0949-2658

Background: This report was conducted to elucidate the current status of spinal endoscopic surgery and relevant incidents through analysis of the results of a questionnaire survey conducted in 2007 by the Committee on Spinal Endoscopic Surgical Skill Qualification of the Japanese Orthopaedic Association (JOA). Methods: Questionnaire forms were sent to 2011 training facilities nationwide certified by the JOA, and 1082 of these facilities returned the filled questionnaires (response rate 53.8%). Of these facilities, 257 (23.8% of the responding facilities) undertook spinal endoscopic surgery in 2007. These institutions were asked to fill in the survey form with the details of the operations and relevant incidents as well as the incident levels. Results: In total, the 257 facilities performed 6239 spinal endoscopic surgeries during 2007. Posterior spinal endoscopic surgery constituted most of the operations (6217 cases, 98.2%) including 4336 cases of microendoscopic discectomy (MED), 1273 cases of microendoscopic laminectomy or fenestration, and 379 cases of transforaminal or posterior lumbar interbody fusion. The total number of incidents was 133 (2.13%). The numbers of incidents by operative method were 75 (56.4%) during MED, 57 (42.9%) during microendoscopic laminectomy or fenestration, and 1 (0.8%) during interbody fusion. Of 133 incidents, dural tear occurred in 99 (74.4%), injury of the cauda equina or a nerve root in 7 (5.3%), facet fracture in 7 (5.3%), hematoma and wrong level in 6 each (4.5%), and wrong side and bedsore in 1 each (0.8%). The incident level was level 1 in 6, level 2 in 24, level 3a in 82, level 3b in 16, level 4 in 5, and level 5 (fatal) in 0. Conclusions: The results of this survey revealed an increasing trend of spinal endoscopic surgery and a decreasing trend of the complication rates. The complication rates of spinal endoscopic surgery were not higher than those of conventional surgery, indicating the safety of this surgical method. © 2010 The Japanese Orthopaedic Association.

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Cordotomy for patients with thoracic malignant astrocytoma

Nakamura Masaya, Tsuji Osahiko, Fujiyoshi Kanehiro, Watanabe Kota, Tsuji Takashi, Ishii Ken, Matsumoto Morio, Toyama Yoshiaki, Chiba Kazuhiro

Journal of Neurosurgery: Spine 13 （ 4 ） 418 - 423 2010年

ISSN 1547-5654

Object. The optimal management of malignant astrocytomas remains controversial, and the prognosis of these lesions has been dismal regardless of the administered treatment. In this study the authors investigated the surgical outcomes of cordotomy in patients with thoracic malignant astrocytomas to determine the effectiveness of this procedure. Methods. Cordotomy was performed in 5 patients with glioblastoma multiforme (GBM) and 2 with anaplastic astrocytoma (AA). A Kaplan-Meier survival analysis was performed, and the associations of the resection level with survival and postoperative complications were retrospectively examined. Results. Cordotomy was performed in a single stage in 2 patients with GBM and in 2 stages in 3 patients with GBM and 2 patients with AA. In the 2 patients with GBM, cordotomy was performed 2 and 3 weeks after a partial tumor resection. In the 2 patients with AA, the initial treatment consisted of partial tumor resection and subtotal resection combined with radiotherapy, and rostral tumor growth and progressive paralysis necessitated cordotomy 2 and 28 months later. One patient with a secondary GBM underwent cordotomy; the GBM developed 1 year after subtotal resection and radiotherapy for a WHO Grade II astrocytoma. Four patients died 4, 5, 24, and 42 months after the initial operation due to CSF dissemination, and 3 patients (2 with GBM and 1 with AA) remain alive (16, 39, and 71 months). No metastasis to any other organs was noted. Conclusions. One-stage cordotomy should be indicated for patients with thoracic GBM or AA presenting with complete paraplegia preoperatively. In patients with thoracic GBM, even if paralysis is incomplete, cordotomy should be performed before the tumor disseminates through the CSF. Radical resection should be attempted in patients with AA and incomplete paralysis. If the tumor persists, radiotherapy and chemotherapy are indicated, and cordotomy should be reserved for lesions growing progressively after such second-line treatments.

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Microendoscopic resection of lumbar discal cysts

Matsumoto M., Watanabe K., Tsuji T., Ishii K., Takaishi H., Nakamura M., Toyama Y., Chiba K.

Minimally Invasive Neurosurgery 53 （ 2 ） 69 - 73 2010年

ISSN 0946-7211

Introduction: A lumbar discal cyst is a relatively rare cystic lesion that communicates with lumbar intervertebral discs. Surgical resection of the cyst is the reported treatment of choice. In this study, the authors report the minimally invasive surgical resection of lumbar discal cysts using a microendoscopy. Patients and Methods: Seven male patients with lumbar discal cysts underwent microendoscopic resections (mean age: 25.1?3.2 years and the mean follow-up period: 27.9 months). During the surgeries, the cysts were subtotally resected in a piecemeal fashion, and the fistulas forming the communications between the cysts and the corresponding intervertebral discs were coagulated using a bipolar coagulator. Results: All the patients obtained relief from their pain after surgery, and no recurrences occurred during a mean follow-up period of 28 months. The mean operation time was 72.6?20.2min, and the mean blood loss was 44.4?13.7 grams. No intra- or peri-operative complications were noted in any of the patients. Conclusions: Microendoscopic resection appears to be a minimally invasive and feasible surgical option for the treatment of lumbar discal cysts. © Georg Thieme Verlag KG Stuttgart.

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Development of stiff shoulder in asymptomatic volunteers during ten-year follow-up in Japan

Okada Eijiro, Matsumoto Morio, Ichihara Daisuke, Chiba Kazuhiro, Toyama Yoshiaki, Fujiwara Hirokazu, Momoshima Suketaka, Nishiwaki Yuji, Hashimoto Takeshi, Watanabe Masahiko, Inoue Tomoo, Takahata Takeshi

Journal of Back and Musculoskeletal Rehabilitation 23 （ 2 ） 69 - 75 2010年

ISSN 1053-8127

Objectives: The purpose of this study was to longitudinally evaluate relationships between the incidence of stiff shoulder and sagittal alignments of the cervical spine, age-related changes on magnetic resonance imaging (MRI) and life styles of the subjects. Methods: The subjects were 69 men and 93 women. The mean follow-up period was 11.3 ± 0.7 years. Sagittal alignments of the cervical spine were classified into the following 4 types: lordosis, straight, kyphosis and sigmoid. MRI findings were evaluated for the progression of 1) decrease in signal intensity of disc, 2) posterior disc protrusion, and 3) disc space narrowing. Results: Stiff shoulder was found in 29.6% of the subjects over the 10 years. In the group of subjects 30-49 years old, the incidence of stiff shoulder was 40.4%, and it was higher than those in other age groups. Stiff shoulder was significantly more frequent in women (45.2%) than in men. Its incidence was significantly lower in those who regularly participated in sports or exercise. There were no significant relationship between the incidence of stiff shoulder and the progressions in any of MRI findings during the follow-up period. Conclusions: Stiff shoulder was more frequent in middle-aged, female and non-exercising subjects. There was no correlation between the incidence of stiff shoulder and sagittal alignments of the cervical spine, or progression of age-related changes of the cervical disc on MRI. © 2010 - IOS Press and the authors. All rights reserved.

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Progressive kyphoscoliosis associated with tethered cord treated by posterior vertebral column resection

Matsumoto Morio, Watanabe Kota, Tsuji Takashi, Ishii Ken, Takaishi Hironari, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro

Spine 34 （ 26 ） 2009年12月

ISSN 0362-2436

Study Design: A case report. OBJECTIVES.: To report a case of progressive yphoscoliosis associated with a tethered cord that was corrected by posterior vertebral column resection after complicated untethering surgery. Summary of Background Data: There have been few clinical reports on posterior vertebral column resection conducted for severe deformity associated with a tethered cord. Methods: A patient with progressive kyphoscoliosis associated with a tethered cord first underwent untethering surgery, resulting in neurologic deterioration. Posterior vertebral column resection was performed to correct the kyphoscoliosis while shortening the spinal column to prevent the spinal cord from stretch injury. Results: Good correction of kyphoscoliosis was obtained without further neurologic deterioration. The Cobb angles of scoliosis was 103° before surgery and 25° after surgery (correction rate; 75.7%), and that of kyphosis was 90° and 36°, respectively (correction rate; 60.0%). Conclusion: Correction of progressive kyphoscoliosis associated with a tethered cord can be achieved successfully by posterior vertebral column resection even after complicated untethering surgery. © 2009, Lippincott Williams & Wilkins.

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Accelerated cartilage resorption by chondroclasts during bone fracture healing in osteoprotegerin-deficient mice

Ota Norikazu, Takaishi Hironari, Kosaki Naoto, Takito Jiro, Yoda Masaki, Tohmonda Takahide, Kimura Tokuhiro, Okada Yasunori, Yasuda Hisataka, Kawaguchi Hiroshi, Matsumoto Morio, Chiba Kazuhiro, Ikegami Hiroyasu, Toyama Yoshiaki

Endocrinology 150 （ 11 ） 4823 - 4834 2009年11月

ISSN 0013-7227

Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG), a decoy receptor of RANKL, maintain bone mass by regulating the differentiation of osteoclasts, which are bone-resorbing cells. Endochondral bone ossification and bone fracture healing involve cartilage resorption, a less well-understood process that is needed for replacement of cartilage by bone. Here we describe the role of OPG produced by chondrocytes in chondroclastogenesis. Fracture healing in OPG^-/- mice showed faster union of the fractured bone, faster resorption of the cartilaginous callus, and an increased number of chondroclasts at the chondroosseous junctions compared with that in wild-type littermates. When a cultured pellet of OPG^-/- chondrocytes was transplanted beneath the kidney capsule, the pellet recruited many chondroclasts. The pellet showed the ability to induce tartrate-resistant acid phosphatase-positive multinucleated cells from RAW 264.7 cells in vitro. Finally, OPG^-/- chondrocytes (but not wild-type chondrocytes) cultured with spleen cells induced many tartrate-resistant acid phosphatase-positive multinucleated cells. The expression of RANKL and OPG in chondrocytes was regulated by several osteotropic factors including 1,25-dihydroxyvitamin D₃, PTHrP, IL-1α, and TNF-α. Thus, local OPG produced by chondrocytes probably controls cartilage resorption as a negative regulator for chondrocyte-dependent chondroclastogenesis. Copyright © 2009 by The Endocrine Society.

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Does the sagittal alignment of the cervical spine have an impact on disk degeneration? Minimum 10-year follow-up of asymptomatic volunteers

Okada Eijiro, Matsumoto Morio, Ichihara Daisuke, Chiba Kazuhiro, Toyama Yoshiaki, Fujiwara Hirokazu, Momoshima Suketaka, Nishiwaki Yuji, Hashimoto Takeshi, Ogawa Jun, Watanabe Masahiko, Takahata Takeshi

European Spine Journal 18 （ 11 ） 1644 - 1651 2009年11月

ISSN 0940-6719

There have been few studies that investigated and clarified the relationships between progression of degenerative changes and sagittal alignment of the cervical spine. The objective of the study was to longitudinally evaluate the relationships among progression of degenerative changes of the cervical spine with age, the development of clinical symptoms and sagittal alignment of the cervical spine in healthy subjects. Out of 497 symptom-free volunteers who underwent MRI and plain radiography of the cervical spine between 1994 and 1996, 113 subjects (45 males and 68 females) who responded to our contacts were enrolled. All subjects underwent another MRI at an average of 11.3 years after the initial study. Their mean age at the time of the initial imaging was 36.6 ± 14.5 years (11-65 years). The items evaluated on MRI were (1) decrease in signal intensity of the intervertebral disks, (2) posterior disk protrusion, and (3) disk space narrowing. Each item was evaluated using a numerical grading system. The subjects were divided into four groups according to the age and sagittal alignment of the cervical spine, i.e., subjects under or over the age of 40 years, and subjects with the lordosis or non-lordosis type of sagittal alignment of the cervical spine. During the 10-year period, progression of decrease in signal intensity of the disk, posterior disk protrusion, and disk space narrowing were recognized in 64.6, 65.5, and 28.3% of the subjects, respectively. Progression of posterior disk protrusion was significantly more frequent in subjects over 40 years of age with non-lordosis type of sagittal alignment. Logistic regression analysis revealed that stiff shoulder was closely correlated with females (P = 0.001), and that numbness of the upper extremity was closely correlated with age (P = 0.030) and male (P = 0.038). However, no significant correlation between the sagittal alignment of the cervical spine and clinical symptoms was detected. Sagittal alignment of the cervical spine had some impact on the progression of degenerative changes of the cervical spine with aging; however, it had no correlation with the occurrence of future clinical symptoms. © 2009 Springer-Verlag.

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Long-Term surgical outcomes for myxopapillary ependymomas of the Cauda equina

Nakamura Masaya, Ishii Ken, Watanabe Kota, Tsuji Takashi, Matsumoto Morio, Toyama Yoshiaki, Chiba Kazuhiro

Spine 34 （ 21 ） 2009年10月

ISSN 0362-2436

Study Design. Retrospective case series. Objective. To evaluate our treatment strategy for myxopapillary ependymomas of the cauda equina. Summary of Background Data. Some patients with myxopapillary ependymoma develop cerebrospinal fluid (CSF) dissemination leading to poor prognosis. Because of the rarity of this tumor, there is no consensus on its optimal treatment options and prognosis. Methods We reviewed 25 cases of myxopapillary ependymomas, treated surgically between 1972 and 2005. The mean postoperative follow-up period was 10.4 years. The effects of surgical margins at surgery and postoperative radiotherapy on tumor recurrence and prognosis were investigated. Results In 15 patients, total resection achieved (6 cases of en bloc resection without postoperative radiation, and in 9 cases piecemeal resection) was followed by whole brain and spinal cord radiation or local irradiation. Fourteen of these patients survived without tumor recurrence. In 1 case of total resection without radiotherapy, the tumor capsule was violated intraoperatively and local recurrence occurred 2 years after surgery. In 4 patients, the tumors were removed subtotally. Of these, 2 patients who received radiation (24 Gy) only to the whole brain and spinal cord developed recurrence, and 2 who received whole brain and spinal cord radiation (24 Gy) supplemented with local radiation (46 Gy) developed no recurrence. The remaining 6 patients received partial resection after local radiation (40-50 Gy) alone, and all 6 died of CSF dissemination. Conclusion. The results of the present study indicate that the surgical margin obtained at the initial surgery and the extent and amount of postoperative radiation can be crucial factors determining the prognosis of patients with myxopapillary ependymoma. Although this tumor is histologically benign, CSF dissemination can occur once tumor capsule is violated, before or during surgery. Therefore, early diagnosis is essential, and a therapeutic strategy including radiotherapy, on the assumption that this tumor is malignant, should be established. © 2009, Lippincott Williams & Wilkins.

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Updates on ossification of posterior longitudinal ligament. Bone metabolism in ossification of posterior longitudinal ligament

Takaishi Hironari, Shiono Yuta, Matsumoto Morio

Clinical calcium 19 （ 10 ） 1442 - 1447 2009年10月

ISSN 0917-5857

Ossification of the longitudinal ligament in the spine is a disorder of unknown cause characterized by ectopic ossification. In the animal models of spinal hyperostosis, the vertebral ligament is gradually replaced by bony tissue forming an osseous bridge around enthesis, and a high turnover osteopenia occurs after the maturation in the trabecular bone of vertebrae. It has been suggested that the recruited vasculature facilitated the filling of the niche with host-derived haematopoietic cells during the ectopic ossification process. Recent data suggest that regulation of hematopoietic and osteogenic stem/progenitor cell populations may contribute to the formation of an ectopic spinal hyperostosis.

Novel apatite fiber scaffolds can promote three-dimensional proliferation of osteoblasts in rodent bone regeneration models.

Morisue Hikaru, Matsumoto Morio, Chiba Kazuhiro, Matsumoto Hideo, Toyama Yoshiaki, Aizawa Mamoru, Kanzawa Nobuyuki, Fujimi Takahiro J., Uchida Hiroshi, Okada Isao

Journal of biomedical materials research. Part A 90 （ 3 ） 811 - 818 2009年09月

We have successfully synthesized hydroxyapatite fibers via a homogenous precipitation method. Using these hydroxyapatite fibers, we have produced the apatite fiber scaffolds (AFS) with well-controlled pore sizes (porosity above 95%). The AFS is relatively simple to synthesize, and its porosity and pore size are controllable. The usefulness of AFS as a scaffold for bone regeneration was evaluated by (1) seeding and culturing cells in the AFS in vitro, (2) implanting the AFS seeded with cells inside the subcutaneous tissue of mice. The AFS had biocompatibility to support cell adhesion, proliferation, and differentiation. Ectopic bone formation could be formed in the AFS at 12 weeks after implantation into the subcutaneous tissue. Because of its high interpore connection, pore diameters, and porosity, it was believed that AFS was an effective scaffold that provided a three-dimensional cell culture environment. In both in vitro and in vivo environments, the more porous AFS was more advantageous in cell proliferation, cell adhesion, proliferating capacity, robust cell differentiation, ultimately inducing bone ingrowth inside the scaffolds.

Longitudinal magnetic resonance imaging study on whiplash injury patients

Ichihara Daisuke, Okada Eijiro, Chiba Kazuhiro, Toyama Yoshiaki, Fujiwara Hirokazu, Momoshima Suketaka, Nishiwaki Yuji, Hashimoto Takeshi, Ogawa Jun, Watanabe Masahiko, Takahata Takeshi, Matsumoto Morio

Journal of Orthopaedic Science 14 （ 5 ） 602 - 610 2009年09月

ISSN 0949-2658

Background: We conducted a prospective long-term follow-up study to assess associations between magnetic resonance imaging (MRI) findings and changes in clinical symptoms, as well as factors relating to the prognosis of symptoms. Methods: A total of 133 patients with acute whiplash injury between 1993 and 1996 participated in this follow-up study. They underwent neurological examinations by spine surgeons and second MRI scans of the cervical spine were obtained. They also filled out a questionnaire regarding cervical symptoms and the accident details. The items evaluated by MRI were (1) a decrease in the signal intensity of the intervertebral disc; (2) anterior compression of the dura and the spinal cord; (3) posterior disc protrusion; (4) disc space narrowing; and (5) foraminal stenosis. Relations between the presence/absence of degenerative changes on MRI, accident details, and patients' symptoms were assessed by calculating the adjusted odds ratio (OR). Results: Progression of some degenerative changes was recognized on MRI in 98.5% of the 133 whiplash injury patients, and clinical symptoms diminished in more than a half of the 133 patients. There were no statistically significant associations between MRI findings and changes in clinical symptoms. The prognosis for neck pain tended to be poor after accidents with double collisions (rear-end collision followed by frontend collision) [adjusted OR 5.83, 95% confidence interval (CI) 1.15-29.71] and accidents with serious car damage (2.87, 1.03-7.99). The prognosis for stiff shoulders tended to be poor in women (2.83, 1.23-6.51); and the prognosis for numbness in the upper extremities tended to be poor after accidents with serious car damage (3.39, 1.14-10.06). Conclusions: This study demonstrated that progression of degenerative changes of the cervical spine on MRI was not associated with clinical symptoms during the 10-year period after whiplash injury. © 2009 The Japanese Orthopaedic Association.

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IL-27 abrogates receptor activator of NF-κB ligand-mediated osteoclastogenesis of human granulocyte-macrophage colony-forming unit cells through STAT1-dependent inhibition of c-Fos

Furukawa Mitsuru, Takaishi Hironari, Takito Jiro, Yoda Masaki, Sakai Sadaoki, Hikata Tomohiro, Hakozaki Akihiro, Uchikawa Shinichi, Matsumoto Morio, Chiba Kazuhiro, Kimura Tokuhiro, Okada Yasunori, Matsuo Koichi, Yoshida Hiroki, Toyama Yoshiaki

Journal of Immunology 183 （ 4 ） 2397 - 2406 2009年08月

ISSN 0022-1767

IL-27 was first discovered as a factor supporting initial Th1 immune responses. Subsequent studies revealed that this cytokine has pleiotropic effects, including inhibition of certain immune cells, a regulatory role in hemopoietic stem cell differentiation, and antitumor activities. However, the role of human IL (hIL)-27 in human osteoclast precursors and inflammatory bone disease is unclear. Here, we examined the direct effect of hIL-27 on human osteoclastogenesis. Human bone marrow cells cultured in MethoCult medium containing human (h) GM-CSF, human stem cell factor, and hIL-3 expressed Mac-1, c-kit, and c-Fms. These cells, called hCFU-GMs, also expressed the IL-27 receptor, an IL-27Rα (WSX-1)/gp130 heterodimer. Cultivation in hM-CSF and human receptor activator of NF-κB ligand induced the differentiation of tartrate-resistant acid phosphatase-positive multinucleated cells (osteoclasts) from hCFU-GMs, and hIL-27 inhibited this osteoclastogenesis in a dose-dependent manner. hIL-27 also repressed bone resorption by osteoclasts on a dentine slice. hIL-27 caused a remarkable increase in STAT1 phosphorylation and enhanced the STAT1 protein level. It also inhibited the expression of receptor activator of NF-κB ligand-induced c-Fos and cytoplasmic, calcineurin-dependent 1 NFAT (NFATc1), which are indispensable transcription factors for osteoclastogenesis. Fludarabine, a STAT1 inhibitor, and STAT1 small interfering RNA partially rescued the inhibition of osteoclastogenesis by IL-27. A WSX-1 deficiency caused severe inflammatory bone destruction primed by Escherichia coli cell wall lysate in vivo. Therefore, hIL-27 may act as an anti-inflammatory cytokine in human bone destruction, by inhibiting osteoclastogenesis from hCFU-GMs via STAT1-dependent down-regulation of the transcription factor c-Fos. Our results suggest that hIL-27 may prove useful as a therapeutic target for inflammatory bone destruction. Copyright © 2009 by The American Association of Immunologists, Inc.

