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Oncolytic Viruses - A New Era for Cancer Therapy (종양 용해성 바이러스-암 치료에서의 새 시대)

  • Ngabire, Daniel;Niyonizigiye, Irvine;Kang, Min-jae;Kim, Gun-Do
    • Journal of Life Science
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    • v.29 no.7
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    • pp.824-835
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    • 2019
  • In recent decades, oncolytic viruses (OVs) have extensively been investigated as a potential cancer drug. Oncolytic viruses have primarily the unique advantage in the fact that they can only infect and destroy cancer cells. Secondary, oncolytic viruses induce the activation of specific adaptive immunity which targets tumor-associated antigens that were hidden during the initial cancer progression. In 2015, one genetically modified oncolytic virus, talimogene laherparepvec (T-VEC), was approved by the American Food and Drug Administration (FDA) for the treatment of melanoma. Currently, various oncolytic viruses are being investigated in clinical trials as monotherapy or in combination with preexistent cancer therapies like immunotherapy, radiotherapy or chemotherapy. The efficacy of oncolytic virotherapy relies on the balance between the induced anti-tumor immunity and the anti-viral response. Despite the revolutionary outcome, the development of oncolytic viruses for the treatment of cancer faces a number of obstacles such as delivery method, neutralizing antibodies and induction of antiviral immunity due to the complexity, variability and reactivity of tumors. Intratumoral administration has been successful reducing considerably solid tumors with no notable side effects unfortunately some tumors are not accessible (brain) and require a systemic administration of the oncolytic viruses. In order to overcome these hurdles, various strategies to enhance the efficacy of oncolytic viruses have been developed which include the insertion of transgenes or combination with immune-modulatory substances.

The Legal Interest of Doctor's Duty to Inform and the Compensation to Damages for Non-pecuniary Loss (의료행위에서 설명의무의 보호법익과 설명의무 위반에 따른 위자료 배상)

  • Yi, Jaekyeong
    • The Korean Society of Law and Medicine
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    • v.21 no.2
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    • pp.37-73
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    • 2020
  • Medical practice with medical adaptability is not illegal. Consent to medical practice is also not intended to exclude causes of Illegality. The patient's consent to medical practice is the exercise of the right to self-determination, and the patient's right to self-determination is take shape through the doctor's information. If a doctor violates his duty to inform, failure to inform or lack of inform constitutes an act of illegality of omission in itself. As a result, the legal interest of self-determination is violated. The patient has the right to know and make decisions on his or her own, even when it is not connected to the benefit of life and body as the subject of the body. If that infringed and lost, the non-property damage shall be recognized and the immaterial damage must be compensated. On the other hand, the violation of the duty of information does not belong to deny the compensation for physical damage. Which the legal interest violated by violation of the obligation to inform is the self-determination, and loss of opportunity of choice is recognized as ordinary damage. However, if the opportunity of choice was lost because of the infringement of the right to self-determination and the patient could not choice the better way, that dose not occur plainly bad results, under the prove of these causal relationship, that bad results could be compensated. But the unexpectable damage could not be compensated, because the physical damage is considered as the special damage due to the violation of the right of the self-determination.

Limb Salvage Using a Combined Distal Femur and Proximal Tibia Replacement in the Sequelae of an Infected Reconstruction on Either Side of the Knee Joint (슬관절 주위 재건물 감염 후유증 시 슬관절 상하부 종양인공관절을 이용한 사지 구제술)

