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Radiosurgical Techniques and Clinical Outcomes of Gamma Knife Radiosurgery for Brainstem Arteriovenous Malformations

  • Choi, Hyuk Jai;Choi, Seok Keun;Lim, Young Jin
    • Journal of Korean Neurosurgical Society
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    • v.52 no.6
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    • pp.534-540
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    • 2012
  • Objective : Brainstem arteriovenous malformation (AVM) is rare and radiosurgical management is complicated by the sensitivity of the adjacent neurological structures. Complete obliteration of the nidus is not always possible. We describe over 20 years of radiosurgical procedures for brainstem AVMs, focusing on clinical outcomes and radiosurgical techniques. Methods : Between 1992 and 2011, the authors performed gamma knife radiosurgery (GKRS) in 464 cerebral AVMs. Twenty-nine of the 464 patients (6.3%) reviewed had brainstem AVMs. This series included sixteen males and thirteen females with a mean age of 30.7 years (range : 5-71 years). The symptoms that led to diagnoses were as follows : an altered mentality (5 patients, 17.3%), motor weakness (10 patients, 34.5%), cranial nerve symptoms (3 patients, 10.3%), headache (6 patients, 20.7%), dizziness (3 patients, 10.3%), and seizures (2 patients, 6.9%). Two patients had undergone a previous nidus resection, and three patients had undergone a previous embolization. Twenty-four patients underwent only GKRS. With respect to the nidus type and blood flow, the ratio of compact type to diffuse type and high flow to low flow were 17 : 12 and 16 : 13, respectively. In this series, 24 patients (82.8%) had a prior hemorrhage. The mean target volume was 1.7 $cm^3$ (range 0.1-11.3 $cm^3$). The mean maximal and marginal radiation doses were 38.5 Gy (range 28.6-43.6 Gy) and 23.4 Gy (range 18-27 Gy), and the mean isodose profile was 61.3% (range 50-70%). Results : Twenty-four patients had brainstem AVMs and were followed for more than 3 years. Obliteration of the AVMs was eventually documented in 17 patients (70.8%) over a mean follow-up period of 77.5 months (range 36-216 months). With respect to nidus type and blood flow, the obliteration rate of compact types (75%) was higher than that of diffuse types (66.7%), and the obliteration rate of low flow AVMs (76.9%) was higher than that of high flow AVMs (63.6%) (p<0.05). Two patients (6.9%) with three hemorrhagic events suffered a hemorrhage during the follow-up period. The annual bleeding rate of AVM after GKRS was 1.95% per year. No adverse radiation effects or delayed cystic formations were found. Conclusion : GKRS has an important clinical role in treatment of brainstem AVMs, which carry excessive surgical risks. Angiographic features and radiosurgical techniques using a lower maximal dose with higher isodose profiles are important for lesion obliteration and the avoidance of complications.

Clinical Outcome in Gamma Knife Radiosurgery for Metastatic Brain Tumors from the Primary Breast Cancer : Prognostic Factors in Local Treatment Failure and Survival

