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Survey of Operation and Status of the Human Research Protection Program (HRPP) in Korea (2019) (임상시험 및 대상자보호프로그램의 운영과 현황에 대한 설문조사 연구(2019))

  • Maeng, Chi Hoon;Lee, Sun Ju;Cho, Sung Ran;Kim, Jin Seok;Rha, Sun Young;Kim, Yong Jin;Chung, Jong Woo;Kim, Seung Min
    • The Journal of KAIRB
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    • v.2 no.2
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    • pp.37-48
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    • 2020
  • Purpose: The purpose of this study is to assess the operational status and level of understanding among IRB and HRPP staffs at a hospital or a research institute to the HRPP guideline set by the Ministry of Food and Drug Safety (MFDS) and to provide recommendations. Methods: Online survey was distributed among members of Korean Association of IRB (KAIRB) through each IRB office. The result was separated according to topic and descriptive statistics was used for analysis. Result: Survey notification was sent out to 176 institutions and 65 (37.1%) institutions answered the survey by online. Of 65 institutions that answered the survey; 83.1% was hospital, 12.3% was university, 3.1% was medical college, 1.5% was research institution. 23 institutions (25.4%) established independent HRPP offices and 39 institutions (60.0%) did not. 12 institutions (18.5%) had separate IRB and HRPP heads, 21 (32.3%) institutions separated business reporting procedure and person in charge, 12 institutions separated the responsibility of IRB and HRPP among staff, and 45 institutions (69.2%) had audit & non-compliance managers. When asked about the most important basic task for HRPP, 23% answered self-audit. And according to 43.52%, self-audit was also the most by both institutions that operated HRPP and institutions that did not. When basic task performance status was analyzed, on average, the institutions that operated HRPP was 14% higher than institutions that only operated IRB. 9 (13.8%) institutions were evaluated and obtained HRPP accreditation from MFDS and the most common reason for obtaining the accreditation was to be selected as Institution for the education of persons conducting clinical trial (6 institutions). The most common reason for not obtaining HRPP accreditation was because of insufficient staff and limited capacity of the institution (28%). Institutions with and without a plan to be HRPP accredited by MFDS were 20 (37.7%) each. 34 institutions (52.3%) answered HRPP evaluation method and accreditation by MFDS was appropriate while 31 institutions (47.7%) answered otherwise. 36 institutions answered that HRPP evaluation and accreditation by MFDS was credible while 29 institutions (44.5%) answered that HRPP evaluation method and accreditation by MFDS was not credible. Conclusion: 1. MFDS's HRPP accreditation program can facilitate the main objective of HRPP and MFDS's HRPP accreditation program should be encouraged to non-tertiary hospitals by taking small staff size into consideration and issuing accreditation by segregating accreditation. 2. While issuing Institution for the education of persons conducting clinical trial status as a benefit of MFDS's HRPP accreditation program, it can also hinder access to MFDS's HRPP accreditation program. It should also be considered that the non-contact culture during COVID-19 pandemic eliminated time and space limitation for education. 3. For clinical research conducted internally by an institution, internal audit is the most effective and sole method of protecting safety and right of the test subjects and integrity for research in Korea. For this reason, regardless of the size of the institution, an internal audit should be enforced. 4. It is necessary for KAIRB and MFDSto improve HRPP awareness by advocating and educating the concept and necessity of HRPP in clinical research. 5. A new HRPP accreditation system should be setup for all clinical research with human subjects, including Investigational New Drug (IND) application in near future.

