1.Quantification and pharmacokinetic study of tumor-targeting agent MHI148-clorgyline amide in mouse plasma using liquid chromatography-electrospray ionization tandem mass spectrometry
Zhijun WANG ; Z.-Bogdan OLENYUK ; Chen-Jean SHIH ; Jeffrey WANG
Journal of Pharmaceutical Analysis 2018;8(3):153-159
A high-performance liquid chromatography-electrospray ionization tandem mass spectrometric (HPLC-ESI-MS/MS) method was developed for the quantification of MHI148-clorgyline amide (NMI-amide), a novel tumor-targeting monoamine oxidase A inhibitor, in mouse plasma. The method was validated in terms of sensitivity, precision, accuracy, recovery and stability and then applied to a pharmacokinetic study of NMI-amide in mice following intravenous administration. NMI-amide together with the internal standard (IS), MHI-148, was extracted by protein precipitation using acetonitrile. Multiple reaction monitoring was used for quantification of NMI-amide by detecting m/z transition of 491.2–361.9, and 685.3–258.2 for NMI-amide and the IS, respectively. The lower limit of quantification (LLOQ) of the HPLC–MS/MS method for NMI-amide was 0.005 μg/mL and the linear calibration curve was acquired with R2> 0.99 in the concentration range of 0.005–2 μg/mL. The intra- and inter-day precisions of the assay were assessed by percentage of the coefficient of variations, which was within 9.8% at LLOQ and 14.0% for other quality control samples, whereas the mean accuracy ranged from 86.8% to 113.2%. The samples were stable under storage and experimental conditions. This method was successfully applied to a pharmacokinetic study in mice following intravenous administration of 5 mg/kg NMI-amide.
2.A brief review of research on chronic disease management based on collaborative care model in China
Huayan LI ; Fuller JEFFREY ; Mei SUN ; Yong WANG ; Shuang XU ; Hui FENG
Journal of Central South University(Medical Sciences) 2014;(11):1203-1210
Objective: To evaluate the situation for chronic disease management in China, and to seek the method for improving the collaborative management for chronic diseases in community. Methods: We searched literature between January 2008 and November 2013 from the Database, such as China Academic Journal Full-Text Database, and PubMed. The screening was strictly in accordance with the inclusion and exclusion criteria and a summary was made among the selected literature based on a collaboration model. Results: We got 698 articles atfer rough screen and ifnally selected 33. All studies were involved in patient’s self-management support, but only 9 studies mentioned the communication within the team, and 11 showed a clear team division of labor. Conclusion: Chronic disease community management in China displays some disadvantages. It really needs a general service team with clear roles and responsibilities for team members to improve the service ability of team members and provide patients with various forms of self-management services.
3.Phytochemical analysis of medicinal plants with kidney protective activities.
Eric Jung-Chi LIEN ; Linda Lin-Min LIEN ; Rubin WANG ; Jeffrey WANG
Chinese journal of integrative medicine 2012;18(10):790-800
In view of the increasing number of patients undergoing kidney dialysis or transplant every year, a survey of the literature on renal protective medicinal plants was undertaken. Most of them are from traditional Chinese medicine (TCM). Although many of the medicinal herbs reported have not been investigated in terms of active chemical ingredients, some do have compounds well characterized. They fall into a wide range of structures. Several groups of compounds with well established activities are discussed. These include: antioxidant phenolic compounds like tannins, flavonoids, isoflavonoids, unsaturated organic acids and lignans; circulation enhancing compounds like saponins, and basic alkaloids with multiple targets (G-protein coupled receptors). Also presented are proinflammatory and antiinflammatory fatty acids like linoleic (n-6) and α-linolenic (n-3) acids, respectively. Attention is also drawn to the plants containing nephrotoxic aristolochic acid. Different directions of future research are also presented. We hope that this review may provide some leads for new drug discovery and development, and more rational application of TCM.
Animals
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Humans
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Kidney
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drug effects
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Plants, Medicinal
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chemistry
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Protective Agents
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chemistry
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pharmacology
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Structure-Activity Relationship
4.Differentiation of human bone marrow precursor cells into neuronal-like cells after transplantation into canine spinal cord organotypic slice cultures.
Zhi-qiang FEI ; Jian-yi XIONG ; Lei CHEN ; Hui-yong SHEN ; Ngo STEPHANIE ; Wang JEFFREY ; Da-ping WANG
Chinese Medical Journal 2012;125(22):4049-4054
BACKGROUNDTreatments to regenerate different tissue involving the transplantation of bone marrow derived mesenchymal precursor cells are anticipated. Using an alternative methods, in vitro organotypic slice culture method, would be useful to transplant cells and assessing the effects. This study was to determine the possibility of differentiating human bone marrow precursor cells into cells of the neuronal lineage by transplanting into canine spinal cord organotypic slice cultures.