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Letters

Matsumoto Morio

Spine 34 （ 17 ） 1886 2009年08月

ISSN 0362-2436

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Intramedullary solitary fibrous tumor of the spinal cord

Ishii Ken, Nakamura Masaya, Matsumoto Morio, Mukai Makio, Toyama Yoshiaki, Chiba Kazuhiro

Journal of Orthopaedic Science 14 （ 4 ） 450 - 454 2009年07月

ISSN 0949-2658

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Clinical significance and prognosis of idiopathic syringomyelia

Nakamura Masaya, Ishii Ken, Watanabe Kota, Tsuji Takashi, Matsumoto Morio, Toyama Yoshiaki, Chiba Kazuhiro

Journal of Spinal Disorders and Techniques 22 （ 5 ） 372 - 375 2009年07月

ISSN 1536-0652

STUDY DESIGN: Retrospective case series. OBJECTIVE: To determine the clinical significance and prognosis of idiopathic syringomyelia. SUMMARY OF BACKGROUND DATA: With the widespread use of magnetic resonance imaging, cases of syringomyelia are found occasionally. However, the clinical significance and optimum treatment strategy for idiopathic syringomyelia remain unclear, because there are few reports on details of this condition. METHODS: The clinical records and magnetic resonance images of 15 patients with idiopathic syringomyelia were reviewed to determine the changes in patient's neurologic status assessed by the Japanese Orthopedic Association scores for cervical myelopathy and the distribution of the syringomyelia on magnetic resonance imaging. Twelve cases were treated conservatively (conservative group) and syringo-subarachnoid shunt was performed in the remaining 3 cases (surgical group). The follow-up period ranged from 7 to 20 years (mean: 10.5 y). RESULTS: The localized type of idiopathic syringomyelia, which extended under 3 vertebras (mean: 2.1 vertebras), was observed in the 12 patients of the conservative group. There were no significant changes in either the size of the syringomyelia or the severity of the neurologic deficits during the follow-up period (mean: 10 y). In contrast, the extended type, which distributed over 4 or more vertebras (mean: 10.2 vertebras), was observed in the 3 patients of the surgical group. Because of severe and progressive neurologic deficits, syringo-subarachnoid shunt was performed and the surgery successfully prevented further neurologic deterioration. The mean Japanese Orthopedic Association score of the surgical group was significantly lower than that of the conservative group, both at the time of the initial examination and at the final follow-up. CONCLUSIONS: There are 2 types of idiopathic syringomyelia. One is a "localized" type, which might represents congenital enlargement of the central canal of the spinal cord, and can be managed conservatively. The other is an "extended" type, which causes progressive neurologic dysfunction, and should be treated surgically to prevent further neurologic deterioration. Further study should be needed to clarify the mechanism of the extended type of idiopathic syringomyelia. © 2009 Lippincott Williams & Wilkins, Inc.

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Diagnostic validity of space available for the spinal cord at C1 level for cervical myelopathy in patients with rheumatoid arthritis

Oda Takenori, Yonenobu Kazuo, Fujimura Yoshikazu, Ishii Yushin, Nakahara Shinnosuke, Matsunaga Shunji, Shimizu Takachika, Matsumoto Morio

Spine 34 （ 13 ） 1395 - 1398 2009年06月

ISSN 0362-2436

STUDY DESIGN. Retrospective cohort study. OBJECTIVE. To evaluate diagnostic validity of space available for the spinal cord (SAC) at C1 level for myelopathy in patients with rheumatoid arthritis (RA). SUMMARY OF BACKGROUND DATA. The relationship of SAC at C1 level with myelopathy has been evaluated by relatively small number of the patients, and 2 criteria have been proposed. METHODS. Two cohorts of the patients with RA were established. Group A consisted of 140 patients with myeopathy due to upper cervical involvement selected from the database. Group B consisted of 99 patients with upper cervical subluxation, but not associated with myelopathy selected from the consecutive series of the hospitalized patients. Distributions of SAC at C1 level in both groups were evaluated. Efficacy indexes for screening (sensitivity, specificity, etc.) were calculated for these patients' population by previously demonstrated 2 criteria. In addition, analysis according to receiver operating characteristic (ROC) curve was performed. RESULTS. The average values of SAC were 11.1 mm in Group A and 16.5 mm in Group B. When cut-off point for myelopathy was defined as 13 mm or less, sensitivity and specificity were 82% and 85%, respectively. When it was defined as 14 mm or less, sensitivity increased (88%) while specificity decreased (74%). Accuracies by these 2 criteria were almost the same (83%, 82%). The left upper corner point of ROC curve was located between these 2 cut-off points. CONCLUSION. Distributions of SAC showed that SAC was a reliable parameter for relating myelopathy in patients with upper cervical subluxation in RA. The plots according to ROC curve showed adequacy of previously demonstrated 2 cut-off points. For the purpose to screen the patients with high risk for myelopathy, 14 mm or less was recommended as a cut-off point of SAC. © 2009 Lippincott Williams & Wilkins, Inc.

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Long-term impact of atlantoaxial arthrodesis on the pediatric cervical spine

Ishikawa Masayuki, Matsumoto Morio, Chiba Kazuhiro, Toyama Yoshiaki, Kobayashi Keiji

Journal of Orthopaedic Science 14 （ 3 ） 274 - 278 2009年05月

ISSN 0949-2658

Background: This study was conducted to elucidate radiographically the long-term impact of atlantoaxial arthrodesis on the pediatric cervical spine. Methods: The records of eight children who underwent atlantoaxial arthrodesis for the treatment of upper cervical spinal disorders and were followed up to their adulthood were retrospectively reviewed. Changes in the curvature of the whole cervical spine, and anteroposterior diameters of the spinal canal at C1 and C2 levels were investigated on lateral radiographs before surgery, at 6 months after surgery, and at the final follow-up. Results: The cervical curvature was lordosis or straight before surgery in all children and became sigmoid in six children at 6 months after surgery. At the final follow-up, three of the six children with postoperative sigmoid curvatures regained some degree of lordosis and became straight. The anteroposterior diameters of the spinal canal at C1 and C2 levels did not increase during the follow-up period. Conclusions: Development of postoperative malalignment of the lower cervical spine and impaired growth of the spinal canal at C1 and C2 levels are common after atlantoaxial arthrodesis in children. Postoperative malalignment diminishes during the follow-up period possibly due to remodeling of the pediatric cervical spine, although remodeling of the spinal canal diameter cannot be expected, suggesting the importance of anatomical reduction before or at the time of surgery. © 2009 The Japanese Orthopaedic Association.

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Aging of the cervical spine in healthy volunteers

Spine 34 （ 7 ） 706 - 712 2009年04月

ISSN 0362-2436

STUDY DESIGN.: Prospective longitudinal study, mean follow-up period; 11.7 ± 0.8 years was conducted from 1995 to 2007. OBJECTIVE.: To clarify normal aging process of cervical spine and correlation between progression of disc degeneration and development of clinical symptoms. SUMMARY OF BACKGROUND DATA.: Aging of the cervical spine can inevitably occur in anyone. Long-term longitudinal studies following the same individuals are necessary to elucidate the accurate aging processes of the cervical spine. METHODS.: Two hundred twenty-three subjects of 497 original cohorts (123 men, 100 women, mean age: 39.0 ± 15.0, follow-up rate: 44.9%). Subjects, who underwent MRI 10 years ago, underwent another MRI, neurologic examination, and questionnaire survey regarding symptoms related to cervical spine and life style. Following 5 MR findings representing intervertebral disc degeneration were evaluated: (1) decrease in signal intensity of disc, (2) anterior compression of dura and spinal cord, (3) posterior disc protrusion (PDP), (4) disc space narrowing (DSN), and (5) foraminal stenosis (FS). RESULTS.: Progression of degenerative findings was observed in 189 subjects (81.1%). Progression of decrease in signal intensity of disc was observed in 59.6%, anterior compression of dura and spinal cord in 61.4%, PDP in 70.0%, DSN in 26.9%, and FS in 9.0%. Logistic regression analysis revealed that incidence of progression of PDP, DSN, FS was higher in elderly subjects. There were no correlations between any degenerative MR findings and sex, smoking, alcohol, sport, or body mass index. Neck pain, shoulder stiffness, and numbness in upper extremities were recognized in 9.9%, 30.0%, and 4.0% of subjects, and 1 or more clinical symptoms have developed in 34.1% during 10 years. CONCLUSION.: Progression of degeneration of cervical spine on MRI was frequently observed during 10-year period, with development of symptoms in 34% of subjects. No factor related to progression of degeneration of cervical spine was identified except for age. © 2009, Lippincott Williams & Wilkins.

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Nocturnal leg cramps

Matsumoto Morio, Watanabe Kota, Tsuji Takashi, Ishii Ken, Takaishi Hironari, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro, Michikawa Takehiro, Nishiwaki Yuji

Spine 34 （ 5 ） 2009年03月

ISSN 0362-2436

STUDY DESIGN.: Questionnaire survey on leg cramps for patients with lumbar spinal canal stenosis (LCS). OBJECTIVE.: To evaluate the prevalence of leg cramps in patients with LCS treated surgically and the relationship between leg cramps and the surgical outcomes. SUMMARY OF BACKGROUND DATA.: Although it has been anecdotally reported that LCS patients have suffered from leg cramps, the true prevalence remains unknown. METHODS.: One hundred twenty LCS patients who underwent decompression surgery (men 85, women 35, mean age 73.5) and 370 elderly subjects from the general population (men 162, women 208, mean age 75.6) were enrolled in the study. The participants filled in a questionnaire regarding: (all participants) (1) experience of leg cramps, (2) frequency and time of the day of the cramp attacks; (for LCS patients only), (3) changes in cramps before and after surgery, (4) activities of daily living disturbance because of leg cramps, (5) satisfaction with surgery and walking ability, (6) the Roland-Morris Disability Questionnaire, and (7) the Oswestry Disability Index. RESULTS.: Eighty-five (70.8%) patients with LCS and 137 (37.2%) of the control population experienced leg cramps (age and sex adjusted odds ratio; 4.6, P < 0.01). Leg cramps occurred once or twice a week in 34.9% of the LCS group and once in several months in 44.5% of the control group, and occurred nocturnally in 73.3% of the LCS patients and in 91.6% of the control group. In LCS patients, leg cramps improved after surgery in 18.2%, remained unchanged in 45.5%, and worsened in 26.1%, and activities of daily living were disturbed in 47.6%. There was no significant difference in satisfaction with surgery, the Oswestry Disability Index, the Roland-Morris Disability Questionnaire scores, or walking ability between the LCS patients with or without leg cramps. CONCLUSION.: LCS patients had significantly more frequent attacks of nocturnal leg cramps than the control population, and leg cramps disturbed the quality of the patients' life, and they rarely improved after decompression surgery. Leg cramps should be recognized as one of the symptoms of LCS, which disturb the patients' quality of life. © 2009, Lippincott Williams & Wilkins.

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A rigid body and spring model of the lumbar spine which considers the mechanical loads at the bone-screw interface

Kiriyama Yoshimori, Matsumoto Morio, Toyama Yoshiaki, Andriacchi Thomas P., Nagura Takeo

1241 - 1242 2009年

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Response

Matsumoto Morio, Chiba Kazuhiro, Toyama Yoshiaki

Journal of Neurosurgery: Spine 9 （ 6 ） 528 - 529 2008年12月

ISSN 1547-5654

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Risk factors for closure of lamina after open-door laminoplasty

Matsumoto Morio, Watanabe Kota, Tsuji Takashi, Ishii Ken, Takaishi Hironari, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro

Journal of Neurosurgery: Spine 9 （ 6 ） 530 - 537 2008年12月

ISSN 1547-5654

Object. This retrospective study was conducted to evaluate the prevalence and clinical consequences of postoperative lamina closure after open-door laminoplasty and to identify the risk factors. Methods. Eighty-two consecutive patients with cervical myelopathy who underwent open-door laminoplasty without plates or spacers in the open side (Hirabayashi's original method) were included (62 men and 20 women with a mean age of 62 years and a mean follow-up of 1.8 years). In 67 patients the cause of cervical myelopathy was spondylotic myelopathy, and in 15 it was caused by ossification of posterior longitudinal ligament. Radiographic measurements were made of the anteroposterior diameters of the spinal canal and vertebral bodies from C3-6, and the presence of kyphosis were assessed. Lamina closure was defined as ≥ 10% decrease in the canal-to-body ratio at the final follow-up compared with that immediately after surgery at ≥ 1 vertebral level. The impact of lamina closure on neck pain, patient satisfaction, Japanese Orthopaedic Association scores, and recovery rates were also evaluated. Results. The mean canal-to-body ratio at C3-6 was 0.69-0.72 preoperatively, 1.25-1.28 immediately after surgery, and 1.18-1.24 at the final follow-up examination. Lamina closure was observed in 34% of patients and was not associated with sex, age, or cause of myelopathy, but was significantly associated with the presence of preoperative kyphosis (p = 0.014). Between patients with and without lamina closure, there was no significant difference in preoperative (9.7 ± 3.1 vs 10.6 ± 2.5) and postoperative (13.7 ± 2.4 vs 13.1 ± 2.7) Japanese Orthopaedic Association scores, recovery rates (53.9 ± 29.9% vs 44.3 ± 29.5%), neck pain scores (3.5 ± 0.7 vs 3.3 ± 1.0), or patient satisfaction level (4.0 ± 1.4 vs 4.8 ± 1.0). Conclusions. Lamina closure at ≥ 1 vertebral level occurred in 34% of patients. Although patients with lamina closure obtained equivalent recovery from myelopathy in a short-term follow-up, they tended to be less satisfied with surgery compared with those who did not have closure. The only significant risk factor identified was the presence of preoperative cervical kyphosis, and preventative methods for lamina closure, therefore, should be considered for patients with preoperative kyphosis.

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Vascular endothelial growth factor-A is a survival factor for nucleus pulposus cells in the intervertebral disc

Fujita Nobuyuki, Imai Jun ichi, Suzuki Toru, Yamada Masayuki, Ninomiya Ken, Miyamoto Kana, Iwasaki Ryotaro, Morioka Hideo, Matsumoto Morio, Chiba Kazuhiro, Watanabe Shinya, Suda Toshio, Toyama Yoshiaki, Miyamoto Takeshi

Biochemical and Biophysical Research Communications 372 （ 2 ） 367 - 372 2008年07月

ISSN 0006-291X

The intervertebral disc (IVD) is composed of two avascular tissue types, the nucleus pulposus (NP) and the annulus fibrosus (AF). IVDs is the largest avascular tissue in the human body, however, how these tissues are maintained without a blood supply is poorly understood. Here we show that vascular endothelial growth factor-A (VEGF-A) is highly expressed in NP and that VEGF-A plays a role in NP survival. High VEGF-A expression in NP was detected by microarray analysis, and NP was positive for the hypoxic probe pimonidazole and hypoxia-responsive genes. VEGF-A expression in NP was promoted by hypoxic conditions in vitro. NP cells also expressed the membrane-bound VEGF receptor-1 (VEGFR-1), and the number of apoptotic cells in cultured cell model of NP increased following treatment with VEGFR-1-Fc, which traps VEGF-A in NP. These results indicate that NP is a hypoxic tissue, and that VEGF-A functions in NP survival in an autocrine/paracrine manner. © 2008 Elsevier Inc. All rights reserved.

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Radiographic predictors of residual low back pain after laminectomy for lumbar spinal canal stenosis

Xia Yingpeng, Ishii Ken, Matsumoto Morio, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro

Journal of Spinal Disorders and Techniques 21 （ 3 ） 153 - 158 2008年05月

ISSN 1536-0652

STUDY DESIGN: Retrospective study of patients who underwent laminectomy for unification. OBJECTIVE: To identify radiographic predictors of residual low back pain (LBP) after laminectomy for lumbar spinal canal stenosis (LCS). SUMMARY OF BACKGROUND DATA: Residual LBP is a common complication of laminectomy and no radiographic predictors of its occurrence have been identified previously. METHODS: Clinical results and radiographic findings in 49 patients (21 males and 28 females, minimum 5-year follow-up) who underwent single level laminectomy for LCS were retrospectively reviewed. Patients who had an improvement in LBP scores in the Japanese Orthopedic Association (JOA) scoring system during the follow-up periods were classified as the recovery group, whereas those without improvements were classified as the nonrecovery group. Patients' clinical data (sex, duration of symptoms, age at surgery, JOA scores) and radiographic parameters (including lumbar lordotic angle, lumbar range of motion (ROM) and the intervertebral rotational angle) were analyzed to detect the factors significantly related with the occurrence of residual LBP. RESULTS: The average preoperative JOA score of 14.8±5.1 points improved to 21.6±5.5 points at the final follow-up providing an average recovery rate of 48.1±36.8%. Thirty-four and 15 patients were classified into the recovery and the nonrecovery groups, respectively. Binary logistic regression analysis revealed that significant predictors of residual LBP were preoperative lumbar lordosis angle and lumbar ROM. The mean preoperative lumbar lordosis and ROM in the nonrecovery group were significantly smaller than those in the recovery group (lordosis: 25.3±15.8 degrees vs. 37.8±13.6 degrees, P=0.006 and ROM: 22.1±10.6 degrees vs. 31.2±9.9 degrees, P=0.006). In addition, increase of the postoperative lumbar ROM was significantly larger in the nonrecovery than that in the recovery group (P=0.009). CONCLUSIONS: Our results indicate that preoperative lordosis angle and lumbar ROM were the significant radiographic predictors for residual LBP after laminectomy for LCS. Patient with flatback and limited lumbar mobility before surgery are prone to suffer residual LBP. It is suggested that these sagittal radiographic parameters should be taken into account when choosing laminectomy as the surgical option for LCS. © 2008 Lippincott Williams & Wilkins, Inc.

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Surgical treatment of intramedullary spinal cord tumors

Nakamura M., Ishii K., Watanabe K., Tsuji T., Takaishi H., Matsumoto M., Toyama Y., Chiba K.

Spinal Cord 46 （ 4 ） 282 - 286 2008年04月

ISSN 1362-4393

Study design: Retrospective case series. Objective: To evaluate our recent treatment strategy for intramedullary spinal cord tumors. Setting: Department of Orthopaedic Surgery, Keio University, Japan. Methods: We reviewed 68 cases of intramedullary tumors (ependymoma, 33; astrocytoma, 23; hemangioblastoma, 12), treated surgically between 1994 and 2003. There were 42 males and 26 females whose mean age at the time of surgery was 43 years. The mean follow-up period was 6.2 years. The tumor malignancy grade according to the WHO classification was astrocytoma grade I, 3; grade II, 8 (low-grade: 11 cases); grade III, 10; grade IV, 2 (high-grade: 12 cases). All ependymomas were grade II. Three of the 12 hemangioblastomas were associated with von Hippel-Lindau disease. Results: Total excision was achieved in 90% of the ependymomas and functional improvement was obtained when the preoperative neurological deficit was mild. Approximately 50% of low-grade astrocytomas could be totally excised with favorable survival outcomes, suggesting that total excision should be attempted for low-grade astrocytomas. However, total excision of high-grade tumors was difficult and the functional outcomes were poor. Cordotomy should be considered in patients with a thoracic high-grade astrocytoma. Total resection was possible in 92% of hemangioblastoma, and the functional outcomes were good, however, more attention should be paid for tumors with feeding arteries on the ventral side and for those associated with von Hippel-Lindau disease. Conclusions: Predictors of good surgical outcome for intramedullary spinal cord tumors were histological grades of the tumors, surgical margins, and neurological status of the patient before surgery. © 2008 International Spinal Cord Society All rights reserved.

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Surgical results and related factors for ossification of posterior longitudinal ligament of the thoracic spine

Matsumoto Morio, Chiba Kazuhiro, Toyama Yoshiaki, Takeshita Katsushi, Seichi Atsushi, Nakamura Kozo, Arimizu Jun, Fujibayashi Shunsuke, Hirabayashi Shigeru, Hirano Toru, Iwasaki Motoki, Kaneoka Kouji, Kawaguchi Yoshiharu, Ijiri Kosei, Maeda Takeshi, Matsuyama Yukihiro, Mikami Yasuo, Murakami Hideki, Nagashima Hideki, Nagata Kensei, Nakahara Shinnosuke, Nohara Yutaka, Oka Shiro, Sakamoto Keizo, Saruhashi Yasuo, Sasao Yutaka, Shimizu Katsuji, Taguchi Toshihiko, Takahashi Makoto, Tanaka Yasuhisa, Tani Toshikazu, Tokuhashi Yasuaki, Uchida Kenzo, Yamamoto Kengo, Yamazaki Masashi, Yokoyama Toru, Yoshida Munehito, Nishiwaki Yuji

Spine 33 （ 9 ） 1034 - 1041 2008年04月

ISSN 0362-2436

STUDY DESIGN. Retrospective multi-institutional study OBJECTIVE. To describe the surgical outcomes in patients with ossification of the posterior longitudinal ligament in the thoracic spine (T-OPLL) and to clarify factors related to the surgical outcomes. SUMMARY OF BACKGROUND DATA. Detailed analyses of surgical outcomes of T-OPLL have been difficult because of the rarity of this disease. METHODS. The subjects were 154 patients with T-OPLL who were surgically treated at 34 institutions between 1998 and 2002. The surgical procedures were laminectomy in 36, laminoplasty in 51, anterior decompression via anterior approach in 25 and via posterior approach in 29, combined anterior and posterior fusion in 8, and sternum splitting approach in 5 patients. Instrumentation was conducted in 52 patients. Assessments were made on (1) The Japanese Orthopedic Association (JOA) scores (full score, 11 points), its recovery rates, (2) factors related to surgical results, and (3) complications and their consequences. RESULTS. (1) The mean JOA score before surgery was 4.6 ± 2.0 and, 7.1 ± 2.5 after surgery. The mean recovery rate was 36.8% ± 47.4%. (2) The recovery rate was 50% or higher in 72 patients (46.8%). Factors significantly related to this were location of the maximum ossification (T1-T4) (odds ratio, 2.43-4.17) and the use of instrumentation (odds ratio, 3.37). (3) The frequent complications were deterioration of myelopathy immediately after surgery in 18 (11.7%) and dural injury in 34 (22.1%) patients. CONCLUSION. The factors significantly associated with favorable surgical results were maximum ossification located at the upper thoracic spine and use of instrumentation. T-OPLL at the nonkyphotic upper thoracic spine can be treated by laminoplasty that is relatively a safe surgical procedure for neural elements. The use of instrumentation allows correction of kyphosis or prevention of progression of kyphosis, thereby, enhancing and maintaining decompression effect, and its use should be considered with posterior decompression. © 2008 Lippincott Williams & Wilkins, Inc.

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Biological evaluation of chelate-setting apatite cement using inositol phosphate

Kida K., Horiguchf Y., Oribe K., Morisue H., Matsumoto M., Toyama Y., Aizawa M.

Key Engineering Materials 361-363 I 335 - 338 2008年

ISSN 1013-9826

We have successfully developed novel "chelate-setting apatite cement" using hydroxyapatite (HAp) particles surface-modified with inositol phosphate (IP₆) . The HAp particles surface-modified with IP ₆ were mixed with water (HAp/water ratio = 1.00/0.50[w/w]) to fabricate apatite cements. We have examined the biocompatibility of the apatite cement using the culture system of MC3T3-E1 cells and the rabbit model. The cell-culture test using MC3T3-E1 cells has shown that the apatite cement has noncytotoxicity. This cement has been implanted into tibiae of rabbits. When tissue response was examined histologically up to 24 weeks, new bone formation was observed around the surface of the cement. The present work demonstrates that this apatite cement is useful as a material for artificial bone grafting.

Microendoscopic discectomy for lumbar disc herniation with bony fragment due to apophyseal separation

Matsumoto M., Watanabe K., Tuji T., Ishii K., Takaishi H., Nakamura M., Chiba K., Toyama Y.

Minimally Invasive Neurosurgery 50 （ 6 ） 335 - 339 2007年12月

ISSN 0946-7211

The purpose of this study was to elucidate the feasibility of microendoscopic discectomy (MED) for the treatment of lumbar disc herniation with a bony fragment due to apophyseal separation. Eighteen patients with low back pain and unilateral sciatic pain due to lumbar disc herniation with a bony fragment were treated by MED using the unilateral approach (15 males and three females; mean age, of 28.9 years; mean follow-up period, 21.1 months); 18 age-and sex-matched patients with lumbar disc herniation without a bony fragment treated by MED served as the control group. The clinical outcomes were evaluated using the Japanese Orthopedic Association Score for Low Back Pain (JOA scores; maximum score, 29 points). Evaluation of the results revealed that good surgical outcomes equivalent to those in the control group were obtained in the subjects of LDH with a bony fragment (JOA scores; 14.1±3.5 in the patient group vs. 15.4±2.6 in the control group before surgery; 26.3±1.8 in the patient group vs. 26.9±1.3 at follow-up after the surgery). Although the mean surgical time was significantly longer in the patient group, there were no intra- or postoperative complications in either group. We conclude that MED using the unilateral approach is a feasible minimally invasive surgical option for patients of lumbar disc herniation with an apophyseal bony fragment. © Georg Thieme Verlag KG Stuttgart.

