• Title/Summary/Keyword: therapeutic target

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Pathophysiology and Treatment of Gout Arthritis; including Gout Arthritis of Hip Joint: A Literature Review

  • Yonghan Cha;Jongwon Lee;Wonsik Choy;Jae Sun Lee;Hyun Hee Lee;Dong-Sik Chae
    • Hip & pelvis
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    • v.36 no.1
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    • pp.1-11
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    • 2024
  • Gout is triggered by the accumulation of uric acid in the body, leading to hyperuricemia. Genetic, metabolic, and environmental factors can influence this condition. Excessive uric acid buildup results in the formation of monosodium urate (MSU) crystals, which precipitate in specific areas of the body, including the joints, where they can cause symptoms of gout. While the acute and chronic symptoms of gout have been well-documented, diagnosis of gout affecting the hip joint poses significant challenges. The global incidence of gout, the most prevalent form of inflammatory arthritis, is on the rise. Evaluation of the clinical signs, laboratory results, and imaging results is generally required for diagnosis of gout in cases where MSU crystals have not been detected. Hyperuricemia is considered a primary cause of arthritis symptoms, and comprehensive guidelines for treatment are available. Therefore, the choice of medication is straightforward, and moderate effectiveness of treatment has been demonstrated. Gout is a chronic disease, requiring lifelong uric acid-lowering medications, thus application of a treatment strategy based on the target blood uric acid concentration is necessary. Consequently, cases of gout will likely be observed more frequently by hip surgeons in clinical scenarios in the future. The objective of this review is to provide an overview of the pathophysiology of gout and subsequently examine recent advances in diagnostic methods and therapeutic agents based on an understanding of its underlying mechanisms. In addition, literature on gout-related issues affecting the hip joint, providing a useful reference for hip surgeons is examined.

Radiosurgery with Linac Based Photon Knife in Cerebral Arteriovenous Malformation (선형가속기를 이용한 Photon Knife 방사선수술에 의한 뇌동정맥기형의 치료)

  • Kim, Jin-Hee;Choi, Tae-Jin
    • Radiation Oncology Journal
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    • v.21 no.1
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    • pp.1-9
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    • 2003
  • Purpose : The purpose of this study was to analyze the effect of a Linear accelerator based Photon Knife Radiosurgery System developed by the staff of Keimyung University Dongsan Medical Center for the treatment of cerebral arterlovenous malformation Material and Methods : Between December 1993 and October 2000, 30 patients with cerebral arteriovenous malformation (AVM) were treated with the Linac based Photon knife Radlosurgery System In the Department of Therapeutlc Radiology at Keimyung University Dongsan Medical Center. The median age was 34, ranging from 7 to 63 years, with a 2 : 1 male to female ratio. The locations of the AVM nidi were the frontal lobe (motor cortex), parletal lobe, and the thalamus, In that order. The diameters of the AVM nidi ranged 1.2 to 5.5 cm with a mean on 2.9 cm, and target volumes of between 0.5 and 20.5 cc, with a mean of 5.8 cc. The majority of patients received radiation doses of between 1,500 and 2,500 cGy, w14h a mean of 2,000 cGy, at 80% the isodose line. Twenty-five patients were treated with one isocenter, 4 with two, and 1 with four. The follow-up radiological evaluations were peformed with cranial computed tomogram (CT) or MRI between 6 month and one year interval, and if the AVM nidus had completely disappeared in the CT or MRI, we confirmed thls was a complete obliteration, with a cerebral or magnetic resonance angiogram (MRA). The median iollow-up period was 39 months with a range of 10 to 103 months. Results : Twenty patients were radloiogicaiiy followed up ior over 20 months, with complete obliteration observed in 14 (70%). According to the maximal diameter, all four of the small AVM (<2 cm) completely obliterated, 8 of the 10 patients with a medium AVW (2~3 cm) showed a complete obliteration, and two showed partial obliteration. Among the patients with a large AVM (>3 cm), only one showed complete obliteration, and S showed partial obliteration, but 3 oT these underwent further radiosurgery 3 years later. One who followed up for 20 months fellowing further radiosurgery eventually showed complete obliteration. Ten patients with seizure symptoms had no recurrent seizure due to radiosurgery and medication. One of the eleven patients who suffered intracranlal bleeding developed further bleeding at 9 and 51 months fellowing the radiosurgery although complete obliteration was eventually observed and the patient was managed in hospital then recovered. No patient suffered severe complications fellowing the radiosurgery. Conclusion : The radiosurgery with Linac-based Photon knife radiosurgery system, developed by the staff at our hospital, is a safe and effective treatment for AVM patients having diameters or volumes of less than 3 cm or 10 cm$^{3}$, respectively, located In Inoperable areas or who refused neurosurgery. We suggest that staged AVM radiosurgery may initially be considered, if the AVM target volume is above 10 cm$^{3}$