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Research to Establish a Common Standard for Assent by Assessing the Current State of the Assent Process and Conducting Interviews with Pediatrician/Pediatric Neurologist (소아승낙 현황조사와 소아청소년과/소아신경과 전문의를 대상으로 면담조사를 통한 소아승낙서 공통기준 수립 연구)

  • Yoon Jin Lee;Sun Ju Lee;Su Jin Kang;Dae Ho Lee;Kyun-Seop Bae;Jong Woo Chung;Byung Soo Kim;Jin Seok Kim;Myung Ah Lee
    • The Journal of KAIRB
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    • v.6 no.1
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    • pp.5-16
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    • 2024
  • Purpose: The purpose of this study is to investigate the current status of pediatric assent in nationwide hospitals and to assess the children's comprehension for pediatric assent by interviewing pediatricians/pediatric neurologists to determine whether children of the age (elementary and middle school students) can understand the purpose, risks, benefits, and concepts of voluntary participation in clinical research described in the assent form, and to help improve the administrative efficiency of multicenter clinical trials. Methods: The status of pediatric assent was surveyed online using Google Forms at 141 university hospitals with administrative staff who are members of the Institutional Review Board (IRB) administrative staff subcommittee with in Korean Association of Institutional Review Boards (KAIRB). Additionally, face-to-face interviews were conducted with 7 pediatricians/pediatric neurologists. Survey and interview responses were summarized using descriptive statistics. Results: Out of the 141 institutions surveyed, 35 institutions (24.8%) responded. Among them, 30 institutions (85.7%) reported having age criteria for acquiring pediatric assent forms in the case of children. The age range for pediatric assent acquisition have been from 7 years old to 12 years old (15 institutions, 50%), and from 7 years old to 15 years old (7 institutions, 23.3%). Nine institutions (25.7%) have had criteria for obtaining both parents' consent in cases involving the participation of children. Nineteen institutions (54.3%) have had checklists or guidelines available for use by IRB members in study protocols involving vulnerable research subjects. Three pediatricians/pediatric neurologists have believed that upper-grade elementary school students (5th-6th grade) could comprehensively understand informed consent forms. Two have believed that middle school students would be able to understand them if they included personal information. Two pediatricians/pediatric neurologists have believed that even lower-grade elementary school students (1st-4th grade) could understand the explanations if they were made simpler. Conclusion: It is suggested that not only elementary school students (7-12 years old) but also middle school students (13-15 years old) should receive pediatric assent forms, as it would facilitate a comprehensive understanding of the forms. To enhance the comprehension of assent form content, it is necessary to use age-appropriate words, language, and expressions in the forms hospital. It is also recommended to create comics or videos to make the content of the assent forms more accessible for children.

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Comparison of Carcass Characteristics, Meat Quality, and Sensory Quality Characteristics of Male Laying Hens, Meat-Type Chickens under Identical Rearing Conditions (동일 사육 조건에서 산란계 수평아리 및 육용계의 도체 특성, 계육 품질 및 관능적 특성 비교)

  • Woo-Do Lee;Hyunsoo Kim;Hee-Jin Kim;IkSoo Jeon;Jiseon Son;Eui-Chul Hong;Hye Kyung Shin;Hwan-Ku Kang
    • Korean Journal of Poultry Science
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    • v.51 no.1
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    • pp.11-19
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    • 2024
  • This study was conducted to evaluate the potential of using laying hens as meat type chickens. Male broiler (Ross 308, R3), laying hens (Hy-Line Brown, HL), and Korean native chickens (Hanhyup-3, H3) were used, and 100 heads of each were prepared. Carcass characteristics, meat quality, and sensory quality characteristics were compared as analysis items. The rearing environment and feed for all treatments were identical to the broiler rearing manual, and the lighting system was maintained at 23L:1D. Feed and water were provided ad libitum. The test ended when the average weight of each treatment group reached 1.5 kg, and individuals of similar weight were randomly selected and compared. As a result of this study, the live weight of the selected individuals was approximately 1.5 kg, which was similar for all treatments (P>0.05). However, carcass weight and ratio and breast meat production were highest in R3, while HL had higher ratios of legs, wings, and neck (P<0.05). The H3 group showed high pH and WHC levels and low cooking loss, and R3 improved chicken meat color (P<0.05). In particular, the fat content in meat was lowest in HL (P<0.01). Nucleic acid substances ATP, Hx, ADP, AMP, and INO were abundant in R3, and IMP content was highest in HL (P<0.05). In sensory evaluation, all treatments showed similar characteristics and overall preferences (P>0.05). Based on the findings, it appears that HL, a male laying hen, produces meat with unique characteristics such as low fat content and high IMP content.

