• Journal of Chest Surgery
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• 제29권8호
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• pp.850-860
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• 1996

활성산소는 동물실험에서 심근 재관류손상의 중요기전으로 알려져 있으나 실제 임상상황에서의 역할은 아직도 논란이 많다. 본 연구에서는 냉혈 심마비 액을 사용한 심근보호법을 이용하여 관상동맥우회술 을 시행받는 환자들을 대상으로 하여 심근허혈후 재관류시 활성산소에 의한 심근의 손상 정도 및 활성 산소 방어효소계의 변동과 그 기전을 규명하고자 하였다. 관상동맥우회술을 받는 환자(n=10)를 대상으로 하여 관상정 맥동 환류혈액 에서 상행대동맥 차단 전과 재관류 20분 후에 lactate dehydrogenase(LDH), creatinG phosphokinase MB 분획(CK-MB)과 malondialdehyde(MDA)의 농도를 측정하였으며 또한 같은 시각에 심근의 superoxide dismutase(SOD), catalase, glutathione peroxidase(GSHPX), glutathione reductase(GSSGRd) 그BT고 glucose 6- phosphate dehydrogenase(GGPDH)의 활성도를 측정하였다 관상정 맥동혈에서의 LDH(268 $\pm$40.3 to 448 $\pm$ 84.9 ml plasma)와 CK-MB(4.50$\pm$ 2.33 to 27.1$\pm$13.5 Ulml plasma)의 활성도 그리고 MDA(5.87$\pm$2.02 to 10.5$\pm$2.23 nmol/ml plsma)의 양은 상행대동맥 차단 전에 비하여 재관류 후에 현저히 증가하였으 \ulcorner심근의 SOD(13.5$\pm$4.04 to 20.7$\pm$8.56 mg protein), GSHPX(279 $\pm$)7.2 to 325$\pm$51.4 mU/mg protein) 그리고 GSSCRd(97.2$\pm$15.9 to 122 $\pm$25.1 m2/mg protein)의 활성도도 재관류후에 현저히 증가하였다 반면 심근의 catalase와GSPDH의 활성도는의미있는 변화가 없었다 한편 SOD에 대한 Western blot결과 Cu, Zn-SOD의 양이 현저하게 증가되었음을 관찰 하였다. 이상의 결과들로 관상동맥우회술시 상행대동맥차단에 따른 심근허혈후 재관류에 의하여 활성산소에 의한 산화성 심근손상이 일어나지만 동시에 활성산소 방어효소계의 활성 또한 증가됨으로써 심근손상 의 정도가 약화되었을 가능성을 추정할 수 있으며 이러한 활성산소 방어효소의 활성증가는효소단백의 광합성 증가에 의한 것으로 여겨진다.

• Journal of Chest Surgery
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• 제30권2호
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• pp.195-199
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• 1997

복부대동맥과 그 이하 주요분지들의 동맥폐쇄에 의한 하지 만성허혈은 동맥경화증이 주원인이며 이 질환의 임상적 중요성은 혈관이 진행적으로 폐쇄됨에 따라 혈류장애가 발생하여 간헐적 파행, 휴식시 동통이 일어나며 더 진행되면 조직의 괴사가 발생,결국괴사된 조직의 절단을 초래하게된다. 본한국보 훈병원 흉부외과에서는 1992년 12월부터 1995년 12월까지 폐쇄성 하지동맥 경화증으로 입원한 20명의 환자를 대상으로 동맥간 우회술을 시 행하였다. 임상증상은 괴사및 괴저 9례(45B4), 파행 7례(35%), 안정 시 동통 4례(20%)순이었다. 사용한 혈관은 복부대동맥및 총대퇴동맥의 경우 Y-형및 I-형 인조혈관을 사 용하였고 대퇴동맥이하의 혈관에서는 주로 자가 대복재정 맥을 사용하였다. 술후 합병증은 4례로 20% 를 보였고 이식된 혈관내 혈전증 2례, 창상감염 2례 였다. 술후 혈관개존율은 복부대동맥과 양측 대퇴동 맥간 우회술의 경우 100%였고 대퇴동맥 이하에서는 6개월이 92.6%, 1년 84.2%, 2년 75.4%, 3년 69.4% 였다.

