가와사끼병에서 감마글로불린 치료 용량(1g/kg 단일요법과 2g/kg 단일요법)의 비교

인수미,안인철,길홍량,정용현 대한소아청소년과학회 2000 Clinical and Experimental Pediatrics (CEP) Vol.43 No.7

목 적 : 가와사끼병에서 아스피린과 IVGG 병용투여가 가장 효과적인 방법으로 알려져 있으나 IVGG의 적절한 용량 및 용법 등이 여전히 논란의 여지가 많다. 이에 저자들은 기존의 IVGG 2g/kg 단일요법과 비교하여 IVGG 1g/kg 단일요법의 임상적 적용과 치료효과에 대하여 알아보고자 하였다.방 법 : 1996년 2월부터 1999년 1월까지 충남대학교병원 소아과에 입원한 가와사끼병 환아중 고위험군(Harada 점수 4점 이상)을 대상(63명)으로 IVGG 1g/ kg 1회 A군(32명), 2g/kg 1회 B군(31명)으로 나누어 IVGG 치료 전, 후의 임상경과, 검사 소견 및 심혈관 합병증을 비교 분석하였다. Purpose : Treatment of Kawasaki disease with intravenous gamma globulin(IVGG), together with aspirin, has been demonstrated to be safe and effective in preventing coronary artery lesion and systemic inflammation, but optimal IVGG dosage and administration method are still controversial. We compared the therapeutic efficacy and clinical response of single IVGG 1g/kg to that of IVGG 2g/kg for comparable risk group of Kawasaki disease. Methods : We conducted a prospective study involving 63 children with Kawasaki disease requiring IVGG treatment(Harada score■4) at Chungnam National University Hospital from February 1996 to January 1999. The children were assigned to receive IVGG either as a single infusion of 1g/kg(A group, 32 person) or 2g/kg(B group, 31 person) and aspirn(100mg/kg/day through acute phase, then 3 to 5mg/kg/day for 8 weeks of duration). Results : There were no significant difference between the two groups according to clinical and laboratry data, including coronary artery lesions(group A, 31.3% and group B, 29.0%) before treatment. After IVGG treatment ratio of complication with coronary artery lesion(group A 1/32=3.1% and group B, 2/31=6.5%) and that of retreatment(group A, 4/32=12.5%, group B, 2/31=6.5%), duration of fever(group A, 1.3■1.6 days and group B, 0.7■1.4 days), hospital stay(group A, 7.0■1.4 days and group B, 6.5■2.0 days), laboratory finding and side effects of IVGG were not significantly different(P>0.05). The total dosage of IVGG was significantly lower in group A than group B(group A, 1.16■0.37g/kg, 375,421■207,351 ￦ and group B, 2.10■0.40g/kg, 641,498■274,750 ￦(P<0.05). Conclusion : The therapeutic efficacy and clinical response of single 1g/kg therapy are comparable to that of single 2g/kg therapy.

Floppy Infant에 관한 연구

이건수,안인철 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.1

16 cases with floppy infant syndrome were observed at the department of Pediatrics at Chungnam National University Hospital during a period of ll years from January, 1986 to December, 1996. The results were as follows: 1. The incidences of disease were Werdnig-Hoffman disease(W-H-D, 7 cases), Guillain-Barre syndrome(GBS, 3 cases), congenital muscular dystrophy(2 case), congenital myasthenia gravis (2 cases), congenital myotonic dystrophy(1 case) and neonatal myasthenia gravis(1 case) in order of frequency. 2. The sex ratio of male to female was 1.3 : 1. 3. The main symptoms and signs were decreased muscle tone(93.8%), decreased tendon reflex (75%), dysphagia(75%), respiratory distress(75%), abnormal traction response(68.8%), abnormal vertical response(68.8%), weak crying(62.5%), poor head control(62.5%), frog leg posture(62.5%) and fasciculation(31.3%) in order of frequency. 4. The EMG findings of W-H-D and GBS were increased amplitude and duration. The EMG findings of congenital muscular dystrophy and congenital myasthenia gravis were reduced amplitude and duration. The EMG findings of congenital myotonic dystrophy and neonatal myasthenia gravis were normal. 5. The ceatine kinase(CK) levels of W-H-D, GBS, congenital myasthenia gravis and neonatal myasthenia gravis were normal. The CK levels of congenital muscular dystrphy and congenital myotonic dystropohy were increased.