Analysis of Intervention in Activities of Daily Living for Stroke Patients in Korea: Focusing on Single-Subject Research Design (국내 뇌졸중 환자를 대상으로 한 일상생활활동 중재 연구 분석: 단일대상연구 설계를 중심으로)

  • Sung, Ji-Young;Choi, Yoo-Im
    • Therapeutic Science for Rehabilitation
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    • v.13 no.1
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    • pp.9-21
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    • 2024
  • Objective : The purpose of this study was to confirm the characteristics and quality of a single-subject research that conducted interventions to improve activities of daily living (ADL) in stroke patients. Methods : 'Stroke,' 'activities of daily living,' and 'single-subject studies' were searched as keywords among papers published in the last 15 years between 2009 and 2023 among Research Information Sharing Service, DBpia, and e-articles. A total of nine papers were examined for the characteristics and quality before analysis. Results : The independent variables applied to improve ADL included constraint-induced therapy, mental practice for performing functional activities, virtual reality-based task training, subjective postural vertical training without visual feedback, bilateral upper limb movement, core stability training program, traditional occupational therapy and neurocognitive rehabilitation, smooth pursuit eye movement, neck muscle vibration, and occupation-based community rehabilitation. Assessment of Motor and Process Skills was the most common evaluation tool for measuring dependent variables, with four articles, and Modified Barthel Index and Canadian Occupational Performance Measure were two articles each. As a result of confirming the qualitative level of the analyzed papers, out of a total of nine studies, seven studies were at a high level, two at a moderate level, and none were at a low level. Conclusion : Various types of rehabilitation treatments have been actively applied as intervention methods to improve the daily life activities of stroke patients; the quality level of single-subject studies applying ADL interventions was reliable.

Multi-classification of Osteoporosis Grading Stages Using Abdominal Computed Tomography with Clinical Variables : Application of Deep Learning with a Convolutional Neural Network (멀티 모달리티 데이터 활용을 통한 골다공증 단계 다중 분류 시스템 개발: 합성곱 신경망 기반의 딥러닝 적용)

  • Tae Jun Ha;Hee Sang Kim;Seong Uk Kang;DooHee Lee;Woo Jin Kim;Ki Won Moon;Hyun-Soo Choi;Jeong Hyun Kim;Yoon Kim;So Hyeon Bak;Sang Won Park
    • Journal of the Korean Society of Radiology
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    • v.18 no.3
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    • pp.187-201
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    • 2024
  • Osteoporosis is a major health issue globally, often remaining undetected until a fracture occurs. To facilitate early detection, deep learning (DL) models were developed to classify osteoporosis using abdominal computed tomography (CT) scans. This study was conducted using retrospectively collected data from 3,012 contrast-enhanced abdominal CT scans. The DL models developed in this study were constructed for using image data, demographic/clinical information, and multi-modality data, respectively. Patients were categorized into the normal, osteopenia, and osteoporosis groups based on their T-scores, obtained from dual-energy X-ray absorptiometry, into normal, osteopenia, and osteoporosis groups. The models showed high accuracy and effectiveness, with the combined data model performing the best, achieving an area under the receiver operating characteristic curve of 0.94 and an accuracy of 0.80. The image-based model also performed well, while the demographic data model had lower accuracy and effectiveness. In addition, the DL model was interpreted by gradient-weighted class activation mapping (Grad-CAM) to highlight clinically relevant features in the images, revealing the femoral neck as a common site for fractures. The study shows that DL can accurately identify osteoporosis stages from clinical data, indicating the potential of abdominal CT scans in early osteoporosis detection and reducing fracture risks with prompt treatment.