Locally Advanced, Unresectable Pancreatic Cancer Treated by Stereotactic Radiation Therapy (국소적으로 진행된, 절제 불가능한 췌장암에서 정위 방사선 치료)

  • Choi Chul-Won;Kim Mi-Sook;Cho Chul-Koo;Yoo Seong-Yul;Yang Kwang-Mo;Yoo Hyung-Jun;Lee Dong-Han;Ji Young-Hoon;Han Chul-Ju;Kim Jin;Kim Young-Han
    • Radiation Oncology Journal
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    • v.24 no.1
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    • pp.11-20
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    • 2006
  • Puroose: In order to find out whether stereotactic radiation therapy (RT) using CyberKnife (CK) could improve survival rate and lower acute toxicity compared to conventional RT. Materials and Methods: From April 2003 through April 2004, 19 patients with Eastern Cooperative Oncology Group (ECOG) performance status ${\leq}3$ and locally advanced pancreas cancer without distant metastasis, evaluated by CT or PET/CT, were included. We administered stereotactic RT consisting of either 33 Gy, 36 Gy or 39 Gy in 3 fractions to 6, 4 and 9 patients, respectively, in an effort to increase the radiation dose step by step, and analyzed the survival rate and gastrointestinal toxicities by the acute radiation morbidity criteria of Radiation Therapeutic Oncology Group (RTOG). Prognostic factors of age, sex, ECOG performance score, chemotherapy, bypass surgery, radiation dose, CA 19-9, planning target volume (PTV), and adjacent organ and vessel invasion on CT scan were evaluated by Log Rank test. Results: The median survival time was 11 months with 1-year survival rate of 36.8%. During follow-up period (range $3{\sim}20$ months, median 10 months), no significant gastrointestinal acute toxicity (RTOG grade 3) was observed. In univariate analysis, age, sex, ECOG performance score, chemotherapy, bypass surgery, radiation dose, CA 19-9 level, and adjacent organ and vessel invasion did not show any significant changes of survival rate, however, patients with PTV (80 cc showed more favorable survival rate than those with PTV>80 cc (p-value<0.05). In multivariate analysis, age younger than 65 years and PTV>80 cc showed better survival rate. Conclusion: In terms of survival, the efficacy of stereotactic radiation therapy using CK was found to be superior or similar to other recent studies achieved with conventional RT with intensive chemotherapy, high dose conformal RT, intraoperative RT (IORT), or intensity modulated RT (IMRT). Furthermore, severe toxicity was not observed. Short treatment time in relation to the short life expectancy gave patients more convenience and, finally, quality of life would be increased. Consequently, this could be regarded as an effective novel treatment modality for locally advanced, unresectable pancreas cancer. PTV would be a helpful prognostic factor for CK.

Clinical Application of in Vivo Dosimetry System in Radiotherapy of Pelvis (골반부 방사선 치료 환자에서 in vivo 선량측정시스템의 임상적용)

  • Kim, Bo-Kyung;Chie, Eui-Kyu;Huh, Soon-Nyung;Lee, Hyoung-Koo;Ha, Sung-Whan
    • Journal of Radiation Protection and Research
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    • v.27 no.1
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    • pp.37-49
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    • 2002
  • The accuracy of radiation dose delivery to target volume is one of the most important factors for good local control and less treatment complication. In vivo dosimetry is an essential QA procedure to confirm the radiation dose delivered to the patients. Transmission dose measurement is a useful method of in vivo dosimetry and it's advantages are non-invasiveness, simplicity and no additional efforts needed for dosimetry. In our department, in vivo dosimetry system using measurement of transmission dose was manufactured and algorithms for estimation of transmission dose were developed and tested with phantom in various conditions successfully. This system was applied in clinic to test stability, reproducibility and applicability to daily treatment and the accuracy of the algorithm. Transmission dose measurement was performed over three weeks. To test the reproducibility of this system, X-tay output was measured before daily treatment and then every hour during treatment time in reference condition(field size; $10 cm{\times} 10 cm$, 100 MU). Data of 11 patients whose pelvis were treated more than three times were analyzed. The reproducibility of the dosimetry system was acceptable with variations of measurement during each day and over 3 week period within ${\pm}2.0%$. On anterior- posterior and posterior fields, mean errors were between -5.20% and +2.20% without bone correction and between -0.62% and +3.32% with bone correction. On right and left lateral fields, mean errors were between -10.80% and +3.46% without bone correction and between -0.55% and +3.50% with bone correction. As the results, we could confirm the reproducibility and stability of our dosimetry system and its applicability in daily radiation treatment. We could also find that inhomogeneity correction for bone is essential and the estimated transmission doses are relatively accurate.