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Traction versus supine side-bending radiographs in determining flexibility

Watanabe Kota, Kawakami Noriaki, Nishiwaki Yuji, Goto Manabu, Tsuji Taichi, Obara Tetsuya, Imagama Shiro, Matsumoto Morio

Spine 32 （ 23 ） 2604 - 2609 2007年11月

ISSN 0362-2436

STUDY DESIGN. Prospective clinical, radiologic study of adolescent idiopathic scoliosis (AIS). OBJECTIVE. We evaluated a Cobb angle in standing position, patient age, the level of the apex, and the number of involved vertebrae in patients with AIS to determine whether the corrective ability of traction or side-bending radiographs was superior. SUMMARY OF BACKGROUND DATA. Side-bending and traction radiographs are used to evaluate curve flexibility during corrective surgery for AIS despite notable differences in the flexibilities of identical curves. Thus, interpretation for the differences among these techniques should be investigated. METHODS. A total of 229 consecutive patients with AIS who were surgically treated were evaluated. Standing, supine side-bending, and traction radiographs were obtained before surgery. Curves were divided into main thoracic (MT) or thoracolumbar/lumbar (TL/L) curves, and proximal thoracic (PT) curves. We evaluated the Cobb angle in standing position, the level of the apex, the number of involved vertebrae, kyphosis angle of main thoracic curve, and patient age in patients with AIS to determine whether the corrective ability of traction or side-bending radiographs was superior. RESULTS. A total of 219 curves were observed in MT lesions. The traction flexibility rate (FR) was higher than the side-bending FR at angle of ≥60° (P = 0.02), in patients younger than 15 years (P = 0.02), in curves whose apex was located at T4-T8/T9(P = 0.01), in curves whose involved vertebrae were 6 or 7 (P = 0.02), and at kyphosis angle between 10° and 39° (P = 0.02). In 96 TL/L curves, side-bending FR was higher at angle of <60° (P < 0.01). In 163 PT curves, traction FR was higher at angles of ≥40° (P = 0.02). CONCLUSION. In addition to a Cobb angle, patient age, the level of the apex, and the number of involved vertebrae also influence the conditions under which the corrective ability of traction radiographs is superior to that of side-bending radiographs. © 2007 Lippincott Williams & Wilkins, Inc.

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The validity of intraoperative angiography for the treatment of spinal arteriovenous fistula

Xia Yingpeng, Ishii Ken, Nakamura Masaya, Onozuka Satoshi, Ueda Ryo, Matsumoto Morio, Chiba Kazuhiro, Toyama Yoshiaki

Journal of Spinal Disorders and Techniques 20 （ 6 ） 442 - 448 2007年08月

ISSN 1536-0652

STUDY DESIGN: Retrospective study of patients with spinal arteriovenous fistula (AVF) who underwent surgical treatment. OBJECTIVE: To evaluate the validity of the intraoperative angiography (IA) for the surgical treatment of spinal AVF. SUMMARY OF BACKGROUND DATA: Owing to the development of interventional techniques, endovascular embolization has become the treatment of choice for AVF, but it is not applicable for every spinal AVF owing to anatomic complexity of the spinal cord vessels. To get effective occlusion of the AVF, IA has been routinely used in the management of cerebral vascular diseases, but report of its use for spinal AVF is rare. METHODS: Since 2004, 4 consecutive cases of spinal AVF (3 males and 1 female, 3 thoracic, and 1 thoracolumbar) were involved in this study. The mean age at the time of operation was 62.3 years (range from 48 to 76 y). Types of AVFs and surgical techniques were reviewed retrospectively and the outcomes were assessed using the Japanese Orthopedic Association scoring system. RESULTS: AVFs in 3 patients were diagnosed as the dural type and that in the remaining patient as the perimedullary type; all feeding arteries were derived from the ninth to 10th intercostal arteries. Preoperative angiography demonstrated that the feeding arteries in 2 patients with a dural AVF were the branches of Adamkiewicz artery and in another dural AVF case, the Adamkiewicz artery could not be determined, therefore, endovascular embolization was not feasible. Including a patient with perimedullary AVF, a microsurgical clipping combined with IA was selected as the treatment. Complete occlusion of the fistula was achieved in all cases, the mean preoperative Japanese Orthopedic Association score of 4.5 improved to 6 at the final follow-up, and no perioperative complications were observed during the follow-up period. CONCLUSIONS: The favorable clinical results in our spinal AVF cases confirmed that IA ensures safe and accurate occlusion of the fistula. This technique provides satisfactory surgical results for spinal AVFs. © 2007 Lippincott Williams & Wilkins, Inc.

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Extensive total spondylectomy for recurrent giant cell tumor in the thoracic spine. Case report

Matsumoto Morio, Ishii Ken, Takaishi Hironari, Nakamura Masaya, Morioka Hideo, Chiba Kazuhiro, Takahata Takeshi, Toyama Yoshiaki

Journal of Neurosurgery: Spine 6 （ 6 ） 600 - 605 2007年06月

ISSN 1547-5654

The authors report the case of a 47-year-old woman who harbored a giant cell tumor at the T-5 level. She had undergone curettage of the tumor via a combined anterior and posterior approach at a regional hospital and was later referred to the authors' institution for treatment after the tumor recurred. On examination she exhibited progressive paraparesis and was nonambulatory due to cord compression caused by the tumor, which had invaded the spinal canal and extended to the right paravertebral muscles and right thoracic cavity. A spondylectomy was performed through a single posterior approach. The tumor, together with a portion of the dura mater, pleura, and muscles, was resected en bloc from T-4 to T-6. After resection, spinal reconstruction was performed by placement of an anterior titanium mesh cage as well as posterior pedicle screw and rod instrumentation. The patient's postoperative course was uneventful, and she exhibited substantial neurological recovery and became ambulatory. Two and a half years after surgery, the patient was tumor free. En bloc resection of a recurrent giant cell tumor was successfully achieved through a single posterior approach. This surgical technique can be an effective option for this pathological condition, which is difficult to manage using other conventional treatment options including repeated curettage and radiotherapy.

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A functional polymorphism in COL11A1, which encodes the α1 chain of type XI collagen, is associated with susceptibility to lumbar disc herniation

Mio Futoshi, Chiba Kazuhiro, Hirose Yuichiro, Kawaguchi Yoshiharu, Mikami Yasuo, Oya Takeshi, Mori Masaki, Kamata Michihiro, Matsumoto Morio, Ozaki Kouichi, Tanaka Toshihiro, Takahashi Atsushi, Kubo Toshikazu, Kimura Tomoatsu, Toyama Yoshiaki, Ikegawa Shiro

American Journal of Human Genetics 81 （ 6 ） 1271 - 1277 2007年

ISSN 0002-9297

Lumbar disc herniation (LDH), degeneration and herniation of the nucleus pulposus of the intervertebral disc (IVD) of the lumbar spine, is one of the most common musculoskeletal diseases. Its etiology and pathogenesis, however, remain unclear. Type XI collagen is important for cartilage collagen formation and for organization of the extracellular matrix. We identified an association between one of the type XI collagen genes, COL11A1, and LDH in Japanese populations. COL11A1, which encodes the a1 chain of type XI collagen, was highly expressed in IVD, but its expression was decreased in the IVD of patients with LDH. The expression level was inversely correlated with the severity of disc degeneration. A single-nucleotide polymorphism (c.4603C→T [rs1676486]) had the most significant association with LDH (P = 3.3 × 10^-6), and the transcript containing the disease-associated allele was decreased because of its decreased stability. These observations indicate that type XI collagen is critical for IVD metabolism and that its decrease is related to LDH. © 2007 by The American Society of Human Genetics. All rights reserved.

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Surgical outcomes of spinal cord astrocytomas

Nakamura M., Chiba K., Ishii K., Ogawa Y., Takaishi H., Matsumoto M., Toyama Y.

Spinal Cord 44 （ 12 ） 740 - 745 2006年12月

ISSN 1362-4393

Study design:Retrospective case series.Objectives:To analyze prognostic factors for patients with spinal cord astrocytomas.Setting:Department of Orthopaedic Surgery, Keio University, Japan.Methods:Seven patients received total excisions (group T), eight underwent partial excisions (group P), and 15 had excisional biopsies (group B). Impacts of the tumor histological grade, the level of the tumor, the types of surgical interventions, and the use of adjuvant radiotherapies on the survival and functional outcomes of 30 patients (18 in low-grade and 12 high-grade malignancy tumors) were analyzed.Results:The survival rate of the low-grade malignancy group was significantly higher than that of the high-grade group. The survival rate of the patients with thoracic astrocytomas was significantly higher than those with cervical astrocytomas. In both the low- and high-grade groups, the survival rates in groups P/T were significantly higher than those in group B. In the low-grade group, five patients, whose preoperative functional statuses were classified as 'fair' or better, remained 'fair' or better after surgery. In the high-grade group, the postoperative functional statuses were classified as 'no change' or 'aggravated' in all except two patients. No significant difference in the survival rates was detected between patients with and without adjuvant radiotherapy.Conclusions: The tumor grade and the extent of tumor resection were significant prognostic factors for survival rate. In low-grade malignancy group, good motor function was retained when surgeries were performed before substantial neurological deterioration. The efficacy of postoperative radiotherapy has yet to be determined and needs further study. © 2006 International Spinal Cord Society All rights reserved.

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Long-term results of expansive open-door laminoplasty for cervical myelopathy - Average 14-year follow-up study

Chiba Kazuhiro, Ogawa Yuto, Ishii Ken, Takaishi Hironari, Nakamura Masaya, Maruiwa Hirofumi, Matsumoto Morio, Toyama Yoshiaki

Spine 31 （ 26 ） 2998 - 3005 2006年12月

ISSN 0362-2436

STUDY DESIGN. Retrospective case series on long-term follow-up results of original expansive open-door laminoplasty for cervical myelopathy due to cervical spondylosis (CSM) and ossification of posterior longitudinal ligament (OPLL). OBJECTIVES. To elucidate efficacy and problems of original open-door laminoplasty to improve future surgical outcomes. SUMMARY OF BACKGROUND DATA. Little information is available on long-term outcomes of original open-door laminoplasty without grafts, implants, or instruments. METHOD. The study group included 80 patients who underwent original open-door laminoplasty and were followed for minimum 10 years. Clinical results, including Japanese Orthopedic Association scores, recovery rates, occurrences of complications, and long-term deterioration were investigated. Cervical alignments, type of OPLL, cervical range of motion, anteroposterior diameter of spinal canal, and progression of OPLL were assessed on plain radiographs. Spinal cord decompression was verified on magnetic resonance imaging. RESULTS. Average Japanese Orthopedic Association score and recovery rate improved significantly until 3 years after surgery and remained at an acceptable level in both cervical spondylosis and OPLL patients with slight deterioration after 5 years. Segmental motor palsy developed in 8 patients. Late deterioration, mainly lower extremity motor score decline, developed in 8 CSM and 16 OPLL patients. Overall cervical range of motion decreased by 36%. Patients with cervical lordosis decreased gradually in both patient groups. Such changes in alignments did not affect surgical results in CSM patients, while OPLL patients with preoperative kyphosis had lower recovery rates than those with straight and lordotic alignments. OPLL progression that was detected in 66% of patients did not affect clinical results. Although infrequent, magnetic resonance imaging revealed atrophy of spinal cord, spinal cord compression at adjacent segments due to degenerative changes and OPLL progression. CONCLUSIONS. Long-term results of open-door laminoplasty without bone graft, graft substitutes, or instruments were satisfactory. However, segmental motor paralysis, kyphosis, established before and after surgery, OPLL progression, and late deterioration due to age-related degeneration remain challenging problems. © 2006 Lippincott Williams & Wilkins, Inc.

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Postoperative factors affecting neurological recovery after surgery for cervical spondylotic myelopathy

Ogawa Yuto, Chiba Kazuhiro, Matsumoto Morio, Nakamura Masaya, Takaishi Hironari, Toyama Yoshiaki

Journal of Neurosurgery: Spine 5 （ 6 ） 483 - 487 2006年12月

ISSN 1547-5654

Object. Many prognostic factors associated with surgery for cervical spondylotic myelopathy (CSM) have been detailed in the literature. All of these factors, however, are defined preoperatively. If it is possible to clarify factors influencing surgical results that can be modulated after surgery, then the overall results of surgery may improve. The purpose of this study was to elucidate such postoperative factors affecting neurological recovery. Methods. The authors assessed the surgical outcomes obtained in 183 patients with CSM who underwent expansive open-door laminoplasty between 1993 and 2004 and who underwent follow up for a minimum of 1 year. They classified the cases into two groups according to the degree of neurological recovery: an excellent recovery group, comprising patients in whom the recovery rates were greater than 75%, and a poor recovery group, composed of patients in whom the recovery rates were lower than 30%. Comparisons of various clinical and imaging parameters revealed that the mean age at surgery was significantly lower in patients in the excellent recovery group than that in the poor recovery group. Therefore, the authors repeated the same analyses after adjustment for age. Postoperative cervical range of motion (ROM) was significantly more reduced in the excellent recovery group than in the poor recovery group. There was a significant positive correlation between reduced cervical ROM and recovery rate in the poor recovery group. Conclusions. Dynamic stress may deteriorate functional recovery of the degenerated spinal cord even after sufficient decompression. Postoperative preservation of cervical ROM may not always be beneficial for neurological recovery in patients with CSM.

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Pathognomonic radiological signs for predicting prognosis in patients with chronic atlantoaxial rotatory fixation

Ishii Ken, Chiba Kazuhiro, Maruiwa Hirofumi, Nakamura Masaya, Matsumoto Morio, Toyama Yoshiaki

Journal of Neurosurgery: Spine 5 （ 5 ） 385 - 391 2006年11月

ISSN 1547-5654

Object. The authors conducted a study to assess the correlation between radiological features and clinical courses in patients with chronic atlantoaxial rotatory fixation (AARF) and to determine diagnostic imaging signs for predicting prognosis. Methods. There were 24 patients (eight boys and 16 girls) whose mean age was 7.8 years (range 4-14 years) and in whom AARF was diagnosed. The mean follow-up duration was 3.7 years (range 5 weeks-12 years). There were two groups of patients: 15 patients who visited the hospital less than 8 weeks after symptom (torticollis) onset comprised the acute group, and nine patients in whom the diagnosis of AARF was established later than 3 months after symptom onset comprised the chronic group. The chronic group was divided into two subgroups: those in whom the closed reduction could be achieved and those in whom it could not. Clinical data and radiographic studies, including plain radiographs and plain and three-dimensional (3D) computed tomography (CT) reconstructions, were reviewed retrospectively. A deformity of the superior C-2 facet joint was frequently observed in the group of patients with chronic AARF (p < 0.0001). This sign represented a risk factor for recurrent dislocation (p = 0.0003, Fisher exact test). Prominent lateral inclination of C-1 was an impeding factor for reduction of chronic AARF (p < 0.0001, analysis of variance with Fisher post hoc test). Greater than 20° of lateral inclination of the atlas indicated an irreducible subluxation (p = 0.0023, Fisher exact test). Conclusions. Both facet joint deformity and lateral inclination observed on 3D CT reconstructions can be useful signs to predict the prognosis and the treatment of choice in patients with chronic AARFs.

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Fabrication of bone like composites material and evaluation of its ossiferous ability

Hisamori Noriyuki, Kimura Megumi, Morisue Hikaru, Matsumoto Morio, Toyama Yoshiaki

International Journal of Modern Physics B 20 （ 25-27 ） 3567 - 3572 2006年10月

ISSN 0217-9792

Many kinds of materials are currently used as artificial bone substitutes. Hydroxyapatite (HA), the same as the main inorganic component of bone, is one of commonly used bio-ceramics and has excellent bioactivity and biocompatibility with hard tissues. However, it has problems as the bone filler or bone tissue-engineering scaffold due to low fracture toughness and low degradation rate. Recently, biodegradable materials for bone tissue have been developed to respond the requirement. Collagen, the same as the main organic component of bone, is biocompatible, biodegradable and promotes cell adhesion. A composites associated with HA is expected to have early osteoconduction and bone replacement ability. The present study was to fabricate bone-like composites consist of HA and collagen. Besides the ossiferous ability of the material in vivo is evaluated by using rabbits. Bone-like composites were successfully fabricated in this study, associating the collagen with HA. And the composites presented good osteoconductive and bone replacement potential. © World Scientific Publishing Company.

Posterior osteotomy and instrumentation for thoracolumbar kyphosis in patients with achondroplasia

Qi Xin, Matsumoto Morio, Ishii Ken, Nakamura Masaya, Chiba Kazuhiro, Toyama Yoshiaki

Spine 31 （ 17 ） 2006年08月

ISSN 0362-2436

STUDY DESIGN. A retrospective case series of surgically treated achondroplastic patients with severe thoracolumbar kyphosis. OBJECTIVE. To evaluate the outcome of surgical treatment for thoracolumbar kyphosis in patients associated with achondroplasia presenting with paraparesis. SUMMARY OF BACKGROUND DATA. Thoracolumbar kyphosis is one of the frequent skeletal manifestations in patients with achondroplasia. Few papers have been published on the surgical treatment of this condition, especially in skeletally mature patients. METHODS. Four patients with achondroplasia who developed neurologic deficit due to severe thoracolumbar kyphosis and underwent surgical treatment were evaluated (mean age, 32.5 years; mean follow-up, 3.0 years). Posterior osteotomy with segmental instrumentation was performed in all cases. The surgical procedures included pedicle subtraction osteotomy in 2 patients without a hypoplastic apical vertebra and spondylectomy with reconstruction of the anterior column in 2 patients with a hypoplastic apical vertebra. Neurologic outcomes (JOA scores), correction of kyphosis, and operative complications were assessed. RESULTS. All patients had gait disturbance, and 2 patients were unambulatory before surgery. The average preoperative JOA score was 5.8 points, which was improved to 9.3 points at the final follow-up (mean recovery rate, 75%). All patients obtained neurologic improvement and became ambulatory either with or without crutches after surgery. The mean preoperative kyphotic angle was 96.3° (range, 57°-117°). The postoperative angles averaged 55.3° (range, 30°-110°), yielding a mean correction rate of 43.6%. Neither loss of correction nor pseudarthrosis has been observed during the follow-up period. Partial nerve root laceration and dural tear resulting in transient postoperative muscle weakness were observed in 2 patients as complications. CONCLUSIONS. Posterior spinal osteotomy with segmental instrumentation is a reasonable surgical option for thoracolumbar kyphosis in patients with achondroplasia. Modification of the surgical procedures depending on the presence or absence of the dysplastic changes of the apical vertebra is necessary to obtain optimal results. ©2006, Lippincott Williams & Wilkins, Inc.

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A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine

Horikoshi Taizo, Maeda Koichi, Kawaguchi Yoshiharu, Chiba Kazuhiro, Mori Kanji, Koshizuka Yu, Hirabayashi Shigeru, Sugimori Kazuhito, Matsumoto Morio, Kawaguchi Hiroshi, Takahashi Makoto, Inoue Hisashi, Kimura Tomoatsu, Matsusue Yoshitaka, Inoue Itsuro, Baba Hisatoshi, Nakamura Kozo, Ikegawa Shiro

Human Genetics 119 （ 6 ） 611 - 616 2006年07月

ISSN 0340-6717

Research to date has identified several genes that are implicated in the etiology of ossification of the posterior longitudinal ligament of the spine (OPLL); however, their pathogenetic relevance remains obscure. The aim of this study is to identify susceptibility genes for OPLL through a large-scale case-control association study and to re-examine previously reported associations. A total of 109 single nucleotide polymorphisms (SNPs) in 35 candidate genes were genotyped for 711 sporadic OPLL patients and 896 controls. The differences in allelic and genotypic distribution between patients and controls were assessed using the χ² test with Bonferroni's correction. We also analyzed the association by separating patients into subgroups according to sex, age and the number of ossified vertebrae. The nominal P values fell below 0.05 for five SNPs in three genes. An intronic SNP in the TGF3 gene (P = 0.00040) showed the most significant association. Previously reported associations of COL11A2, NPPS and TGFB1 with OPLL could not be reproduced. Further, no significant associations were detected in stratified analyses based on sex, age or the number of ossified vertebrae. TGFB3 warrants further investigation because it is located within a genomic region that has been positively linked with OPLL. © Springer-Verlag 2006.

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Pleomorphic xanthoastrocytoma of the spinal cord

Nakamura Masaya, Chiba Kazuhiro, Matsumoto Morio, Ikeda Eiji, Toyama Yoshiaki

Journal of Neurosurgery: Spine 5 （ 1 ） 72 - 75 2006年07月

ISSN 1547-5654

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Prediction of deformity correction by pedicle screw instrumentation in thoracolumbar scoliosis surgery (Computer simulation study)

Kiriyama Yoshimori, Yamazaki Nobutoshi, Nagura Takeo, Matsumoto Morio, Chiba Kazuhiro, Toyama Yoshiaki

JSME International Journal, Series C: Mechanical Systems, Machine Elements and Manufacturing 48 （ 4 ） 577 - 585 2006年06月

ISSN 1344-7653

In segmental pedicle screw instrumentation, the relationship between the combinations of pedicle screw placements and the degree of deformity correction was investigated with a three-dimensional rigid body and spring model. The virtual thoracolumbar scoliosis (Cobb's angle of 47 deg.) was corrected using six different combinations of pedicle-screw placements. As a result, better correction in the axial rotation was obtained with the pedicle screws placed at or close to the apical vertebra than with the screws placed close to the end vertebrae, while the correction in the frontal plane was better with the screws close to the end vertebrae than with those close to the apical vertebra. Additionally, two screws placed in the convex side above and below the apical vertebra provided better correction than two screws placed in the concave side. Effective deformity corrections of scoliosis were obtained with the proper combinations of pedicle screw placements. Copyright © 2006 by The Japan Society of Mechanical Engineers.

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Lateral translation of the lumbar spine

Okushima Yuichiro, Yamazaki Nobutoshi, Matsumoto Morio, Chiba Kazuhiro, Nagura Takeo, Toyama Yoshiaki

Journal of Applied Biomechanics 22 （ 2 ） 83 - 92 2006年05月

ISSN 1065-8483

A biomechanical study of lateral translation in lumbar spine with human cadavers was performed in order to explore the direction of the force increasing lateral translation and the contributions of discs and facet joints to lateral translation. Whole lumbar spines from 12 fresh cadavers were attached to a specially designed loading apparatus whose five cables simulated the muscles of the trunk without restricting natural movement. Three-dimensional positions of each vertebra were recorded with position-sensitive detectors. Force in the anterolateral direction increased the lateral translation more than force in the posterolateral direction. Lateral translation was increased to a significantly greater extent when the facet joints were removed than when the discs were removed at L4-5 at the levels of shear loading applied in this study. © 2006 Human Kinetics, Inc.