• Journal of Chest Surgery
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• 제30권9호
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• pp.876-884
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• 1997

서울대학교병원 흉부외과에서는 1994년 3월부터 1996년 5월까지 14명의 환자에 있어서 심장이식술을 시행 하였다. 남자가 9명 여자가 5명이었으며 평균나이는 40.8 $\pm$ 12.4세 이었다. 수술전 모든 환자들은 UiID Fc III 또는 IV이었으며 술전 진단은 확장성 심근병증이 11명, 제한성 심근병증이 3명이었다. 장기 공여자의 평균연령은 24.9 $\pm$ 10.2세 이었으며 뇌사의 원인으로는 교통사고에 의한 뇌손상이 8명으로 가장 많았으며 거미막하 출혈이 2명, 이 물질에 의한 기도폐쇄, 추락사고, 뇌종양, 익사사고 등이 각각 1명이 었다. 수혜자와 공여자의 혈액형은 11명에 있어서는 일치되었고 2명에 있어서는 적합하였으나 1명의 환자에 있 어서는 부적합하였다. 11명의 환자에 있어서는 양대정맥을 직접 문합하는 방법을 사용하였으며 3명의 환자에 있어서는 우심방을 연결하는 방법을 사용하였으며 평균 이식심장 허혈시간은 157.8 $\pm$ 43.8분(94-220분) 이었다. 2명이 사망하 여 병원 사망률은 14.3%이었다. 사망원인은 우심실부전, 사이클로스포린 유발성 용혈성요독증후군, 거부반응 으로 인한 다발성 장기부전과 대동맥 문합부위 가성동맥류의 파열로 의심되는 酉\ulcorner銖汰潔駭\ulcorner 평균추적기간은 16.2 $\pm$ 9.0개월(3-28개월) 이었으며 만기사망은 1례 있었다. (8.3%) 마지막 추적당시 급성 거부반응으로 치료를 받고 있는 1명을 제외한 모든 환자들은 UnD Fc I이었다. 병원사망을 포함한 1개월 및 6개월, 2년 생존율은 각각 n.9 $\pm$ 6.9%, 85.7 $\pm$ 9.4% , 77.1 $\pm$ 11.7% 이었다. 결론적으로 심장이식술은 말기 심부전환자의 이상적인 치료법이며 앞으로 장기적인 추적검사가 필요하리라 생각된다.

• Journal of Chest Surgery
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• 제31권10호
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• pp.1004-1008
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• 1998

본 논문은 동맥관개존증으로 인한 Eisenmenger 증후군 환자에서 시행된 심장-폐이식 수술에 대한 증례 보고이다. 동맥관 개존증으로 인한 Eisenmenger 증후군인 32세의 여자 수혜자는 1996년 6월 이후 심부전으로 심한 호흡곤란을 겪고 있었으며, 1997년 7월초에 빈맥, 호흡곤란, 하지부종을 주소로 응급실을 통하여 입원한 후 호흡곤란, 저산소증, 상심실성 빈맥, 전해질 이상 등으로 치료받으면서 퇴원하지 못하고 심장-폐 이식 대상자로 등록되었다. 수술전에 시행한 심초음파검사에서 우-좌단락의 동맥관개존증, 우심실 및 우심방의 심한 확장, 100 mmHg의 우심실 수축기압 소견을 보였다. 폐동맥압이 체동맥압보다 높게 역전되어 있었고 심한 이산화탄소 정체 및 저산소증의 소견을 보여서 중환자실에서 인공호흡기로 호흡기능을 보조받고 있었다. 공여자는 교통사고로 두부손상을 입고 뇌사판정을 받은 1 8세 남자였다. 공여자 및 수헤자의 혈액형은 모두 AB(+)형이었다. 1997년 10월 26일 심장-폐이식을 시행하였다. 심장 -폐분절은 공여자가 있던 타병원에서 구득하여 냉장보존 상태로 본원으로 이송하였다. 이식된 심장 및 폐의 총 허혈 시간은 각각 249분 및 270분이었다. 면역억제요법은 cyclosporine, azathioprine을 수술전부터 투여하였으며 steroid 는 기관 문합부위의 치유와 감염예방을 위하여 수술후 3주 이후부터 사용하였다. 환자는 수술후 31일째에 특별한 합 병증없이 퇴원하였으며 심장-폐이식후 4개월이 지난 현재, 심폐기능의 이상소견과 거부반응의 증거없이 NYHA funct ional class I의 상태로 지내고 있으며 면역억제제와 예방적 항생제, 소량의 이뇨제 및 항고혈압제를 복용하고 있다.