METHODSBone marrow aspirates were obtained from posterior superior iliac spine (PSIS) of patients that had undergone spinal fusion due to a degenerative spinal disorder. For cell imaging, mesenchymal precursor cells (MPCs) were pre-stained with PKH-26 just before transplantation to canine spinal cord slices. Canine spinal cord tissues were obtained from three adult beagle dogs. Spinal cords were cut into transverse slices of 1 mm using tissue chopper. Two slices were transferred into 6-well plate containing 3 ml DMEM with antibiotics. Prepared MPCs (1×10(4)) were transplanted into spinal cord slices. On days 0, 3, 7, 14, MPCs were observed for morphological changes and expression of neuronal markers through immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR).
RESULTSThe morphological study showed: spherical cells in the control and experiment groups on day 0; and on day 3, cells in the control group had one or two thick, short processes and ones in the experiment group had three or four thin, long processes. On day 7, these variously-sized processes contacted each other in the experiment group, but showed typical spindle-shaped cells in the control group. Immunofluorescence showed that PKH-26(+) MPCs stained positive for NeuN(+) and GFAP(+) in experimental group only. Also RT-PCR showed weak expression of β-tubulin III and GFAP.
CONCLUSIONSHuman bone marrow mesenchymal precursor cells (hMPCs) have the potential to differentiate into the neuronal like cells in this canine spinal cord organotypic slice culture model. Furthermore, these findings suggested the possibility that these cells can be utilized to treat patients with spinal cord injuries.
Animals ; Bone Marrow Cells ; cytology ; Cell Differentiation ; physiology ; Cells, Cultured ; Dogs ; Humans ; Mesenchymal Stromal Cells ; cytology ; Spinal Cord ; cytology
5.Screening of pancreatic lipase and alpha-glucosidase inhibitors from Chinese dietary herbs.
Xiaoli SUN ; Kaibin ZHANG ; Xiuhong JI ; Yanwen WANG ; Zidichouski JEFFREY ; Yan TONG ; Huimin GAO ; Junzeng ZHANG ; Zhimin WANG
China Journal of Chinese Materia Medica 2012;37(9):1319-1323
The present study was conducted to develop new inhibitors of pancreatic lipase and alpha-glucosidase from Chinese dietary herbs. Sixty-three dietary herbs from 39 taxonomic families were selected and extracted with aqueous ethanol or water. The extracts were then tested with in vitro enzyme assays for their ability to inhibit pancreatic lipase and alpha-glucosidase activities. Orlistat and acarbose were used as two positive controls. The extracts of Nelumbo nucifera, Curcuma longa, Piper longum and Morus alba showed strong pancreatic lipase inhibitory effects with IC50 at (28.00 +/- 5.51), (5.24 +/- 0.51), (14.76 +/- 2.58), (4.78 +/- 0.58), (3.41 +/- 0.67) mg x L(-1), respectively. These extracts also showed potent alpha-glucosidase inhibitory activities with IC50 at (1.98 +/- 0.13), (0. 18 + 0.007), (0.71 +/- 0.08), (0.077 +/- 0.005), (0.089 +/- 0.006) g x L(-1), respectively. The results provide useful information for developing new drugs or natural health products for hyperlipidemia and hypoglycemia from Chinese dietary herbs.
Curcuma
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chemistry
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Drugs, Chinese Herbal
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chemistry
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pharmacology
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Enzyme Inhibitors
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chemistry
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pharmacology
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Lipase
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antagonists & inhibitors
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Morus
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chemistry
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Nelumbo
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chemistry
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Pancreas
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enzymology
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Piper
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chemistry
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Plant Extracts
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chemistry
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pharmacology
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alpha-Glucosidases
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metabolism
6.Radiographic Parameters of Segmental Instability in Lumbar Spine Using Kinetic MRI.
Se Youn JANG ; Min Ho KONG ; Henry J HYMANSON ; Tae Kyung JIN ; Kwan Young SONG ; Jeffrey C WANG
Journal of Korean Neurosurgical Society 2009;45(1):24-31
OBJECTIVE: To investigate the effectiveness of radiographic parameters on segmental instability in the lumbar spine using Kinetic magnetic resonance imaging (MRI). METHODS: Segmental motion, defined as excessive (more than 3 mm) translational motion from flexion to extension, was investigated in 309 subjects (927 segments) using Kinetic MRI. Radiographic parameters which can help indicate segmental instability include disc degeneration (DD), facet joint osteoarthritis (FJO), and ligament flavum hypertrophy (LFH). These three radiographic parameters were simultaneously evaluated, and the combinations corresponding to significant segmental instability at each level were determined. RESULTS: The overall incidence of segmental instability was 10.5% at L3-L4, 16.5% at L4-L5, and 7.3% at L5-S1. DD and LFH at L3-L4 and FJO and LFH at L4-L5 were individually associated with segmental instability (p<0.05). At L4-L5, the following combinations had a higher incidence of segmental instability (p<0.05) when compared to other segments : (1) Grade IV DD with grade 3 FJO, (2) Grade 2 or 3 FJO with the presence of LFH, and (3) Grade IV DD with the presence of LFH. At L5-S1, the group with Grade III disc and Grade 3 FJO had a higher incidence of segmental instability than the group with Grade I or II DD and Grade 1 FJO. CONCLUSION: This study showed that the presences of either Grade IV DD or grade 3 FJO with LFH at L4-L5 were good indicators for segmental instability. Therefore, using these parameters simultaneously in patients with segmental instability would be useful for determining candidacy for surgical treatment.