Open-door laminoplasty for cervical myelopathy resulting from adjacent-segment disease in patients with previous anterior cervical decompression and fusion

Matsumoto Morio, Nojiri Kenya, Chiba Kazuhiro, Toyama Yoshiaki, Fukui Yasuyuki, Kamata Michihiro

Spine 31 （ 12 ） 1332 - 1337 2006年05月

ISSN 0362-2436

STUDY DESIGN.: This is a retrospective study of patients with cervical myelopathy resulting from adjacent-segment disease who were treated by open-door expansive laminoplasty. OBJECTIVES.: The purpose of this study was to evaluate the effectiveness of laminoplasty for cervical myelopathy resulting from adjacent-segment disease. SUMMARY OF BACKGROUND DATA.: Adjacent-segment disease is one of the problems associated with anterior cervical decompression and fusion. However, the optimal surgical management strategy is still controversial. METHODS.: Thirty-one patients who underwent open-door expansive laminoplasty for cervical myelopathy resulting from adjacent-segment disease and age- and sex-matched 31 patients with myelopathy who underwent laminoplasty as the initial surgery were enrolled in the study. The pre- and postoperative Japanese Orthopedic Association scores (JOA scores) and the recovery rate were compared between the two groups. RESULTS.: The average JOA scores in the patients with adjacent-segment disease and the controls were 9.2 ± 2.6 and 9.4 ± 2.3 before the expansive laminoplasty and 11.9 ± 2.8 and 13.3 ± 1.7 at the follow-up examination, respectively; the average recovery rates in the two groups were 37.1 ± 22.4% and 50.0 ± 21.3%, respectively (P = 0.04). The mean number of segments covered by the high-intensity lesions on the T2-weighted magnetic resonance images was 1.87 and 0.9, respectively (P = 0.001). CONCLUSIONS.: Moderate neurologic recovery was obtained after open-door laminoplasty in patients with cervical myelopathy resulting from adjacent-segment disc disease, although the results were not as satisfactory as those in the control group. This may be attributed to the irreversible damage of the spinal cord caused by persistent compression at the adjacent segments. ©2006, Lippincott Williams & Wilkins, Inc.

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A novel hydroxyapatite fiber mesh as a carrier for recombinant human bone morphogenetic protein-2 enhances bone union in rat posterolateral fusion model

Morisue Hikaru, Matsumoto Morio, Chiba Kazuhiro, Matsumoto Hideo, Toyama Yoshiaki, Aizawa Mamoru, Kanzawa Nobuyuki, Fujimi Takahiro J., Uchida Hiroshi, Okada Isao

Spine 31 （ 11 ） 1194 - 1200 2006年05月

ISSN 0362-2436

Study Design. An experimental study, in which spinal fusion in rats was conducted using a hydroxyapatite fiber mesh (HAM) as a carrier for recombinant human bone morphogenetic protein (rhBMP)-2. Objectives. To study the usefulness of the HAM as a carrier and seek the possibility of clinical application in spinal fusion. Summary of Background Data. Several biomaterials have been used as a carrier for BMP to achieve spine fusion, however, to our knowledge, the most effective carrier has not been established. Methods. In experiment No. 1, HAMs and the controls (commercially available hydroxyapatite ceramic body), loaded with rhBMP-2, were immersed in phosphate-buffered saline to evaluate the time course of the release of rhBMP-2. In experiment No. 2, posterolateral fusion was conducted in rats using HAM and the control loaded with rhBMP-2. The fusion status was evaluated radiologically and histologically after surgery. Results. In experiment No. 1, HAMs released a larger amount of rhBMP-2 for up to 28 days than the controls (49.5% vs 7.8%). In experiment No. 2, the fusion rate was significantly higher in the HAM group (>80%) than in the control group (20%). Dense new bone formed close to the spine, and the HAMs were markedly absorbed compared with the controls. Conclusion. HAM provided more solid fusion mass than the control, suggesting that HAM is an efficient carrier for BMP. ©2006, Lippincott Williams & Wilkins, Inc.

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Microendoscopic partial resection of the sacral ala to relieve extraforaminal entrapment of the L-5 spinal nerve at the lumbosacral tunnel

Matsumoto Morio, Chiba Kazuhiro, Ishii Ken, Watanabe Kota, Nakamura Masaya, Toyama Yoshiaki

Journal of Neurosurgery: Spine 4 （ 4 ） 342 - 346 2006年04月

ISSN 1547-5654

The authors report the cases of three patients with L-5 radiculopathy caused by extraforaminal entrapment of the L-5 spinal nerve at the lumbosacral tunnel; this structure comprises the lumbosacral ligament, the sacral ala, and the L-5 and S-1 vertebral bodies. All three patients suffered severe leg pain and neurological deficits compatible with L-5 radiculopathy. Decompressive surgery involved the microendoscopic partial resection of the sacral ala along the L-5 spinal nerve. All patients experienced immediate pain relief postoperatively. Microendoscopic partial resection of the sacral ala is an effective and minimally invasive surgical option for patients with extraforaminal entrapment of the L-5 spinal nerve.

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Molecular pathology of Shprintzen-Goldberg syndrome [4]

Kosaki Kenjiro, Takahashi Daisuke, Udaka Toru, Kosaki Rika, Matsumoto Morio, Ibe Shigeharu, Isobe Takeshi, Tanaka Yoko, Takahashi Takao

American Journal of Medical Genetics 140 A （ 1 ） 104 - 108 2006年01月

ISSN 1552-4825

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Clinical manifestations of thoracic OPLL and OLF

Matsumoto Morio, Chiba Kazuhiro, Toyama Yoshiaki

121 - 125 2006年

Introduction Ossification of the posterior longitudinal ligament (OPLL) is far less common in the thoracic spine than in the cervical spine; and the rate of occurrence, natural history, and optimal treatment of this condition are yet to be investigated. Because progressive deterioration of the neurological symptoms due to thoracic OPLL often severely impairs patients? activities of daily living and quality of life, awareness of this clinical entity is important. Ossification of the ligamentum fl avum (OLF) is mostly found in the thoracic spine and is a frequent cause of thoracic myelopathy. In this chapter, the clinical and neurological manifestations of thoracic OPLL and OLF are reviewed. © Springer 2006.

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Expansive open-door laminoplasty for ossification of the posterior longitudinal ligament of the cervical spine

Chiba Kazuhiro, Ogawa Yuto, Matsumoto Morio, Toyama Yoshiaki

193 - 199 2006年

Introduction In 1968, Kirita devised a sophisticated extensive laminectomy technique in which the laminae were thinned and divided at the midline by a high-speed drill followed by en bloc resection of the laminae to achieve decompression of the spinal cord safely in patients with cervical spondylosis and ossification of the posterior longitudinal ligament (OPLL) [1]. This technique added much safety to conventional laminectomy and signifi - cantly reduced the rate of neurological complications. Hirabayashi et al. simplifi ed Kirita's method, in which the bilateral bony gutters at the junction of the laminae and the facet joints were made using a high-speed drill followed by en bloc removal of the laminae [2]. The idea of open-door laminoplasty evolved when they noticed dural pulsation when one side of the laminae was lifted before their total removal. They performed the fi rst case using this technique in 1977, leaving the ventral cortex on one side as a hinge and lifting the lamina on the other side, just like opening a book cover; they named it "expansive open-door laminoplasty (ELAP)" [3,4]. The advent of ELAP has contributed signifi cantly to the establishment of the concept "laminoplasty," which later became the treatment of choice for cervical myelopathy in Japan and has also led to the development of various technical modifi cations. Laminoplasty has become the treatment of choice for cervical myelopathy, and satisfactory results have been reported [2,5-7]. Although ELAP is not radical decompression surgery that directly removes the ossifi ed ligament, it has a total decompression effect induced by the dorsal shift of the spinal cord in addition to local decompression of the spinal cord by posterior displacement of the laminae (Fig. 1) [8]. Several studies have proven that the decompression effect of ELAP is virtually equivalent to that of laminectomy and anterior corpectomy and fusion [9]. The posterior structures, including the lamina and the supraspinous and interspinous ligaments, are preserved; and the cervical muscles are reattached to reconstruct the spinal canal, thereby maintaining the preoperative cervical alignments and at the same time restoring cervical stability. Herkowitz concluded from his biomechanical study that the stability of the cervical spine after ELAP was not signifi cantly different from that of the intact spine [10]. Indeed, kyphotic deformity or instability after ELAP that required salvage surgery has rarely been experienced in our institution [6,11]. Moreover, the incidence of adjacent-segment disease, which may also lead to a salvage operation, was much lower after ELAP than after anterior decompression and fusion [2]. © Springer 2006.

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CD24 is expressed specifically in the nucleus pulposus of intervertebral discs

Fujita Nobuyuki, Miyamoto Takeshi, Imai Jun Ichi, Hosogane Naobumi, Suzuki Toru, Yagi Mitsuru, Morita Kozo, Ninomiya Ken, Miyamoto Kana, Takaishi Hironari, Matsumoto Morio, Morioka Hideo, Yabe Hiroo, Chiba Kazuhiro, Watanabe Shinya, Toyama Yoshiaki, Suda Toshio

Biochemical and Biophysical Research Communications 338 （ 4 ） 1890 - 1896 2005年12月

ISSN 0006-291X

Intervertebral disc (IVD) consists of a soft gelatinous material in its center, the nucleus pulposus (NP), bounded peripherally by fibrocartilage, annulus fibrosus (AF). Despite the number of patients with IVD degeneration, gene expression analysis has not been undertaken in NP and therefore little is known about the molecular markers expressed in NP. Here, we undertook a microarray screen in NP with the other nine tissues to identify the specific cell surface markers for NP. Five membrane associating molecules out of 10,490 genes were identified as highly expressing genes in NP compared with the other tissues. Among them, we identified CD24, a glycosylphosphatidylinositol (GPI) anchor protein as a cell surface marker for NP. CD24 expression was also detected in the herniated NP and chordoma, a malignant primary tumor derived from notochordal cells, while it was absent in chondrosarcoma. Therefore, CD24 is a molecular marker for NP as well as the diseases of IVD. © 2005 Elsevier Inc. All rights reserved.

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Comparative assessment of pedicle morphology of the lumbar spine in various degenerative diseases

Nojiri Kenya, Matsumoto Morio, Chiba Kazuhiro, Toyama Yoshiaki, Momoshima Suketaka

Surgical and Radiologic Anatomy 27 （ 4 ） 317 - 321 2005年11月

ISSN 0930-1038

Measurement of the morphological dimensions of the pedicles of the lumbar spine was conducted using computed tomography (CT) to clarify the difference in pedicle morphology among different lumbar degenerative diseases. The subjects were 136 patients with lumbar spinal disorders who underwent myelography followed by CT scans. They were divided into four groups, that is a group of 25 patients with degenerative spondylolisthesis (DS group), a group of 54 patients with lumbar canal stenosis (LCS group), a group of 42 patients with lumbar disc herniation (LDH group), and a control group of 15 patients with spinal cord tumor in cervicothoracic region but without lumbar diseases (control group). Measurements of the transverse diameter, axial length, and axial angle of the pedicles were performed on CT slices obtained at the middle of the pedicle. The transverse diameter was the width of the isthmus, the axial length was the distance between the anterior of the vertebral body and the posterior of the vertebral arch on a line perpendicular to the line bisecting the isthmus, and the axial angle was the angle between the line perpendicular to the line bisecting the isthmus and the midline of the vertebral body. While there were no significant differences in the mean transverse diameter or axial length among the four groups, the mean axial angle was significantly smaller in the DS and LCS groups when compared to that in the LDH and control groups. In the DS and LCS groups, the pedicles were more sagitally oriented than in the LDH and control groups. Such difference in the axial angle of the pedicles in different lumbar diseases should be taken into consideration when placing at the insertion of pedicle screws, because precise orientation of screw insertion would scarcely allow penetration of the pedicle wall. © Springer-Verlag 2005.

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Lumbar spinous process-splitting laminectomy for lumbar canal stenosis. Technical note.

Watanabe Kota, Hosoya Toshihiko, Shiraishi Tateru, Matsumoto Morio, Chiba Kazuhiro, Toyama Yoshiaki

Journal of neurosurgery. Spine. 3 （ 5 ） 405 - 408 2005年11月

ISSN 1547-5654

In conventional laminectomy for lumbar canal stenosis (LCS), intraoperative damage of posterior supporting structures can lead to irreversible atrophy of paraspinal muscles. In 2001, the authors developed a new procedure for lumbar laminectomy, the lumbar spinous process-splitting laminectomy (LSPSL). In this new procedure, the spinous process is split longitudinally in the middle and then divided at its base from the posterior arch, leaving the bilateral paraspinal muscles attached to the lateral aspects. Ample working space for laminectomy is obtained by retracting the split spinous process laterally together with its attached paraspinal muscles. After successfully decompressing nerve tissues, each half of the split spinous process is reapproximated using a strong suture. Thus, the supra- and interspinous ligaments are preserved, as is the spinous process, and damage to the paraspinal muscles is minimal. Eighteen patients with LCS underwent surgery in which this new technique was used. Twenty patients in whom conventional laminectomy was undertaken were chosen as controls. At 2 years, the clinical outcomes (as determined using the Japanese Orthopaedic Association [JOA] scores and recovery rate) and the rate of measured magnetic resonance imaging-documented paravertebral muscle atrophy were evaluated and compared between the two groups. The mean JOA score recovery rates were 67.6 and 59.2%, respectively, for patients treated with LSPSL and conventional laminectomy; the mean rates of paravertebral muscle atrophy were 5.3 and 23.9%, respectively (p = 0.0005). Preservation of posterior supporting structures and satisfactory recovery rate after 2 years indicated that this technique can be a useful alternative to conventional decompression surgery for lumbar canal stenosis.

Long-term results after expansive open-door laminoplasty for the segmental-type of ossification of the posterior longitudinal ligament of the cervical spine

Ogawa Yuto, Chiba Kazuhiro, Matsumoto Morio, Nakamura Masaya, Takaishi Hironari, Hirabayashi Hisashi, Hirabayashi Kiyoshi, Nishiwaki Yuji, Toyama Yoshiaki

Journal of neurosurgery. Spine 3 （ 3 ） 198 - 204 2005年09月

ISSN 1547-5654

OBJECT: The segmental-type of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine is distinct from other types in its morphological features. Whether the results of expansive open-door laminoplasty for the segmental-type are different from those for other types remains unclear. To clarify this issue, the long-term results after surgical treatment of segmental-type OPLL were compared with those of other types. METHODS: Clinical results were documented in 57 patients who underwent expansive open-door laminoplasty and were followed for a minimum of 7 years, results were quantified using the Japanese Orthopaedic Association (JOA) scoring system to determine function. Segmental-type OPLL was observed in 10 patients (Group 1) and other types in 47 patients (Group 2). Preoperative JOA scores were not significantly different between the two groups. As many as 5 years after surgery, clinical results were favorable and maintained in both groups, and no significant intergroup difference in postoperative JOA scores was observed; however, after 5 years postoperatively, JOA scores decreased in both groups. The decrease was greater in Group 1, and a significant intergroup difference in JOA scores was demonstrated when analyzing final follow-up data. In Group 1, the authors found that the degree of late-onset deterioration relating to cervical myelopathy positively correlated with the cervical range of motion. CONCLUSIONS: The long-term results of expansive open-door laminoplasty in the treatment of segmental-type OPLL were inferior to those for other types. Cervical mobility may contribute to the development of late deterioration of cervical myelopathy.

Endoscopic resection of cystic lesions in the lumbar spinal canal. A report of two cases

Ishii Ken, Matsumoto M., Watanabe K., Nakamura M., Chiba K., Toyama Y.

Minimally Invasive Neurosurgery 48 （ 4 ） 240 - 243 2005年08月

ISSN 0946-7211

We report excellent outcomes in two patients with cystic lesions in the lumbar spinal canal who underwent resection using the METRx™ microendoscopic discectomy (MED) system. Pathological examinations revealed the diagnoses of a synovial cyst and a discal cyst, respectively. Both of them were allowed to walk the next day after surgery with complete pain relief. Microendoscopic surgery provides excellent visualization of the spinal canal and allows minimally invasive removal of the pathological lesions. This technique can be an effective alternative to conventional open surgery for cystic lesions in the lumbar spine. © Georg Thieme Verlag KG Stuttgart.

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Usefulness of neurological examination for diagnosis of the affected level in patients with cervical compressive myelopathy

Matsumoto Morio, Ishikawa Masayuki, Ishii Ken, Nishizawa Takashi, Maruiwa Hirofumi, Nakamura Masaya, Chiba Kazuhiro, Toyama Yoshiaki

Journal of neurosurgery. Spine 2 （ 5 ） 535 - 539 2005年05月

ISSN 1547-5654

OBJECT: Although neurological examination is the key step to reaching a correct diagnosis of cervical compressive myelopathy (CCM), the accuracy of diagnosis of the affected spinal level for CCM has not yet been tested. METHODS: The authors conducted a prospective study to elucidate how accurately the affected intervertebral level can be determined and decompressed based on neurological examination. Fifty patients who underwent successful decompressive surgery for cervical myelopathy caused by single-level disc herniation or spondylosis were included in this study (38 men and 12 women, mean age 60 years). Three board-certified spine surgeons participated in establishing the neurological diagnoses. One of the three surgeons made a diagnosis of CCM, and the other two conducted the neurological examination including deep tendon reflex, pinprick response, muscle weakness, and numbness in the hand only, knowing that the patient had CCM, and established the neurological-level diagnosis. A single intervertebral level responsible for patient's symptoms was determined concordantly based on magnetic resonance imaging and myelography findings by two spine surgeons, and this served as the standard. Agreement between neurological and neuroimaging/radiological level diagnoses was determined. The rate of agreement between neurological and neuroimaging diagnosis was 66%. Among the neurological tests, patient-perceived location of numbness in the hands was the most useful for establishing the affected level. For the other three tests the agreement rate was lower than 50% and thus each individual test may not be reliable for diagnosing the affected level. CONCLUSIONS: The results of this study suggested that neurological examination in patients with CCM is moderately accurate and reliable for determining the neurological level of disease.

Morphometric analysis of the thoracic and lumbar spine in Japanese on the use of pedicle screws

Nojiri Kenya, Matsumoto Morio, Chiba Kazuhiro, Toyama Yoshiaki

Surgical and Radiologic Anatomy 27 （ 2 ） 123 - 128 2005年04月

ISSN 0930-1038

The pedicle screw and hook have become popular instruments in treating spinal deformity and disease. This study gathered morphological data on thoracic and lumbar spines in a Japanese population that should serve as useful reference for posterior instrumentation surgery. One hundred and three dry bones were used to investigate the morphology of pedicle and facet in thoracic and lumbar spines. Measurements included the diameter and axial length of pedicle from T8 to L5, height and width of facets and thickness of articular processes from T1 to T12, and axial angle of pedicle from T1 to L5. The diameter and axial length of pedicle were smallest at T8, diameter was largest at L5 and axial length was largest at L3. Height of facets and thickness of articular processes were largest at T12. Men tended to have larger pedicles and facets than women. Transverse angle of pedicle was smallest at T12. These precise data may provide useful information when performing posterior instrumentation surgery and when developing new spinal implant systems for Asians. © Springer-Verlag 2005.

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Impact of interlaminar graft materials on the fusion status in atlantoaxial transarticular screw fixation.

Matsumoto Morio, Chiba Kazuhiro, Nakamura Masaya, Ogawa Yuto, Toyama Yoshiaki, Ogawa Jun

Journal of neurosurgery. Spine 2 （ 1 ） 23 - 26 2005年01月

ISSN 1547-5654

OBJECT: Structural interlaminar graft materials were used for atlantoaxial transarticular screw fixation (TSF), and its impact on the fusion status was investigated. METHODS: Forty-two patients (10 men, 32 women, mean age 51 years, mean follow-up period 45 months; 30 with rheumatoid arthritis, and 12 with os odontoideum) underwent TSF and modified Brooks posterior wiring involving titanium cables. As interlaminar graft materials, autologous bone from posterior iliac crest alone was used in 20 patients (Group A), and a structural spacer (13 ceramic spacers, nine titanium mesh cages) in 22 (Group B). Lateral radiographs were evaluated to determine bone fusion, alignment of the cervical spine, and wire loosening. Solid osseous fusion was obtained in 95% of Group A and 96% of Group B patients. The mean atlantoaxial angle was 19.1+/-9.7 degrees and 16.7+/-10.4 degrees before surgery (p = 0.45), and 27.4+/-7.8 degrees and 22.1+/-5.5 degrees after surgery (p = 0.02) in Groups A and B, respectively. Atlantoaxial hyperlordosis (atlantoaxial angle > or = 30 degrees) was observed in 32% of Group A and 18% of Group B patients (p = 0.26). Postoperative kyphosis occurred in 40% of Group A and 23% of Group B patients (p = 0.28). Loosening of the cable was demonstrated in 50% of Group A and 36% of Group B patients(p = 0.37). In Group B patients maintenance of cervical lordosis was more likely than in those in Group A, although the differences did not reach statistical significance. CONCLUSIONS: These results indicate that structural interlaminar spacers can maintain proper cervical alignment without a decease in the fusion rate; the authors recommend their use in conjunction with TSF.

Spinal disorders associated with rheumatoid arthritis

Matsumoto Morio, Toyama Yoshiaki

Nippon rinsho. Japanese journal of clinical medicine 63 Suppl 1 261 - 265 2005年

ISSN 0047-1852

Long-term results of expansive open-door laminoplasty for ossification of the posterior longitudinal ligament of the cervical spine.

Ogawa Yuto, Toyama Yoshiaki, Chiba Kazuhiro, Matsumoto Morio, Nakamura Masaya, Takaishi Hironari, Hirabayashi Hisashi, Hirabayashi Kiyoshi

J Neurosurg Spine 1 （ 2 ） 168 - 174 2004年09月

ISSN 1547-5654

OBJECT: Numerous surgical procedures have been developed for treatment of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine, and these can be performed via three approaches: anterior, posterior, or combined anterior-posterior. The optimal approach in cases involving OPLL-induced cervical myelopathy, however, remains controversial. To address this issue, the authors assessed the benefits and limitations of expansive open-door laminoplasty for OPLL-related myelopathy by evaluating mid- and long-term clinical results. METHODS: Clinical results obtained in 72 patients who underwent expansive open-door laminoplasty between 1983 and 1997 and who were followed for at least 5 years were assessed using the Japanese Orthopaedic Association (JOA) scoring system. The mean preoperative JOA score was 9.2 +/- 0.4; at 3 years postoperatively, the JOA score was 14.2 +/- 0.3 and the recovery rate (calculated using the Hirabayashi method) was 63.1 +/- 4.5%, both having reached their highest level. These favorable results were maintained up to 5 years after surgery. An increase in cervical myelopathy due to progression of the ossified ligament was observed in only two of 30 patients who could be followed for more than 10 years. Severe surgery-related complications were not observed. Preoperative JOA score, age at the time of surgery, and duration between onset of initial symptoms and surgery affected clinical results. CONCLUSIONS: Mid-term and long-term results of expansive open-door laminoplasty were satisfactory. Considering factors that affected surgical results, early surgery is recommended for OPLL of the cervical spine.