A Study on the Costume Style of Civil Servants' Stone Images Erected at Tombs of the Kings for Yi-dynasty (조선왕조(朝鮮王朝) 왕릉(王陵) 문인석상(文人石像)의 복식형태(服飾形態)에 관한 연구)

  • Kwon, Yong-Ok
    • Journal of the Korean Society of Costume
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    • v.4
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    • pp.87-114
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    • 1981
  • A costume reveals the social characteristics of the era in which it is worn, thus we can say that the history of change of the costume is the history of change of the living culture of the era. Since the Three States era, the costume structure of this country had been affected by the costume system of the China's historical dynasties in the form of the grant therefrom because of geographical conditions, which affection was conspicuous for the bureaucrat class, particularly including but not limited to the Kings' familities. Such a grant of the costume for the bureaucrat class (i.e., official uniform) was first given by the Dang-dynasty at the age of Queen Jinduck, the 28th of the Shilla-dynasty. Since then, the costume for the bureaucrats had consecutively been affected as the ages had gone from the unified Shilla, to the Koryo and to the Yi-dynasty. As the full costumes officially used by government officials (generally called "Baek Gwan") in the Yidynasty, there existed Jo-bok, Gong-bok and Sang-bok. Of such official costumes, Gong-bok was worn at the time of conducting official affairs of the dynasty, making a respectful visit for the expression of thanks or meeting diplomatic missions of foreign countries. It appears no study was made yet with regard to the Gong-bok while the studies on the Jo-bok and the Sangbok were made. Therefore, this article is, by rendering a study and research on the styles of costumes of civil servants' stone images erected at the Kings' tombs of the Yi-dynasty, to help the persons concerned understand the Gong-bok, one of the official costume for Baek Kwan of that age and further purports to specifically identify the styles and changes of the Gong-bok, worn by Baek Gwan during the Yi-dynasty, consisting of the Bok-doo (a hat, four angled and two storied with flat top), Po (gown), Dae (belt), and Hol (small and thin plate which was officially held by the government officials in hand, showing the courtesy to and writing brief memorandums before the King) and Hwa (shoes). For that purpose, I investigated by actually visiting the tombs of the Kings of the Yi-dynasty including the Geonwon-neung, the tomb of the first King Tae-jo and the You-neung, the tomb of the 27th King Soon-jong as well as the tombs of the lawful wives and concubines of various Kings, totalling 29 tombs and made reference to relevant books and records. Pursuant. to this study, of the 29 Kings' tombs the costume styles of civil servants' stone images erected at the 26 Kings' tombs are those of Gong-bok for Baek-gwan of the Yi-dynasty wearing Bok-doo as a hat and Ban-ryeong or Dan-ryenog Po as a gown with Dae, holding Hol in hand and wearing shoes. Other than those of the 26 tombs, the costume styles of the Ryu-neung, the tomb of the Moon-jo who was the first son of 23rd King Soon-jo and given the King's title after he died and of the You-neung, the tomb of the 27th King Soon-jong are those of Jobok with Yang-gwan (a sort of hat having stripes erected, which is different from the Bok-doo), and that of the Hong-neung, the tomb of the 26th King Go-jong shows an exceptional one wearing Yang-gwan and Ban-ryeong Po ; these costume styles other than Gongbok remain as the subject for further study. Gong-bok which is the costume style of civil servants' stone images of most of the Kings' tombs had not been changed in its basic structure for about 500 years of the Yi-dynasty and Koryo categorized by the class of officials pursuant to the color of Po and materials of Dae and Hol. Summary of this costume style follows: (1) Gwan-mo (hat). The Gwan-mo style of civil servants' stone images of the 26 Kings' tombs, other than Ryu-neung, Hong-neung and You-neung which have Yang-gwan, out of the 29 Kings' tombs of the Yi-dynasty reveals the Bok-doo with four angled top, having fore-part and back-part divided. Back part of the Bok-doo is double the fore-part in height. The expression of the Gak (wings of the Bokdoo) varies: the Gyo-gak Bok-doo in that the Gaks, roundly arisen to the direction of the top, are clossed each other (tombs of the Kings Tae-jong), the downward style Jeon-gak Bok-doo in that soft Gaks are hanged on the shoulders (tombs of the Kings Joong-jong and Seong-jong) and another types of Jeon-gak Bok-doo having Gaks which arearisen steeply or roundly to the direction of top and the end of which are treated in a rounded or straight line form. At the lower edge one protrusive line distinctly reveals. Exceptionally, there reveals 11 Yang-gwan (gwan having 11 stripes erected) at the Ryu-neung of the King Moon-jo, 9 Yang-gwan at the Hong-neung of the King Go-jong and 11 Yang-gwan at the You-neung of the King Soon-jong; noting that the Yang-gwan of Baek Kwan, granted by the Myeong-dynasty of the China during the Yi-dynasty, was in the shape of 5 Yang-gwan for the first Poom (class) based on the principle of "Yideung Chaegang" (gradual degrading for secondary level), the