Humans
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Hypertrophy
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Incidence
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Intervertebral Disc Degeneration
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Ligaments
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Magnetic Resonance Imaging
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Osteoarthritis
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Spine
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Zygapophyseal Joint
7.A Preliminary Survey of Emergency Medicine in 12 Asian Countries.
Jae Myung CHUNG ; Soon Joo WANG ; Moo Up AHN ; Jae Hyoung PARK ; Ki Chul YOO ; Joon Suk PARK ; Jae Gu KANG ; Jeffrey L ARNOLD
Journal of the Korean Society of Emergency Medicine 1999;10(4):549-559
BACKGROUND: To assess the current level of development of emergency medicine (EM) systems in Asia. METHOD: Survey of EM professionals from 12 Asian countries during a 90-day period from August to November 1998. 12 EM professionals from 12 Asian countries completed the survey. All participants were physicians. 7 participants (58%) gave presentations at an international EM conference during the study period. Respondents completed a 103 question questionnaire about the status of EM specialty, academic, patient care, information and management systems and the factors influencing the future of EM in their countries. RESULTS: 92% of respondents stated that their countries have hospital-based emergency departments (ED). More than 80% of respondents reported that their countries have EMS systems and ED systems for trauma care and patient transfer. More than 70% stated that their countries have national EM organizations, EM research, national EMS activation phone numbers, ED systems for pediatric emergency care, emergency physician (EP) training in ACLS and ATLS and peer review. More than 60% reported official recognition of EM as an independent specialty status, ED triage systems and systems for customer service. More than 50% reported EM residency training programs, EM journals and EP ability to perform rapid sequence intubation (RSI). 50% reported EP ability to perform thrombolysis for acute MI and 33% reported EP ultrasonography. 92% felt that a lack of funding posed a moderate or great obstacle to the future development of EM in their countries. CONCLUSION: Many essential systems of EM now exist throughout Asia. In the systems of administration and emergency medical information in many countries, there are some parts to be developed further.
Asia
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Asian Continental Ancestry Group*
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Surveys and Questionnaires
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Education
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Emergencies*
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Emergency Medical Services
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Emergency Medicine*
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Emergency Service, Hospital
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Financial Management
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Humans
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Internship and Residency
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Intubation
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Patient Care
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Patient Transfer
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Peer Review
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Triage
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Ultrasonography
8.Relationship of Facet Tropism with Degeneration and Stability of Functional Spinal Unit.
Min Ho KONG ; Wubing HE ; Yu Duan TSAI ; Nan Fu CHEN ; Gun KEOROCHANA ; Duc H DO ; Jeffrey C WANG
Yonsei Medical Journal 2009;50(5):624-629
PURPOSE: The authors investigated the effect of lumbar facet tropism (FT) on intervertebral disc degeneration (DD), facet joint degeneration (FJD), and segmental translational motion. MATERIALS AND METHODS: Using kinetic MRI (KMRI), lumbar FT, which was defined as a difference in symmetry of more than 7degrees between the orientations of the facet joints, was investigated in 900 functional spinal units (300 subjects) in flexion, neutral, and extension postures. Each segment at L3-L4, L4-L5, and L5-S1 was assessed based on the extent of DD (grade I-V) and FJD (grade 1-4). According to the presence of FT, they were classified into two groups; one with FT and one with facet symmetry. For each group, demographics, DD, FJD and translational segmental motion were compared. RESULTS: The incidence of FT was 34.5% at L3-L4, 35.1% at L4-L5, and 35.2% at L5-S1. Age and gender did not show any significant relationship with FT. Additionally, no correlation was observed between DD and FT. FT, however, wasfound to be associated with a higher incidence of highly degenerated facet joints at L4-L5 when compared to patients without FT (p < 0.01). Finally, FT was not observed to have any effects upon translational segmental motion. CONCLUSION: No significant correlation was observed between lumbar FT and DD or translational segmental motion. However, FT was shown to be associated significantly with the presence of high grades of FJD at L4-L5. This suggests that at active sites of segmental motion, FT may predispose to the development of facet joint degeneration.