• Journal of Chest Surgery
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• 제31권10호
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• pp.945-951
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• 1998

개심술시 총순환정지는 매우 유용한 방법이나 뇌손상등 부작용으로 그 사용이 제한되고 있다. 이러한 뇌손상의 분석에 유용한 지표로서 뇌 허혈성 손상의 특이한 효소인 크레아티닌 카이네이즈 BB(CK-BB)의 유용성을 재고하고 뇌손상에 영향을 미치는 인자들의 분석을 시도하였다. 총순환정지를 이용하여 개심술을 시행한 18명의 환자를 대상으로 하였다. 이들은 다시 비청색증형 심기 형군과 청색증형 심기형군으로 나누어 각각 6명과 12명으로 하였다. 각 환자에서 총순환정지전 및 후 15, 30, 60, 120, 240, 480, 720분에 동맥혈을 채취하여 CK-BB분획을 측정하였고 이와 동시에 혈색소농도, 이 온화 칼슘농도, 혈당량 등을 측정하였다. 총순환정지시간과 CK-BB와 통계적으로 유의한 관계를 보이는 채혈시간은 찾을 수 없었다. 또 총순환 정지전의 문제로 인한 영향을 줄이기 위하여 각각의 측정치에서 총순환정지전의 측정치를 뺀 값을 구하 여 각기 CKBBD15, CKBBD30....등으로 표시하고 상관관계를 구하였으나 역시 유의한 상관관계를 보이 지 않았다. CKBB30과 CKBBD30값은 비청색증형 군과 청색증형 군 사이에 유의한 차이를 보이지 않았 다. CK-BB농도와 혈색소 농도는 유의한 상관관계를 보였다. 단일 채혈에 의한 CK-BB농도의 지표는 순환정지시간과 유의한 관계가 없음이 확인되었다. 또한 청색 증형 심질환군이 총순환정지에 의한 뇌손상에 비청색증형 심질환군에 비해 더 취약하지는 않은 것으로 생각된다.

• 한국임상약학회지
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• 제21권2호
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• pp.90-99
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• 2011

Health Insurance Review & Assessment Service (HIRA) claims database has a high potential to detect signals of new drug interactions. The aim of this study was to evaluate the usefulness of information component (IC) and relative risk (RR) as a tool for signal detection, and to analyze the possible drug interactions caused by clopidogrel using HIRA claims database. This study was performed in elderly patients over 65 years of age who administered clopidogrel from January 2005 to June 2006 in South Korea. Serious Adverse Events (SAEs) as drug interactions of clopidogrel were defined as any ambulatory hospitalization for ischemic diseases within comcomitant medication period of clopidogrel. Information Component (IC) and Relative Risk (RR) were calculated to compare the proportion of drug-SAE pairs in order to select drug specific SAEs. IC and RR signals of clopidogrel drug interaction were screened when IC's 95% confidence interval was greater than 0 and RR's 95% confidence interval was greater than 1 respectively. All detected signals were compared to references such as $Micromedex^{(R)}$ and 2010 Drug Interaction $Facts^{TM}$. Sensitivity, specificity, positive predicted value and negative predicted value were used to evaluate usefulness of this method. Among 13,252,930 cases of elderly patients who co-administered clopidogrel and other drugs, 47,485 cases were detected as SAE. Of these, one-hundred nine cases were detected by the IC-based data-mining approach and ninety one cases were detected by the RR-based data-mining approach. Total One-hundred sixty three unrecognized signals were detected by IC or RR. Twelve signals from IC-based data-mining (57.1%) were corresponded with drug interactions from references and eight signals from RR-based data-mining (38.1%) were corresponded with drug interactions from references. These signals include proton pump inhibitors, calcium channel blockers and HMG CoA reductase Inhibitors, which were known to affect CYP450 metabolism. Further studies using HIRA claims database are necessary to develop appropriate data-mining measure.