Radiation Dose of Lens and Thyroid in Linac-based Radiosurgery in Humanoid Phantom (선형가속기형 방사선수술시 인형 팬텀에서 수정체 및 갑상선 선량)

  • Kim, Dae-Yong;Kim, Il-Han
    • Radiation Oncology Journal
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    • v.16 no.4
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    • pp.517-529
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    • 1998
  • Purpose : Although many studies have investigated the dosimetric aspects of stereotactic radiosurgery in terms of target volume, the absorbed doses at extracranial sites: especially the lens or thyroid - which are sensitive to radiation for deterministic or stochastic effect -have infrequently been reported. The aim of this study is to evaluate what effects the parameters of radiosurgery have on the absorbed doses of the lens and thyroid in patients treated by stereotactic radiosurgery, using a systematic plan in a humanoid phantom. Materials and Methods : Six isocenters were selected and radiosurgery was planned using the stereotactic radiosurgery system which the Department of Therapeutic Radiology at Seoul National University College of Medicine developed. The experimental radiosurgery plan consisted of 6 arc planes per one isocenter, 100 degrees for each arc range and an accessory collimator diameter size of 2 cm. After 250 cGy of irradiation from each arc, the doses absorbed at the lens and thyroid were measured by thermoluminescence dosimetry. Results : The lens dose was 0.23$\pm$0.08$\%$ of the maximum dose for each isocenter when the exit beam did not pass through the lens and was 0.76$\pm$0.12$\%$ of the maximum dose for each isocenter when the exit beam passed through the lens. The thyroid dose was 0.18$\pm$0.05$\%$ of the maximum dose for each isocenter when the exit beam did not pass through the thyroid and was 0.41$\pm$0.04$\%$ of the maximum dose for each isocenter when the exit beam Passed through the thyroid. The passing of the exit beam is the most significant factor of organ dose and the absorbed dose by an arc crossing organ decides 80$\%$ of the total dose. The absorbed doses of the lens and thyroid were larger as the isocenter sites and arc planes were closer to each organ. There were no differences in the doses at the surface and 5 mm depth from the surface in the eyelid and thyroid areas. Conclusion : As the isocenter and arc plane were placed closer to the lens and thyroid, the doses increased. Whether the exit beams passed through the lens or thyroid greatly influenced the lens and thyroid dose. The surface dose of the lens and thyroid consistently represent the tissue dose. Even when the exit beam passes through the lens and thyroid, the doses are less than 1$\%$ of the maximum dose and therefore, are too low to evoke late complications, but nevertheless, we should try to minimize the thyroid dose in children, whenever possible.

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Preliminary Investigations of the Dosimetric Properties of a Normoxic Polymethacrylic Acid Gel Dosimeter Using a Respiration-Motion Simulator (호흡모의움직임장치를 이용한 정상산소 폴리메타크릴산 겔 선량계의 선량특성)

  • Park, Chae Hee;Cho, Yu Ra;Cho, Kwang Hwan;Park, Ji Ae;Kim, Kyeong Min;Kim, Kum Bae;Jung, Hai Jo;Ji, Young Hoon;Kwon, Soo-Il
    • Progress in Medical Physics
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    • v.23 no.3
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    • pp.138-144
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    • 2012
  • Dose distribution throughout the clinical organ range of motion was analyzed using a respiratory-motion simulator that was equipped with a polymer gel dosimeter and EBT2 film. The normoxic polymer gel dosimeter was synthesized from gelatin, MAA, HQ, THPC and HPLC. The gel dosimeter and EBT2 film were irradiated with Co-60 gamma rays that were moved along the x-axis and y-axis in ${\pm}1.5cm$ steps at five-second intervals. The field size was $5{\times}5cm^2$. The SSD was 80 cm and set to 10 Gy at a depth of 2 cm. The PDD at a depth of 50 mm was 75.2% in the ion chamber, 82.3% in the static state and 86.1% in the dynamic state in the gel dosimeter. The penumbra for the dynamic state target, which was measured using the gel dosimeter, averaged 10.89 mm, this is a 40.5% increase over the penumbra of the static state target of 7.74 mm. In addition, when measuring with gel dosimetry, the value for the penumbra is 36.6% smaller in the static state and 29.4% smaller in the dynamic state compared to measuring with film. The aim of this study was to investigate the dosimetric properties of a normoxic polymethacrylic acid gel dosimeter in static and dynamic states and to evaluate the potentiality as a relative dosimeter for dynamic therapeutic radiation.