  • Choi, Seung Won;Kwon, Do Hoon;Kim, Chang Jin
    • Journal of Korean Neurosurgical Society
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    • v.54 no.4
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    • pp.329-335
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    • 2013
  • Objective : Brain metastases in primary breast cancer patients are considerable sources of morbidity and mortality. Gamma knife radiosurgery (GKRS) has gained popularity as an up-front therapy in treating such metastases over traditional radiation therapy due to better neurocognitive function preservation. The aim of this study was to clarify the prognostic factors for local tumor control and survival in radiosurgery for brain metastases from primary breast cancer. Methods : From March 2001 to May 2011, 124 women with metastatic brain lesions originating from a primary breast cancer underwent GKRS at a tertiary medical center in Seoul, Korea. All patients had radiosurgery as a primary treatment or salvage therapy. We retrospectively reviewed their clinical outcomes and radiological responses. The end point of this study was the date of patient's death or the last follow-up examination. Results : In total, 106 patients (268 lesions) were available for follow-up imaging. The median follow-up time was 7.5 months. The mean treated tumor volume at the time of GKRS was 6273 $mm^3$ (range, 4.5-27745 mm3) and the median dose delivered to the tumor margin was 22 Gy (range, 20-25 Gy). Local recurrence was assessed in 86 patients (216 lesions) and found to have occurred in 36 patients (83 lesions, 38.6%) with a median time of 6 months (range, 4-16 months). A treated tumor volume >5000 $mm^3$ was significantly correlated with poor local tumor control through a multivariate analysis (hazard risk=7.091, p=0.01). Overall survival was 79.9%, 48.3%, and 15.3% at 6, 12, and 24 months, respectively. The median overall survival was 11 months after GKRS (range, 6 days-113 months). Multivariate analysis showed that the pre-GKRS Karnofsky performance status, leptomeningeal seeding prior to initial GKRS, and multiple metastatic lesions were significant prognostic factors for reduced overall survival (hazard risk=1.94, p=0.001, hazard risk=7.13, p<0.001, and hazard risk=1.46, p=0.046, respectively). Conclusion : GKRS has shown to be an effective and safe treatment modality for treating brain metastases of primary breast cancer. Most metastatic brain lesions initially respond to GKRS, though, many patients have further CNS progression in subsequent periods. Patients with poor Karnofsky performance status and multiple metastatic lesions are at risk of CNS progression and poor survival, and a more frequent and strict surveillance protocol is suggested in such high-risk groups.

Differential Diagnosis of Chemical-induced Hepatobiliary Toxicities Using a New Hepatobiliary Imaging Agent in Mice

  • Ryu, Chong-Kun;Pie, Jae-Eun;Choe, Jae-Gol;Cheon, Joon;Sohn, Jeong-Won;Jurgen Seidel;David S. Paik;Michael V. Green;Chang H. Paik;Kim, Meyoung-Kon
    • Environmental Mutagens and Carcinogens
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    • v.21 no.1
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    • pp.1-8
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    • 2001
  • We have synthesized $^{99m}$Tc-mercaptoacetyltriglycine (MAG3)-biocytin as a new imaging agent for hepatobiliary scintigraphy. The aim of this study was to evaluate the usefulness of $^{99m}$Tc-MAG3-biocytin scintigraphy in differentiating carbon tetrachloride ( $CCl_4$)-induced hepatotoxicity from $\alpha$-naphthylisothiocyanate (ANIT)-induced cholestasis in mice, which reflecting the differential diagnosis of neonatal jaundice caused by neonatal hepatitis from congenital biliary atresia in humans. Methods: Balb/c mice (female, 20 g, n=4-6) were pretreated with $CCl_4$(0.5 or $1.0m\ell$/kg) and ANIT ($150 or 300 m\ell$/kg) 18 h before scintigraphy. Biochemical and histopathological examinations showed a pattern of typical acute hepatitis (increase of transaminases and hepatocellular necnsis) in $CCl_4$-treated mice and cholestasis (increase of alkaline phosphatase and ${\gamma}$-glutamyltransferase, and biliary hyperplasia) in ANIT-treated mice, respectively, Mice were fasted at least 4 hr prior to the intravenous injection of $^{99m}$Tc-MAG3-biocytin (18.5 MBq/20$\mu\textrm{g}$) in 2% human serum albumin in saline. Scintigraphy was performed with a ${\gamma}$-camera equipped with a 1-mm diameter pin-hole collimator for 30 min and images were acquired every 15 s. We compared the values of physical parameters, such as peak liver/heart ratio ($${\gamma}$_{max}$) and peak ratio time ($t_{max}$) far $^{99m}$Tc-MAG3-biocytin scintigraphy. Results: Scintigraphic parameters of the $CCl_4$-pretreated (0.5 $m\ell$/kg) group showed a 81.9% decrease of r$_{max}$, and 42.2% decrease of $t_{max}$, whereas the ANIT-pretreated ( $150m\ell$/kg) group showed a 53% decrease of $r_{max}$, and 2.36-fold increase of $t_{max}$, (P<0.05). These results demonstrate that the decrease of $r_{max}$ and the shortening of $t_{max}$ are characteristic features for hepatotoxicity, in contrast to the increase of $t_{max}$ and decrease of $r_{max}$ for biliary hyperplasia. Conclusion: $^{99m}$Tc-MAG3-biocytin hepatobiliary scintigraphy can distinguish hepatitis from cholestasis in mice model and may be similarly useful in humans which differentiating the cause of neonatal jaundice in clinical study.cal study.cal study.cal study.