Adolescent
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Adult
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Age Factors
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Aged
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Aged, 80 and over
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Female
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Humans
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Intervertebral Disk Displacement/*etiology/pathology
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Joint Diseases/*complications/pathology
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Lumbar Vertebrae/*pathology
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Magnetic Resonance Imaging
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Male
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Middle Aged
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Sex Factors
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Zygapophyseal Joint/*pathology/physiopathology
9.Rabbit Model for in vivo Study of Intervertebral Disc Degeneration and Regeneration.
Min Ho KONG ; Duc H DO ; Masashi MIYAZAKI ; Feng WEI ; Sung Hwan YOON ; Jeffrey C WANG
Journal of Korean Neurosurgical Society 2008;44(5):327-333
OBJECTIVE: The purpose of this study is to verify the usefulness of the rabbit model for disc degeneration study. MATERIALS: The L1-L2, L2-L3, L3-L4, or L4-L5 lumbar intervertebral disc (IVD) of 9 mature male New Zealand White rabbits were injured by inserting a 16-gauge needle to a depth of 5 mm in the left anterolateral annulus fibrosus while leaving L5-L6 IVD uninjured. Three other rabbits also received intradiscal injections of rabbit disc cells transfected with adenovirus and bone morphogenetic protein-2 (ad-BMP-2) at L4-L5 in addition to injury by 16-gauge needle at the L1-L2 level. Using digitized radiographs, measurements of IVD height were made and analyzed by using the disc height index (DHI). Magnetic resonance imaging (MRI) scans of the injured discs, injected discs, and uninjured L5-L6 discs were performed at 15 weeks post surgery and compared with preoperative MRI scans. RESULTS: All twelve rabbits showed consistent results of disc degeneration within 15 weeks following annular puncture. DHIs of injured discs were significantly lower than that of the uninjured L5-L6 discs (p<0.05). The mean value of disc degeneration grade of injured discs was significantly higher than that of uninjured discs (p<0.05). The injection of disc cell transfected with ad-BMP-2 did not induce disc regeneration at 15 weeks after injection. CONCLUSION: This study showed that the injured disc had a significant change in DHI on simple lateral radiograph and disc degeneration grade on MRI scans within 15 weeks in all rabbits. Rabbit annular puncture model can be useful as a disc degeneration model in vivo.
Adenoviridae
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Humans
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Intervertebral Disc
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Intervertebral Disc Degeneration
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Magnetic Resonance Imaging
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Male
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Models, Animal
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Needles
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Punctures
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Rabbits
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Regeneration
10.Clinical Relationship of Degenerative Changes between the Cervical and Lumbar Spine
Yuichiro MORISHITA ; Zorica BUSER ; Anthony D'ORO ; Keiichiro SHIBA ; Jeffrey C WANG
Asian Spine Journal 2018;12(2):343-348
STUDY DESIGN: Retrospective, observational, case series. PURPOSE: To elucidate the prevalence of degenerative changes in the cervical and lumbar spine and estimate the degenerative changes in the cervical spine based on the degeneration of lumbar disc through a retrospective review of magnetic resonance (MR) images. OVERVIEW OF LITERATURE: Over 50% of middle-aged adults show evidence of spinal degeneration. However, the relationship between degenerative changes in the cervical and lumbar spine has yet to be elucidated. METHODS: A retrospective review of positional MR images of 152 patients with symptoms related to cervical and lumbar spondylosis with or without a neurogenic component was conducted. The degree of intervertebral disc degeneration (IDD) was assessed on a grade of 1–5 for each segment of the cervical and lumbar spine using MR T2-weighted sagittal images. The grades across all segments were summed to produce the degenerative disc score (DDS) for the cervical and lumbar spine. The patients were divided into two groups based on the IDD grade for each lumbar segment: normal (grades 1 and 2) and degenerative (grades 3–5). RESULTS: DDSs for the cervical and lumbar spine were positively correlated. Significant differences in cervical DDSs between the groups were observed in all lumbar segments. Although there were no significant differences in cervical DDSs among the degenerative lumbar segment, cervical DDSs at the L1–2 and L2–3 segments tended to be higher than those at the L3–4, L4–5, and L5–S degenerative segments. CONCLUSIONS: Our study shows that participants with degenerative changes in the upper lumbar segments are more likely to have a certain amount of cervical spondylosis. This information could be used to lower the incidence of a missed diagnosis of cervical spine disorders in patients presenting with lumbar spine symptomology.
Adult
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Diagnosis
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Humans
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Incidence
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Intervertebral Disc Degeneration
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Prevalence
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Retrospective Studies
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Spine
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Spondylosis