1.Freeze-Dried Human Platelet-Rich Plasma Retains Activation and Growth Factor Expression after an Eight-Week Preservation Period.
Yasuhiro SHIGA ; Go KUBOTA ; Sumihisa ORITA ; Kazuhide INAGE ; Hiroto KAMODA ; Masaomi YAMASHITA ; Toru ISEKI ; Michihiro ITO ; Kazuyo YAMAUCHI ; Yawara EGUCHI ; Takeshi SAINOH ; Jun SATO ; Kazuki FUJIMOTO ; Koki ABE ; Hirohito KANAMOTO ; Masahiro INOUE ; Hideyuki KINOSHITA ; Takeo FURUYA ; Masao KODA ; Yasuchika AOKI ; Tomoaki TOYONE ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Asian Spine Journal 2017;11(3):329-336
STUDY DESIGN: Controlled laboratory study. PURPOSE: This study aimed to evaluate the efficacy of platelet-rich plasma (PRP) stored at room temperature (RT), frozen, or after freeze-drying. OVERVIEW OF LITERATURE: PRP enriches tissue repair and regeneration, and is a novel treatment option for musculoskeletal pathologies. However, whether biological activity is preserved during PRP storage remains uncertain. METHODS: PRP was prepared from blood of 12 healthy human volunteers (200 mL/person) and stored using three methods: PRP was stored at RT with shaking, PRP was frozen and stored at −80℃, or PRP was freeze-dried and stored at RT. Platelet counts and growth factor content were examined immediately after preparation, as well as 2, 4, and 8 weeks after storage. Platelet activation rate was quantified by flow cytometry. RESULTS: Platelet counts were impossible to determine in many RT samples after 2 weeks, but they remained at constant levels in frozen and freeze-dried samples, even after 8 weeks of storage. Flow cytometry showed approximately 80% activation of the platelets regardless of storage conditions. Almost no growth factors were detected in the RT samples after 8 weeks, while low but significant expression was detected in the frozen and freeze-dried PRP. Over time, the mean relative concentrations of various growth factors decreased significantly or disappeared in the RT group. In the frozen group, levels were maintained for 4 weeks, but decreased significantly by 8 weeks (p <0.05). The freeze-dried group maintained baseline levels of growth factors for the entire 8-week duration. CONCLUSIONS: Freeze-drying enables PRP storage while maintaining bioactivity and efficacy for extended periods.
Blood Preservation
;
Flow Cytometry
;
Freeze Drying
;
Healthy Volunteers
;
Humans*
;
Intercellular Signaling Peptides and Proteins
;
Pathology
;
Platelet Activation
;
Platelet Count
;
Platelet-Rich Plasma*
;
Regeneration
2.Inhibiting Vascular Endothelial Growth Factor in Injured Intervertebral Discs Attenuates Pain-Related Neuropeptide Expression in Dorsal Root Ganglia in Rats.
Jun SATO ; Kazuhide INAGE ; Masayuki MIYAGI ; Yoshihiro SAKUMA ; Kazuyo YAMAUCHI ; Masao KODA ; Takeo FURUYA ; Junichi NAKAMURA ; Miyako SUZUKI ; Go KUBOTA ; Yasuhiro OIKAWA ; Takeshi SAINOH ; Kazuki FUJIMOTO ; Yasuhiro SHIGA ; Koki ABE ; Hirohito KANAMOTO ; Masahiro INOUE ; Hideyuki KINOSHITA ; Masaki NORIMOTO ; Tomotaka UMIMURA ; Kazuhisa TAKAHASHI ; Seiji OHTORI ; Sumihisa ORITA
Asian Spine Journal 2017;11(4):556-561
STUDY DESIGN: An experimental animal study. PURPOSE: To evaluate effects of anti-vascular endothelial growth factor (VEGF) on the content and distribution of the calcitonin gene-related peptide (CGRP) in the dorsal ganglia in a rat model. OVERVIEW OF LITERATURE: Increased expression of VEGF in degenerative disc disease increases the levels of inflammatory cytokines and nerve ingrowth into the damaged discs. In animal models, increased levels of VEGF can persist for up to 2 weeks after an injury. METHODS: Through abdominal surgery, the dorsal root ganglia (DRG) innervating L5/L6 intervertebral disc were labeled (FluoroGold neurotracer) in 24, 8-week old Sprague Dawley rats. The rats were randomly allocated to three groups of eight rats each. The anti-VEGF group underwent L5/6 intervertebral disc puncture using a 26-gauge needle, intradiscal injection of 33.3 µg of the pegaptanib sodium, a VEGF165 aptamer. The control-puncture group underwent disc puncture and intradiscal injection of 10 µL saline solution, and the sham-surgery group underwent labeling but no disc puncture. Two rats in each group were sacrificed on postoperative days 1, 7, 14, and 28 after surgery. L1–L6 DRGs were harvested, sectioned, and immunostained to detect the content and distribution of CGRP. RESULTS: Compared with the control, the percentage of CGRP-positive cells was lower in the anti-VEGF group (p<0.05; 40.6% and 58.1% on postoperative day 1, 44.3% and 55.4% on day 7, and 42.4% and 59.3% on day 14). The percentage was higher in the control group compared with that of the sham group (p<0.05; sham group, 34.1%, 40.7%, and 33.7% on postoperative days 1, 7, and 14, respectively). CONCLUSIONS: Decreasing CGRP-positive cells using anti-VEGF therapy provides fundamental evidence for a possible therapeutic role of anti-VEGF in patients with discogenic lower back pain.