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Effects of soybean extracts fermented with Lactic acid bacteria on immune system activity (유산균을 이용한 대두 발효 추출물이 면역계 활성에 미치는 영향)

  • Park, Byung-Doo;Kim, Hye-Ja
    • Journal of Society of Preventive Korean Medicine
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    • v.16 no.3
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    • pp.139-153
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    • 2012
  • Objectives : NK cells are spontaneously cytotoxic lymphocytes. These are not only important parts in the first line of defence against bacterial and viral infections of outside, but they may also play a critical role in chronic viral diseases. NK cells kill their targets spontaneously, without the need for prior sensitization and class I MHC restriction by the regulation of cytolytic functions and secretion of a variety of cytokines, such as interleukin-12(IL-12), MCP-1, IL-6, TNF-${\alpha}$, IFN-${\gamma}$. In addition, macrophage and NK cells cooperate through the production of cell mediates. These cooperation and modulation are one of major factors to prevent for evading immune surveillance of cancer. Hence, it could be assumed that if any candidate to enhance activities of macrophage and NK cell, it is considered as a potentially useful agents against cancer. Methods : In our study, to investigate effect of fermented soybean extracts by Lactic acid bacteria (SFE, soybean fermented extracts) work on intestinal immune cell to maintain general immune modulating and anti-cancer activity. We analyzed NK cytotoxicity assay and gene expressions of cytokine related with macrophage and NK cell activity. Results : In vitro experiment, SFE was verified as safety material for cell toxicicty to tumor cell strain without any toxicity of tumor growth inhibition and various cell strain. Effects of macrophage activity stimulating directly by SFE measured induced cytokine. The studies showed that IL-12 production by stimulation of SFE depended on concentration from 0.16mg/mL to 0.63mg/mL with non toxicity to cell, and it was the best activity at 0.63mg/mL. Besides, the effective concentration of SFE producing TNF-${\alpha}$ is similar to IL-12, but it was the best activity at 1.25mg/mL. The level of MCP-1, IL-6 and IFN-${\gamma}$ depended on concentration from 0.16mg/mL to 10mg/mL, IFN-${\gamma}$ showed the best activity at the effective concentration of 0.63mg/mL. With the result of NK cell activity measurement, the spleen cell of mouse injected SFE had 1.5 times higher killing effect than non injected cell. Conclusions : The result of this studies is that Soybean fermetated extracts(SFE) has possibility to immune aided material for the function not only inhibition of microbial infection to macrophage but also activity of adaption immune and cellular immune system.

A Study of Quality Control of Nuclear Medicine Counting System and Gamma Camera (핵의학 계측기기 및 감마카메라의 정도관리 연구)

