저산소 허혈 뇌 손상을 유발시킨 미성숙 흰쥐에서 마우스 골수 기원 중간엽 줄기 세포 이식 후 기능 회복

최욱선,유기환,홍영숙,강훈철,은소희,이주원,박성원,신혜경,은백린 대한소아청소년과학회 2009 Clinical and Experimental Pediatrics (CEP) Vol.52 No.7

Purpose : We aimed to investigate the efficacy of and functional recovery after intracerebral transplantation of different doses of mouse mesenchymal stem cells (mMSCs) in immature rat brain with hypoxic-ischemic encephalopathy (HIE). Methods : Postnatal 7-days-old Sprague-Dawley rats, which had undergone unilateral HI operation, were given stereotaxic intracerebral injections of either vehicle or mMSCs and then tested for locomotory activity in the 2nd, 4th, 6th, and 8th week of the stem cell injection. In the 8th week, Morris water maze test was performed to evaluate the learning and memory dysfunction for a week. Results : In the open field test, no differences were observed in the total distance/the total duration (F=0.412, P=0.745) among the 4 study groups. In the invisible-platform Morris water maze test, significant differences were observed in escape latency (F=380.319, P<0.01) among the 4 groups. The escape latency in the control group significantly differed from that in the high-dose mMSC and/or sham group on training days 2-5 (Scheffe's test, P<0.05) and became prominent with time progression (F=6.034, P<0.01). In spatial probe trial and visible-platform Morris water maze test, no significant improvement was observed in the rats that had undergone transplantation. Conclusion : Although the rats that received a high dose of mMSCs showed significant recovery in the learning-related behavioral test only, our data support that mMSCs may be used as a valuable source to improve outcome in HIE. Further study is necessary to identify the optimal dose that shows maximal efficacy for HIE treatment. 목 적 : HIE의 치료법으로 줄기 세포가 대안으로 떠오르고 있다. mMSC가 성인 동물 모델에서의 뇌졸중 및 퇴행성 뇌질환에 유의한 기능 회복을 보인다는 보고가 많이 있으나 미성숙 동물 모델에서의 연구 보고는 거의 없는 상태이다. 이에 HIE가 유발된 미성숙뇌에 mMSC를 투여하여 기능 회복에 대한 효과를 평가하고자 본 연구를 시행하였다. 방 법 : 생후 7일된 수컷 Sprague-Dawley 흰쥐를 sham 대조군, 뇌 손상 대조군, 고용량 mMSC 이식군 및 저용량 mMSC 이식군으로 나누었으며 저산소 허혈 뇌 손상 유도 2주 후에 mMSC를 병변부 국소 이식을 시행하였다. 세포 이식 2, 4, 6 및 8주째에 개방장 시험을 시행하여 운동 기능 회복 정도를 평가하였고, 이후 1주일 동안 Morris 수중 미로 시험을 3개 부문으로 시행하여 학습 및 기억력 회복 정도를 평가하였다. 결 과 : 개방장 시험 결과 네 군간에서 통계적으로 유의한 차이는 없었다(F=0.412, P=0.745). 공간 획득 검사에서 네 군간 평균 탈출 시간에 서로 차이가 있었고(F=380.319, P<0.01), 고용량 mMSC 이식군 및 sham 대조군은 뇌 손상 대조군에 비해 검사 2일째부터 5일째까지 각각 평균 탈출 시간이 감소하였으며(P< 0.05), 시간이 갈수록 더 유의하게 차이를 보였다(F=16.034, P< 0.01). 참조 기억 검사에서는 네 군간 차이는 없었으며 시각 검사에서는 다섯번째 시행 검사에서만 고용량 mMSC 이식군과 뇌 손상 대조군간에 통계적으로 유의한 차이가 있었다(P<0.05). 결 론 : 일부 검사에서만 고용량 mMSC 이식의 효과가 뚜렷하였고 그 외의 검사에는 통계적으로 유의한 결과는 보이지는 않았으나 산술적인 호전을 보이는 것을 확인할 수 있었다. 향후 최적의 효과를 보이는 줄기 세포의 농도와 이식 시기를 결정하는 연구가 필요할 것으로 보이며 HIE에서 mMSC가 대안적인 치료 수단으로 이용될 수 있다고 생각된다.