above-mentioned Yang-gwans are very contrary to the principle and I do not touch such issue in this study, leaving for further study. (2) Po (gown). (a) Git (collar). Collar style of Po was the Ban-ryeong (round collar) having small neck-line in the early stage and was changed to the Dan-ryeong (round collar having deep neck-line) in the middle of the: dynasty. In the Dan-ryeong style of the middle era (shown at the tomb of the King Young-jo); a, thin line such as bias is shown around the internal side edge and the width of collar became wide a little. It is particularly noted that the Ryu-neung established in the middle stage and the You-neung in the later stage show civil servants in Jo-bok with the the Jikryeong (straight collar) Po and in case of the Hong-neung, the Hong-neung, the tomb of the King Go-jong, civil servants, although they wear Yang-gwan, are in the Ban-ryeong Po with Hoo-soo (back embroidery) and Dae and wear shoes as used in the Jo-bok style. As I could not make clear the theoretical basis of why the civil servants' costume styles revealed, at these tombs of the Kings are different from those of other tombs, I left this issue for further study. It is also noted that all the civil servants' stone images show the shape of triangled collar which is revealed over the Godae-git of Po. This triangled collar, I believe, would be the collar of the Cheomri which was worn in the middle of the Po and the underwear, (b) Sleeve. The sleeve was in the Gwan-soo (wide sleeve) style. having the width of over 100 centimeter from the early stage to the later stage arid in the Doo-ri sleeve style having the edge slightly rounded and we can recognize that it was the long sleeve in view of block fold shaped protrusive line, expressed on the arms. At the age of the King Young-jo, the sleeve-end became slightly narrow and as a result, the lower line of the sleeve were shaped curved. We can see another shape of narrow sleeve inside the wide sleeve-end, which should be the sleeve of the Cheom-ri worn under the Gong-bok. (c) Moo. The Moo revealed on the Po of civil servants' stone images at the age of the King Sook-jong' coming to the middle era. Initially the top of the Moo was expressed flat but the Moo was gradually changed to the triangled shape with the acute top. In certain cases, top or lower part of the Moo are not reveald because of wear and tear. (d) Yeomim. Yeomim (folding) of the Po was first expressed on civil servants' stone images of the Won-neung, the tomb of the King Young-jo and we can seemore delicate expression of the Yeomim and Goreum (stripe folding and fixing the lapel of the Po) at the tomb of the Jeongseong-wanghoo, the wife of the King Young-jo, At the age of the King Soon-jo, we can see the shape of Goreum similar to a string rather than the Goreum and the upper part of the Goreum which fixes Yeomim was expressed on the right sleeve. (3) Dae. Dae fixed on the Po was placed half of the length of Po from the shoulders in the early stage. Thereafter, at the age of the King Hyeon-jong it was shown on the slightly upper part. placed around one third of the length of Po. With regard to the design of Dae, all the civil servants' stone images of the Kings' tombs other than those of the Geonwon-neung of the King Tae-jo show single or double protrusive line expressed at the edge of Dae and in the middle of such lines, cloud pattern, dangcho (a grass) pattern, chrysanthemum pattern or other various types of flowery patterns were designed. Remaining portion of the waist Dae was hanged up on the back, which was initially expressed as directed from the left to the right but thereafter expressed. without orderly fashion,. to the direction of the left from the right and vice versa, Dae was in the shape of Yaja Dae. In this regard, an issue of when or where such a disorderly fashion of the direction of the remaining portion of waist Dae was originated is also presented to be clarified. In case of the Ryuneung, Hong-neung and You-neung which have civil servants' stone images wearing exceptional costume (Jo-bok), waist Dae of the Ryu-neung and Hong-neung are designed in the mixture of dual cranes pattern, cosecutive beaded pattern and chrvsenthemum pattern and that of You-neung is designed in cloud pattern. (4) Hol. Although materials of the Hol held in hand of civil servants' stone images are not identifiable, those should be the ivory Hol as all the Baek Gwan's erected as stone images should be high class officials. In the styles, no significant changes were found, however the Hol's expressed on civil servants' stone images of the Yi-dynasty were shaped in round top and angled bottom or round top and bottom. Parcicularly, at the age of the King Young-jo the Hol was expressed in the peculiar type with four angles all cut off. (5) Hwa (shoes). As the shoes expressed on civil servants' stone images are covered with the lower edges of the Po, the styles thereof are not exactly identifiable. However, reading the statement "black leather shoes for the first class (1 Poom) to ninth class (9 Poom)," recorded in the Gyeongkook Daejon, we can believe that the shoes were worn. As the age went on, the front tips of the shoes were soared and particularly, at the Hong-neung of the King Go-jong the shoes were obviously expressed with modern sense as the country were civilized.