  • 손혜경;김희중;정해조;정하규;이종두;유형식
    • Progress in Medical Physics
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    • v.12 no.2
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    • pp.103-112
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    • 2001
  • Purpose: The purpose of this study was to investigate the current status of performing nuclear medicine quality control in korea and to test selected protocols of quality control of nuclear medicine counting system and gamma camera. Materials and Methods: Fifty three hospitals were included to investigate the current status of nuclear medicine quality control in korea. The precision of dose calibrator and thyroid uptake system was measured with Tc-99m 35.52 MBq for 2 minuets and Tc-99m 5.14 MBq for 10 sec every one minute, respectively. The sensitivity of CeraSPECT$^{TM}$ with low energy high resolution parallel hole collimator was measured using two cylindrical phantoms with 15 cm in diameter and 12 cm and 30 cm in heights containing Tc-99m. The correction factor for sensitivity of CeraSPECT$^{TM}$ was calculated using phantom data. The system planar sensitivity, uniformity, count rate and spatial resolution were measured for Varicam gamma camera with low energy high resolution parallel hole collimator using 140 keV centered 20% energy window, 256$\times$256 or 512$\times$512 matrix sizes. Results: The quality control of dose calibrator and well counter were showed poor performance status. On the other hand, The quality control of gamma camera and other systems were showed relatively good performance status. The results of precision of dose calibrator and thyroid uptake system was $\pm$1.4%(<$\pm$5%) and chi^2=29.7(>16.92), respectively. It showed that the sensitivity of CeraSPECT$^{TM}$ was higher in center slices compared with the edge slices. After correction of nonuniform sensitivities for patient data, it showed better results compare with prior to correction. System planar sensitivity of Varicam gamma camera was 4.39 CPM/MBq. The observed count rate at 20% loss was 102,407 counts/sec (head 1), 113,427 counts/sec (head 2), when input count rate was 81,926 counts/sec (head 1), 90,741 counts/sec (head 2). The spatial resolution without scatter medium were 8.16 mm of FWHM and 14.85 mm of FWTM. The spatial resolution with scatter medium were 8.87 mm of FWHM and 18.87 mm of FWTM. Conclusion: It is necessary to understand the importance of quality control and to perform quality control of nuclear medicine devices.vices.

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Oral Exposure to Mercury Alters T Lymphocyte Phenotypes and Augments LPS-induced Cytokine Expressions in Spleen and Thymus (비장과 흉선의 림프세포와 LPS에 의해 유도된 사이토카인의 발현에 대한 수은의 영향)

  • 김상현;최철희;임종필;신태용
    • YAKHAK HOEJI
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    • v.48 no.4
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    • pp.241-246
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    • 2004
  • Mercury is a widespread metal and consequently there are large populations that currently exposed to low levels of mercury. Endotoxin is a component of the gram-negative bacteria and promotes inflammatory responses. The present study was designed to determine the impact of mercury on lymphocytes phenotype populations and endotoxin-induced inflammatory cytokine expressions in immune organ, spleen and thymus. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm of mercuric chloride in drinking water for 14 days and at the end of the treatment period, lipopolysaccharide (LPS, 0.5 mg/kg) was injected intraperitoneally 2 h prior to euthanasia. The dose-range of mercury used did not cause hepatotoxicity. Mercury at 7.5 and 37.5 ppm dose-dependently decreased CD3$^{+}$ T lymphocytes in spleen; both CD4$^{+}$ and CD8$^{+}$ single positive lymphocyte populations were decreased. Exposure to 7.5 and 37.5 ppm of mercury decreased the CD8$^{+}$ T lymphocyte population in the thymus, whereas double positive CD4$^{+}$ / CD8$^{+}$ and CD4$^{+}$ thymocytes were not altered. Mercury altered LPS-induced inflammatory cytokine gene expressions such as, tumor necrosis factor $\alpha$, interferon ${\gamma}$, and interleukin-12 in spleen and thymus. Results indicated that decreases in T lymphocyte populations in immune organs and altered cytokine gene expression may contribute to the immune-modulative effects of inorganic mercury.ganic mercury.

Derris scandens Benth Extract Potentiates Radioresistance of Hep-2 Laryngeal Cancer Cells

  • Hematulin, Arunee;Meethang, Sutiwan;Ingkaninan, Kornkanok;Sagan, Daniel
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1289-1295
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    • 2012
  • The use of herbal products as radiosensitizers is a promising approach to increase the efficacy of radiotherapy. However, adverse effects related to the use of herbal medicine on radiotherapy are not well characterized. The present study concerns the impact of Derris scandens Benth extract on the radiosensitivity of Hep-2 laryngeal cancer cells. Pretreatment with D. scandens extract prior to gamma irradiation significantly increased clonogenic survival and decreased the proportion of radiation-induced abnormal nuclei of Hep-2 cells. Furthermore, the extract was found to enhance radiation-induced G2/M phase arrest, induce Akt activation, and increase motility of Hep-2 cells. The study thus indicated that D. scandens extract potentiates radioresistance of Hep-2 cells, further demonstrating the importance of cellular background for the adverse effect of D. scandens extract on radiation response in a laryngeal cancer cell line.