Animals
;
Back Pain
;
Calcitonin Gene-Related Peptide
;
Cytokines
;
Diagnosis-Related Groups
;
Endothelial Growth Factors
;
Ganglia
;
Ganglia, Spinal*
;
Humans
;
Intervertebral Disc*
;
Low Back Pain
;
Models, Animal
;
Needles
;
Neuropeptides*
;
Punctures
;
Rats*
;
Rats, Sprague-Dawley
;
Sodium
;
Sodium Chloride
;
Spinal Nerve Roots*
;
Vascular Endothelial Growth Factor A*
3.Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain.
Kazuhide INAGE ; Sumihisa ORITA ; Kazuyo YAMAUCHI ; Takane SUZUKI ; Miyako SUZUKI ; Yoshihiro SAKUMA ; Go KUBOTA ; Yasuhiro OIKAWA ; Takeshi SAINOH ; Jun SATO ; Kazuki FUJIMOTO ; Yasuhiro SHIGA ; Koki ABE ; Hirohito KANAMOTO ; Masahiro INOUE ; Hideyuki KINOSHITA ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Asian Spine Journal 2016;10(4):685-689
STUDY DESIGN: Retrospective study. PURPOSE: To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. OVERVIEW OF LITERATURE: Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. METHODS: Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. RESULTS: No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). CONCLUSIONS: Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent the transition of acute low back pain to chronic low back pain.
Anti-Inflammatory Agents, Non-Steroidal
;
Diagnosis
;
Drug Therapy
;
Humans
;
Incidence
;
Low Back Pain*
;
Retrospective Studies
;
Spine
;
Tramadol*
;
Visual Analog Scale
4.Dose Optimization for Single Intradiscal Administration of the Tumor Necrosis Factor-α Inhibitor, Etanercept, in Rat Disc Injury Models.
Kazuhide INAGE ; Sumihisa ORITA ; Kazuyo YAMAUCHI ; Takane SUZUKI ; Miyako SUZUKI ; Yoshihiro SAKUMA ; Go KUBOTA ; Yasuhiro OIKAWA ; Takeshi SAINOH ; Jun SATO ; Kazuki FUJIMOTO ; Yasuhiro SHIGA ; Koki ABE ; Hirohito KANAMOTO ; Masahiro INOUE ; Hideyuki KINOSHITA ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Asian Spine Journal 2016;10(4):619-623
STUDY DESIGN: Experimental animal study. PURPOSE: We aimed to determine the optimal dose of a single direct injection of the tumor necrosis factor (TNF)-α inhibitor, etanercept, by using the rat model of degenerative intervertebral disc from injury. OVERVIEW OF LITERATURE: The pain-related peptide expression was suppressed in the etanercept (100 µg and 1,000 µg)-administered groups in a dose-dependent manner. METHODS: The neurotracer FluoroGold (FG) was applied to the surfaces of L4/5 discs to label their innervating dorsal root ganglion (DRG) neurons (n=50). Ten rats were included in the nonpunctured disc sham surgery control group, whereas the other 40 were included in the experimental group in which intervertebral discs were punctured with a 23-gauge needle. Saline or etanercept (10 µg, 100 µg, or 1,000 µg) was injected into the punctured discs (n=10 for each treatment). After 14 days of surgery, DRGs from L1 to L6 were harvested, sectioned, and immunostained for calcitonin gene-related peptide (CGRP). The proportion of FG-labeled CGRP-immunoreactive DRG neurons was evaluated in all the groups. RESULTS: There were no significant differences between the puncture+saline group and the puncture+10-µg etanercept group (p >0.05). However, a significant decrease in the percentage of FG and CGRP double-positive cells in FG-positive cells was observed in the etanercept (100 µg and 1,000 µg)-administered groups in a dose-dependent manner (p <0.05). CONCLUSIONS: When a low dose of the TNF-α inhibitor (10 µg of etanercept) was directly administered to the rat intervertebral disc in the rat model of degenerative intervertebral disc from injury, no suppressive effect on the pain-related peptide expression was observed. However, when a higher dose of etanercept (100 µg and 1,000 µg) was administered, the pain-related peptide expression was suppressed in a dose-dependent manner.