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Dosimetric evaluation of using in-house BoS Frame Fixation Tool for the Head and Neck Cancer Patient (두경부암 환자의 양성자 치료 시 사용하는 자체 제작한 BoS Frame 고정장치의 선량학적 유용성 평가)

  • Kim, kwang suk;Jo, kwang hyun;Choi, byeon ki
    • The Journal of Korean Society for Radiation Therapy
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    • v.28 no.1
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    • pp.35-46
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    • 2016
  • Purpose : BoS(Base of Skull) Frame, the fixation tool which is used for the proton of brain cancer increases the lateral penumbra by increasing the airgap (the distance between patient and beam jet), due to the collision of the beam of the posterior oblique direction. Thus, we manufactured the fixation tool per se for improving the limits of BoS frame, and we'd like to evaluate the utility of the manufactured fixation tool throughout this study. Materials and Methods : We've selected the 3 patients of brain cancer who have received the proton therapy from our hospital, and also selected the 6 beam angles; for this, we've selected the beam angle of the posterior oblique direction. We' ve measured the planned BoS frame and the distance of Snout for each beam which are planned for the treatment of the patient using the BoS frame. After this, we've proceeded with the set-up that is above the location which was recommended by the manufacturer of the BoS frame, at the same beam angle of the same patient, by using our in-house Bos frame fixation tool. The set-up was above 21 cm toward the superior direction, compared to the situation when the BoS frame was only used with the basic couch. After that, we've stacked the snout to the BoS frame as much as possible, and measured the distance of snout. We've also measured the airgap, based on the gap of that snout distance; and we've proceeded the normalization based on each dose (100% of each dose), after that, we've conducted the comparative analysis of lateral penumbra. Moreover, we've established the treatment plan according to the changed airgap which has been transformed to the Raystation 5.0 proton therapy planning system, and we've conducted the comparative analysis of DVH(Dose Volume Histogram). Results : When comparing the result before using the in-house Bos frame fixation tool which was manufactured for each beam angle with the result after using the fixation tool, we could figure out that airgap than when not used in accordance with the use of the in-house Bos frame fixation tool was reduced by 5.4 cm ~ 15.4 cm, respectively angle. The reduced snout distance means the airgap. Lateral Penumbra could reduce left, right, 0.1 cm ~ 0.4 cm by an angle in accordance with decreasing the airgap while using each beam angle in-house Bos frame fixation tool. Due to the reduced lateral penumbra, Lt.eyeball, Lt.lens, Lt. hippocampus, Lt. cochlea, Rt. eyeball, Rt. lens, Rt. cochlea, Rt. hippocampus, stem that can be seen that the dose is decreased by 0 CGE ~ 4.4 CGE. Conclusion : It was possible to reduced the airgap by using our in-house Bos frame fixation tool for the proton therapy; as a result, it was possible to figure out that the lateral penumbra reduced. Moreover, it was also possible to check through the comparative analysis of the treatment plan that when we reduce the lateral penumbra, the reduction of the unnecessary irradiation for the normal tissues. Therefore, Using the posterior oblique the Brain cancer proton therapy should be preceded by decreasing the airgap, by using our in-house Bos frame fixation tool; also, the continuous efforts for reducing the airgap as much as possible for the proton therapy of other area will be necessary as well.