Marfanoid habitus with abnormal situs

Kosaki Kenjiro, Bird Lynne M., Maeda Jun, Higuchi Masataka, Jones Marilyn C., Matsumoto Morio

American Journal of Medical Genetics 127 （ 3 ） 310 - 312 2004年06月

ISSN 1552-4825

Marfanoid habitus suggests abnormal microfibril formation, whereas a situs ambiguus or situs inversus phenotype points to detective left-right axis determination. The concurrence of these two abnormalities has been reported only once in the literature. We report a similar phenotype in two unrelated patients. Documentation of this specific combination of Marfanoid habitus and abnormal situs gives further credence to the notion that the combination may represent a distinct syndrome. © 2004 Wiley-Liss, Inc.

Postoperative changes of spinal curvature and range of motion in adult patients with cervical spinal cord tumors

Asazuma Takashi, Nakamura Masaya, Matsumoto Mario, Chibo Kazuhiro, Toyama Yoshiaki

Journal of Spinal Disorders and Techniques 17 （ 3 ） 178 - 182 2004年06月

ISSN 1536-0652

Objective: We sought to determine factors likely to influence postoperative changes in cervical spinal curvature and range of motion (ROM) in patients with cervical spinal cord tumors. Methods: Fifty-one patients who underwent tumor excision via a single posterior approach were examined. Surgical methods were classified as follows: group A, expansive open-door laminoplasty (ELAP); group B, conventional laminectomy; and group C, hemilaminectomy (HL). Pre- and postoperative cervical spinal curvature, cervical curvature type, and ROM were evaluated using lateral radiographs. Results: Worsening of cervical curvature type was statistically less frequent in group C than in group A or B (P < 0.05), although no significant difference was evident overall between pre- and postoperative cervical curvature indexes or ROM in any group. Cases of C2 surgery showed more frequent curvature worsening (80%) in group A than in other groups (P < 0.05). Postoperative changes of the cervical curvature in patients with cervical spinal cord tumors were greatly influenced by the surgical method; the cervical curvature was particularly unfavorable when patients had C2 decompression. Conclusions: Careful attention to postoperative changes in the spinal curvature is needed when ELAP is performed, especially if surgery involves C2. HL is the best posterior approach for resection of cervical spinal cord tumors from the viewpoint of postoperative spinal curvature and ROM.

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Retrospective study of surgery-related outcomes in patients with syringomyelia associated with Chiari I malformation

Nakamura Masaya, Chiba Kazuhiro, Nishizawa Takashi, Maruiwa Hirofumi, Matsumoto Morio, Toyama Yoshiaki

Journal of Neurosurgery 100 （ 3 SUPPL. ） 241 - 244 2004年03月

ISSN 0022-3085

Object. Pain is one of the major symptoms in patients with syringomyelia; however, its origin is not fully understood, and postoperative improvement of pain is difficult to predict. The objectives of this study were to assess the surgery-related results obtained in patients who underwent treatment for syringomyelia associated with Chiari I malformation, particularly related to pain status, and to identify factors that may influence improvement in postoperative pain by comparing pre- and postoperative magnetic resonance (MR) imaging findings. Methods. The correlation between pre- and postoperative changes in the size and the location of the syrinx and pain improvement was investigated in 25 patients. The shapes of the syringes were classified into three types: central, enlarged, and deviated. In most cases in which the syrinx deviated toward the posterolateral aspect of the spinal cord at the level corresponding to dermatomal distribution of preoperative pain, the lesion remained at the same position postoperatively, and improvement in pain was poor. On the other hand, enlarged-type syringes were the most frequently observed prior to surgery, exhibited diverse changes postoperatively, and improvement in pain status was difficult to predict. When postoperative MR imaging revealed a transformation to the deviated type, poor pain improvement was noted. Conclusions. Neurons in the dorsal horn were thought to be involved in the development of pain as a result of the deafferentiation mechanism in cases of syringomyelia.

Biological in vitro evaluations of three-dimensional scaffold developed from single-crystal apatite fibers for tissue engineering of bone

Aizawa M., Shinoda H., Uchida H., Okada I., Fujimi T. J., Kanzawa N., Morisue H., Matsumoto M., Toyama Y.

1568 2004年

The biological properties of using two kinds of cells, MC3t3-E1 of an osteoblastic cell line and the rat bone-marrow cell (RBMC) as mesenchymal stem cell model were discussed. The HAp fiber was synthesized via a homogeneous precipitation method using urea. The HAp fiber was mixed with the spherical carbon beads having a diameter of ∼ 150 μm in the mixed solvent. The single HAp phase was present in the S0, S1000, and S2000 scaffolds with porosity of 95% over. The results show that the high porosity and large pore size fulfilled by S2000 could provide an excellent environment for enhancing bone marrow cell activity.

Observation and estimation of osteoblast differentiation markers cultured in/on the three-dimensional apatite fiber scaffold

Kanzawa N., Fujimi T. J., Izawa K., Uchida H., Morisue H., Matsumoto M., Toyama Y., Aizawa M.

918 2004年

The expression levels of osteoblast differentiation markers and the effect of geometry of porous hydroxyapatite (HAp) fiber scaffold on the differentiation were investigated. The glyceraldehyde-3-phosphate dehydrogenases (GAPDH) mRNA was used as internal control to estimate expression level of differential marker mRNA. An apparent acceleration of the expression was observed for osteoblast differentiation in induced condition. The results show that the materials with various pore sizes effects the three-dimensional apatite fiber scaffold on cell profileration and differentiation.

In vivo/in vitro fracture characteristic of apatite ceramics

Hisamori N., Ueda S., Takai K., Aizawa M., Morisue H., Matsumoto M., Toyama Y.

1762 2004年

The structural changes of apatite ceramics with bioactive function and mechanical property in in vivo and in vitro were investigated. For starting materials for making HA ceramics, submicrometer HA ceramics powder was used, and pressureless sintering was performed at 1573K in O₂ atmosphere using pre-sintered bodies. Fracture resistance tests were performed using compact tension specimens, whose configuration was the tension test piece into which a notch of 16mm long was introduced. The results showed improvement of fracture resistance in simulated body fluids (SBF) environment, and maintenance of fracture resistance was also shown in rat abdomen subcutis.

In vivo bone formation using three-dimensional scaffold developed from single-crystal apatite fibers

Morisue H., Matsumoto M., Matsumoto H., Toyama Y., Aizawa M., Uchida H., Okada I., Fujimi T., Kanzawa N.

271 2004年

The effectiveness of hydroxyapatite fibers (HAF) as a scaffold of osteoblastic cells for bone generation was investigated. Three types of HAF with different diameters of pores and porosity were used in the study. The results showed that HAF is degradable and can be eventually replaced by bone tissue in vivo. The results suggested that HAF can be used as an effective scaffold for osteoblast-like cells having capability for bone conduction and that HAF with larger pore sizes can be replaced by newly formed bone tissue in vivo.

Surgeon perceptions of the complications and value of threaded fusion cages as a spine fusion technique

Carl Allen L., Kostuik John, Huckell Cameron B., Abitbol Jean Jacques, Matsumoto Morio, Sieber Ann

Spine Journal 3 （ 5 ） 356 - 359 2003年09月

ISSN 1529-9430

Background context: Threaded cage technology has had a meteoric rise in usage. It has been touted as a procedure with low risk and minimal complications. PURPOSE: To gauge the spine surgical community's general consensus regarding cage usage and its complications. Study design/setting: A canvassing questionnaire regarding threaded cage usage and complications was sent to members of the North American Spine Society. Patient sample: A total of 665 doctors reported on their perception of 22,585 cages placed by the second year after pre-market approval from the Food and Drug Administration approval. Outcome measures: A nonscientific canvassing questionnaire was thought to give a consensus of surgical outcome perception in a large number of caregivers with hopes of understanding general trends. Methods: Simple statistical measurements were used to report perceived complications by surgeons involved in performing threaded cage surgical procedures. Results: Sixty-nine percent of doctors reported at least one complication with threaded cages, but the complication incidence was low. Visceral injuries were reported in 0.1%; vascular injuries, 1.0%; cage displacement and dislodgement, 1.4%; temporary and permanent neurologic injuries, 2.25% and 0.56%, respectively; infection 0.34%; retrograde ejaculation 1.2% and revision surgery recorded for 2.7%. Those rating cages as fair to poor (16.5%) were those physicians reporting the longest experience with this technology. Conclusions: The general consensus is that threaded cages have low complication rates and high satisfaction rates, 83.5%. The data represent a convenience sampling and is not scientific. © 2003 Elsevier Inc. All rights reserved.

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Relationship between alignment of upper and lower cervical spine in asymptomatic individuals

Nojiri Kenya, Matsumoto Morio, Chiba Kazuhiro, Maruiwa Hirofumi, Nakamura Masaya, Nishizawa Takashi, Toyama Yoshiaki

Journal of Neurosurgery 99 （ 1 SUPPL. ） 80 - 83 2003年07月

ISSN 0022-3085

Object. The aim of this study was to establish standard values for the normal alignment of the upper cervical spine and to clarify its relationship with the lower cervical spine in terms of alignment. Methods. Three hundred thirteen asymptomatic volunteers (155 men and 158 women) participated in this study. Lateral radiographs were obtained with the neck in neutral position, and the angles formed by the occiput (Oc) and the axis, the atlas and the axis, and C-2 to C-7 were measured. The mean Oc-C2 angle was 14.5 ± 8° in men and 16 ± 8.5° in women; the mean C1-2 angle was 26.5 ± 7° and 28.9 ± 6.7°, respectively; and the mean C2-7 angle was 16.2 ± 12.9° and 10.5 ± 10.3°, respectively. Although weak, statistically significant negative correlation was observed between Oc-C2 and C2-7 angles (r = -0.31 in men and -0.37 in women), and between C1-2 and C2-7 angles (r = -0.22 in men and -0.22 in women). The correlation coefficient between the Oc-C2 and C2-7 angles was greater than that between the C1-2 and C2-7 angles. Conclusions. Such relationships between alignment of the upper and lower cervical spines should be taken into consideration when performing occipitocervical fusion.

Changes of cervical spinal cord and cervical spinal canal with age in asymptomatic subjects

Ishikawa M., Matsumoto M., Fujimura Y., Chiba K., Toyama Y.

Spinal Cord 41 （ 3 ） 159 - 163 2003年03月

ISSN 1362-4393

Study design: Prospective study on magnetic resonance imaging (MRI) and radiographic findings of the cervical spine. Objective: To elucidate the age-related changes of the cervical spinal cord and the cervical spinal canal and the relationship between the spinal cord and the spinal canal in asymptomatic subjects using MRI and radiography. Setting: Tokyo, Japan. Methods: The transverse area of the cervical spinal cord and the ratio of the anteroposterior diameter to the transverse diameter (RAPT) were investigated, using MRI in 229 asymptomatic subjects. The sagittal spinal canal diameter and anteroposterior diameter of the cervical vertebral body were also measured on plain lateral radiographs. The canal body ratio (CBR), which was defined as the diameter of the spinal canal divided by that of the vertebral body, was calculated. Results: The transverse spinal cord area correlated negatively with age. RAPT did not correlate with age. The CBR correlated negatively with age. The correlation between spinal cord area and CBR was significant but weak and the correlation between RAPT and CBR was not significant. Conclusion: The transverse area of the cervical spinal cord measured by MRI decreased with age, while RAPT remained unchanged. The bony spinal canal became narrower with age. The spinal cord area and the shapes of the spinal cord were independent from the spinal canal diameter in asymptomatic subjects. These facts should be considered when evaluating radiological findings in patients with cervical spinal disorders.

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Changes of cervical spinal cord and cervical spinal canal with age in asymptomatic subjects

Ishikawa Masayuki, Matsumoto Morio, Fujimura Yoshikazu, Chiba Kazuhiro, Toyama Yoshiaki

Spinal cord 41 （ 3 ） 159-163 2003年03月

研究論文（学術雑誌）, 共著

腰椎変性すべり症に対する後方除圧術の成績—固定・非固定例の分析

松本守雄，西澤隆，中村雅也，丸岩博文，千葉一裕，戸山芳昭

臨床整形外科 38 （ 3 ） 271-277 2003年03月

研究論文（学術雑誌）, 共著

特集／腰椎椎間スペーサーとしての生体材料；脊椎固定術における生体材料—最近の試みと今後の展望

松本守雄，千葉一裕，戸山芳昭，相澤守

骨・関節・靱帯 16 （ 3 ） 239-245 2003年03月

研究論文（学術雑誌）, 共著

Solitary cervical fibrous tumor

Obara Yukihiko, Matsumoto Morio, Chiba Kazuhiro, Yabe Hiroo, Toyama Yoshiaki, Mukai Makio

Journal of Neurosurgery 98 （ 1 ） 111 2003年01月

ISSN 0022-3085

Solitary cervical fibrous tumor <Case illustration>

Obana Yukihiko, Matsumoto Morio, Chiba Kazuhiro, Yabe Hiroo, Toyama Yoshiaki, Mukai Makio

Journal of neurosurgery 98 （ 1Suppl ） 111-111 2003年01月

研究論文（学術雑誌）, 共著

腰椎変性すべり症に対する後方除圧術の成績 - 固定・非固定例の分析

松本守雄

臨床整形外科 38 （ 3 ） 271-277 2003年

研究論文（学術雑誌）, 単著

特集／腰椎椎間スペーサーとしての生体材料；脊椎固定術における生体材料 -最近の試みと今後の展望

松本守雄

骨・関節・靱帯 16 （ 3 ） 239-245 2003年

研究論文（学術雑誌）, 単著

特集／脊椎脊髄損傷；画像診断とその意義 - 単純X線：頸椎

松本守雄

脊椎脊髄ジャーナル 16 （ 4 ） 300-306 2003年

研究論文（学術雑誌）, 単著

Biocompatibility of hydroxyapatite films formed on Ti matal by a simple urea and urease treatment

Nozaki Jun, Aizawa Mamoru, Uchida Hiroshi, Itatani Kiyoshi, Suemasu Hiroshi, Nozue Akira, Okada Isao, Matsumoto Morio, Matsumoto Hideo, Toyama Yoshiaki

Key Engineering Materials 240 603-606 2003年

研究論文（学術雑誌）, 共著

Development and biological evaluation of apatite fibre scaffolds with large pore size and high porosity for bone regeneration

Aizawa Mamoru, Uchida Hiroshi, Itatani Kiyoshi, Okada Isao, Matsumoto Morio, Morisue Hikaru, Matsumoto Hideo, Toyama Yoshiaki

Key engineering materials 240 647-650 2003年

研究論文（学術雑誌）, 共著

Development and biological evaluation of apatite fibre scaffolds with large pore size and high porosity for bone regeneration

Aizawa Mamoru, Shinoda Hiroki, Uchida Hiroshi, Itatani Kiyoshi, Okada Isao, Matsumoto Morio, Morisue Hikaru, Matsumoto Hideo, Toyama Yoshiaki

Key Engineering Materials 240-242 647 - 650 2003年

ISSN 1013-9826

Novel scaffolds have been developed from single-crystal apatite fibres synthesized by a homogeneous precipitation method using urea. The resulting apatite fibre scaffolds have large pores with diameters of 110-250 μm and high porosities of 98-99%. The scaffolds were biologically evaluated using two kinds of cells, osteoblast cells (MC3T3-E1) and rat bone marrow cells. In both cases, the cells cultured in the scaffolds showed excellent cellular response, such as good cell proliferation and enhanced differentiation into osteoblasts. We conclude that such scaffolds with high porosity and large pore size may be effective as the matrix of tissue engineered structures in order to promote regeneration of bone.

Biocompatibility of hydroxyapatite films formed on Ti metal by a simple urea and urease treatment

Nozaki J., Aizawa M., Uchida H., Itatani K., Suemasu H., Nozue A., Okada I., Matsumoto M., Matsumoto H., Toyama Y.

Key Engineering Materials 240-242 603 - 606 2003年

ISSN 1013-9826

HAp films with good adhesive property were formed by a simple surface treatment utilizing an enzyme reaction of urea with urease. The resulting coating layer consisted of carbonate-containing HAp with poor crystallinity. The in vitro evaluation using osteoblastic cells showed that HAp-coated Ti substrate had a good cellular response, such as cell proliferation and differentiation into osteoblast. From the results of in vivo evaluation using rabbit models, the HAp-coated Ti substrate directly bonded to bones to form large amount of new bone around implant. It has been found from both the in vitro and in vivo evaluations that the present HAp-coated Ti substrate has excellent biocompatibility.

Segmental motor paralysis after expansive open-door laminoplasty

Chiba Kazuhiro, Toyama Yoshiaki, Matsumoto Morio, Maruiwa Hirofumi, Watanabe Masahiko, Hirabayashi Kiyoshi

Spine 27 （ 19 ） 2108 - 2115 2002年10月

ISSN 0362-2436

Study Design. A retrospective study was conducted to investigate patients in whom segmental motor paralysis developed after expansive open-door laminoplasty for cervical myelopathy. Objective. To propose the involvement of the spinal cord as a possible mechanism in the development of segmental motor paralysis. Summary of Background Data. Segmental motor paralysis is seen occasionally in patients who undergo expansive open-door laminoplasty for cervical myelopathy, and has long been attributed to nerve root lesions caused by either traumatic surgical techniques or a tethering effect induced by excessive posterior shift of the spinal cord after decompression. Involvement of spinal cord pathology is not suggested in the English literature. Methods. The study group consisted of 15 patients (11 men and 4 women) in whom postoperative segmental motor paralysis developed after expansive open-door laminoplasty during a minimum follow-up of 2 years. Their average age at the time of surgery was 56 years. Characteristics of the paralysis, clinical symptoms, recovery rates calculated using pre- and postoperative Japanese Orthopedic Association scores, and radiographic findings including pre- and postoperative magnetic resonance images were analyzed retrospectively and compared with those of 126 patients without segmental paralysis who underwent expansive open-door laminoplasty. Results. The paralysis occurred mainly, but not only, at C5, and eight patients had multilevel involvements predominantly in the hinge side, whereas two patients had paralysis on both sides. The paralysis had developed after an average of 4.6 days. Of the 15 patients, 14 reported severe numbness or dysesthesia in their hands before surgery, and their average recovery rate for upper extremity sensory disturbance was lower than for those without paralysis. Postoperative magnetic resonance imaging showed the presence of a T2 high-signal intensity zone in the spinal cord of all the patients. The level of such abnormal signal areas corresponded to the level of paralyzed segments in 10 of the 15 patients. Paralysis resolved completely in 11 patients. Conclusions. Delayed onset of paralysis, dysesthesiain the upper extremities, and the presence of T2 highsignal intensity zones suggest that a certain impairment in the gray matter of the spinal cord may play an important role in the development of postoperative segmental motor paralysis.

Access to Document (DOI)

Segmentgal motor paralysis after expansive ope:n-door laminoplasty

Chiba Kazuhiro, Toyama Yoshiaki, Matsumoto Morio, Maruiwa Hirofumi, Watanabe Masahiko, Hirabayashi Kiyoshi

Spine 27 （ 19 ） 2108-2115 2002年10月

研究論文（学術雑誌）, 共著

髄内外にわたるendodermal cyst 再発の1治験例

池上健，千葉一裕，西澤隆，中村雅也，丸岩博文，松本守雄，戸山芳昭，向井万起男

関東整形災害外科学会誌 33 （ 5 ） 311-315 2002年10月

研究論文（学術雑誌）, 共著

特集―腰部脊柱管狭窄症；脊柱管狭窄に伴う脊椎変化―腰椎変性側弯症

松本守雄，千葉一裕，戸山芳昭

整形外科 53 （ 8 ） 927-934 2002年08月

研究論文（学術雑誌）, 共著

キアリ奇形に伴う脊髄空洞症の手術成績―特に疼痛の改善と空洞の局在に着目して

中村雅也，千葉一裕，田村睦弘，西澤隆，丸岩博文，松本守雄，戸山芳昭

臨床整形外科 37 （ 8 ） 911-916 2002年08月

研究論文（学術雑誌）, 共著

頸椎前方固定術後の血腫により脊髄症状の増悪をきたした1例

丹治敦，千葉一裕，渡辺雅彦，松本守雄，丸岩博文，藤村祥一，戸山芳昭

関東整形災害外科学会誌 33 （ 4 ） 166-170 2002年08月

研究論文（学術雑誌）, 共著

硬膜内に発生した傍神経節腫の1例

市原大輔，西澤隆，渡辺雅彦，中村雅也，丸岩博文，松本守雄，千葉一裕，戸山芳昭

臨床整形外科 37 （ 8 ） 971-974 2002年08月

研究論文（学術雑誌）, 共著

腰椎椎間板レーザー治療後再手術例の検討

高橋和久，遠藤友規，守屋秀繁，松本守雄，千葉一裕，戸山芳昭，宮本敬，西本博文，清水克時

臨床整形外科 37 （ 7 ） 813-818 2002年07月

研究論文（学術雑誌）, 共著

特殊病態に対する手術療法とその治療成績；若年者の頸椎症性脊髄症に対する手術療法

鎌田修博，丸岩博文，松本守雄，千葉一裕，戸山芳昭

脊椎脊髄ジャーナル 15 （ 6 ） 663-667 2002年06月

研究論文（学術雑誌）, 共著

高齢者に対する頸椎・腰椎同時後方除圧手術について

奥島雄一郎，千葉一裕，松本守雄，丸岩博文，西澤隆，戸山芳昭

関東整形災害外科学会誌 33 （ 3 ） 122-125 2002年06月

研究論文（学術雑誌）, 共著

頸椎症の手術療法；片開き式脊柱管拡大術

千葉一裕，丸岩博文，松本守雄，中村雅也，西澤隆，戸山芳昭

脊椎脊髄ジャーナル 15 （ 6 ） 663-667 2002年06月

研究論文（学術雑誌）, 共著

頸椎症の保存療法；頸椎症および頸椎椎間板ヘルニアに対する保存療法―脊髄症例を中心に―

松本守雄，千葉一裕，戸山芳昭

脊椎脊髄ジャーナル 15 （ 6 ） 538-542 2002年06月

研究論文（学術雑誌）, 共著

腰椎変性すべり症に対する後方除圧術による腰痛治療成績の検討

西澤隆，千葉一裕，中村雅也，松本守雄，丸岩博文，戸山芳昭

臨床整形外科 37 （ 5 ） 601-605 2002年05月

研究論文（学術雑誌）, 共著

脊髄円錐高位の椎間板ヘルニア

松本守雄，千葉一裕，戸山芳昭

脊椎脊髄ジャーナル 15 （ 4 ） 293-297 2002年04月

研究論文（学術雑誌）, 共著

腰椎部に発生し硬膜内外および椎体内に進入した髄膜腫の1例

西脇徹，西澤隆，千葉一裕，渡辺雅彦，中村雅也，松本守雄，丸岩博文，戸山芳昭

関東整形災害外科学会誌 33 （ 2 ） 65-68 2002年04月

研究論文（学術雑誌）, 共著

腰椎部に発生した硬膜内外および椎体内に侵入した髄膜腫の1例

西脇徹，西澤隆，千葉一裕，渡辺雅彦，中村雅也，松本守雄，丸岩博文，戸山芳昭

関東整形災害外科学会雑誌 33 （ 2 ） 92-98 2002年04月

研究論文（学術雑誌）, 共著

腰椎変性側弯症に対するinstrumentation surgery（広範囲固定例）の中・長期成績（5年以上）

戸山芳昭，松本守雄，丸岩博文，中村雅也，西澤隆，千葉一裕

臨床整形外科 37 （ 4 ） 467-473 2002年04月

研究論文（学術雑誌）, 共著

Extraforaminal entrapment of the fifth lumbar spinal nerve by osteophytes of the lumbosacral spine

Matsumoto Morio, Chiba Kazuhiro, Nojiri Kenya, Ishikawa Masayuki, Toyama Yoshiaki, Nishikawa Yuji

Spine 27 （ 6 ） 2002年03月

ISSN 1528-1159

STUDY DESIGN: An anatomic study of the associations between the fifth lumbar spinal nerve (L5 spinal nerve) and a lumbosacral tunnel, consisting of the fifth lumbar vertebral body (L5 vertebral body), the lumbosacral ligament, and sacral ala, and clinical case reports of four patients with lumbar radiculopathy secondary to entrapment of the L5 spinal nerve in the lumbosacral tunnel. OBJECTIVES: To delineate the anatomic, clinical, and radiologic features and surgical outcome of patients with entrapment of the L5 spinal nerve in the lumbosacral tunnel. SUMMARY OF BACKGROUND DATA: Although several cadaveric studies on a lumbosacral tunnel as a possible cause of L5 radiculopathy have been reported, few studies had focused on osteophytes of the L5-S1 vertebral bodies as the major component of this compressive lesion, and clinical reports on patients with this disease have been rare. METHODS: Lumbosacral spines from 29 geriatric cadavers were examined with special attention to the associations between osteophytes of the L5-S1 vertebral bodies and the L5 spinal nerve. Four patients with a diagnosis of the entrapment of the L5 spinal nerve by osteophytes at the lumbosacral tunnel were treated surgically, and their clinical manifestations and surgical results were reviewed retrospectively. RESULTS: The anatomic study demonstrated osteophytes of the L5-S1 vertebral bodies in seven of the 29 cadavers. Entrapment of the L5 spinal nerve in the lumbosacral tunnel was observed in six of the seven cadavers with L5-S1 osteophytes but in only one of the 22 cadavers without such osteophytes (P < 0.05, chi2 test). All four patients had neurologic deficits in the L5 nerve root distribution. MRI and myelography showed no abnormal findings in the spinal canal, but CAT scans demonstrated prominent osteophytes on the lateral margins of L5-S1 vertebral bodies in all four. Selective L5 nerve block completely relieved all patients of pain but only temporarily. Three patients were treated via a posterior approach by resecting the sacral ala along the L5 spinal nerve, and the other patient was treated by laparoscopic anterior resection of the osteophytes. Pain relief was obtained in the four patients immediately after surgery, but one patient experienced recurrence of pain 1 year after the first surgery and was successfully treated by additional posterior decompression and fusion. CONCLUSIONS: Extraforaminal entrapment of L5 spinal nerve in the lumbosacral tunnel can cause L5 radiculopathy, and osteophytes of L5-S1 vertebral bodies are a major cause of the entrapment.