Animals
;
Calcitonin Gene-Related Peptide
;
Diagnosis-Related Groups
;
Etanercept*
;
Ganglia, Spinal
;
Intervertebral Disc
;
Intervertebral Disc Degeneration
;
Models, Animal
;
Necrosis*
;
Needles
;
Neurons
;
Rats*
;
Tumor Necrosis Factor-alpha
5.Does Discontinuing Teriparatide Treatment and Replacing It with Bisphosphonate Maintain the Volume of the Bone Fusion Mass after Lumbar Posterolateral Fusion in Women with Postmenopausal Osteoporosis?.
Seiji OHTORI ; Sumihisa ORITA ; Kazuyo YAMAUCHI ; Yawara EGUCHI ; Yasuchika AOKI ; Junichi NAKAMURA ; Miyako SUZUKI ; Gou KUBOTA ; Kazuhide INAGE ; Yasuhiro SHIGA ; Koki ABE ; Kazuki FUJIMOTO ; Hirohito KANAMOTO ; Masahiro INOUE ; Hideyuki KINOSHITA ; Takeo FURUYA ; Masao KODA
Asian Spine Journal 2017;11(2):272-277
STUDY DESIGN: Retrospective case series. PURPOSE: The purpose of this study was to determine whether discontinuing teriparatide treatment and replacing it with bisphosphonate treatment maintains the volume of the fusion mass after posterolateral fusion (PLF) in women with postmenopausal osteoporosis. OVERVIEW OF LITERATURE: Clinical data support the efficacy of parathyroid hormone (PTH) for lumbar PLF. However, the use of PTH is limited to 2 years. METHODS: We treated 19 women diagnosed with osteoporosis and degenerative spondylolisthesis with teriparatide (20 µg daily subcutaneously). All patients underwent one-level instrumented PLF. Teriparatide was used during 2 months prior to surgery and more than 8 months after surgery. After discontinuing teriparatide treatment, all patients used bisphosphonate (17.5 mg risedronate weekly, oral administration). Area of the fusion mass across the transverse processes at one segment was determined on an anteroposterior radiograph at 1, 2, and 3 years after surgery. RESULTS: We followed 19 patients for 3 years. The average duration of teriparatide treatment was 11.5 months. The bone union rate was 95%. The average area of the bone fusion mass was not significantly different between the right and left sides at 1, 2, or 3 years after surgery (p>0.05). CONCLUSIONS: This study showed that replacing teriparatide treatment with bisphosphonate maintained the bone fusion mass volume after PLF in women with postmenopausal osteoporosis.
Female
;
Humans
;
Osteoporosis
;
Osteoporosis, Postmenopausal*
;
Parathyroid Hormone
;
Retrospective Studies
;
Risedronate Sodium
;
Spine
;
Spondylolisthesis
;
Teriparatide*
6.Long-Term Outcomes of In Situ Fusion for Treating Dysplastic Spondylolisthesis.