• Journal of Korean Neurosurgical Society
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• 제29권8호
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• pp.1008-1018
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• 2000

Objective : Glutamate induced excitotoxicity is one of the leading causes of cell death under pathologic condition. However, there is controversy whether excitotoxicity may also participate in the neuronal death under low intensity insult such as simple hypoxia or hypoglycemia. To investigate the role of NMDA receptor in low intensity insult, we chose anoxia as the method of injury and used organotypically cultured hippocampal slice as the material of experiment. Materials & Methods : The hippocampal slices cultured for 2-3 weeks were exposed to 60 minutes of complete oxygen deprivation(anoxia). Neuronal death was assessed with Sytox stain. Corrected optical density of fluorescence in gray scale, used as cellular death indicator, was obtained from pictures taken at 24 and 48 hours following the insult. The well-known in vivo phenomenon of regional difference in susceptibility of hippocampal sub-fields to ischemic insult was reproduced in HOSC(hippocampal organotypic slice culture) by complete oxygen deprivation injury. Results : $CA_1$ was the most vulnerable to complete oxygen deprivation in hippocampus while $CA_3$ was resistant. Oxygen deprivation for 10 and 20 minutes with glucose(6.5g/l) present was insufficient to induce neuronal death in the cultured hippocampal slice. However, after 30 minutes exposure under anoxic condition, neuronal death was able to be detected in the center of $CA_1$ area. The intensity and area of fluorescence indicating cell death correlated with the duration of oxygen deprivation. NMDA receptor and non-NMDA receptor blocking with MK-801(30 & $60{\mu}M$) and CNQX($100{\mu}M$) did not provide cellular protection to HOSC against damage induced by oxygen deprivation, but increased intracellular calcium buffering capacity with BAPTA-AM($10{\mu}M$) was effective in preventing neuronal death (p=0.01, Student's t-test). Cycloheximide($1{\mu}g/ml$, $10{\mu}g/ml$) provided no protection to HOSC against insult of complete oxygen deprivation for 60 minutes and combined therapy of MK-801(30 & $60{\mu}M$) and cycloheximide(1 & $10{\mu}g/ml$) was also ineffective in preventing neuronal death. Conclusion : The results of this study show that the another mechanism not associated with glutamate receptor(NMDA & non NMDA) may play major role in cell death mechanisms induced by complete oxygen deprivation and increased intracellular calcium during anoxia may participate in the neuronal death mechanism of oxygen deprivation. Further investigation of the calcium entry channel activated during oxygen deprivation is necessary to understand the neuronal death of anoxia.

• Journal of Korean Neurosurgical Society
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• 제44권4호
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• pp.228-233
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• 2008

Objective : The standard treatment strategy of intracranial aneurysms includes either endovascular coiling or microsurgical clipping. In certain situations such as in giant or dissecting aneurysms, bypass surgery followed by proximal occlusion or trapping of parent artery is required. Methods : The authors assessed the result of extracranial-intracranial (EC-IC) bypass surgery in the treatment of complex intracranial aneurysms in one institute between 2003 and 2007 retrospectively to propose its role as treatment modality. The outcomes of 15 patients with complex aneurysms treated during the last 5 years were reviewed. Six male and 9 female patients, aged 14 to 76 years, presented with symptoms related to hemorrhage in 6 cases, transient ischemic attack (TIA) in 2 un ruptured cases, and permanent infarction in one, and compressive symptoms in 3 cases. Aneurysms were mainly in the internal carotid artery (ICA) in 11 cases, middle cerebral artery (MCA) in 2, posterior cerebral artery (PCA) in one and posterior inferior cerebellar artery (PICA) in one case. Results : The types of aneurysms were 8 cases of large to giant size aneurysms, 5 cases of ICA blood blister-like aneurysms, one dissecting aneurysm, and one pseudoaneurysm related to trauma. High-flow bypass surgery was done in 6 cases with radial artery graft (RAG) in five and saphenous vein graft (SVG) in one. Low-flow bypass was done in nine cases using superficial temporal artery (STA) in eight and occipital artery (OA) in one case. Parent artery occlusion was performed with clipping in 9 patients, with coiling in 4, and with balloon plus coil in 1. Direct aneurysm clip was done in one case. The follow up period ranged from 2 to 48 months (mean 15.0 months). There was no mortality case. The long-term clinical outcome measured by Glasgow outcome scale (GOS) showed good or excellent outcome in 13/15. The overall surgery related morbidity was 20% (3/15) including 2 emergency bypass surgeries due to unexpected parent artery occlusion during direct clipping procedure. The short-term postoperative bypass graft patency rates were 100% but the long-term bypass patency rates were 86.7% (13/15). Nonetheless, there was no bypass surgery related morbidity due to occlusion of the graft. Conclusion : Revascularization technique is a pivotal armament in managing complex aneurysms and scrupulous prior planning is essential to successful outcomes.