Alteration of MicroRNAs Targeted Integrins by PD-MSCs Transplantation Is Involved in Hepatic Regeneration in a Rat Model with BDL (담관결찰 쥐 모델에서 태반유래중간엽줄기세포 이식에 의한 miRNA 표적 인테그린 변화의 간재생 효과)

  • Park, Sohae
    • Journal of Life Science
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    • v.31 no.8
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    • pp.710-718
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    • 2021
  • Placenta-derived mesenchymal stem cells (PD-MSCs) are promising candidates for cell-based therapy in regenerative medicine. The migration and homing potential of PD-MSCs to injured sites is a critical property of MSC engraftment. MicroRNAs (miRNAs) have recently been shown to regulate the critical functions of MSCs, such as proliferation, survival, and migration. The objective of the present study was to identify the miRNA and target genes involved in PD-MSCs homing in a bile duct ligation (BDL) rat model. We selected candidate miRNAs targeting genes for PD-MSCs homing based on microarray analysis. PD-MSC engraftment in BDL-injured rat liver was identified by immunofluorescence assay and human-specific Alu gene expression by quantitative real-time polymerase chain reaction (qRT-PCR) one week after transplantation. Compared with migrated naïve PD-MSCs under hypoxic and normoxic conditions (Hyp/Nor), the transplanted group with PD-MSCs (Tx) showed distinct differences in miRNA expressions in BDL-injured rat liver. We also validated the miRNAs and their target genes for PD-MSCs homing. The expressions of integrin α4 (ITGA4) and integrin α5 (ITGA5) target genes for miR-199a-5p and miR-148a-3p were significantly upregulated in the Tx group (p<0.05). In addition, integrin β1 (ITGB1) and integrin β8 (ITGB8) were upregulated by suppressing miR-183-5p and miR-145-5p, respectively. These results demonstrated that PD-MSCs regulate miRNA expression related to the integrin family for their homing effects on the BDL-injured rat liver. The findings further suggest that miRNA-mediated regulation of the integrin family contributes to the therapeutic efficacy of PD-MSCs in the rat hepatic fibrosis model by BDL.

AMP-activated Kinase Regulates Adipocyte Differentiation Process in 3T3-L1 Adipocytes Treated with Selenium (AMP-activated protein kinase가 셀레늄으로 처리된 3T3-L1 지방세포의 분화과정 억제에 관한 연구)

  • Park, Song-Yi;Hwang, Jin-Taek;Lee, Yun-Kyoung;Kim, Young-Min;Park, Ock-Jin
    • Journal of Life Science
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    • v.19 no.4
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    • pp.423-428
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    • 2009
  • Selenium was investigated using human origin preadipocytes to see whether it possesses preventive or therapeutic effects for obesity. Unveiling the potential of selenium in the reduction of adipogenesis can help predict the therapeutic capabilities of selenium in obesity. In the present study, the molecular mechanism of the inhibition of adipogenesis by selenium was explored to unravel the involvement of the AMP-activated protein kinase. There is emerging evidence that AMPK, a sensor of cellular energy status, is a possible molecular target of controlling adipocyte differentiation on the basis of discovery that AMPK is responsible for the major metabolic responses to exercise, and integration of nutritional and hormonal signals to modulate feeding behavior or energy expenditure in the hypothalamus. Treatment of selenium resulted in inhibition of the adipocyte differentiation process and induction of mature apoptosis in 3T3-L1 adipocytes. We hypothesized that selenium may exert anti-adipogenic potential though modulating AMPK. We have found that selenium significantly activated AMPK and phosphorylated its substrate acetyl-CoA carboxylase ($ACC-serine^{79}$) during the inhibitory process of adipocytes. Also, the inhibition process of adipocyte differentiation by selenium was comparable to either reveratrol or a synthetic AMPK activator, AICAR (5-aminoimidazole-4-carboxamide-1-${\beta}$-D-ribofuranoside). To evaluate the involvement of AMPK in anti-lipogensis, we applied AICAR and Compound C, an AMPK inhibitor, to 3T3-L1-adipocytes and found that AMPK is required for the adipocyte differentiation blocking process. These results suggest that selenium has a potential to control adipogenesis and that this effect is mediated by AMPK, an essential kinase for both inhibition of adipocyte differentiation and apoptosis of mature adipocytes.