심초음파를 이용한 태아심장 기형의 평가

진병로,안인철,이윤이,길홍량 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.1

Congenital heart disease is the most common congenital malformation and its incidence is 8/1000 live birth, and contributes to significant perinatal morbidities and mortalities. With the advancement of echocardiogrphic equipment and technique, it is enable to detect the heart anomalies in utero. We performed 94 fetal (93 mothers) echocardiographic examinaton. 10 confirmed and 3 unconfirmed cardiac anomalies were identified. The common cardiac anomalies were ventricular septal defect(4), tetralogy of Fallot(2), and tricuspid valve regurgitation(2). The common indications of fetal echocardiography were as follows: family history of congenital heart disease(26), suspection by obstericians(24), fetal arrhythmia(13), and other organ anomaly(7). But the relative yield of indication were; suspected by obstericians 33.3%, other organ anomaly 14.3%, family history of congenital heart disease 7.6%, and fetal arrhythmia 7.6%. The false positive result was only 1 case of ventricular septal defect, which was normal in postnatal examination. The mean maternal age was 27years 5months in confirmed cases and 25years 5month s in unconfirmed cases. The fetal echocardiographic study for cardiac anomalies is reliable and accurate method in selected indicated groups, but systematic approach for screening method and identified cardiac anomalies would be needed.

신경세포 이주장애에 관한 연구

이건수,안인철 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.1

25 cases under 15 years of age with neuronal migration disorders were observed at the department of Pediatrics at Chungnam National University Hospital during a period of 6 years from January, 1992 to December, 1997. The results were as follows: 1. The peak incidence of age was 5 to 10 years(40.3%). The sex ratio of male to female was 1.8 : 1. 2. The types of neuronal migration disorders were cortical dysplasia (36%), lissencephaly(28%), schizencephaly(16%), heterotopia(12%) and megalencephaly(8%) in order of frequency. 3. The clinical findings were seizure(76%), delayed development(48%), delayed speech(32%), mental retardation(24%) and motor deficit(20%) in order of frequency. 4. The locations of disorder were frontal lobe(72%), parietal lobe(60%), temporal lobe(40%) and occipital Iobe(32%) in order of frequency. 5. The abnormal EEG findings were 17 cases(68%). Among these cases, focal abnormalities were 5 cases(29.4%), general abnormalities were 11 cases(64.7%) and abnormal background was 1 case(5.9%). 6. The seizure types were generalized seizure(63.2%), partial seizure (31.6%) and mixed seizure (5.3%) in order of frequency. 7. The patients with larger size of lesions had more delayed development, delayed speech and mental retardation.

간질 환아의 혈청 지질에 관한 연구

이건수,안인철 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.2

Purpose : To assess the changes of treatment of phenobarbital, carbamazepine, valproic acid and polytherapy on serum lipids in epileptic children. Method : We determined serum levels of total cholesterol(TC), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), and triglycerides in 50 healthy children and in 80 children with epilepsy who had been receiving phenobarbital(9 patients), carbamazepine(20 patients), valproic acid(30 patients), or polytherapy (21 patients) Results : In the group receiving phenobarbital, mean TC, HDL-C and LDL-C levels were significantly higher than in the control group. In the group receiving carbamazepine, mean TC levels were significantly higher than in the control group. In the group receiving valproic acid, mean triglyceride and HDL-C levels were significantly lower than in the control group, but mean LDL-C/HDL-C ratio were significantly higher than in the control group. In the group receiving polytherapy, mean TC and LDL-C levels were significantly higher than in the control group. In neither group did mean TG/HDL-C ratio differs significantly from the corresponding control groups. Conclusion : Our results suggest long-term treatment of anticonvulsants significantly modify serum lipids in epileptic children.