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Regulatory Mechanism of Insulin-Like Growth Factor Binding Protein-3 in Non-Small Cell Lung Cancer (비소세포성 폐암에서 인슐린 양 성장 인자 결합 단백질-3의 발현 조절 기전)

  • Chang, Yoon Soo;Lee, Ho-Young;Kim, Young Sam;Kim, Hyung Jung;Chang, Joon;Ahn, Chul Min;Kim, Sung Kyu;Kim, Se Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.5
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    • pp.465-484
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    • 2004
  • Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.

A Clinical Study of Tsutsugamushi Fever in Children during 1997~2000 in the Western Kyungnam Province (최근 4년간 서부 경남지역의 소아에서 발생한 쯔쯔가무시열의 임상적 고찰)

  • Ju, Hye Young;Lee, Jun Su;Kim, Jeong Hee;Yoo, Hwang Jae;Kim, Chun Soo
    • Pediatric Infection and Vaccine
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    • v.8 no.2
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    • pp.213-221
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    • 2001
  • Propose : Tsutsugamushi fever is a acute febrile disease, which is caused by O. tsutsugamushi. Recently, this disease is increasingly reported in children. This study was undertaken to investigate clinical features of tsutsugamushi fever in children. Methods : This study involved 17 children with tsutsugamushi fever who were admitted to Masan Samsung hospital between September 1997 and December 2000. We investigated the age, sex ratio, clinical manifestations, laboratory findings, response of therapy and prognosis. Results : The age of patients was $6.9{\pm}3.6$ years, ranging from 6 months to 12 years and male predilection(58.8%) was noted and all cases of patients occured in October or November. The most common symptoms were fever in all cases and headache in 8(47.1%). The most common signs were skin rash in all cases, eschar in 14(82.4%) and lymphadenopathy 8(47.1%). Locations of the eschars were back and inguinal area in each 3 cases, neck and chest in each 2, popliteal area in 2, scalp and thigh in each 1. Laboratory findings included anemia in 1 case, leukopenia and thrombocytopenia in each 5, hematuria and proteinuria in each 1, ESR elevation in 2 and positive CRP in 12, AST elevation in 9 and ALT elevation in 7. Serologic diagnosis was made by passive hemagglutination assay(PHA) in 8 cases(47%) on admission, 4 cases in initial negative group were performed follow-up test at 2nd or 3rd weeks of illness and then all cases of 4 were converted to positive reaction. Clinical improvement was noticed in all cases after treatment to chloramhenicol or doxycycline. Mean duration for defervescence after treatment was $1.4{\pm}0.8$ days. Complications were interstitial pneumonia in 1 case and aseptic meningitis in 3, but all cases of patients were recovered without sequelae or recurrence. Conclusions : Tsutsugamushi fever in children was similiar to adult in the clinical features except male predilection. Early diagnosis and empirical treatment based on clinical manifestations such as fever, skin rash, eschar, lymphadenopathy is important and serologic diagnosis need to perform follow-up test at 2nd or 3rd weeks of illness.