L5-S1椎体骨棘による第5腰神経障害―解剖学的および臨床的検討―

松本守雄，野尻賢哉，石川雅之，西澤隆，中村雅也，丸岩博文，千葉一裕戸山芳昭，市原眞仁，西川雄司

臨床整形外科 37 （ 3 ） 257-267 2002年03月

研究論文（学術雑誌）, 共著

健常人の頸椎alignmentに関するX線学的検討―上位頸椎と下位頸椎alignmentとの関係

野尻賢哉，松本守雄，千葉一裕，丸岩博文，藤村祥一，戸山芳昭

東日本臨床整形学会誌 14 （ 1 ） 73-76 2002年03月

研究論文（学術雑誌）, 共著

健常人頚椎alignmentに関するX線学的検討―上位頚椎と下位頚椎alignmentとの関係―

野尻賢哉，松本守雄，千葉一裕，丸岩博文，藤村祥一，戸山芳昭

東日本整形災害外科学会雑誌 14 （ 1 ） 73-76 2002年03月

研究論文（学術雑誌）, 共著

男女間における腰椎変性すべり症の臨床像の違いについて―後方除圧術の分析

西澤隆，千葉一裕，中村雅也，松本守雄，丸岩博文，藤村祥一，戸山芳昭

臨床整形外科 37 （ 3 ） 257-262 2002年03月

研究論文（学術雑誌）, 共著

男女間における腰椎変性すべり症の臨床像の違いについて―後方除圧術例の分析―

西澤隆，千葉一裕，中村雅也，松本守雄，丸岩博文，藤村祥一，戸山芳昭

臨床整形外科 37 （ 3 ） 249-255 2002年03月

研究論文（学術雑誌）, 共著

L5 - S1椎体骨棘による第5腰神経障害―解剖学的および臨床的検討

松本守雄，野尻賢哉，石川雅之，西澤隆，中村雅也，丸岩博文，千葉一裕，戸山芳昭，市原眞人，西川雄司

臨床整形外科 37 （ 3 ） 257-262 2002年03月

研究論文（学術雑誌）, 共著

Extraforaminal entrapment of the fifth study and a report of four cases [Case reports]

Matsumoto Morio, Chiba Kazuhiro, Nojiri Kenya, Ishikawa Masayuki, Toyama Yoshiaki, Nishikawa Yuji

Spine 27 （ 6 ） E169-E173 2002年03月

研究論文（学術雑誌）, 共著

Extraforaminal entrapment of the fifth lumbar spinal nerve by osteophytes of the lumbosacral spine-Anatomical study and a report of four cases-

Matsumoto Morio, Chiba Kazuhiro, Nojiri Kenya, Ishikawa Masayuki, Toyama Yoshiaki, Nishikawa Yuji

Spine 27 （ 6 ） E169-E173 2002年03月

研究論文（学術雑誌）, 共著

外科的治療-脊椎の手術

松本守雄，戸山芳昭

リウマチ科 27 530-538 2002年02月

研究論文（学術雑誌）, 共著

経静脈的patient controlled analgesiaによる脊椎術後疼痛管理

松本守雄，千葉一祐，西澤隆，中村雅也，丸岩博文，藤村祥一，戸山芳昭，橋口さおり

臨床整形外科 37 （ 2 ） 159-162 2002年02月

研究論文（学術雑誌）, 共著

総論（治療法の選択と使い方）―外科的療法；脊椎の手術

松本守雄，戸山芳昭

リウマチ科 27 （ Suppl1 ） 530-538 2002年02月

研究論文（学術雑誌）, 共著

頸椎椎間板ヘルニアによる頸髄症に対する保存療法の有用性と限界―手術例との比較検討

松本守雄，千葉一裕，西澤隆，中村雅也，丸岩博文，藤村祥一，戸山芳昭

臨床整形外科 37 （ 2 ） 129-133 2002年02月

研究論文（学術雑誌）, 共著

球麻痺により発症した上位頸椎奇形の1治験例

岩波明生，丸岩博文，西澤隆，松本守雄，千葉一裕，藤村祥一，戸山芳昭

臨床整形外科 37 （ 2 ） 169-173 2002年02月

研究論文（学術雑誌）, 共著

特集―腰痛症発生メカニズムと診断，治療；腰痛症に対する各種画像検査法とその意義

松本守雄，千葉一裕，戸山芳昭

現代医療 34 （増刊） 562-565 2002年02月

研究論文（学術雑誌）, 共著

球麻痺により発症した上位頸椎奇形の1治験例

岩波明生，丸岩博文，西澤隆，松本守雄，千葉一裕，藤村祥一，戸山芳昭

臨床整形外科 37 （ 2 ） 169-173 2002年02月

研究論文（学術雑誌）, 共著

経静脈的patient controlled analgesiaによる脊椎術後疼痛管理

松本守雄，千葉一裕，西澤隆，中村雅也，丸岩博文，藤村祥一，戸山芳昭，橋口さおり

臨床整形外科 37 （ 2 ） 159-162 2002年02月

研究論文（学術雑誌）, 共著

頚椎椎間板ヘルニアによる頚髄症に対する保存療法の有用性と限界―手術例との比較検討―

松本守雄，千葉一裕，西澤隆，中村雅也，丸岩博文，藤村祥一，戸山芳昭

臨床整形外科 37 （ 2 ） 129-133 2002年02月

研究論文（学術雑誌）, 共著

腰痛症に対する各種画像検査法とその意義

松本守雄，千葉一裕，戸山芳昭

現代医療 34 （増刊） 562-566 2002年02月

研究論文（学術雑誌）, 共著

Use of a titanium mesh cage for posterior atlantoaxial arthrodesis

Matsumoto Morio, Chiba Kazuhiro, Tsuji Takashi, Maruiwa Hirofumi, Toyama Yoshiaki, Ogawa Jun

Journal of Neurosurgery 96 （ 1 ） 127-130 2002年01月

研究論文（学術雑誌）, 共著

Use of a titanium mesh cage for posterior atlantoaxial arthrodesis

Matsumoto Morio, Chiba Kazuhiro, Tsuji Takashi, Maruiwa Hirofumi, Toyama Yoshiaki, Ogawa Jun

Journal of neurosurgery 96 （ 1Suppl ） 127-130 2002年01月

研究論文（学術雑誌）, 共著

Use of a titanium mesh cage for posterior atlantoaxial arthrodesis. Technical note

Matsumoto Morio, Chiba Kazuhiro, Tsuji Takashi, Maruiwa Hirofumi, Toyama Yoshiaki, Ogawa Jun

Journal of Neurosurgery 96 （ 1 SUPPL. ） 127 - 130 2002年

ISSN 0022-3085

The authors placed titanium mesh cages to achieve posterior atlantoaxial fixation in five patients with atlantoaxial instability caused by rheumatoid arthritis or os odontoideum. A mesh cage packed with autologous cancellous bone was placed between the C-1 posterior arch and the C-2 lamina and was tightly connected with titanium wires. Combined with the use of transarticular screws, this procedure provided very rigid fixation. Solid fusion was achieved in all patients without major complications. The advantages of this method include more stable fixation, better control of the atlantoaxial fixation angle, and reduced donor-site morbidity compared with a conventional atlantoaxial arthrodesis in which an autologous iliac crest graft is used.

仙骨全摘後2期的再建を行った脊索腫の2例

松本守雄，千葉一裕，丸岩博文，中村雅也，西澤隆，戸山芳昭

脊椎・脊髄神経手術手技 4 （ 1 ） 104-106 2002年

研究論文（学術雑誌）, 共著

In vivo and in vitro evaluation of the biocompatiblitiy of the hydroxyapatite-PMMA hybrid materials having mechanical property similar to that of cortical bone

Aizawa Mamoru, Ito Masato, Itatani Kiyoshi, Suemasu Hiroshi, Nozue Akira, Okada Isao, Matsumoto Morio, Ishikawa Masayuki, Matsumoto Hideo, Toyama Yoshiaki

Key engineering materials 218 465-468 2002年

研究論文（学術雑誌）, 共著

In vivo and in vitro evaluation of the biocompatibility of the hydroxyapatite-PMMA hybrid materials having mechanical property similar to that of cortical bone

Aizawa M, Ito M, Itatani K, Suemasu H, Nozue A, Okada I, Matsumoto Morio, Ishikawa Masayuki, Matsumoto Hideo, Toyama Yoshiaki

Key Engineering Materials 189-210 2002年

研究論文（学術雑誌）, 共著

In vivo and in vitro evaluation of the biocompatibility of the hydroxyapatite-PMMA materials having mechanical property similar to that of cortical bone

Aizawa Mamoru, Ito Msako, Itatani H, Suemasu H, Nozue Akira, Okada Isao, Matsumoto Morio, Ishikawa Masayuki, Matsumoto Hideo, Toyama Yoshiaki

Bioceramics 14 465-468 2002年

研究論文（学術雑誌）, 共著

In vivo and in vitro evaluation of the biocompatibility of the hydroxyapatite-PMMA hybrid materials having mechanical property similar to that of cortical bone

Aizawa M., Ito M., Itatani K., Suemasu H., Nozue A., Okada I., Matsumoto M., Ishikawa M., Matsumoto H., Toyama Y.

Key Engineering Materials 218-220 465 - 468 2002年

ISSN 1013-9826

We fabricated the Hydroxyapatite(HAp)-PMMA hybrid material having mechanical properties similar to those of the cortical bone, using porous HAp ceramics with well-controlled pore sizes and bulk polymerization of MMA monomer without solvents. The histological results showed that the present hybrid material bonded directly to bone without intervening fibrous tissue between hybrid material and newly formed bone, and that a large amount of new bone was formed around the hybrid material. In addition, the results of in vitro evaluation also showed that the hybrid material in the present investigation has good biocompatibility.

自然縮小を認めた脊柱管内嚢腫の3例

松本守雄，千葉一裕，西澤隆，中村俊康，丸岩博文，藤村祥一，戸山芳昭

日本パラプレジア医学会誌 15 （ 1 ） 84-85 2002年

研究論文（学術雑誌）, 共著

環軸関節固定術におけるTitanium Mesh Cageの使用経験

辻崇，松本守雄，丸岩博文，千葉一裕，戸山芳昭

脊椎・脊髄神経手術手技 4 （ 1 ） 36-38 2002年

研究論文（学術雑誌）, 共著

間欠跛行の改善が得られた変性すべり症による腰部脊柱管狭窄症の1例

松本守雄

Progress in Medicine 21 （ 12 ） 133-134 2001年12月

研究論文（学術雑誌）, 単著

むち打ち損傷における診断―治療上の問題点と今後の課題―

松本守雄，千葉一裕，戸山芳昭

脊椎脊髄ジャーナル 14 （ 11 ） 975-979 2001年11月

研究論文（学術雑誌）, 共著

高齢者に見られる腰椎変性側弯―病態と治療―

千葉一裕，松本守雄，戸山芳昭

Monthly Book Orthopaedics 14 （ 12 ） 96-101 2001年11月

研究論文（学術雑誌）, 共著

Intraspinal cyst communicating with the intervertebral disc in the lumbar spine

Chiba Kazuhiro, Toyama Yoshiaki, Matsumoto Morio, Maruiwa Hirofumi, Watanabe Masahiko, Nishizawa Takashi

Spine 26 （ 19 ） 2112 - 2118 2001年10月

ISSN 0362-2436

Study Design. A retrospective case study of patients with intraspinal cyst having a distinct connection with the corresponding intervertebral disc. Objectives. To propose a new clinical entity, "discal cyst," by clarifying the clinical, radiographic, and histologic aspects of the disease. Summary of Background Data. Several types of intraspinal cysts with different pathogenesis, causing symptoms indistinguishable from those of lumbar disc herniation, have been reported, such as perineural cysts, synovial cysts, and ganglion cysts. However, to the authors' knowledge, no detailed analysis has been made of cysts that have a distinct connection with the corresponding intervertebral disc. Methods. Clinical pictures, radiographic findings, and surgical and histologic findings in eight surgically treated patients with intraspinal cyst having a distinct connection with the intervertebral disc were reviewed. Possible pathogenesis and a proposal for nomenclature were also discussed. Results. This disease can be characterized by (1) clinical symptoms indistinguishable from those of typical disc herniation, manifesting as a unilateral single nerve root lesion; (2) incidence at slightly younger age and at upper intervertebral levels than with typical disc herniation; (3) T1 low signal and T2 high signal intensity, round to oval mass lesion on magnetic resonance imaging, compatible with a liquid-containing cyst; (4) minimal degeneration of the involved disc, either on discography/computed tomographic discography or magnetic resonance imaging; (5) a connection between the cyst and the corresponding intervertebral discs on discograms with severe radiating pain in the affected leg at the time of injection; (6) immediate relief of symptoms after simple removal of the cyst; (7) cyst wall consisting of dense fibrous connective tissue containing bloody to clear serous discharge; and (8) absence of disc materials and a specific lining cell layer on histologic examination, Although the exact cause is unknown, underlying minor disc injury may serve as a basis for cyst formation. Conclusion. Eight cases of intraspinal cysts communicating with the intervertebral disc presenting symptoms identical to those of disc herniation are presented. Because all cysts were connected to the corresponding disc and the development of the cyst was assumed to be related to underlying disc injury, it is proposed to name-this clinical entity discal cyst.

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上位頚椎損傷の治療

松本守雄，戸山芳昭

Monthly Book Orthopedics 14 （ 11 ） 15-21 2001年10月

研究論文（学術雑誌）, 共著

Intraspinal cyst communication with the intervertebral space; Discal cyst

Chiba Kazuhiro, Toyama Yoshiaki, Matsumoto Morio, Maruiwa Hirofumi, Nishizawa Takashi

Spine 26 （ 19 ） 2112-2118 2001年10月

研究論文（学術雑誌）, 共著

L5椎体下縁の骨棘により生じたfar-out syndromeの1例

奥島雄一郎，千葉一裕，松本守雄，丸岩博文，中村雅也，西澤隆，戸山芳昭

関東整形災害外科学会雑誌 32 （ 5 ） 262-265 2001年10月

研究論文（学術雑誌）, 共著

Surgical management of idiopathic spinal cord herniation-A review of 9 cases treated by the enlargement of the dural defect-

Watanabe Masahiko, Chiba Kazuhiro, Matsumoto, Maruiwa Hirofumi, Fujimura Yoshikazu, Toyama Yoshiaki

Journal of Neurosurgery 95 （ 2 Suppl ） 169-172 2001年10月

研究論文（学術雑誌）, 共著

脊柱管狭窄を伴う頚椎椎間板ヘルニアの手術療法―前後合併手術と後方除圧術との比較―

丸岩博文，千葉一裕，西澤隆，中村雅也，松本守雄，戸山芳昭

脊椎脊髄ジャーナル 14 （ 9 ） 799-803 2001年09月

研究論文（学術雑誌）, 共著

MRIによる遠位腰椎神経根の3次元表示

松本守雄，Souza S，Vosburgh K，Carl A，戸山芳昭

臨床整形外科 36 （ 8 ） 949-951 2001年08月

研究論文（学術雑誌）, 共著

頚椎症性脊髄症（ヘルニアを含む）に対する腸骨inlay graftによる前方固定術

丸岩博文，千葉一裕，松本守雄，中村雅也，西澤隆，戸山芳昭

Monthly Book Orthopedics 14 （ 8 ） 1-8 2001年08月

研究論文（学術雑誌）, 共著

第5腰椎椎体骨棘による第5腰神経根障害に対して腹腔鏡視下骨棘切除を行った1例

松本守雄，千葉一裕，西澤隆，中村雅也，丸岩博文，戸山芳昭

脊椎脊髄ジャーナル 14 （ 8 ） 112-115 2001年08月

研究論文（学術雑誌）, 共著

Relationships between outcomes of conservative treatment and magnetic resonance imaging findings in patients with mild cervical myelopathy caused by soft disc herniations

Matsumoto Morio, Chiba Kazuhiro, Ishikawa Masayuki, Maruiwa Hirofumi, Fujimura Yoshikazu, Toyama Yoshiaki

Spine 26 （ 14 ） 1592 - 1598 2001年07月

ISSN 0362-2436

Study Design. A retrospective follow-up study of conservatively treated patients with mild cervical myelopathy caused by cervical soft disc herniation. Objective. To investigate the outcome of conservative treatment for patients with mild myelopathy caused by cervical soft disc herniation and to evaluate usefulness of magnetic resonance findings in the prediction of the outcomes. Summary of Background Data. Recent studies on conservative treatment of cervical soft disc herniation have focused mainly on radiculopathy, and not on myelopathy. Methods. Twenty-seven patients with mild cervical myelopathy secondary to cervical soft disc herniation were treated conservatively for more than 6 months by cervical bracing and restriction of daily activities. Of the 27 patients, 17 patients (Group A) underwent conservative treatment only and it was associated with improvement in their neurologic deficits, while the other 10 patients (Group B) ultimately underwent decompression surgery because of neurologic deterioration. Comparisons between the two groups were made in regard to JOA score, patient satisfaction, and magnetic resonance findings, including location of the disc herniation (focal or diffuse in the sagittal plane, median or paramedian in the axial plane). Results. The JOA scores were 13.6 ± 1.6 in Group A and 14.1 ± 1.6 in Group B before treatment, 14.9 ± 1.0 and 12.9 ± 2.1, respectively, at 3 months, and 16.2 ± 0.8 and 16.0 ± 1.2, respectively, at the final follow-up. The JOA scores at 3 months were significantly lower in Group B than in Group A. Satisfaction with the results of treatment at the final follow-up was reported by 77% of the patients in Group A and 90% in Group B. Focal-type herniation was present in 47% of the patients in Group A and 70% in Group B, while median-type herniation was diagnosed in 77% in Group A and 30% in Group B. Follow-up magnetic resonance imaging of the patients in Group A showed spontaneous regression of a herniated mass in 10 patients (59%), Diffuse-type herniations were more likely to regress spontaneously than focal-type herniation (78% vs. 37%). Conclusions. Conservative treatment is an effective treatment option for mild cervical myelopathy caused by cervical soft disc herniation. A good outcome can be expected in patients with a median-type and/or diffuse-type herniation on magnetic resonance imaging.

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高齢者の歯突起骨折―その臨床像と治療成績について

松本守雄，千葉一裕，西澤隆，中村雅也，丸岩博文，藤村祥一，戸山芳昭，渡辺公三

臨床整形外科 36 （ 7 ） 881-884 2001年07月

研究論文（学術雑誌）, 共著

特集／腰椎椎間板ヘルニアの治療―最近の動向；ヘルニアの自然縮小―単純MRIによる観察

奥島雄一郎，千葉一裕，松本守雄，丸岩博文，中村雅也，西澤隆，西川雄司，戸山芳昭

骨・関節・靭帯 14 （ 7 ） 655-658 2001年07月

研究論文（学術雑誌）, 共著

Relationships between outcomes of conservative treatment and MR findings in patients with mild cervical myelopathy caused by soft disc herniations

Matsumoto Morio, Chiba Kazuhiro, Ishikawa Masayuki, Fujimura Yoshikazu, Toyama Yoshiaki

Spine 26 （ 14 ） 1592-1598 2001年07月

研究論文（学術雑誌）, 共著

特集腰部脊柱管狭窄症―病態・診断・治療―；手術的治療―腰椎変性側弯症（DLS）

松本守雄，千葉一裕，戸山芳昭

現代医療 33 （増2 ） 1381-1386 2001年06月

研究論文（学術雑誌）, 共著

腰椎変性側弯症に対するインストゥルメンテーション手術（広範囲固定）の中・長期成績

戸山芳昭，千葉一裕，松本守雄

関節外科 20 （ 6 ） 689-698 2001年06月

研究論文（学術雑誌）, 共著

手術的治療　腰椎変性側弯症(DLS)

松本守雄，千葉一裕，戸山芳昭

現代医療 33 （増刊） 1381-1386 2001年06月

研究論文（学術雑誌）, 共著

高齢者軸椎骨折の治療経験

松本守雄，千葉一裕，西澤隆，中村雅也，丸岩博文，戸山芳昭

日本パラプレジア医学会雑誌 14 （ 1 ） 116-117 2001年05月

研究論文（学術雑誌）, 共著

頚椎椎間板ヘルニアによる頚髄症軽症例に対する保存療法

松本守雄，丸岩博文，石川雅之，西澤隆，千葉一裕，藤村祥一，戸山芳昭

臨床整形外科 36 （ 4 ） 429-434 2001年04月

研究論文（学術雑誌）, 共著

腰椎椎間板ヘルニアの自然縮小―MRI　T2強調横断画像上の輝度変化に注目して―

奥島雄一郎，千葉一裕，松本守雄，丸岩博文，西澤隆，戸山芳昭

臨床整形外科 36 （ 4 ） 473-479 2001年04月

研究論文（学術雑誌）, 共著

脊髄腫瘍複数回手術例の検討

渡辺雅彦，千葉一裕，松本守雄，丸岩博文，藤村祥一，戸山芳昭

臨床整形外科 36 （ 4 ） 387-392 2001年04月

研究論文（学術雑誌）, 共著

脊髄腫瘍複数回手術例の検討

渡辺雅彦，千葉一裕，松本守雄，丸岩博文，藤村祥一，戸山芳昭

臨床整形外科 36 （ 4 ） 387-392 2001年04月

研究論文（学術雑誌）, 共著

Traumatic subluxation of the axis after hyperflexion injury in children

Matsumoto Morio, Toyama Yoshiaki, Chiba Kazuhiro

Journal of Spinal Disorders 14 （ 2 ） 172-179 2001年04月

研究論文（学術雑誌）, 共著

Infantile spinal cord meningioma-Case illustration-

Watanabe Masahiko, Chiba Kazuhiro, Matsumoto Morio, Maruiwa Hirofumi, Fujimura Yoshikazu, Toyama Yoshiaki

Journal of Neurosurgery 94 （ 2 Suppl ） 334 2001年04月

研究論文（学術雑誌）, 共著

小児頚椎疾患の診断と治療

松本守雄，戸山芳昭

脊椎脊髄ジャーナル 14 （ 2 ） 111-119 2001年02月

研究論文（学術雑誌）, 共著

小児頚椎疾患の診断と治療

松本守雄，戸山芳昭

脊椎脊髄ジャーナル 14 （ 2 ） 111-119 2001年02月

研究論文（学術雑誌）, 共著

Traumatic subluxation of the axis after hyperflexion injury of the cervical spine in children

Matsumoto M., Toyama Y., Chiba K., Fujimura Y., Fukui K., Kobayashi K.