• Journal of Korean Neurosurgical Society
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• 제54권6호
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• pp.467-476
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• 2013

Objective : This study aimed to evaluate the hypotheses that administration routes [intra-arterial (IA) vs. intravenous (IV)] affect the early stage migration of transplanted human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in acute brain infarction. Methods : Male Sprague-Dawley rats (n=40) were subjected to photothrombotic infarction. Three days after photothrombotic infarction, rats were randomly allocated to one of four experimental groups [IA group : n=12, IV group : n=12, superparamagnetic iron oxide (SPIO) group : n=8, control group : n=8]. All groups were subdivided into 1, 6, 24, and 48 hours groups according to time point of sacrifice. Magnetic resonance imaging (MRI) consisting of T2 weighted image (T2WI), $T2^*$ weighted image ($T2^*WI$), susceptibility weighted image (SWI), and diffusion weighted image of rat brain were obtained prior to and at 1, 6, 24, and 48 hours post-implantation. After final MRI, rats were sacrificed and grafted cells were analyzed in brain and lung specimen using Prussian blue and immunohistochemical staining. Results : Grafted cells appeared as dark signal intensity regions at the peri-lesional zone. In IA group, dark signals in peri-lesional zone were more prominent compared with IV group. SWI showed largest dark signal followed by $T2^*WI$ and T2WI in both IA and IV groups. On Prussian blue staining, IA administration showed substantially increased migration and a large number of transplanted hBM-MSCs in the target brain than IV administration. The Prussian blue-positive cells were not detected in SPIO and control groups. Conclusion : In a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration. MRI and histological analyses revealed the time course of cell migration, and the numbers and distribution of hBM-MSCs delivered into the brain.

• Journal of Korean Neurosurgical Society
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• 제61권1호
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• pp.42-50
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• 2018

Objective : Massive intracerebral hemorrhage (ICH) and major infarction (MI) are devastating cerebral vascular diseases. Decompression craniectomy (DC) is a common treatment approach for these diseases and acceptable clinical results have been reported. Author experienced the postoperative intracranaial pressure (ICP) trend is somewhat different between the ICH and MI patients. In this study, we compare the ICP trend following DC and evaluate the clinical significance. Methods : One hundred forty-three patients who underwent DC following massive ICH (81 cases) or MI (62 cases) were analyzed retrospectively. The mean age was $56.3{\pm}14.3$ (median=57, male : female=89 : 54). DC was applied using consistent criteria in both diseases patients; Glasgow coma scale (GCS) score less than 8 and a midline shift more than 6 mm on brain computed tomography. In all patients, ventricular puncture was done before the DC and ICP trends were monitored during and after the surgery. Outcome comparisons included the ictus to operation time (OP-time), postoperative ICP trend, favorable outcomes and mortality. Results : Initial GCS (p=0.364) and initial ventricular ICP (p=0.783) were similar among the ICH and MI patients. The postoperative ICP of ICH patients were drop rapidly and maintained within physiological range if greater than 80% of the hematoma was removed. While in MI patients, the postoperative ICP were not drop rapidly and maintained above the physiologic range (MI=18.8 vs. ICH=13.6 mmHg, p=0.000). The OP-times were faster in ICH patients (ICH=7.3 vs. MI=40.9 hours, p=0.000) and the mortality rate was higher in MI patients (MI=37.1% vs. ICH=17.3%, p=0.007). Conclusion : The results of this study suggest that if greater than 80% of the hematoma was removed in ICH patients, the postoperative ICP rarely over the physiologic range. But in MI patients, the postoperative ICP was above the physiologic range for several days after the DC. Authors propose that DC is no need for the massive ICH patient if a significant portion of their hematoma is removed. But DC might be essential to improve the MI patients' outcome and timely treatment decision.