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Clinical Study of Tuberculous Meningitis in Children (소아 결핵성 뇌막염의 임상적 고찰)

  • Kim, Woo Sik;Kim, Jong Hyun;Kim, Dong Un;Lee, Won Bae;Kang, Jin Han
    • Pediatric Infection and Vaccine
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    • v.4 no.1
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    • pp.64-72
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    • 1997
  • Purpose : The incidence of tuberculous meningitis in Korean children has been markedly decreased after 1980s, but this disease has still occurred with low rate. Therefore, it may be suspected that delayed diagnosis and treatment will be happened because of lacking of clinical experiences and indistinguishable other meningitis, so it is important to make early diagnosis and treatment of tuberculous meningitis concerning with the prognosis. In this aspect, we conducted study to concern and investigate sustainly about the diagnostic criteria, clinical characteristics, radiological findings, complications, and prognosis of typical or atypical tuberculous meningitis in children. Methods : Forty four children who were hospitalized and treated due to tuberculous meningitis in pediatric wards of Our Lady of Mercy Hospital, St. Holy Hospital, St. Vincent Hospital and Uijungbu St. Mary Hospital from January 1985 to June 1996 were included in this study. We reviewed medical records of these patients retrospectively. Results : 1) The tuberculous meningitis has occured continuosly since mid-1980s. The highest 2) The diagnosis was made by contact history of active tuberculous patients, positive tuberculin test, responses of antituberculous antibiotics and discovery of Mycobacterium tuberculosis from CSF or other specimens. Among patients, 7 children(16%) were not vaccinated with BCG, and only 18 children(40%) were positive in tuberculin test. 3) The symptoms and signs of our patients on initial examinations were fever, vomiting, headache, lethargy, poor feeding, weight loss, neck stiffness, convulsion, abdominal pain and motor deficits. 4) The findings of initial CSF samples revealed leukocyte $239.5/mm^3$(mean) with lymphocyte predominant, elevated protein levels(mean;259.5mg%) and low sugar level(mean;40.7mg%). And the ratio of CSF/blood sugar was 0.407. But, atypical CSF findings were seen in 31.8% patients. 5) On brain imaging study, 34 out of 39 children had findings of hydrocephalus, basilar meningeal enhancement, infarction and subarachnoidal inflammations etc. On chest X-ray, the findings of miliary tuberculosis(34.1%), normal finding(29.5%), parenchymal infiltrations (11.4%) and calcifications(9.1%) were showed. 6) In neurological clinical stage, there were twenty-six children(59%) in stage 1, fourteen children(32%) in stage 2 and four children(9%) in stage 3. The late sequeles were encountered by 29.5% with mild and 4.6% with severe neurological injury. The most common neurological injury was quadriplegia and the mortality rate was 6.8%. 7) The SIADH was developed in 20 children(45.5%) after the 4th hospital day. Half of all SIADH patients were symptomatic. Conclusion : Tuberculosis meningitis is still an important extrapulmonary disease with high morbidity and mortality. Early diagnosis with clinical contact history of active tuberculosis and radiological imaging examinations and early treatments are essential in order to prevent and decrase the rate of late sequeles and death.

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