Journal of Spinal Disorders 14 （ 2 ） 172 - 179 2001年

ISSN 0895-0385

Six cases of children (four boys and two girls, mean age 11 years) who had traumatic subluxation of the axis (C2) were reviewed retrospectively. Initial radiographs demonstrated no detectable vertebral fracture in any of the children. However, a slight anterior subluxation of C2 was observed in three of the patients. Radiographs, taken at 1 month after injury in all but one patient, revealed a progression of the subluxation and a local kyphosis in all of the patients. Four of the children were treated conservatively with a cervical brace, and an improvement of both the kyphosis and the anterior slippage of C2 was obtained accompanied by an anteroposterior growth of the C3 vertebral body. The kyphosis of two of the patients became severe and, ultimately, these patients underwent fusion surgery. At the follow-up, none of the patients presented with any significant symptom. For the correct diagnosis of traumatic subluxation of C2, sequential radiographs to confirm the progression of subluxation and local kyphosis are mandatory. Conservative treatment rather than early surgical treatment may be chosen for this injury, because mild and moderate kyphosis can be corrected spontaneously by remodeling of the cervical spine.

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Eyes on RA-RAにおける脊椎の圧迫骨折とその治療・予防―二次性オステオポローシスを含めて

西澤隆，戸山芳昭，千葉一裕，松本守雄

RA ＆セラピー 7 （ 1 ） 4-8 2001年

研究論文（学術雑誌）, 共著

高齢者軸椎骨折の治療経験

松本守雄，千葉一裕，西澤隆，中村俊康，丸岩博文，藤村祥一，戸山芳昭

日本パラプレジア医学会雑誌 14 （ 1 ） 116-117 2001年

研究論文（学術雑誌）, 共著

Surgical management of idiopathic spinal cord herniation

Watanabe Masahiko, Chiba Kazuhiro, Matsumoto Morio, Maruiwa Hirofumi, Fujlmura Yoshikazu, Toyama Yoshiaki

Journal of Neurosurgery 95 （ 2 SUPPL. ） 169 - 172 2001年

ISSN 0022-3085

Object. Spinal cord herniation is a rare cause of progressive myelopathy and can be corrected surgically. In most previous reports, closure of the dural defect was the recommended procedure. The object of this paper is to describe a new procedure in which spinal cord constriction is released by enlarging the hiatus; additionally the postoperative results will be discussed. Methods. In nine patients with spinal cord herniation, enlargement of the dural defect was performed. In eight patients, neurological deficits resolved immediately after surgery. In one patient with a severe preoperative neurological deficit whose spinal cord herniated massively, deterioration occurred postoperatively. To date, no recurrence of herniation has been observed. Conclusions. The goals of surgery are to reduce the herniation, return the spinal cord to the normal position, and prevent the recurrence of herniation. The use of sutures to close the dural defect has been the method of choice to date. The surgical space in front of the spinal cord, however, is insufficient to accommodate this procedure safely. Because symptoms are caused by the constriction of the spinal cord at the hiatus, surgical expansion of the hiatus allows the goals of surgery to be achieved. This procedure, which is technically easier and less invasive with regard to the vulnerable spinal cord than the closure of the dural defect, could be a viable alternative for the treatment of this rare disease.

Infantile spinal cord meningioma

Watanabe M., Chiba K., Matsumoto M., Maruiwa H., Fujimura Y., Toyama Y.

Journal of Neurosurgery 94 （ 2 SUPPL. ） 334 2001年

ISSN 0022-3085

仙骨嚢腫の臨床像―その発生機序を中心に―

丸岩博文，千葉一裕，渡辺雅彦，松本守雄，藤村祥一，戸山芳昭

東日本整形災害外科学会雑誌 12 （ 4 ） 414-417 2000年12月

研究論文（学術雑誌）, 共著

Impact of longitudinal distance of the cervical spine on the results of expansive open-door laminoplasty

Chiba Kazuhiro, Toyama Yoshiaki, Watanabe Masahiko, Maruiwa Hirofumi, Matsumoto Morio, Hirabayashi Kiyoshi

Spine 25 （ 22 ） 2893 - 2898 2000年11月

ISSN 0362-2436

Study Design. A retrospective study in patients who underwent expansive open-door laminoplasty (ELAP) for cervical myelopathy and in whom the cervical alignment was nonlordotic at the final follow-up to analyze the correlation between the longitudinal distance of the cervical spine and surgical results. Objectives. To determine the impact of longitudinal distance of the cervical spine on surgical results of ELAP and to propose a new concept, the redundant spinal cord, that may influence patient selection for ELAP. Summary of Background Data. Results in many studies have demonstrated that postoperative cervical alignment has significant effect on surgical results, and spines that are malaligned are thought to deteriorate. The current surgical data showed that not all patients with postoperative malalignment had poor surgical results. Patients with cervical spondylotic myelopathy (CSM) tended to have better clinical results than those with ossification of the posterior longitudinal ligament (OPLL). Methods. Results in 70 patients who underwent ELAP for cervical myelopathy with postoperative cervical malalignment were investigated. The longitudinal distance index (LDI) was defined as the length of a vertical line between the posteroinferior edges of C2 and C7 divided by the anteroposterior diameter of C4 and was measured on lateral neutral radiographs at final follow-up. Correlation between LDI and surgical results represented by Japanese Orthopedic Association scores and percentage of recovery were analyzed statistically in each patient. Results. Patients with CSM had smaller LDI and better surgical results than those with OPLL. Weak but significant negative correlation was detected between LDI and percentage of recovery, indicating that longitudinal distance of the cervical spine may have some degree of impact on the surgical results of ELAP. Conclusion. A decrease in LDI represents shortening of the cervical spine caused by multiple disc degeneration and may influence surgical results of ELAP by inducing redundancy of the spinal cord in patients with postoperative malalignment.

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整形外科疾患における最近の画像診断―脊椎・脊髄疾患における最近のMRI―

松本守雄，戸山芳昭

関節外科 19 （ 10 ） 108-118 2000年10月

研究論文（学術雑誌）, 共著

von Recklinghausen病に伴う巨大頚髄腫瘍の1治験例

井上浩，千葉一裕，渡辺雅彦，松本守雄，丸岩博文，戸山芳昭，向井万起男

関東整形災害外科学会雑誌 31 （ 5 ） 503-508 2000年10月

研究論文（学術雑誌）, 共著

Anterior dural laceration caused by thoracolumbar and lumbar burst fractures

Carl Allen, Matsumoto Morio, Whalen John

Journal Spinal Disorders 13 （ 5 ） 399-403 2000年10月

研究論文（学術雑誌）, 共著

脊柱側弯症の診断と治療

松本守雄，千葉一裕，戸山芳昭

小児科診療 63 （ 8 ） 1144-1150 2000年08月

研究論文（学術雑誌）, 共著

腰椎椎間板ヘルニアLove法後の再手術例の検討

依光悦郎，千葉一裕，松本守雄，戸山芳昭

脊椎脊髄ジャーナル 13 （ 8 ） 762-767 2000年08月

研究論文（学術雑誌）, 共著

腰椎変性すべり症に対する前方固定術の長期成績

西澤隆，千葉一裕，渡辺雅彦，松本守雄，丸岩博文，藤村祥一，戸山芳昭

脊椎脊髄ジャーナル 13 （ 7 ） 709-714 2000年07月

研究論文（学術雑誌）, 共著

腰椎変性疾患に対する固定術の意義

松本守雄，千葉一裕，戸山芳昭

脊椎脊髄ジャーナル 13 （ 6 ） 652-658 2000年06月

研究論文（学術雑誌）, 共著

In vivo pedicle screw placement: Image-guided virtual vision

Carl Allen, Khanuja Hosper, Gatto Chales, Matsumoto Morio, VomLehn John, Schenck John, Rohling Kenneth, Lorensen Williams, Vosburgh Kirby

Journal Spinal Disorders 13 （ 3 ） 225-229 2000年06月

研究論文（学術雑誌）, 共著

片開き式脊柱管拡大術後の髄節性麻痺の検討

千葉一裕，渡辺雅彦，丸岩博文，松本守雄，藤村祥一，戸山芳昭

臨床整形外科 35 （ 6 ） 607-612 2000年05月

研究論文（学術雑誌）, 共著

乳児脊髄髄膜腫の1例

渡辺雅彦，千葉一裕，松本守雄，丸岩博文，藤村祥一，戸山芳昭

日本パラプレジア医学会誌 13 （ 4 ） 144-145 2000年04月

研究論文（学術雑誌）, 共著

頚椎症性脊髄症に対する前方除圧固定術の長期成績―術後10年以上における成績不良例の検討―

高石官成，松本守雄，渡辺雅彦，丸岩博文，千葉一裕，藤村祥一，平林洌，戸山芳昭

臨床整形外科 35 （ 5 ） 401-407 2000年04月

研究論文（学術雑誌）, 共著

胸腰椎部硬膜外くも膜嚢腫の治療経験―Flexible fiber scopeにより交通孔を確認した2例―

丸岩博文，千葉一裕，渡辺雅彦，松本守雄，藤村祥一，戸山芳昭

日本パラプレジア医学会雑誌 13 （ 1 ） 262-263 2000年04月

研究論文（学術雑誌）, 共著

頚椎症性脊髄症に対する片開き式脊柱管拡大術の長期成績―術後10年以上―

丸岩博文，千葉一裕，渡辺雅彦，松本守雄，藤村祥一，平林洌，戸山芳昭

臨床整形外科 35 （ 5 ） 411-416 2000年04月

研究論文（学術雑誌）, 共著

Increased signal intensity of the spinal cord on magnetic resonance images in cervical compressive myelopathy

Matsumoto Morio, Toyama Yoshiaki, Ishikawa Masayuki, Chiba Kazuhiro, Suzuki Nobumasa, Fujimura Yoshikazu

Spine 25 （ 6 ） 677 - 682 2000年03月

ISSN 0362-2436

Study Design. Correlation between a lesion of the spinal cord that elicits increased signal intensity (ISI) on magnetic resonance images (MRIs) and the outcome of conservative treatment for cervical compressive myelopathy was retrospectively investigated. Objective. To investigate whether ISI could predict the outcome of conservative treatment for cervical compressive myelopathy. Summary of Background Data. It is unknown whether ISI is related to the outcome of conservative treatment for cervical compressive myelopathy. Methods. Fifty-two patients with mild cervical myelopathy underwent conservative treatment with a cervical brace. The compressive lesions were spondylosis in 29 patients, disc herniation in 12, and an ossification of the longitudinal ligament in 11. They also underwent MRI (1.5 T), and ISI was evaluated on T2-weighted sagittal and axial images. The ISI areas were classified as focal or multisegmental. Thirty-nine patients underwent follow- up MRI after a mean interval of 2 years, 4 months. The transverse area of the spinal cord was also measured on T2-weighted axial images. The outcome of conservative treatment was assessed using the Japanese Orthopedic Association Score (JOA score). Patients showing either an improvement in the JOA score or with a JOA score of 15 or more were considered to have a satisfactory outcome. Results. The average JOA score was 14.0 ± 1.4 (range, 10-16) before conservative treatment and 14.4 ± 1.9 (range, 10-17) at follow-up. The average gain in the JOA score was 0.4 points ± 1.9 (range, -5 to +6). The outcome was satisfactory in 36 patients (69%). An area of ISI was observed in 34 patients (65%) before treatment (24 focal and 10 multisegmental). A satisfactory outcome was obtained in 78% of the patients without ISI, in 63% of those with focal ISI, and in 70% of those with multisegmental ISI. No statistically significant difference was seen among these three groups in the percentages of patients with satisfactory outcome, JOA scores before and after treatment or transverse spinal cord area. Of the 39 patients who were re-examined by MRI, 28 showed an area of ISI. The ISI regressed in five patients (18%). Satisfactory outcome was obtained in all 5 patients with regression of ISI, in 16 (70%) of the 23 patients without regression of ISI, and in 10 (91%) of the 11 patients without ISI apparent on the the first images (difference, not significant). Conclusions. Increased signal intensity was not related to a poor outcome of conservative treatment or severity of myelopathy in the patients with mild cervical myelopathy.

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Increased signal intensity of the spinal cord on magnetic resonance images in cervical compressive myelopathy does it predict the outcome of conservative treatment?

Matsumoto Morio, Toyama Yoshiaki, Ishikawa Masayuki, Chiba Kazuhiro, Suzuki Nobumasa, Fujimura Yoshikazu

Spine 25 （ 6 ） 677-682 2000年03月

研究論文（学術雑誌）, 共著

脊髄腫瘍術後長期経過例（10年以上）の検討

渡辺雅彦，千葉一裕，丸岩博文，松本守雄，藤村祥一，戸山芳昭

東日本整形災害外科学会雑誌 12 （ 1 ） 96-99 2000年03月

研究論文（学術雑誌）, 共著

腰椎変性側弯に対するinstrumentation surgery

千葉一裕，松本守雄，丸岩博文，渡辺雅彦，戸山芳昭

脊椎脊髄ジャーナル 13 （ 3 ） 185-190 2000年03月

研究論文（学術雑誌）, 共著

Axis location of tibial rotation and its change with flexion angle

Matsumoto Hideo, Seedhom Bahaa B, Suda Yasunori, Otani Toshiro, Fujikawa Kyosuke

Clinical Orthopaedics and Related Research 371 178-182 2000年03月

研究論文（学術雑誌）, 共著

In vivo pedicle screw placement

Carl A. L., Khanuja H. S., Gatto C. A., Matsumoto M., VomLehn J., Schenck J., Rohling K., Lorensen W., Vosburgh K.

Journal of Spinal Disorders 13 （ 3 ） 225 - 229 2000年

ISSN 0895-0385

Near-real-time frameless stereotaxy registering intraoperative anatomy to a preoperative three-dimensional computer model has been developed for use with in vivo pedicle screw placement. Eight patients underwent thoracolumbar and lumbar spine stabilization surgery using this new technology, and 32 pedicle screws were placed. Three additional patients had 12 pedicle screws removed during revision surgery and they allowed the authors to estimate the accuracy of this navigational system. Accuracy was determined by comparing pedicle screw position on postoperative computed tomographs for the first eight patients and on preoperative computed tomographs for the latter three patients, with the intraoperative computer trajectory data gathered during operation. In the group of eight patients, all screws were intrapedicular. In evaluating all 11 patients, the overall accuracy was ± 2 mm, but the greatest error of 5.4 mm was noted in the sagittal plane measurement. During the development phase of this technology, time constraints prolong surgery, but this may be addressed once the tool's accuracy has been confirmed and intraoperative radiographic confirmation becomes unnecessary. In vivo real-time frameless stereotaxy for pedicle screw placement offers promise for the future. Refinements are needed to improve accuracy and address time constraints.

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Impact of longitudinal distance of the cervical spine on the results of expansive open-door laminoplasty

Chiba Kazuhiro, Toyama Yoshiaki, Watanabe Masahiko, Maruiwa Hirofumi, Matsumoto, Morio Hirabayashi Kiyoshi

Spine 25 （ 22 ） 2893-2898 2000年

研究論文（学術雑誌）, 共著

Anterior dural laceration caused by thoracolumbar and lumbar burst fractures

Carl A. L., Matsumoto M., Whalen J. T.

Journal of Spinal Disorders 13 （ 5 ） 399 - 403 2000年

ISSN 0895-0385

A retrospective review of the records of 60 patients with thoracolumbar and lumbar burst fractures was undertaken to document the incidence and evaluate the sequelae of dural injuries found during anterior procedures. In the entire series, six (10%) patients each had a preexisting vertically oriented dural tear. All patients with anterior dural lacerations were male and had associated neurologic deficits. In all six patients, preoperative computed tomography showed an asymmetrically retropulsed bone fragment. Dural tears were repaired primarily. A postoperative cerebrospinal fluid leak developed into the chest cavity of one patient, who was treated successfully with subarachnoid drainage. In patients with anterior dural laceration, primary repair is warranted and can be performed more easily after intraoperative correction of kyphosis. Subarachnoid drainage may be effective in cases of continued postoperative anterior cerebrospinal fluid leakage before repeated operation is considered.

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環軸椎亜脱臼に対するMagerl法─自家考案環軸関節ピンニングセットを用いて─

小川潤，戸山芳昭，鎌田修博，松本守雄

日本脊椎外科学会雑誌 10 346-352 1999年12月

研究論文（学術雑誌）, 共著

腰椎固定術

藤村祥一，松本守雄

Monthly Book Orthopaedics 12 （ 10 ） 68-74 1999年09月

研究論文（学術雑誌）, 共著

思春期小児に発生した頸椎屈曲損傷（軸椎　突起骨端裂離）の3例

野尻賢哉，松本守雄，鈴木信正，藤村祥一，福井康之，戸山芳昭

関東整形災害外科学会雑誌 30 （ 4 ） 306-310 1999年08月

研究論文（学術雑誌）, 共著

胸腔内に巨大に発育した砂時計型神経鞘腫の2例

岩本範顕，市村正一，松本守雄，鈴木信正，藤村祥一，戸山芳昭

関東整形災害外科学会雑誌 30 252-256 1999年06月

研究論文（学術雑誌）, 共著

脊髄髄内腫瘍摘出術後の経時的MRIの臨床的意義

千葉一裕，松本守雄，市村正一，鈴木信正，藤村祥一，戸山芳昭

東日本整形災害外科学会雑誌 11 （ 2 ） 160-163 1999年06月

研究論文（学術雑誌）, 共著

腰椎変性すべり症に対する前方固定術の長期成績─術後5年以上─

石井賢，松本守雄，藤村祥一，千葉一裕，鈴木信正，戸山芳昭

東日本整形災害外科学会雑誌 11 125-128 1999年06月

研究論文（学術雑誌）, 共著

健常者における頸髄面積および脊柱管前後径との関連

石川雅之，藤村祥一，松本守雄，鈴木信正，戸山芳昭

東日本整形災害外科学会雑誌 11 （ 2 ） 122-124 1999年06月

研究論文（学術雑誌）, 共著

成人尾椎椎間板に石灰化を生じた1例

森山一郎，松本守雄，市原眞仁

整形外科 50 （ 4 ） 402-403 1999年04月

研究論文（学術雑誌）, 共著

成人尾椎椎間に石灰化を生じた1例

戸山芳昭，松本守男，森山一郎

整形外科（ 50 ） 402-403 1999年04月

研究論文（学術雑誌）, 共著

脊髄くも膜嚢腫の12例─その臨床像と手術成績─

千葉一裕，戸山芳昭，松本守雄，市村正一，鈴木信正，藤村祥一

日本パラプレジア医学会雑誌 12 （ 1 ） 158-159 1999年04月

研究論文（学術雑誌）, 共著

高齢者に対する整形外科手術─適応と限界─；高齢者腰椎椎間板ヘルニアの病態と治療

千葉一裕，戸山芳昭，松本守雄，渡辺雅彦

関節外科 18 （ 4 ） 132-139 1999年04月

研究論文（学術雑誌）, 共著

第1・第2腰椎椎間板ヘルニアの臨床像と手術療法

松本守雄，藤村祥一，鈴木信正，市村正一，千葉一裕，戸山芳昭，市原眞仁

整形外科 50 （ 4 ） 330-334 1999年04月

研究論文（学術雑誌）, 共著

子宮頚癌の放射線治療後に発生した恥骨化膿性骨髄炎の2例

森山一郎，松本守雄，山内健二，堀内極，森末光，山岸正明，田中守

臨床整形外科 34 （ 3 ） 359-362 1999年03月

研究論文（学術雑誌）, 共著

第1，第2腰椎椎間板ヘルニアの臨床像と手術療法

松本守雄，藤村祥一，鈴木信正，市村正一，千葉一裕，戸山芳昭，市原眞仁

整形外科 50 （ 3 ） 330-334 1999年03月

研究論文（学術雑誌）, 共著

The end-point and the remnant of the injured cruciate ligaments of the knee

Matsumoto Hideo, Toyoda Takashi, Kawakubo Makoto, Otani Toshiro, Fujikawa Kyosuke

The Knee 6 （ 1 ） 43-47 1999年02月

研究論文（学術雑誌）, 共著

Extensive post-traumatic ossification of the patellar tendon. A report of two cases

Matsumoto Hideo, Kawakubo Makoto, Otani Toshiro, Fujikawa Kyosuke

Journal of Bone and Joint Surgery 81B （ 2 ） 34-36 1999年02月

研究論文（学術雑誌）, 共著

外傷性頚部症候群における画像所見の診断的意義について―無症候性健常者との比較検討から―

松本守雄，藤村祥一，平林冽

Monthly Book Orthopaedics 12 （ 1 ） 37-43 1999年01月

研究論文（学術雑誌）, 共著

RA頚椎の脊髄症発現機序と手術療法

渡辺雅彦，戸山芳昭，千葉一裕，松本守雄

関節外科 18 （ 2 ） 138-142 1999年01月

研究論文（学術雑誌）, 共著

Intervertebral disc calcification in the adult coccyx

Matsumoto M., Moriyama I., Toyama Y., Ichihara M.