바이러스성 수막염에서 뇌척수액 IL-6의 임상적 의의

주은주,안인철,이재호 대한소아청소년과학회 2000 Clinical and Experimental Pediatrics (CEP) Vol.43 No.4

Purpose : Cytokines found at a inflammatory site may be a good indicator of clinical severity of an infectious inflammatory disease. We assayed interleukin 6(IL-6) concentrations in cerebrospinal fluid(CSF) from patients affected with viral meningitis, and verified the relationship between IL-6 and inflammatory parameters and whether IL-6 can be used as a diagnostic marker in the diagnosis of viral meningitis. Methods : We measured CSF IL-6 concentration in viral meningitis(30 cases) and healthy children(3 cases) by using ELISA, and also measured serum and cerebral spinal fluid(CSF) chemistry and inflammatory markers, including C-reactive protein(CRP). We compared the data and analyzed the relationship between the results. Results : The CSF IL-6 levels of viral meningitis(520.1■384.3pg/dL) were significantly higher than that of normal control(2.3■4.0pg/dL)(P<0.05). The relationship between CSF IL-6 level and serum CRP was significant(P=0.0041). The relationship between CSF protein level and CSF IL-6 level was significant(P=0.001). There was no significant correlation between CSF IL-6 level and CSF WBC count. Conclusion : According to these results, we concluded that viral meningitis is highly associated with CSF IL-6, and we predict CSF IL-6 is useful in the diagnosis and prediction of treatment for viral meningitis. 목 적 : 바이러스성 수막염 환아의 척수액에서 IL-6 농도와 세포수, 당 및 단백질 농도와 혈청 CRP를 측정하여 IL-6와 기타 검사결과들과의 상관관계를 조사 연구함으로써 바이러스성 수막염에서 나타나는 IL-6의 임상적 의미를 규명하고자 본 연구를 실시하였다.방 법 : 바이러스성 수막염으로 입원하였던 환아 30례를 대상으로 내원시 혈청과 척수액을 동시에 채취하여 뇌척수액의 세포수, 당, 단백질 검사와 혈청 CRP 를 측정하였으며 뇌척수액의 IL-6는 척수액을 채취한 후 영하 70도에 보관하였다가 ELISA방법으로 측정하였다.

신생 백서에서 IGF-I 투여가 저산소성 허혈성 뇌병증에 관련된 유전자 발현에 미치는 효과

이형신,변상현,안인철,송규상,이영익,한유정,정용현 대한소아청소년과학회 2001 Clinical and Experimental Pediatrics (CEP) Vol.44 No.7

Pilocarpine 에 의한 중첩경련에서 성장호르몬의 신경 보호 작용

유재홍,송규상,안인철 대한내분비학회 2001 Endocrinology and metabolism Vol.16 No.1

Background: Several growth factors, including growth hormone (GH) and Insulin like growth factor-I, have been reported to have a neuroprotective effect in experimental models of hypoxic ischemia. This study is aimed at assessing the clinical significance of growth hormone for neuroprotection in status epilepticus induced neuronal cell deaths. Methods: Pilocarpine induced status epilepticus (SE) was studied in rats (male, Sprague-Dawley). Rats were divided into pre- or post-treatment groups that had either a low (5 U/kg/day) or high (10 U/kg/day) dose of recombinant human GH (Eutropin, LGCI, Korea), and then subdivided into 24 hour, 72 hour and 1 week groups. This was done in the pretreatment groups for 5 days before SE and in the post-treatment groups for 5 days after 2 hrs of SE injection, after SE, the GH was daily injected via intraperitoneal route. Status epilepticus was induced by pilocarpine (360mg/kg) with scoplamine (1 mg/kg) 30 minutes before pilocarpine injection using a stereotaxic instrument and EEG monitoring. Rats were killed at 24 and 72 hours after the SE in the pretreatment groups and at 1 week after the SE in the post-treatment groups for pathology studies. Neuronal injuries in the rat brain were studied by Hematoxylin & Eosin stain and the TUNEL method. Results: Neuronal necrosis was found in the hippocampal CA1 and CA3 regions in all experimenatal groups after SE, and was more severe in the CA3 region. Apoptosis was found only in the pre-GH treated group and there were TUNEL-positive and morphologically necrotic cells in the hippocampal CA1 and CA3 regions at 72 hours after SE. Neuronal necrosis and apoptosis were significantly decreased in the high dose GH treated groups (p$lt;0.05) compare to controlsd, but not in the low dose GH hormone treated groups (p$gt;0.0.5). Conclusion: Growth hormone has a neuroprotective effect in neuronal cell death (necrosis and apoptosis) that is caused by pilocarpine induced status epilepticus in a dose dependent manner and prevents the activation of apoptosis by SE in neurons which eventually become necrotic (J Kor Soc Endocrinol 16:26-38, 2001).