  • Jeon, Dae-Geun;Cho, Wan Hyeong;Park, Hwanseong;Nam, Heeseung
    • Journal of the Korean Orthopaedic Association
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    • v.54 no.1
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    • pp.37-44
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    • 2019
  • Purpose: Tumor infiltration around the knee joint or skip metastasis, repeated infection sequelae after tumor prosthesis implantation, regional recurrence, and mechanical failure of the megaprosthesis might require combined distal femur and proximal tibia replacement (CFTR). Among the aforementioned situations, there are few reports on the indication, complications, and implant survival of CFTR in temporarily arthrodesed patients who had a massive bony defect on either side of the knee joint to control infection. Materials and Methods: Thirty-four CFTR patients were reviewed retrospectively and 13 temporary arthrodesed cases switched to CFTR were extracted. All 13 cases had undergone a massive bony resection on either side of the knee joint and temporary arthrodesis state to control the repeated infection. This paper describes the diagnosis, tumor location, number of operations until CFTR, duration from the index operation to CFTR, survival of CFTR, complications, and Musculoskeletal Tumor Society (MSTS) score. Results: According to Kaplan-Meier plot, the 5- and 10-year survival of CFTR was 69.0%±12.8%, 46.0%±20.7%, respectively. Six (46.2%) of the 13 cases had major complications. Three cases underwent removal of the prosthesis and were converted to arthrodesis due to infection. Two cases underwent partial change of the implant due to loosening and periprosthetic fracture. The remaining case with a deep infection was resolved after extensive debridement. At the final follow-up, the average MSTS score of 10 cases with CFTR was 24.6 (21-27). In contrast, the MSTS score of 3 arthrodesis cases with failed CFTR was 12.3 (12-13). The average range of motion of the 10 CFTR cases was 67° (0°-100°). The mean extension lag of 10 cases was 48° (20°-80°). Conclusion: Although the complication rates is substantial, conversion of an arthrodesed knee to a mobile joint using CFTR in a patient who had a massive bony defect on either side of the knee joint to control infection should be considered. The patient's functional outcome was different from the arthrodesed one. For successful conversion to a mobile joint, thorough the eradication of scar tissue and creating sufficient space for the tumor prosthesis to flex the knee joint up to 60° to 70° without soft tissue tension.

Changes in Subjective Symptom, Tear Film Stabilization and Blinking Rates when Wearing RGP Lenses with Different Polishing Conditions for Certain Period of Time (연마상태가 다른 RGP렌즈의 일정기간 착용 시 렌즈착용자의 자각적 증상, 눈물막 안정 및 순목횟수 변화)

  • Park, Mijung;Kim, Hyo Gyum;Bae, Jun Seob;Park, Jung Ju;Kim, So Ra
    • Journal of Korean Ophthalmic Optics Society
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    • v.19 no.1
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    • pp.31-42
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    • 2014
  • Purpose: The present study was conducted to investigate the effect of the physical properties of RGP lens induced by lens polishing on the actual wearer's subjective comfort, the tear film break-up time and the blinking rate as a follow-up study that revealed the relationship between the lens physical properties during lens manufacturing and lens wearer's factors. Methods: RGP lenses made from the three different polishing conditions (25, 50 and 100 seconds) were applied on 28 eyes of 17 subjects, aged 20 to 29 years, without any known disease and surgical history in the eyes. While the subjects were asked to wear the RGP lenses longer than a week, the questionnaire for the comfortability was administered everyday. Subjective and objective tear break-up time and blinking rate of the wearers were further measured. Results: The wearer's subjective comfortability showed some difference in the type of discomfort and satisfaction score according to the polishing status when wearing RGP lenses made from different polishing conditions longer than a week, and a bigger difference in satisfaction score induced by polishing condition was especially shown in experienced RGP lens wearer rather than un-experienced wearer. In the case of RGP lens wearer compared with the ones without the wearing experience, as the wearing time increased subjective and objective tear break-up time were increased and the blinking rate was decreased. However, subjective and objective tear break-up time were tended to decrease with even longer wearing time when wearing the RGP lens made from the polishment for 100 seconds. Conclusions: These results confirmed that the optimization of physical properties of the lens may not give the same effect on the wearer's subjective and objective symptoms and other factors when actual wearing. From the results, it can suggest that the success rate of RGP lens wear may be changed by physiological factors such as the stabilization of wearer's tear film, comfortability and lens wearing experience when wearing RGP lens based on 'The manufacturing standard for soft contact lens/hard contact lens' provided by Korea Food and Drug Administration.

Automatic Interpretation of Epileptogenic Zones in F-18-FDG Brain PET using Artificial Neural Network (인공신경회로망을 이용한 F-18-FDG 뇌 PET의 간질원인병소 자동해석)