Glioblastoma Multiforme with Subcutaneous Metastases, Case Report and Literature Review

  • Guo, Liemei;Qiu, Yongming;Ge, Jianwei;Zhou, Dongxue
    • Journal of Korean Neurosurgical Society
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    • v.52 no.5
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    • pp.484-487
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    • 2012
  • Glioblastoma multiforme (GBM) is the most common primary brain tumor and the most malignant astrocytoma in adults, with rare extra-cranial metastases, especially for subcutaneous metastases. It could be easily misdiagnosed as primary subcutaneous tumor. In this report, we describe a patient with pontine GBM who developed a subcutaneous swelling at the ipsilateral posterior cervical region 8 months after operation, and the pathological and immunocytochemical examination carry the same characteristics as the primary intracranial GBM cells, which defined it as subcutaneous metastasis. GBM with subcutaneous metastasis is extremely rare, and knowledge of a prior intracranial GBM, pathological examinations and immunocytochemical tests with markers typically expressed by GBM are of vital importance for the diagnosis of GBM metastasis. Surgical resection of subcutaneous swelling, followed by chemotherapy and radiotherapy, could be the best strategy of treatment for the patients with GBM subcutaneous metastasis.

Recrystallization Behavior in the Two-Phase (α+γ) Region of Micro-Alloyed Steels (페라이트-오스테나이트 2상역 온도에서 미량합금 원소가 첨가된 탄소강의 재결정 거동)

  • Lee, Seung-Yong;Kim, Ji-Yeon;Hwang, Byoungchul
    • Korean Journal of Materials Research
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    • v.26 no.11
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    • pp.583-589
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    • 2016
  • In this study, recrystallization behaviors in the two-phase (${\alpha}+{\gamma}$) region of micro-alloyed steels such as Base, Nb, TiNbV and CAlN were investigated in terms of flow stress, microstructure and associated grain boundary characteristics. The flow stress of all specimens reached peak stress and gradually decreased, which means that recrystallization or recovery of proeutectoid deformed ferrite and recovery or transformation to ferrite of deformed austenite occurred by thermal activation. The precipitation of carbide or nitride via the addition of micro-alloying elements, because it reduced prior austenite grain size upon austenitization, promoted transformation of austenite to ferrite and increased flow stress. The strain-induced precipitation under deformation in the two-phase region, on the other hand, increased the flow stress when the micro-alloying elements were dissolved during austenitization. The recrystallization of the Nb specimen was more effectively retarded than that of the TiNbV specimen during deformation in the two-phase region.

Power Investigation of the Entropy-Based Test of Fit for Inverse Gaussian Distribution by the Information Discrimination Index

  • Choi, Byungjin
    • Communications for Statistical Applications and Methods
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    • v.19 no.6
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    • pp.837-847
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    • 2012
  • Inverse Gaussian distribution is widely used in applications to analyze and model right-skewed data. To assess the appropriateness of the distribution prior to data analysis, Mudholkar and Tian (2002) proposed an entropy-based test of fit. The test is based on the entropy power fraction(EPF) index suggested by Gokhale (1983). The simulation results report that the power of the entropy-based test is superior compared to other goodness-of-fit tests; however, this observation is based on the small-scale simulation results on the standard exponential, Weibull W(1; 2) and lognormal LN(0:5; 1) distributions. A large-scale simulation should be performed against various alternative distributions to evaluate the power of the entropy-based test; however, the use of a theoretical method is more effective to investigate the powers. In this paper, utilizing the information discrimination(ID) index defined by Ehsan et al. (1995) as a mathematical tool, we scrutinize the power of the entropy-based test. The selected alternative distributions are the gamma, Weibull and lognormal distributions, which are widely used in data analysis as an alternative to inverse Gaussian distribution. The study results are provided and an illustrative example is analyzed.