Kazuhide INAGE ; Sumihisa ORITA ; Kazuyo YAMAUCHI ; Miyako SUZUKI ; Yoshihiro SAKUMA ; Go KUBOTA ; Yasuhiro OIKAWA ; Takeshi SAINOH ; Jun SATO ; Kazuki FUJIMOTO ; Yasuhiro SHIGA ; Koki ABE ; Hirohito KANAMOTO ; Masahiro INOUE ; Hideyuki KINOSHITA ; Masaki NORIMOTO ; Tomotaka UMIMURA ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Asian Spine Journal 2017;11(2):213-218
STUDY DESIGN: Retrospective, observational, single-center study. PURPOSE: To investigate the long-term outcomes of in situ fusion procedures for treating dysplastic spondylolisthesis. OVERVIEW OF LITERATURE: In situ fusion performed in patients with dysplastic spondylolisthesis avoids the development of nerve complications. METHODS: In total, 12 of 28 patients who underwent in situ fusion for treating dysplastic spondylolisthesis at Chiba University Hospital from 1974 to 2004 were followed up in August 2013. Surgical complications were evaluated. Low back pain and leg pain were assessed using a visual analog scale (VAS). Vertebral alignment, including the lumbosacral angle and lumbar lordosis angle measurement on radiographic images (profile view in the neutral standing position), was evaluated during preoperative, postoperative, and final examinations. RESULTS: The mean follow-up duration, patient age at the final examination, and patient age at operation were 20.0±7.2, 42.3±13.3, and 22.3±11.4 years, respectively. No complications were reported. Mean VAS scores for low back pain and leg pain were significantly lower at the final examination than at the preoperative examination (p<0.05). At the preoperative, postoperative, and final examinations, the mean lumbosacral angle was 32.3°±14.2°, 33.7°±11.8°, and 36.5°±16.4°, while the mean lumbar lordosis angle was 51.0°±14.8°, 48.6°±18.8°, and 49.6°±15.5°, respectively. No significant differences were noted among these values across the different time periods (p<0.05). CONCLUSIONS: In situ fusion performed in patients with dysplastic spondylolisthesis avoids the development of nerve complications such as nerve paralysis that may occur after repositioning operation and maintains appropriate long-term sagittal alignment, even 20 years after operation.
Animals
;
Follow-Up Studies
;
Humans
;
Leg
;
Lordosis
;
Low Back Pain
;
Paralysis
;
Retrospective Studies
;
Spondylolisthesis*
;
Visual Analog Scale
7.Correlation among Inflammatory Cytokine Expression Levels, Degree of Disk Degeneration, and Predominant Clinical Symptoms in Patients with Degenerated Intervertebral Discs.
Takeshi SAINOH ; Kazuhide INAGE ; Sumihisa ORITA ; Masao KODA ; Takeo FURUYA ; Kazuyo YAMAUCHI ; Miyako SUZUKI ; Yoshihiro SAKUMA ; Go KUBOTA ; Yasuhiro OIKAWA ; Jun SATO ; Kazuki FUJIMOTO ; Yasuhiro SHIGA ; Koki ABE ; Hirohito KANAMOTO ; Masahiro INOUE ; Hideyuki KINOSHITA ; Masaki NORIMOTO ; Tomotaka UMIMURA ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Asian Spine Journal 2017;11(3):472-477
STUDY DESIGN: Observational study. PURPOSE: To assess the correlation among inflammatory cytokine expression levels, degree of intervertebral disk (IVD) degeneration, and predominant clinical symptoms observed in degenerative disk disease (DDD). OVERVIEW OF LITERATURE: Low back pain (LBP) is associated with inflammatory cytokine expression levels, including those of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and nerve growth factor (NGF). However, the association between cytokine expression levels and the physiological mechanisms of disk degeneration and clinical pain remain controversial. METHODS: Using the enzyme-linked immunosorbent assay, TNF-α, IL-6, and NGF expression levels were analyzed in 58 IVD samples that were harvested from patients with lumbar DDD. Patient samples were grouped according to the degree of IVD degeneration using the Pfirrmann grading system and magnetic resonance imaging, and the correlations between the disease groups and each cytokine expression level were assessed. In addition, on the basis of their predominant preoperative symptoms, the patients were assigned to either an LBP or leg pain group to determine the correlation among these disease manifestations and individual cytokine expression levels. RESULTS: A gradual increase in TNF-α (R=0.391) and IL-6 (R=0.388) expression levels correlated with the degree of IVD degeneration, whereas NGF (R=0.164) expression levels exhibited a minimal decrease with disease progression. Regarding the predominant clinical manifestation, only the LBP group exhibited a significant increase in TNF-α expression levels (p=0.002). CONCLUSIONS: These results suggested that TNF-α and IL-6 play an important role in the pathophysiology of IVD degeneration at any stage, whereas NGF plays an important role during the early disease stages. Moreover, because TNF-α expression levels were significantly high in the LBP group, we propose that they are involved in LBP onset or progression.
Dichlorodiphenyldichloroethane
;
Disease Progression
;
Enzyme-Linked Immunosorbent Assay
;
Humans
;
Interleukin-6
;
Intervertebral Disc Degeneration*
;
Intervertebral Disc*
;
Leg
;
Low Back Pain
;
Magnetic Resonance Imaging
;
Nerve Growth Factor
;
Observational Study
;
Tumor Necrosis Factor-alpha
8.Response to: “Long-term Outcomes of In Situ Fusion for Treating Dysplastic Spondylolisthesis”.