Journal of Orthopaedic Surgery 7 （ 2 ） 77 - 80 1999年

ISSN 1022-5536

We report a case of a 31-year-old male with coccygodynia caused by calcification of the coccygeal intervertebral disc. He developed coccygodynia without any history of trauma. A plain radiograph of the coccyx showed no obvious abnormality. Plain CT scans clearly demonstrated calcification in the coccygeal intervertebral disc right at the tenderness spot in the coccyx. Conservative treatment with nonsteroidal anti-inflammatory drugs was effective, and his symptom diminished in 3 weeks. To the authors' knowledge, this is the first report regarding symptomatic calcification of the coccygeal intervertebral disc.

Computer-assisted guidance systems for spinal instrumentation

Allen Carl, Matsumoto Morio

Current Opinion in Orthopedics 10 154-161 1999年

研究論文（学術雑誌）, 共著

Dynamized anterolateral compression system for thoracolumbar and lumbar burst fractures

Allen Carl, Matsumoto Morio

State of the art reviews. Spine 13 281-294 1999年

研究論文（学術雑誌）, 共著

頸髄症保存療法例におけるMRI所見と治療成績との関連

松本守雄，石川雅之，千葉一裕，市村正一，鈴木信正，藤村祥一，戸山芳昭

臨床整形外科 34 （ 4 ） 537-542 1999年

研究論文（学術雑誌）, 共著

Computer-assisted guidance systems for spinal instrumentation

Carl Allen L., Matsumoto Morio

Current Opinion in Orthopaedics 10 （ 2 ） 154 - 161 1999年

ISSN 1041-9918

The new era of spinal implants, such as pedicle screws, has enhanced mechanical stability of the spine but also has resulted in increased risks. Misplaced pedicle screws cause complications, including neurovascular injuries and instrumentation failure. With the advent of accurate tracking devices, computer-assisted frameless image guidance has been used to improve the safety and efficacy of pedicle screw placement. Early in vitro and in vivo studies have shown that stereotaxic guidance increases the accuracy and safety of implant placement. Improvement of registration technique using intraoperative ultrasonography may extend the use of the registration technique to less invasive percutaneous indications in the future.

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Cervical curvature in acute whiplash injuries

Matsumoto Morio, Fujimura Yoshikazu, Suzuki Nobumasa, Yoshiaki Toyama Toyama, Shiga Hayao

Injury 29 （ 10 ） 775 - 778 1998年12月

ISSN 0020-1383

The cervical curvature of 488 patients with acute whiplash injury was prospectively studied by comparison with 495 asymptomatic healthy volunteers. Plain radiography of the cervical spine in the neutral position was evaluated qualitatively. No significant difference was noted in frequencies of non-lordotic cervical curative and local angular kyphosis between acute whiplash injury patients and asymptomatic subjects. No significant association was apparent between clinical symptoms and cervical curvature. These results suggest that non-lordotic cervical curvature and angular kyphosis in acute whiplash injury patients constitute normal variants rather than pathological findings.

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MRIによる健常者頚椎椎間板の加齢変化（特に椎間板ヘルニアについて）

松本守雄，藤村祥一

整形外科最小侵襲手術ジャーナル（ 8 ） 9-13 1998年10月

研究論文（学術雑誌）, 共著

Cervical curvature in acute whiplash injuries; prospective comparative study with asymptomatic subjects

Matsumoto Morio, Fujimura Yoshikazu, Suzuki Nobumasa, Toyama Yoshiaki, Shiga Hayao

Injury 29 （ 10 ） 775-778 1998年10月

研究論文（学術雑誌）, 共著

軸椎棘突起剥離骨折を伴った小児頚椎屈曲損傷の治療経験

松本守雄，戸山芳昭，千葉一裕，市村正一，鈴木信正，藤村祥一，福井康之，里見和彦

臨床整形外科 33 （ 9 ） 1053-1059 1998年09月

研究論文（学術雑誌）, 共著

Tensile load and the metabolism of anterior cruciate ligament cells

Toyoda Takashi, Matsumoto Hideo, Fujikawa Kyosuke, Saito Seiji, Inoue Kazuhiko

Clinical Orthopaedic and Related Research 353 247-255 1998年08月

研究論文（学術雑誌）, 共著

MRI for cervical intervertebral discs in asymptomatic subjects

Matsumoto M, Fujimura Y, Suzuki N, Nishi Y, Nakamura M, Yabe Y, Shiga H

J Bone and Joint Surg 19-24 1998年08月

研究論文（学術雑誌）, 共著

趾と爪の肥大を伴う母趾末節骨に発生した類骨骨腫の1例

森末光，山内健司，松本守雄，森山一郎，堀内極，田中守，矢部啓夫

関東整形災害外科学会誌 29 （ 3 ） 262-266 1998年06月

研究論文（学術雑誌）, 共著

脊髄腫瘍非手術例の検討

鎌田修博，戸山芳昭，松本守雄，市村正一，鈴木信正，藤村祥一，福井康之

臨床整形外科 33 （ 4 ） 433-437 1998年04月

研究論文（学術雑誌）, 共著

円錐部脊髄腫瘍（硬膜内髄外）の臨床像

稲見州治，戸山芳昭，松本守雄，千葉一裕，市村正一，鈴木信正，藤村祥一

日本パラプレジア医学会誌 11 （ 1 ） 150-151 1998年04月

研究論文（学術雑誌）, 共著

Amplification of JC virus reguratory DNA sequences from cerebrospinal fluid : Diagnositic value for progressive multifocal leukoencephalopathy

Sugimoto C, Ito D, Tnaka K, Matsumoto H, Sakai H, Fijihara K, Itoyama Y, Yamada T, Kira J, Matsumoto R, Mori M, Nagashima K, Yogo Y

Arch Virology 143 249-262 1998年03月

研究論文（学術雑誌）, 共著

腰椎変性側弯に対するinstrumentation

戸山芳昭，松本守雄，小野俊明

脊椎脊髄ジャーナル 11 （ 3 ） 341-347 1998年03月

研究論文（学術雑誌）, 共著

MRI of cervical intervertebral discs in asymptomatic subjects

Matsumoto Morio, Fujimura Yoshikazu, Suzuki Nobuyuki, Nishi Yukimi, Nakamura Masaya, Yabe Yutaka, Shiga Hayao

J Bone Joint Surg 80-B （ 1 ） 19-24 1998年01月

研究論文（学術雑誌）, 共著

MRI of cervical intervertebral discs in asymptomatic subjects

Matsumoto Morio, Fujimura Yoshikazu, Suzuki Nobumasa, Nishi Yukimi, Nakamura Masaya, Yabe Yutaka, Shiga Hayao

Journal of Bone and Joint Surgery - Series B 80 （ 1 ） 19 - 24 1998年01月

ISSN 0301-620X

We studied degenerative changes in the cervical intervertebral discs of 497 asymptomatic subjects by MRI and evaluated disc degeneration by loss of signal intensity, posterior and anterior disc protrusion, narrowing of the disc space and foraminal stenosis. In each subject, five disc levels from C2-C3 to C6-C7 were evaluated. The frequency of all degenerative findings increased linearly with age. Disc degeneration was the most common observation, being present in 17% of discs of men and 12% of those of women in their twenties, and 86% and 89% of discs of both men and women over 60 years of age. We found significant differences in frequency between genders for posterior disc protrusion and foraminal stenosis. The former, with demonstrable compression of the spinal cord, was observed in 7.6% of subjects, mostly over 50 years of age. Our results should be taken into account when interpreting the MRI findings in patients with symptomatic disorders of the cervical spine.

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整形外科外来での病態把握のコツ；脊椎FBS(failed back surgery syndrome)

松本守雄，戸山芳昭

関節外科 17 （ 5 ） 108-111 1998年

研究論文（学術雑誌）, 共著

青壮年（35歳以下）頚髄症の臨床像と手術成績

鎌田修博，戸山芳昭，松本守雄，鈴木信正，藤村祥一，里見和彦

東日本臨床整形外科学会誌 10 195-197 1998年

研究論文（学術雑誌）, 共著

リウマチ性環軸椎亜脱臼に対する人工骨を用いた後方固定術

小川潤，戸山芳昭，松本守雄，里見和彦，石井良章

東日本臨床整形外科学会誌 10 393-396 1998年

研究論文（学術雑誌）, 共著

Anterior Decompression and Fusion via the Extrapleural Approach for Thoracic Disc Herniation Causing Myelopathy

Fujimura Yoshikazu, Nakamura Masaya, Matsumoto Mono

Keio Journal of Medicine 46 （ 4 ） 173 - 176 1997年12月

ISSN 0022-9717

Anterior decompression and fusion via an extrapleural approach was performed for 33 patients with myelopathy arising from thoracic disc herniation and the clinical usefulness and problems related to this procedure were assessed on the basis of surgical results and complications. The severity of the myelopathy was evaluated by the Japanese Orthopaedic Association score, and the surgical results were based on the recovery rate. The upper-level limit of decompression and fusion via the extrapleural approach was T4-5. The recovery rate for the mean postoperative follow-up period of 41 months was 66.7%. An age of 60 years or more, long duration of illness and severe preoperative myelopathy were indicators of a poor prognosis. Two patients suffered from a postoperative transient pulmonary complication due to hemothorax. X-ray examinations revealed good bone union in all the patients. The present study indicates that anterior decompression and fusion via the extrapleural approach is a useful technique which can be used to achieve a high success rate in the surgical treatment of thoracic disc herniation, if intervention is early.

Anterior decompression and fusion via extrapleural approach for thoracic disc herniation causing myelopathy

Fujimura Yoshikazu, Nakamura Masaya, Matsumoto Morio

Keio J Med 46 （ 4 ） 173-176 1997年12月

研究論文（学術雑誌）, 共著

Radiographic chages in the patella after total knee arthroplasty without resurfacing the patella. Comparison of osteoarthrosis and rheumatoid arthritis

Kawakubo Makoto, Matsumoto Hideo, Otani Toshirou, Fujikawa Kyosuke

Bull Hosp Jt Dis 56 （ 4 ） 237-244 1997年12月

研究論文（学術雑誌）, 共著

腰椎分離すべり症に対するPLIF&instrumentation手術(特集：最新腰椎分離・すべり症診療マニユアル)

戸山芳昭，千葉一裕，松本守雄

M B Orthop 10 （ 11 ） 163-172 1997年11月

研究論文（学術雑誌）, 共著

Myelopathy secondary to ossification of the posterior longitudinal ligament of the thoracic spine treated by anterior decompression and bony fusion

Fujimura Yoshikazu, Nishi Yukimi, Nakamura Masaya, Watanabe Masahiko, Matsumoto Morio

Spinal Cord 35 （ 11 ） 777-784 1997年11月

研究論文（学術雑誌）, 共著

MRI finding of acute whiplash injury and relationship to clinical symptoms

Fujimura Yoshikazu, Matsumoto Morio

Int Med J 4 （ 3 ） 223-226 1997年09月

研究論文（学術雑誌）, 共著

Diagnostic value of magnetic resonance imaging in whiplash injury

Fujimura Yoshikazu, Matsumoto Morio

Int Med J 4 （ 3 ） 177-180 1997年09月

研究論文（学術雑誌）, 共著

イラストレイテッド・サージェリー(手術編)：環軸椎後方固定術--Magerl+Brooks

戸山芳昭，鎌田修博，松本守雄，小川潤

脊椎脊髄ジャーナル 10 （ 6 ） 535-542 1997年06月

研究論文（学術雑誌）, 共著

Influence of secondary damage to menisci and articular cartilage on return to sports after anterior cruciate ligament reconstruction

Takeda Tsuyoshi, Matsumoto Hideo, Fujikawa Kyosuke

J Orthop Sci 2 （ 4 ） 215-221 1997年06月

研究論文（学術雑誌）, 共著

胸部椎間板ヘルニアの症候学

藤村祥一，中村雅也，松本守雄，千葉一裕

脊椎脊髄ジャーナル 10 （ 5 ） 455-460 1997年05月

研究論文（学術雑誌）, 共著

椎間板ヘルニアの自然消褪について

松本守雄

医研センタージャーナル（ 28 ） 5-7 1997年04月

研究論文（学術雑誌）, 単著

頸椎後縦靭帯骨化症における髄内高信号の臨床的意義

中村雅也，藤村祥一，松本守雄，鎌田修博，戸山芳昭，鈴木信正

日パラプレジア医会誌 10 （ 1 ） 72-73 1997年04月

研究論文（学術雑誌）, 共著

頸椎後縦靭帯骨化症の治療成績と外傷の関連--MRI髄内高信号の臨床的意嚢--

中村雅也，藤村祥一，松本守雄，鎌田修博，戸山芳昭，鈴木信正

臨整外 32 （ 4 ） 321-325 1997年04月

研究論文（学術雑誌）, 共著

術中脊髄モニタリングに輿味ある変化のみられた脊髄髄内腫瘍の2例

鎌田修博，戸山芳昭，松本守雄，鈴木信正，藤村祥一，小川潤

脊髄電気診断学 19 （ 1 ） 141-144 1997年04月

研究論文（学術雑誌）, 共著

脊椎脊髄疾患における各画像検査法の臨床的意義

戸山芳昭，松本守雄

脊椎脊髄ジャーナル 10 （ 4 ） 267-273 1997年04月

研究論文（学術雑誌）, 共著

椎間板と交通する脊柱管内嚢腫(椎間板嚢腫) --発生機序の考察と新しい疾患名の提唱--

戸山芳昭，鎌田修博，松本守雄，西沢隆，小柳貴裕，鈴木信正，藤村祥一

臨整外 32 （ 4 ） 393-400 1997年04月

研究論文（学術雑誌）, 共著

頸椎部の放射線的解剖--椎骨，靱帯，椎間板を中心として--

松本守雄

脊椎脊髄ジャーナル 10 （ 4 ） 275-281 1997年04月

研究論文（学術雑誌）, 単著

MRI findings of acute whiplash injury and relationship to clinical symptoms

Fujimura Y., Matsumoto M.

International Medical Journal 4 （ 3 ） 223 - 226 1997年

ISSN 1341-2051

This study was designed to evaluate the relationship between findings of disc degeneration on magnetic resonance imaging and clinical symptoms in 415 patients with acute whiplash injury. The images were examined for signs of disc degeneration and spinal cord compression. Loss of disc signal intensity occurred significantly more often in patients with shoulder stiffness and numbness in the upper extremities, while the frequency of posterior disc protrusion was significantly higher in patients with shoulder stiffness than in patients without these symptoms. There was no significant relationship between other MRI findings and the presence or absence of clinical symptoms. These findings suggest that disc degeneration has no pathogenic implications in many patients with acute whiplash injury.

脊髄砂時計形腫瘍の手術手技--脊柱再建ないし固定術の適応とその方法--

戸山芳昭，松本守雄，鎌田修博

脊椎脊髄 10 （ 2 ） 125-133 1997年

研究論文（学術雑誌）, 共著

健常者における頚椎弯曲と椎間板変性との関連について

松本守雄，藤村祥一，鈴木信正，小野俊明，石川雅之，矢部裕

東日本整災会誌 9 （ 1 ） 1-4 1997年

研究論文（学術雑誌）, 共著

Effect of alcohol on patients with diabetes, hypertension or cardiovascular disease

Matsumoto M., Kato S., Yokoyama H., Ishii H.

Nippon rinsho. Japanese journal of clinical medicine 55 Suppl 597 - 603 1997年

ISSN 0047-1852

Myelopathy secondary to ossification of the posterior longitudinal ligament of the thoracic spine treated by anterior decompression and bony fusion

Fujimura Y., Nishi Y., Nakamura M., Watanabe M., Matsumoto M.

Spinal Cord 35 （ 11 ） 777 - 784 1997年

ISSN 1362-4393

We examined the utility of anterior decompression and bony fusion via the extrapleural approach in the treatment of thoracic myelopathy secondary to ossification of the posterior longitudinal ligament (OPLL). Patient outcome and complications were analyzed in 48 patients treated with this procedure, with a follow-up of at least 2 years. The Japanese Orthopaedic Association score was used to evaluate the severity of the thoracic myelopathy, and the recovery rate was used to evaluate the surgical outcome. The outcome, postoperative complications, radiographic evaluations of bony union, and progression of OPLL within the area of anterior decompression were examined. The T3 vertebral body was the highest level to which anterior decompression was applied. The average follow-up period was 57 months with a recovery rate of 56.7% which stabilized 1 year after operation. However, the surgical outcome was less favorable in patients with long-standing myelopathy, extensive OPLL, or thoracic OPLL with coexisting intraspinal ligament ossification. Four patients experienced deterioration of their myelopathy, and seven patients had the postoperative complication of extraspinal leakage of cerebrospinal fluid. The myelopathy was transient in all but one patient. Radiographic studies showed that bony union was achieved and restenosis of the spinal canal due to progression of OPLL within the area of decompression did not occur. We conclude that anterior decompression and bony fusion using the extrapleural approach provides a good outcome and is useful in treating mid- and lower thoracic OPLL when performed carefully at an early stage of disease.

Diagnostic value of magnetic resonance imaging in whiplash injury

Fujimura Y., Matsumoto M.

International Medical Journal 4 （ 3 ） 177 - 180 1997年

ISSN 1341-2051

This study was designed to investigate the diagnostic value of magnetic resonance imaging (MRI) of the cervical spine in acute whiplash injury. The subjects were 506 patients with acute whiplash injury, with 497 asymptomatic volunteers as a control group. No difference in the occurrence of signs of disc degeneration or cord compression were observed between the whiplash injury and control groups. The correlation between the appearance of these signs and the subject's age was, however, significant. In addition, ligament injuries were found in only 0.8% of the patients. We conclude that the diagnostic value of MRI in acute whiplash injury is limited.

外傷歴と退行変性--頚部椎間板ヘルニア--

平林洌，松本守雄

日災医会誌 44 （ 4 ） 248-254 1996年04月

研究論文（学術雑誌）, 共著

Usefulness and reliability of neurological signs for level diagnosis in cervical myelopathy caused by soft disc herniation

Matsumoto Morio, Fujimura Yoshikazu, Toyama Yoshiaki

Journal of Spinal Disorders 9 （ 4 ） 317 - 321 1996年

ISSN 0895-0385

We retrospectively analyzed neurological signs of 106 patients with cervical myelopathy caused by single-level soft disc herniation. Neurological signs that were intensively analyzed were deep tendon reflexes, the uppermost level of impaired pinprick sensation, the uppermost weak muscle, and region of numbness in the bands. Characteristic signs for each intervertebral level were deduced, and sensitivity, specificity, and accuracy of these signs were calculated. Deep tendon reflexes were specific signs for each intervertebral level, although not as sensitive as the neurological signs. Muscle weakness and pinprick sensation were neither sensitive nor specific. Hand numbness was moderately sensitive and specific. On the whole, there was no neurological sign that was both highly sensitive and specific for an intervertebral level, and therefore, neurological level diagnosis in cervical myelopathy should be performed comprehensively according to more specific signs, i.e., deep tendon reflexes and hand numbness.

頚椎後縦靭帯骨化症の手術治療成績と外傷の関連について

中村雅也，藤村祥一，松本守雄，鎌田修博，戸山芳昭，鈴木信正

臨整外 31 （ 12 ） 1339-1342 1996年

研究論文（学術雑誌）, 共著

AW－GC椎弓スペーサーを用いた環軸椎後方固定術(Brooks法)の試み

小川潤，戸山芳昭，松本守雄，田中守

整形外科 47 （ 10 ） 1373-1375 1996年

研究論文（学術雑誌）, 共著

Usefulness and reliability of neurological signs for level diagnosis in cervical myelopathy caused by soft disc herniation

Matsumoto Morio, Fujimura Yoshikazu, Toyama Yoshiaki

J Spinal Disord 9 （ 4 ） 317-321 1996年

研究論文（学術雑誌）, 共著

外傷歴と退行変性--頸部椎間板ヘルニア--

平林洌，松本守雄

日災医会誌 44 （ 4 ） 248-254 1996年

研究論文（学術雑誌）, 共著

MRIにおける健常者頚椎椎間板の加齢変化

松本守雄，藤村祥一，鈴木信正，戸山芳昭，小野俊明，西幸美，矢部裕

臨整外 31 （ 4 ） 391-396 1996年

研究論文（学術雑誌）, 共著

リウマチ性頚椎病変手術例の予後

戸山芳昭，松本守雄，藤森祥一，平林洌，里見和彦

整形外科 46 （ 12 ） 1585-1591 1995年12月

研究論文（学術雑誌）, 共著

成人発症Still病に合併した環軸関節亜脱臼の1例

釼持太郎，市村正一，戸山芳昭，松本守雄，藤村祥一

関東整災誌 26 （ 6 ） 543-547 1995年12月

研究論文（学術雑誌）, 共著

リウマチ性頚椎病変手術例の予後

戸山芳昭，松本守雄，藤村祥一，平林洌，里見和彦

整形外科 46 （ 12 ） 1581-1591 1995年12月

研究論文（学術雑誌）, 共著

特集　上位頸椎疾患・・その病体と治療小児の環軸椎後方固定術が頸椎の成長に及ぼす影響について

松本守雄，戸山芳昭，鈴木信正，藤村祥一，平林洌，小林慶二，市原眞仁

臨床整形外科 30 （ 4 ） 345-353 1995年04月

研究論文（学術雑誌）, 共著

Tension characteristics of the ilio-tibial tract and role of its superficial layer

Matsumoto H, Seedhom BB

Clin Orthop 313 （ 4 ） 253-255 1995年04月

研究論文（学術雑誌）, 共著

小児の環軸椎後方固定術が頚椎の成長に及ぼす影響について

松本守雄，戸山芳昭，鈴木信正，藤村祥一，平林洌，小林慶二，市原眞仁

臨整外 30 （ 4 ） 345-353 1995年04月

研究論文（学術雑誌）, 共著

Realignment of postoperative cervical kyphosis in children by vertebral remodeling

Toyama Y., Matsumoto M., Chiba K., Asazuma T., Suzuki N., Fujimura Y., Hirabayashi K.

Spine 19 （ 22 ） 2565 - 2570 1994年

ISSN 0362-2436

Study Design. This study analyzed radiographically change in the sagittal curvature of the cervical spine after atlantoaxial (C1-C2) posterior fusion in children. Objectives. This study clarified the process of spinal remodeling after postoperative cervical deformation in children. Summary of Background Data. Postoperative spinal deformations in children are observed frequently. However, there have been only a few reports on postoperative changes in the sagittal curvature of the cervical spine and spinal remodeling after those changes. Methods. Between 1979 and 1991, there was a total of 12 children who underwent C1-C2 posterior fusions. The average age at the time of surgery was 9.8 years. The alignment of the cervical spine was classified into four groups (lordosis, straight, kyphosis, and swan-neck deformity). Radiographic findings suggestive of the remodeling were as follows: 1) new bone formation on the anterior vertebral cortex, and 2) increase in body/canal ratio (BCR). The follow-up period averaged 6.2 years. Results. Postoperative cervical malalignment (kyphosis or swan-neck deformity) occurred in four patients. In all four patients, new bone formation and increase in BCR at the apex of kyphosis were observed. Therefore, there was gradual improvement of the malalignment by vertebral remodeling. This phenomenon was not observed in eight patients with normal alignment. Conclusion. Realignment of postoperative cervical kyphosis by vertebral remodeling was observed in children. The results of this study suggested that remodeling occurred even in the spine, which was similar to the remodeling in long bones.

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