  • 이재성;김석기;이명철;박광석;이동수
    • Journal of Biomedical Engineering Research
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    • v.19 no.5
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    • pp.455-468
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    • 1998
  • For the objective interpretation of cerebral metabolic patterns in epilepsy patients, we developed computer-aided classifier using artificial neural network. We studied interictal brain FDG PET scans of 257 epilepsy patients who were diagnosed as normal(n=64), L TLE (n=112), or R TLE (n=81) by visual interpretation. Automatically segmented volume of interest (VOI) was used to reliably extract the features representing patterns of cerebral metabolism. All images were spatially normalized to MNI standard PET template and smoothed with 16mm FWHM Gaussian kernel using SPM96. Mean count in cerebral region was normalized. The VOls for 34 cerebral regions were previously defined on the standard template and 17 different counts of mirrored regions to hemispheric midline were extracted from spatially normalized images. A three-layer feed-forward error back-propagation neural network classifier with 7 input nodes and 3 output nodes was used. The network was trained to interpret metabolic patterns and produce identical diagnoses with those of expert viewers. The performance of the neural network was optimized by testing with 5~40 nodes in hidden layer. Randomly selected 40 images from each group were used to train the network and the remainders were used to test the learned network. The optimized neural network gave a maximum agreement rate of 80.3% with expert viewers. It used 20 hidden nodes and was trained for 1508 epochs. Also, neural network gave agreement rates of 75~80% with 10 or 30 nodes in hidden layer. We conclude that artificial neural network performed as well as human experts and could be potentially useful as clinical decision support tool for the localization of epileptogenic zones.

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A study on 'audience participation' of contemporary theatre in 'Sleep No More" of Punchdrunk (동시대 공연에 나타나는 '관객 참여'방식 연구 - 런던 펀치드렁크(Punchdrunk)극단의 를 중심으로)

  • Jeon, Yunkyung
    • (The) Research of the performance art and culture
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    • no.32
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    • pp.651-700
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    • 2016
  • The keyword of contemporary art in 21st is audience participation. London has emphasized the importance of audience participation since 2000. The National Theater of London is trying a new method, which is live performance to search new audiences. Also, they are trying to cross the boundaries between 'stage' and 'spectator'. This leads the other theaters to search new audiences and try new genre of performance. Therefore, they establish a new form of performance, which is that audience actively moves and find a new story in a theater. For example, "environmental theater" is the one. This theater escapes from the traditional stage, but it is based on "site-specific performance." Lots of new forms of theater have emerged. In this study, I focused on one of these new forms of theater, which is "Punchdrunk." "Punchdrunk" was founded by few students graduated from London University's Laban Center in 1999. They started at an empty stage in small school with only three audiences. 7 years after, it became one of major theaters in London. 10 years after, it showed their performances in the United state. Since then, their performances in New York have never been stopped. More strikingly, for last decades, this theater has been always full. In this study, I reasoned that the key of "Punchdrunk" success is audience participation. Therefore, I investigated the features of Punchdrunk theater and how they engage their audience in this performance. In this study, I focused on one of their performances, . Also, I categorized the audiences in three different ways: narrative visitor, walking visitor, and engaging visitor with mask. Three-part transition of Disney Theme Park from Louis Marin was applied to study "narrative visitor." For "walking visitor", Normadism from Gilles Deleuze was applied. For "engaging visitor with mask", Voyeurism was applied.

A study on the figurative art expression reflected on the relationship with the animal companion and the inner self - Focusing on works by Lee Heeyeong -

  • Lee, Hee-Young;Cho, Myung-Shik
    • Cartoon and Animation Studies
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    • s.42
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    • pp.293-313
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    • 2016
  • The target stimulating human's sensitivity can include several things; the first is human like us including beautiful women and cute babies. The next ranking is the dog animal that established itself as a human's companion. It is the 3B law(beauty, baby, beast - much used in the ad or election due to the positive image) that is widely used in the advertising. This relationship is being expressed in the art history for a long time. Dogs that have lived a history more than 10 thousand years with humans hunted, protected flock of sheep, and kept the farmer's house and property. They have been human's assistants and companion who entered into the modern urban culture. Like this, dogs have adapted to several situations endlessly such as the nomadic life, farming, country life, and urban life. This paper will explore the close relationship of humans and companion animals through various icons of dogs and pups that appeared through a number of artists' skills. The companion animal means an animal that lives with people, which means the relationship of round-trip rather than the one-way relation those each other gives a help. Therefore, there artist tries to examine the figure of great hunter for survival, highly evaluated figure as the royal dignity, and the mascot-like figure delivering the daily happiness to modern people as presenting joy through a discussion of the 'countenance', a visual signal of the dogs and pups. They have been influenced by screen and popular media in 20C. Snoopy, a main character of and the movie <101 Dalmatians> made a success on the theater and television when Beagle and Dalmatian were prevalent. These main characters make audience feel happy involuntarily. Like this, the continuous and old friendship of the human and dogs will be confirmed again through the icon of dogs and pups consisting of the communication of artists and readers in the modern shape art, and it is hoped to be a psychological stabilizing effect to modern people living in the intense modern society. Therefore, it is expected this study paper will be reborn as a new text and be expanded as an effective communication in the journey of dogs and human in the future in investigating the communion of dogs and human.