Kazuhide INAGE ; Sumihisa ORITA ; Kazuyo YAMAUCHI ; Miyako SUZUKI ; Yoshihiro SAKUMA ; Go KUBOTA ; Yasuhiro OIKAWA ; Takeshi SAINOH ; Jun SATO ; Kazuki FUJIMOTO ; Yasuhiro SHIGA ; Koki ABE ; Hirohito KANAMOTO ; Masahiro INOUE ; Hideyuki KINOSHITA ; Masaki NORIMOTO ; Tomotaka UMIMURA ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Asian Spine Journal 2017;11(5):845-846
No abstract available.
Spondylolisthesis*
9.Correlation Between Walking Ability and Monthly Care Costs in Elderly Patients After Surgical Treatments for Hip Fractures.
Koki ABE ; Kazuhide INAGE ; Keishi YAMASHITA ; Masaomi YAMASHITA ; Akiyoshi YAMAMAOKA ; Masaki NORIMOTO ; Yoshinori NAKATA ; Takeshi MITSUKA ; Kaoru SUSEKI ; Sumihisa ORITA ; Kazuki FUJIMOTO ; Yasuhiro SHIGA ; Hirohito KANAMOTO ; Masahiro INOUE ; Hideyuki KINOSHITA ; Tomotaka UMIMURA ; Yawara EGUCHI ; Takeo FURUYA ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Annals of Rehabilitation Medicine 2018;42(4):569-574
OBJECTIVE: To validate the relationship between residual walking ability and monthly care cost as well as long-term care insurance (LTCI) certification level in elderly patients after surgical treatment for hip fractures in Japan. METHODS: Elderly patients aged >75 years who underwent surgical treatment for hip fractures in our hospital were included. The preand post-surgical (6-month) walking ability and LTCI certification and the presence or absence of dementia was determined from medical records and questionnaires. Walking ability was classified into 6 levels used in our daily medical practice. Based on these data, we correlated the relationship between walking ability and the LTCI certification level. Further, based on the official statistics pertaining to the average monthly costs per person at each LTCI certification level, we evaluated the relationship between walking ability and monthly care cost. RESULTS: A total of 105 cases (mean age, 80.2 years; 16 men; 39 patients with dementia) were included. The correlation between walking ability and average monthly cost per person as well as LTCI certification level at 6 months postoperatively (r=0.58) was demonstrated. The correlation was found in both groups with and without dementia. CONCLUSION: The ability to walk reduced the cost of care in elderly patients who experienced hip fracture, regardless of the presence of dementia.
Aged*
;
Certification
;
Cost-Benefit Analysis
;
Dementia
;
Hip Fractures*
;
Hip*
;
Humans
;
Insurance, Long-Term Care
;
Japan
;
Long-Term Care
;
Male
;
Medical Records
;
Mobility Limitation
;
Walking*
10.Diffusion Tensor Imaging of the Spinal Canal in Quantitative Assessment of Patients with Lumbar Spinal Canal Stenosis
Masaki NORIMOTO ; Yawara EGUCHI ; Hirohito KANAMOTO ; Yasuhiro OIKAWA ; Koji MATSUMOTO ; Yoshitada MASUDA ; Takeo FURUYA ; Sumihisa ORITA ; Kazuhide INAGE ; Satoshi MAKI ; Yasuhiro SHIGA ; Hideyuki KINOSHITA ; Koki ABE ; Masahiro INOUE ; Tomotaka UMIMURA ; Takashi SATO ; Masashi SATO ; Masahiro SUZUKI ; Keigo ENOMOTO ; Seiji OHTORI
Asian Spine Journal 2021;15(2):207-215
Methods:
Study participants comprised five healthy volunteers (mean age, 27.2 years) and 27 patients with LSS (mean age, 58.4 years) who were individually assessed using 3.0 Tesla magnetic resonance imaging. Intraspinal ADC and FA values of 10 intervertebral discs from healthy volunteers and 52 intervertebral discs from LSS patients were measured. Also, intraspinal canal area, Schizas classification (A: normal, B: mild stenosis, C: severe stenosis) and correlations with symptoms were investigated. Clinical symptoms were checked for the presence of low back pain (LBP), intermittent claudication (IMC), and bladder and bowel dysfunction (BBD).
Results:
Compared to healthy individuals, LSS patients had significantly lower ADC (