구연 : 소화기 ; 궤양성 대장염과 크론병의 상대적 발생률 변화에 대한 연구

최욱선,김영민,양석균,명승재,김경조,김현영,정성희,류수형,정훈용,홍원선,김진호,민영일 대한내과학회 2001 대한내과학회 추계학술대회 Vol.61 No.-

Primary peritoneal drainage as a treatment for perforated necrotizing enterocolitis with bacterial peritonitis in an extremely low birth weight infant : a case report

최욱선,문일홍,이장훈,이승화,최병민,은백린,홍영숙,이주원 대한소아청소년과학회 2006 Clinical and Experimental Pediatrics (CEP) Vol.49 No.7

Necrotizing enterocolitis(NEC) is the most common life-threatening surgical emergency in neonates, and remains a major cause of morbidity and mortality. In addition to conventional laparotomy, intraperitoneal drains have been used for the treatment of perforated NEC, especially in extremely low birth weight(ELBW) infants. We report a case of perforated NEC with bacterial peritonitis in an ELBW infant managed with primary peritoneal drainage(PD) without further need for surgery. To our knowledge, this is the first documented Korean case of an ELBW infant where PD was used as primary treatment for perforated NEC. Primary PD is effective and safe in ELBW infants with perforated NEC; although it is not considered a definitive procedure, it should be considered in all cases where infants are too unstable to tolerate anesthesia and surgery. 괴사성 장염은 미숙아에서 외과적 응급 수술을 요하는 가장 흔한 질환이며 여전히 높은 이환율과 사망률을 차지하고 있다. 괴사성 장염의 치료로는 전통적으로 천공성 괴사성 장염인 경우 개복술이 시행되어 왔으나 미숙아에서 일차적 복강 배액술이 시도된 이후 초극소 저출생 체중아에서도 양호한 결과를 보인 사례들이 보고되고 있다. 저출생 체중아에서 천공성 괴사성 장염 치료시 일차적 복강 배액술과 개복술 중 어느 시술이 더 우수한 결과를 보이는지에 대한 연구는 아직 진행 중에 있으나 일차적 복강 배액술은 전신 마취나 수술을 시행하기에는 불안정한 환자 상태인 경우에 시행을 고려할 수 있다. 저자들은 초극소 저출생 체중아에서 천공성 괴사성 장염으로 인한 세균성 복막염 치료로 환아 상태상 전신 마취 및 수술을 바로 시행하기에는 어려워 일차적 복강 배액술을 시행 후 호전된 1례를 경험하였기에 문헌 고찰과 함께 보고하는 바이다.

미숙아 동맥관 개존 치료에서 indomethacin과 ibuprofen의 효과

최욱선,신정연,최병민,은백린,유기환,홍영숙,이주원 대한소아청소년과학회 2006 Clinical and Experimental Pediatrics (CEP) Vol.49 No.12