The Effects of Autologous Blood Pleurodesis in the Pneumothorax with Persistent Air Leak (지속성 기흉에서 자가혈액을 이용한 흉막유착술의 효과)

  • Yoon, Su-Mi;Shin, Sung-Joon;Kim, Young-Chan;Shon, Jang-Won;Yang, Seok-Chul;Yoon, Ho-Joo;Shin, Dong-Ho;Chung, Won-Sang;Park, Sung-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.6
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    • pp.724-732
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    • 2000
  • Background : In patients with severe chronic lung diseases even a small pneumothorax can result in life-threatening respiratory distress. It is important to treat the attack by chest tube drainage until the lung expands. Pneumothorax with a persistent air leak that does not resolve under prolonged tube thoracostomy suction is usually treated by open operation to excise or oversew a bulla or cluster of blebs to stop the air leak. Pleurodesis by the instillation of chemical agents is used for the patient who has persistent air leak and is not good candidate for surgical treatment. When the primary trial of pleurodesis with common agent fails, it is uncertain which agent should be used f or stopping the air leak by pleurodesis. It is well known that inappropriate drainage of hemothorax results in severe pleural adhesion and thickening. Based on this idea, some reports described a successful treatment with autologous blood instillation for pneumothorax patients with or without residual pleural space. We tried pleurodesis with autologous bood for pneumothorax with persistent air leak and then we evaluated the efficacy and safety. Methods : Fifteen patients who had persistent air leak in the pneumothorax complicated from the severe chronic lung disease were enrolled. They were not good candidates for surgical treatment and doxycycline pleurodesis failed to stop up their air leaks. We used a mixture of autologous blood and 50% dextrose for pleurodesis. Effect and complications were assessed by clinical out∞me, chest radiography and pulmonary function tests. Results : The mean duration of air leak was 18.4${\pm}$6.16 days before ABP (autologous blood and dextrose pleurodesis) and $5.2{\pm}1.68$ days after ABP. The mean severity of pain was $2.3{\pm}0.70$ for DP(doxycycline pleurodesis) and $1.7{\pm}0.59$ for ABDP (p<0.05). There was no other complication except mild fever. Pleural adhesion grade was a mean of $0.6{\pm}0.63$. The mean dyspnea scale was $1.7{\pm}0.46$ before pneumothrax and $2.0{\pm}0.59$ after ABDP (p>0.05). The mean $FEV_1$ was $1.47{\pm}1.01$ before pneumothorax and $1.44{\pm}1.00$ after ABDP (p>0.05). Except in 1 patient, 14 patients had no recurrent pneumothorax. Conclusion : Autologous blood pleurodesis (ABP) was successful for treatment of persistent air leak in the pneumothorax. It was easy and inexpensive and involved less pain than doxycycline pleurodesis. It did not cause complications and severe pleural adhesion. We report that ABP can be considered as a useful treatment for persistent air leak in the pneumothorax complicated from the severe chronic lung disease.

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Video Assisted Thoracoscopic Sympathetic Ramus Clipping in Essential Hyperhidrosis -Cadaver Fitting Test and Clinical Application (다한증 환자에서 클립을 이용한 교감신경 교통가지 차단술 -사체 연구 및 임상적용-)

