[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate forelimb motor function after cervical spinal cord injury in juvenile and adult rats. Both rats received a left segmental hemisection of the spinal cord after C3-C4 laminectomy. Behavioral evaluation of motor function was monitored and assessed using the New Rating Scale (NRS) and Forelimb Locomotor Scale (FLS) and by measuring the range of motion (ROM) of both the elbow and wrist. Complete left forelimb motor paralysis was observed in both rats. The NRS showed motor function recovery restored to
in juvenile rats and
in adult rats. FLS was
in juvenile rats and
in adult rats. ROM of the elbow and wrist were
in juvenile rats and
in adult rats. Thus, the NRS and ROM of the elbow showed a significant difference between age groups. These results indicate that left hemisection of the cervical spinal cord was not related to right-sided motor functions. Moreover, while motor paralysis of the left forelimb gradually recovered in both groups, the improvement was greater in juvenile rats.
Preview · Article · Jan 2016 · Behavioural neurology
[Show abstract][Hide abstract] ABSTRACT: Background/Aim: Plasma D-dimer levels have been known to be associated with tumor progression; we, therefore, investigated whether the D-dimer levels during preoperative systemic chemotherapy can be prognostic indicators in patients with high-grade musculoskeletal sarcoma. Patients and Methods: We investigated 28 cases of high-grade sarcomas, and evaluated the utility of D-dimer levels for preoperative evaluation of the effects of systemic chemotherapy. Results: Among the candidate parameters determined based on D-dimer levels at several time-points of neoadjuvant chemotherapy and several oncological outcomes, the plasma D-dimer level completion of the second course of chemotherapy and the ratio of plasma D-dimer levels at completion of preoperative chemotherapy to the level of plasma D-dimer on referral, could significantly predict patient prognosis (p=0.049 and p=0.02, respectively). Conclusion: D-dimer level changes could be a helpful marker for preoperative evaluation of the effect of systemic chemotherapy in terms of prognosis prediction in high-grade musculoskeletal sarcoma patients.
No preview · Article · Dec 2015 · Anticancer research
[Show abstract][Hide abstract] ABSTRACT: Background:
Chondrosarcoma is refractory to conventional chemotherapy. BH-3 mimetics ABT-737 and ABT-263 are synthetic small-molecule inhibitors of anti-apoptotic proteins B-cell lymphoma-2 (Bcl2) and Bcl-xL, which play a critical role in survival of chondrosarcoma cells.
Materials and methods:
Chondrosarcoma cell lines SW-1353 and CS-1 were used as the disease model. We used immunoblotting to assess the expression of target molecules Bcl2 and Bcl-xL, and the apoptotic inducers Bcl2-associated X (Bax) and Bcl2-antagonist/killer (Bak). In vitro growth inhibition by BH-3 mimetics was confirmed by photomicroscopic cell counting and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Apoptotic induction was confirmed by Enzyme-Linked ImmunoSorbent Assay (ELISA). In vivo growth inhibition was assessed in a non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse model.
Expression of the target and effector molecules was confirmed in chondrosarcoma cell lines. BH3 mimetics significantly inhibited cell growth and induced apoptosis in vitro. Administration of ABT-263 inhibited chondrosarcoma growth and improved survival in a mouse model.
BH3 mimetics represent a novel treatment modality for chondrosarcoma.
No preview · Article · Nov 2014 · Anticancer research
[Show abstract][Hide abstract] ABSTRACT: Background:
Lipoma and well-differentiated liposarcoma (WDLS) are two representative lipogenic soft tissue tumors that have similar clinical, radiological, and pathological characteristics. Accordingly, it is difficult to distinguish these tumors preoperatively. Plasma D-dimer levels are associated with the status of tumor progression, and we hypothesized that D-dimer levels could contribute to differential diagnosis. The D-dimer levels of these two entities have not yet been reported.
Patients and methods:
We investigated 43 cases of lipoma and 14 cases of WDLS. We evaluated the utility of D-dimer levels and other clinicopathological factors for preoperative differential diagnosis between the two entities.
Receiver operating characteristic analysis revealed that the D-dimer level may contribute to differential diagnosis (area under the curve=0.73). Univariate and multivariate models demonstrated that plasma D-dimer levels (p=0.001 (univariate), and p=0.006 (multivariate)) and lower extremity location (p=0.006 (univariate), and p=0.03 (multivariate)) were independent risk factors for WDLS.
The D-dimer level may be a helpful marker for preoperative differential diagnosis between lipoma and WDLS.
No preview · Article · Sep 2014 · Anticancer research
[Show abstract][Hide abstract] ABSTRACT: Zoledronate (Zol), an anti-osteoclastic and anticancer drug, is used to control bone metastasis in several cancer types, including non-small cell lung cancer (NSCLC). However, the mechanisms behind Zol resistance in NSCLC are unclear.