Purpose : This study was conducted to compare the efficacy and safety of ibuprofen and indomethacin in the treatment of patent ductus arteriosus (PDA) in preterm infants and to determine whether ibuprofen can be an alternative drug. Methods : A total of 32 preterm infants with symptomatic PDA were enrolled in the study. Twelve infants received intravenous ibuprofen 10 mg/kg, followed by 5 mg/kg after 24 and 48 hours. As a comparative group, twenty premature infants received three doses of indomethacin 0.1-0.2 mg/kg every 12 hours. Results : PDA was closed in 11 of 12 infants of the ibuprofen group (92 percent) and in 18 of 20 infants of the indomethacin group (90 percent). Serum sodium concentration decreased along with time significantly (P<0.0001) and to its lowest level at 48 hours after administration of the third dose (P=0.0011) in both groups, but showed no significant difference between two groups. Serum BUN and creatinine concentrations were not changed significantly before or after treatment in each group and showed no difference between thetwo groups. The amount of urine output did not change along with time significantly in both groups (P=0.0725), and showed no significant difference between two groups. Conclusion : Ibuprofen has similar effects to indomethacin in the rate of PDA closure and complication when compared. It has similar changes in serum sodium level and complications when compared to indomethacin for the treatment of PDA in preterm infants. Therefore, intravenous ibuprofen may be used as an alternative agent in the treatment of symptomatic PDA in preterm infants. Purpose : This study was conducted to compare the efficacy and safety of ibuprofen and indomethacin in the treatment of patent ductus arteriosus (PDA) in preterm infants and to determine whether ibuprofen can be an alternative drug. Methods : A total of 32 preterm infants with symptomatic PDA were enrolled in the study. Twelve infants received intravenous ibuprofen 10 mg/kg, followed by 5 mg/kg after 24 and 48 hours. As a comparative group, twenty premature infants received three doses of indomethacin 0.1-0.2 mg/kg every 12 hours. Results : PDA was closed in 11 of 12 infants of the ibuprofen group (92 percent) and in 18 of 20 infants of the indomethacin group (90 percent). Serum sodium concentration decreased along with time significantly (P<0.0001) and to its lowest level at 48 hours after administration of the third dose (P=0.0011) in both groups, but showed no significant difference between two groups. Serum BUN and creatinine concentrations were not changed significantly before or after treatment in each group and showed no difference between thetwo groups. The amount of urine output did not change along with time significantly in both groups (P=0.0725), and showed no significant difference between two groups. Conclusion : Ibuprofen has similar effects to indomethacin in the rate of PDA closure and complication when compared. It has similar changes in serum sodium level and complications when compared to indomethacin for the treatment of PDA in preterm infants. Therefore, intravenous ibuprofen may be used as an alternative agent in the treatment of symptomatic PDA in preterm infants.

구연 : 소화기 ; 한국인 궤양성 대장염 환자의 진단시 임상적 특징과 장기적 예후에 관한 고찰

김영민,최욱선,양석균,명승재,손정민,김태훈,박영환,송희곤,정훈용,홍원선,김진호,민영일 대한내과학회 2001 대한내과학회 추계학술대회 Vol.61 No.-

Prevention of chronic graft-versus-host disease by stimulation with glucocorticoid-induced TNF receptor

김주양,최욱선,김혜정,권병석 생화학분자생물학회 2006 Experimental and molecular medicine Vol.38 No.1

GITR (glucocorticoid-induced TNF receptor) is a recently identified member of the TNF receptor superfamily. The receptor is preferentially ex-pressed on CD4+CD25+regulatory T cells and GITR signals break the suppressive activity of the subset. In this study, we wanted to reveal the in vivo function of GITR in chronic graft-versus-host disease (cGVHD), a lupus-like autoimmune disease. A single injection of anti-GITR monoclonal antibody (DTA-1) was effective in blocking the progression of cGVHD in the parent-into-F1 model. Treatment of DTA-1 significantly decreased levels of IgG1 anti-DNA increased survival. The DTA-1-mediated inhibition of autoantibody production correlated with deletion of B cells and could occur independently of CD4+CD25+regulatory T cells. Our results indicate that anti-GITR monoclonal antibody may be used as a potential immunotherapeutic agent for preventing cGVHD.

소아와 청소년의 돌발적 비간질 발작의 진단에 있어 비디오-뇌파 모니터링의 유용성

이지연,이희선,최욱선,은소희,이기형,은백린,이주원 대한소아청소년과학회 2008 Clinical and Experimental Pediatrics (CEP) Vol.51 No.1