  • Lee, Sung-Ho;Cho, Seong-Joon;Jung, Jae-Seung;Kim, Tae-Sik;Son, Ho-Sung;Sun, Kyung;Kim, Kwang-Taik;Kim, Hyoung-Mook
    • Journal of Chest Surgery
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    • v.36 no.8
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    • pp.595-601
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    • 2003
  • Background: It has been known that the most effective treatment method of hyperhidrosis is video-assisted thoracoscopic sympathetic nerve block. Postoperative compensatory hyperhidrosis and anhidrosis are major factors that decrease the postoperative satisfaction. Although sympathetic rami have been selectively blocked to decrease the complications, technical difficulties and excessive bleeding have prevented the universal application. Material and Method: Three pre-fixative cadavers were dissected before clinical application. Bilateral sympathetic chains were exposed in supine position after the whole anterior chest wall was removed. Second and third sympathetic rami were blocked using clips. After the sympathetic chains including ganglia were removed, we evaluated the extents of rami block. Twenty-five patients were subjected to the clinical application. Surgeries were performed in semi-fowlers position under general anesthesia and bilateral ventilation. 2 mm thoracoscopy and 5 mm trocar were intro-duced through third and fourth intercostal space, respectively. Second and third sympathetic rami were blocked using thoracoscopic clips. The postoperative complications, satisfaction, and compensatory hyperhidrosis rate were evaluated retrospectively. Result: Sympathetic rami were completely blocked in cadaver dissection study Hyper-hidrosis symptom was improved in all patients without operative complication. Operative time was shorter than that of traditional ramicotomy. All patients, except four, were satisfied with postoperative palmar hyperhidrosis. Com-pensatory hyperhidrosis was more severely happened in fifteen patients (60%). The remaining six patients had no complaint. Two patients had a minimal degree of gustatory hyperhidrosis. Conclusion: This operative method had shorter operative time and less complication rate, compared with traditional ramicotomy Operative success rate was similar to the traditional syrnpathicotorny; lower extent and occurrence rate of compensatory hyperhidrosis. The thoracic sympathetic rami clipping was suggested as an alternative method for treatment of palmar hyperhidrosis.

The Clinical Application and Results of Palliative Damus-Kaye-Stansel Procedure (고식적 Damus-Kaye-Stansel 술식의 임상적 적용 및 결과)

  • Lim, Hong-Gook;Kim, Soo-Jin;Kim, Woong-Han;Hwang, Seong-Wook;Lee, Cheul;Shinn, Sung-Ho;Yie, Kil-Soo;Lee, Jae-Woong;Lee, Chang-Ha
    • Journal of Chest Surgery
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    • v.41 no.1
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    • pp.1-11
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    • 2008
  • Background: The Damus-Kaye-Stansel (DKS) procedure is a proximal MPA-ascending aorta anastomosis used to relieve systemic ventricular outflow tract obstructions (SVOTO) and pulmonary hypertension. The purpose of this study was to review the indications and outcomes of the DKS procedure, including the DKS pathway and semilunar valve function. Material and Method: A retrospective review of 28 patients who underwent a DKS procedure between May 1994 and April 2006 was performed. The median age at operation was 5.3 months ($13\;days{\sim}38.1\;months$) and body weight was 5.0 kg ($2.9{\sim}13.5\;kg$). Preoperative pressure gradients were $25.3{\pm}15.7\;mmHg$ ($10{\sim}60\;mmHg$). Eighteen patients underwent a preliminary pulmonary artery banding as an initial palliation. Preoperative main diagnoses were double outlet right ventricle in 9 patients, double inlet left ventricle with ventriculoarterial discordance in 6,. another functional univentricular heart in 5, Criss-cross heart in 4, complete atrioventricular septal defect in 3, and hypoplastic left heart variant in 1. DKS techniques included end-to-side anastomosis with patch augmentation in 14 patients, classical end-to-side anastomosis in 6, Lamberti method (double-barrel) in 3, and others in 5. The bidirectional cavopulmonary shunt and Fontan procedure were concomitantly performed in 6 and 2 patients, respectively. Result: There were 4 hospital deaths (14.3%), and 3 late deaths (12.5%) with a follow-up duration of $62.7{\pm}38.9$ months ($3.3{\sim}128.1$ months). Kaplan-Meier estimated actuarial survival was $71.9%{\pm}9.3%$ at 10 years. Multivariate analysis showed right ventricle type single ventricle (hazard ratio=13.960, p=0.004) and the DKS procedure as initial operation (hazard ratio=6.767, p=0.042) as significant mortality risk factors. Four patients underwent staged biventricular repair and 13 received Fontan completion. No SVOTO was detected after the procedure by either cardiac catheterization or echocardiography except in one patient. There was no semiulnar valve regurgitation (>Gr II) or semilunar valve-related reoperation, but one patient (3.6%) who underwent classical end-to-side anastomosis needed reoperation for pulmonary artery stenosis caused by compression of the enlarged DKS pathway. The freedom from reoperation for the DKS pathway and semilunar valve was 87.5% at 10 years after operation. Conclusion: The DKS procedure can improve the management of SVOTO, and facilitate the selected patients who are high risk for biventricular repair just after birth to undergo successful staged biventricular repair. Preliminary pulmonary artery banding is a safe and effective procedure that improves the likelihood of successful DKS by decreasing pulmonary vascular resistance. The long-term outcome of the DKS procedure for semilunar valve function, DKS pathway, and relief of SVOTO is satisfactory.