MicroRNA-23b is a Potential Tumor Suppressor in Diffuse Large B-cell Lymphoma (미만성 거대 B 세포 림프종(DLBCL)에서 microRNA-23b의 잠재적 종양 억제자로서의 효과)

  • Nam, Jehyun;Kim, Eunkyung;Kim, Jinyoung;Jeong, Dawoom;Kim, Donguk;Kwak, Bomi;Kim, Sang-Woo
    • Journal of Life Science
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    • v.27 no.2
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    • pp.149-154
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    • 2017
  • Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-hodgkin lymphoma. Advances in the chemotherapeutic treatment of this disease have improved the outcomes of DLBCL; nonetheless, many patients still die of DLBCL, and therefore, a better understanding of this disease and identification of novel therapeutic targets are urgently required. In a recent gene expression profiling study, PDE (phosphodiesterase) 4B was found to be overexpressed in chemotherapy-resistant tumors. The major function of PDE4B is to inactivate the second messenger cyclic 3',5' monophosphate (cAMP) by catalyzing the hydrolysis of cAMP to 5'AMP. It is known that cAMP induces cell cycle arrest and/or apoptosis in B cells, and PDE4B abolishes cAMP's effect on B cells. However, the mechanism by which PDE4B is overexpressed remains unclear. Here, we show that the aberrant expression of miRNA may be associated with the overexpression of this gene. The PDE4B 3' untranslated region (UTR) has three functional binding sites of miR-23b, as confirmed by luciferase reporter assays. Interestingly, miR-23b-binding sites were evolutionarily conserved from humans to lizards, implying the critical role of PDE4B-miR-23b interaction in cellular physiology. The ectopic expression of miR-2 3b repressed PDE4B mRNA levels and enhanced intracellular cAMP concentrations. Additionally, miR-23b expression inhibited cell proliferation and survival of DLBCL cells only in the presence of forskolin, an activator of adenylyl cyclase, suggesting that miR-23b's effect is via the downregulation of PDE4B. These results together suggest that miR-23b could be a therapeutic target for overcoming drug resistance by repressing PDE4B in DLBCL.

Benefit of Ultrasound-guided Therapeutic Medial Branch Blocks after Percutaneous Epidural Neuroplasty (신경 성형술 후 초음파 유도하 내측 분지 차단술의 유용성)

  • Moon, Sang Ho;Lee, Song;Jung, Jae-Hyun;Shin, Won Shik
    • The Journal of Korean Orthopaedic Ultrasound Society
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    • v.7 no.1
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    • pp.33-38
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    • 2014
  • Purpose: To determine the therapeutic effectiveness of ultrasound-guided medial branch block (MBB) for the herniated lumbar disc patients who did not relieve their symptoms after percutaneous epidural neuroplasty (PEN). Materials and Methods: From August 2011 to February 2013, 559 patients with herniated lumbar disc have undergone PEN. Among them, ultrasound-guided MBBs were performed for the patients who had sustained low back pain and refered pain to lower extremities. Eighty eight patients were followed at 1 month and 39 patients could be followed at 6 month. All procedures have been performed by the one operator, and 23 G, 10 cm needle was placed and 0.5% lidocaine was injected under ultrasound guide. To target medial branches from L1 to L5, the groove at the root of transverse process and the base of superior articular process has been identified on transverse scan. Patients were evaluated by Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) at each follow-up. Significant pain relief was described as a 50% or more reduction in VAS and significant improvement in function was described as at least a 40% reduction in ODI. Results: VAS showed that preprocedure pain ($7.35{\pm}1.68$; $mean{\pm}SD$) significantly decreased 1 month after block ($3.36{\pm}2.98$) and 6 month ($3.05{\pm}2.27$) (p<0.05). ODI also showed that preprocedure score ($32.82{\pm}8.77$) significantly decreased at 1 month ($15.14{\pm}14.01$) and 6 month ($12.97{\pm}8.82$) (p<0.05). Significant pain relief was observed in 64.49% at 1 month and 64.10% at 6 month. Significant functional improvement in 59.81% at 1 month and 61.54% at 6 month. Conclusion: Ultrasound-guided medial branch block may sufficiently treat the facet problems secondary from disc disease.

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