Purpose:In addition to epileptic seizures (ES), a variety of physiologic, organic and psychogenic disorders can manifest as paroxysmal behavioral events. Paroxysmal nonepileptic events (PNEs) are quite encountered in infants, young children, and adolescents. In a substantial proportion of cases, a careful history and examination will elucidate their nature. However, in other cases, it is necessary to differentiate PNEs from ES by video-electroencephalographic (EEG) monitoring. We report our experiences with PNEs in a group of children and adolescents who underwent video-EEG monitoring. Methods:From September, 2004 to June, 2006, one hundred thirty patients were monitored in the Pediatric Epilepsy Monitoring Units of Korea University Guro and Ansan hospitals. Their hospital charts were reviewed and video records of these events were analyzed. We observed all patients after video- EEG monitoring for more than 3 months. Results:Typical spells occurred during monitoring in 33 patients, not associated with a seizure pattern on EEG recordings. Two patients were diagnosed as frontal lobe epilepsy on basis of typical semiology and clinical characteristics, so 31 patients were documented to have PNEs finally. The mean age of patients was 7.2±5.8 years. The male to female ratio was 15 (48.4%) to 16 (51.6%). Among 31 patients, fifteen patients had associated disorders such as epilepsy, developmental delay, cerebral palsy, gastric ulcer, attention deficit hyperactivity disorder or depressive disorder. Somatoform disorder and factitious disorder was frequently seen in children more than 5 years old (P<0.05). Psychogenic disorder was more frequent in female (n=6) than in male (n=2) but there was no statistical significance (P>0.05). Conclusion:Our study suggests that video-EEG monitoring is an important diagnostic tool in the evaluation of paroxysmal behavioral events. With correct diagnosis of the PNEs, several unnecessary treatment could be avoided. (Korean J Pediatr 2008;51:62-66)

Enterobacter 균혈증의 임상양상 및 예후인자에 관한 고찰

김구엽,서환조,이성배,박종오,최욱선,홍승재,정일우,이희주 대한감염학회 1996 감염 Vol.28 No.5

목 적 : Enterobacter균은 인체 병원균으로, 기저질환이 있거나 병원에 입원중인 환자들에게 있어서 매우 중요하다. 최근들어, 항생제의 광범위한 사용, 고령층의 증가, 카테터 사용의 증가, 악성 신생물 질환의 증가, 장기이식의 증가 등에 따라 Enterobacter 균혈증이 증가되고 있으며 항생제에 대한 내성도 증가되어 점차 그 중요성이 강조되어지고 있다. 따라서 이의 임상양상 및 예후인자에 대하여 알아보고자 본 연구를 시행하였다. 방 법 : 1990년 1월부터 1994년 12월 까지 경희의대 부속병원에서 Enterobacter 균혈증을 보인 49예의 임상양상 및 치료, 예후와 관련된 인자 등을 후향적으로 조사하였다. 결 과 : 1) 49명 환자의 평균 연령은 39.1세(1일-88세)였고, 남녀비는 1.72:1 이었다. 2) 병원내 감염은 29명(59.1%)이었고, 복합균혈증은 6예(12.2%)였다. 3) 기저질환을 갖고 있었던 경우가 46예(93.8%)였으며, 감염경로로는 호흡기를 통한 경우가 가장 많았다. 4) 임상양상은 고열(75.5%), 백혈구 증가증(46.9%), 혈소판 감소증(34.6%), 그리고 패혈성 쇽(38.7%) 등이었다. 5) 항생제에 대한 감수성은 amikacin 89.9%, ciprofloxacine 87.5%의 감수성을 보였으나, ampicillin 4.2%, cephalothin 6.2%로 강한 내성을 보였다. 5) 15명이 균혈증으로 사망하였으며(30.6%), 사망과 관련된 예후인자로는 폐렴, 패혈성 쇽, 기저질환이 위중하였던 경우에서는 의미있게 높은 사망률을 보였으나(p<0.05), 성별, 병원내감염, 복합균혈증 유무에 따른 차이는 없었다(p>0.05). 결 론 : Enterobacter 균혈증은 기저질환으로 면역기능이 저하된 환자에서 많이 발생하며, 폐렴, 패혈성 쇽이 동반된 경우와 기저질환이 위중한 환자에서 높은 사망율을 보이며, 따라서 이들에 있어 항생제 감수성 결과에 따른 적절한 항생제의 투여가 매우 중요하다. Background : Enterobacter species have emerged as important human pathogens, particularly in hospitalized patients. Recently, the morbidity and mortality associated with Enterobacter bacteremia have increased. sick because popalativn of old ages, neoplasms, use of indwelling catheter, use of antibiotics and organ transplantations have increased, In this study the epidemiologic factors, clinical characteristics, treatment and outcome of 49 patients with Enterobacter bacteremia are reviewed in Kyung-Hee medical center during a 5-year period. Methods : Fourty-nine cases of Enterobacter bacteremia diagnosed from January 1990 to December 1994 in Kyunghee medical center were analysed by their clinical records retrospectively. Results : 1) Male to female ratio was 1.72:1 and mean age was 39.1. 2) Twenty-nine cases were nosocomially acquired; Enterobacter bacteremia six showed polymicrobial infections. 3) Significant underlying conditions were present in 46 patients(93.85%), and the respiratory tract infection was the most common source of bacteremia. 4) Common clinical manifestations were fever(75.5%), leukocytosis(46.9%) and thrombocytopenia(34.6%), and there were no symptom discrimating from or signs bacteremias by other gram negative organisms. 5) In vitro tests showed susceptibility rates of 89.9% to amikacin, 87.5% to ciprofloxacine, 4.2% to ampicillin and 6.2% to cephalothin. 6) Case fatality rate was 30.6% and the mortality was significantly increased with the presence of pneumonia, septic shock or other fatal underlying diseases. Conclusion : This study suggests that Enterobacter bacteremia is common in patients with altered host defenses secondary to serious underlying disease. Appropriate antibiotics are necessary to decrease the morbidity and mortality rates in enterobacter bacteremia with fatal underlying disease.