Zol-resistant cell lines were developed by repeated treatment of A549 and H1650 NSCLC cell lines with Zol. We measured cell proliferation and apoptosis following Zol treatment and also examined the BCL2 superfamily expression. RNAi was used to confirm the role of key molecules in development of resistance.
Repeated Zol treatment engendered resistance, in which apoptosis induction was attenuated. From the BCL2 superfamily, BAX was commonly down-regulated in resistant cells, and silencing of BAX in parental cell lines also induced drug resistance.
Repeated treatment of NSCLC cell lines with Zol leads to drug resistance, which is in part due to BAX down-regulation.
No preview · Article · Dec 2013 · Anticancer research
[Show abstract][Hide abstract] ABSTRACT: Background:
Although intensive studies have been conducted to clarify the incidence, risks, and management methods of deep infection of tumor endoprostheses, limited data have been published in respect of the impact of such deep infection on the function of the corresponding limb.
Clinical data of 125 patients (infection group 57, control group 68) with malignant bone and soft tissue tumors around the knee enrolled with the Japanese Musculoskeletal Oncology Group were collected. We analyzed the impact of deep infection of tumor endoprostheses on the limb salvage status together with that on the function of the salvaged limb. The definition of deep infection was based on the recommendations of the Centers for Disease Control and Prevention. The functional evaluation was based on the functional classification system established by the International Society of Limb Salvage and the Musculoskeletal Tumor Society.
Infection together with extracapsular resection was demonstrated to be a risk factor for late amputation. There were no significant differences in the functional scores for "pain," "support," "walking," or "gait" between the infection and control groups. The risk factors identified for a loss of score for "functional activities" were deep infection, age, duration of operation, and extracapsular resection. The infection group also showed a significant lower score loss in "emotion". As for the overall functional scores, the risk factors identified for lower scores were deep infection and age. The mean scores for the infection group and control group were 19.3 (64.3 %) and 21.6 (72 %), respectively. Although the difference was confirmed to be statistically significant, the actual difference was only 2.3 (10.6 % reduction).
Infection was a major risk factor for late amputation. Limbs salvaged by management of deep infection may show loss of function; however, the impact may be limited.
No preview · Article · Apr 2013 · Journal of Orthopaedic Science
[Show abstract][Hide abstract] ABSTRACT: Background
The incidence of endoprosthesis failure has been well studied, but few studies have described the clinical characteristics of deep infection in tumor prostheses. This study aimed to analyze the characteristics of deep infection in tumor endoprostheses around the knee.
We analyzed clinical data of 57 patients with deep infections involving tumor endoprostheses around the knee enrolled from the Japanese Musculoskeletal Oncology Group. Profile of clinical presentation including time between surgery and infection, initial symptoms/blood tests and microbial cultures was evaluated. In addition pre-, intra-, and postoperative clinical factors influencing clinical presentation and treatment outcomes of infections were analyzed.
Mean interval between the initial operation and diagnosis was 13 months, and mean time required for infection control was 12 months. The most common pathogen was Staphylococcus. Infection control rates were significantly higher when prostheses were removed rather than salvaged. Ten-year prosthesis survival and limb salvage rates were 41.6% and 75.6%, respectively. Analysis of underlying clinical factors suggested that soft-tissue condition significantly influenced the duration of the infection control period and likelihood of limb salvage.
Infection control is a prolonged process. Deep infection frequently results in amputation or prosthesis loss. Intensive analysis of clinical characteristics may aid infection control.
Preview · Article · Jan 2013 · BMC Musculoskeletal Disorders
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Nov 2012 · Journal of Bone and Mineral Metabolism
[Show abstract][Hide abstract] ABSTRACT: Postoperative wound complications, including surgical site infections, which frequently occur in the course of management of musculoskeletal sarcomas, sometimes necessitate repeat surgeries, including amputation, and may result in a prolonged healing time, prolonged hospital stay, or fatal outcome. A comprehensive understanding of surgical site infections associated with specific diseases is needed to reduce the risk.
This series comprised 84 patients with malignant soft tissue tumors treated at our institute. The occurrence rate, management modality and clinical course of surgical site infections, impact of surgical site infections on the length of hospitalization, risk factors for the development of surgical site infections, and the impact of surgical site infections on the oncological outcomes were analyzed. Surgical site infection was defined according to Centers for Disease Control and Prevention guidelines.
Surgical site infections occurred in 7 cases (8.3%). Although successful clinical cure was achieved in all cases, surgical site infection was identified as one of the independent risk factors for prolongation of hospitalization. Both univariate and multivariate analyses identified larger intraoperative blood loss and a trunk location as risk factors associated with deep infections. No association was detected between age, tumor grade, chemotherapy, tumor volume, or plastic surgery and the risk of surgical site infections. Although the differences were not statistically significant, patients with surgical site infections showed worse oncological outcomes in terms of local recurrence and total survival.