소아 간질 환자에서 oxcarbazepine의 효용성과 안전성

신혜경,이윤,이지연,최욱선,은소희,은백린,홍영숙,이주원 대한소아청소년과학회 2008 Clinical and Experimental Pediatrics (CEP) Vol.51 No.2

Purpose:Oxcabarzepine (OXC), newly recommended antiepileptic drug, has been prescribed for patients with partial seizures and generalized tonic clonic seizures in Korea from 1999. There are limited reports about an efficacy of OXC therapy in epileptic children in Korea. This study evaluated the efficacy and safety of OXC in the light of our experience. Methods:The patients, who had visited the pediatric neurology clinic of Korea University Guro Hospital from January 2001 to December 2006, were included. The data of 144 patients who were administrated OXC as monotherapy or polytherapy, was summarized retrospectively and we evaluated the efficacy and safety of OXC. Results:After 6 months of OXC therapy, 77 patients (53.5%, n=144) achieved seizure freedom, 48 patients (33.3%) experienced >50% improvement. After 12 months of OXC therapy, cessation of seizure was observed in 88 patients (61.1%, n=133), and 27 patients (18.8%) manifested an improvement. Monotherapy group showed superior efficacy to polytherapy one. The frequent side effects of OXC were drowsiness (20.1%), headache (12.5%), dizziness (9.7%) and rash (8.3%). They did not related to patient's age or sex, and dosage of OXC. Twenty four patients (16.7%) experienced hyponatremia, but which were neither symptomatic nor significant one. Conclusion:The efficacy and safety of OXC in our patients were excellent and had less significant side effects than established international one. We expect this report contributes toward OXC therapy in epileptic children. (Korean J Pediatr 2008;51:162-169)

뇌경색을 동반한 특발성 과호산구성 증후군 1 예

이성배,배종화,강흥선,김명식,송정상,최욱선,조정휘,김권삼 대한내과학회 1997 대한내과학회지 Vol.52 No.3

The idiopathic hypereosinophilic syndrome represent a heterogenous group of disorders with common features of prolonged eosinophilia of an undetectable cause and organ system dysfunction. Recently, we experienced a case of idiopathic hypereosinophilic syndrome with multifocal cerebral infarction. The patient was 33-year-old male and visited our hospital with right upper extremity weakness and headache. The blood eosinophil counts were 8,316/mma and the marrow showed eosinophils were predominant and in mature forms The two-dimensional echocardiogram showed hyperechoic density at left ventricular apical wall without thrombus formation. Multifocal infarctions were seen at left cerebellar hemisphere, left thalamus, right frontal lobe and left periventricular white matter on brain MRI scan. No cause for hypereosinophilia was found. He was treated with prednisone and hydroxyurea.