The incidence rate of surgical site infection was larger than that associated with conventional orthopedic surgeries, such as osteosynthesis, spine surgery, or arthroplasty. Surgical site infections remain a critical and frequent complication of surgical treatment of soft-tissue malignancies and often result in prolongation of hospital stay. Although practical options to prevent surgical site infections seem quite limited, the present data provide a rationale for perioperative evaluation in patients at a high risk of surgical site infections.
No preview · Article · Nov 2011 · Journal of Orthopaedic Science
[Show abstract][Hide abstract] ABSTRACT: Plasma d-dimer levels have been associated with the status of tumor progression or oncological outcomes in cancer. Although there are many evidences suggesting the involvement of procoagulant trend in musculoskeletal sarcoma, no clinical data on d-dimer levels and oncological outcome of musculoskeletal sarcoma has been reported.
In this study, we included a total of 85 patients who were diagnosed with musculoskeletal sarcoma and treated at our institute. Plasma d-dimer levels were determined before performing any clinical intervention, including open biopsy, chemotherapy, radiotherapy or tumor resection. We evaluated the effect of d-dimer levels and other clinicopathological factors on oncological outcomes of patients.
Upregulation of plasma d-dimer levels proved to be an independent risk factor for metastasis and lethal outcome of patients with musculoskeletal sarcoma.
Upregulation of plasma d-dimer levels were indicated poor oncological outcome in metastasis and total survival rate of musculoskeletal sarcoma patients. Hence d-dimer levels may be a helpful marker for evaluating the tumor progression status and prognosis of musculoskeletal sarcoma.
Preview · Article · Nov 2011 · BMC Musculoskeletal Disorders
[Show abstract][Hide abstract] ABSTRACT: The therapeutic effect of Raloxifene (RLX) on bone turnover markers was investigated in the elderly women with osteoporosis. The mean age of the control group (< 75 years old) was 67.0 years old, similar to a large-scale clinical trial (MORE study) , and that of the elderly group ( > or =years old) was 80.7 years old. The degrees of percentage change from baseline of serum NTX, urine NTX, and BAP in the elderly group were the same as in the control group. The interval of measurement to assess the effect of RLX seems to be appropriate 3 months after treatment in serum and urine NTX, and 6 months in BAP.
No preview · Article · Mar 2010 · Clinical calcium
[Show abstract][Hide abstract] ABSTRACT: Fracture may influence the serum and urine levels of bone turnover markers, however, the changes in bone markers seem to be not constant. The magnitude of change may be dependent on the size of the fractured bone, the amount of bone involved, and difference in bone markers. In patients with hip fracture, there was early increase in bone resorption markers within 2 weeks after fracture, and resorption markers started to decrease 2-3 months after fracture and stabilized close to prefracture level by about 6 months after fracture. Bone formation markers peaked later than bone resorption markers and remained elevated up to 1 year after fracture. This elevation in bone turnover markers reflects the repair process after fracture, and also immobilization following fracture, bone loss close to the fracture, and post-traumatic systemic reactions contribute to the accelerated bone formation and resorption.
No preview · Article · Sep 2009 · Clinical calcium
[Show abstract][Hide abstract] ABSTRACT: A multicenter cohort study was performed retrospectively.
To identify radiographic predictors for the development of myelopathy in patients with ossification of the posterior longitudinal ligaments (OPLL).
The pathomechanism of myelopathy in the OPLL remains unknown. Some patients with large OPLL have not exhibited myelopathy for a long periods of time. Predicting the course of future neurologic deterioration in asyptomatic patients with OPLL is difficult at their initial visit.
A total of 156 OPLL patients from 16 spine institutes with an average of 10.3 years of follow-up were reviewed. Subjects underwent a plain roentgenogram, computed tomography (CT), and magnetic resonance imaging of the cervical spine during the follow-up. The trauma history of the cervical spine, maximum percentage of spinal canal stenosis in a plain roentgenogram and CT, range of motion of the cervical spine, and axial ossified pattern in magnetic resonance imaging or CT were reviewed in relation to the existence of myelopathy.
All 39 patients with greater than 60% spinal canal stenosis on the plain roentgenogram exhibited myelopathy. Of 117 patients with less than 60% spinal canal stenosis, 57 (49%) patients exhibited myelopathy. The range of motion of the cervical spine was significantly larger in patients with myelopathy than in those of without it. The axial ossified pattern could be classified into 2 types: a central type and a lateral deviated type. The incidence of myelopathy in patients with less than 60% spinal canal stenosis was significantly higher in the lateral deviated-type group than in the central-type group. Fifteen patients of 156 subjects developed trauma-induced myelopathy. Of the 15 patients, 13 had mixed-type OPLL and 2 had segmental-type OPLL.
Static and dynamic factors were related to the development of myelopathy in OPLL.