항경련제 투여 환아의 간기능 변화

황치관,이건수,안인철 충남대학교 의과대학 지역사회의학연구소 2000 충남의대잡지 Vol.27 No.1

Routine liver function test is done in epileptic children receiving antiepileptic drugs to prevent hepatotoxicity induced by these drugs. The abnormalities of liver function test are rarely seen, but these abnormalities accompanied by the clinical manifestation of hepatotoxicity are seldomly seen. This study carried out in order to assess the efficacy of routine liver function test in epileptic children. We examed the changes of the serum level of aspartate transferase(AST), alanine aminotransferase(ALT), total bilirubin, total protein, albumine, alkaline phosphatase(ALP) before and after antiepileptic drug medication in 60 epileptic children who had been receiving valproic acid(n=25명), ethosuximide(n=6명), carbamazepine(n=4명), valproic acid and carbamazepine(n= 14명), and other polytherapy(n=11명) for 3months or more. Results are as follows ; 1) The difference in each groups according to age, duration of treatment, and drug plasma concentration was not found. 2) AST was within normal range in any group, but decreased after valproic acid, ethosuximide, carbamazepine, and other polytherapy treatment. 3) ALT was within normal range in any group, but decreased after valproic acid treatment. 4) Total bilirubin, total protein, albumin, and ALP were within normal range in any groups. 5) Y-GT was within normal range, but the values were increasing tendency in polytherapy groups. 6) No clinical significant menifestations had developed during study period in any groups. The result suggest that the routine liver function test itself can not be the indicator of hepatotoxicity, and that the liver function test exammed when the clinical symptoms appear is more effective than the routine liver function test.

Pilocarpine에 의한 간질 중첩증 동물 모델에서 MK 801이 뇌 손상, 자발적 경련 발생 및 태상 섬유 발아에 미치는 영향

황규은(Gyu Eun Whoang),안인철(Ren Zhe An),임혜경(Hae Hyung Lim),이건수(Keon Su Lee) 대한소아신경학회 2001 대한소아신경학회지 Vol.9 No.1

목적: Pilocarpine 동물 모델을 이용하여 NMDA 수용체 길항제인 MK 801이 뇌 손상, 태상 섬유 발아 및 자발성 반복성 경련에 미치는 영향을 관찰하고, 또한 간질발생에서 위의 여러 인자간의 상호 작용 및 역할에 대해 알아보고자 하였다. 방법: 52마리의 생후 7-8주된 몸무게 180-240g 되는 수컷 Sprague-Dawley 종의 흰쥐를 ketamine/xylazine을 복강내 마취 후 고정 장치를 사용하여 뇌의 F3, P3, F4, P4 부위에 전극을 부착시켰다. Pilocarpine(360㎎/㎏)을 복강내에 주사한 흰쥐의 70%(70/100)에서 주사 후 10분에서 40분 사이에 경련이 유발되었으며, 1시간 이내에 경련이 유발되지 않으면 Pilocarpine(175㎎/㎏)을 재차 투여한 경우 86.6%(26/30)의 동물에서 경련이 유발되었다. 결과: MK 801 치료군과 대조군의 두 군으로 나누어 실험한 결과 다음과 같은 결과를 얻었다. 1) MK 801 치료군에서 평균 경련 지속시간은 62.00±6.80분이었고, 대조군에서는 평균 61.10±7.37분으로 두 군에서 의미있는 차이는 없었다(P>0.05). 2)경련 지속 상태 후 24시간, 72시간, 6주에 H & E 염색으로 해마 부위의 세포 괴사를 관찰한 결과, MK 801 치료군에서는 신경 세포 괴사가 관찰되었다. 3) 경련 지속 후 6주에 대조군은 자발성 반복성 경련이 70%(7/10)에서 발생한 반면, MK 801 치료군에서는 한 마리도 발생하지 않았다. 4) 평균 태상 섬유 발아 점수가 대조군에서는 2.05±0.47으로 치료군의 0.40±0.31에 비하여 의미 있는 차이를 보였다(P<0.05). 결론: 본 연구 결과 MK 801은 자발성 반복성 경련의 발생과 태상 섬유 발아의 발생을 차단하는 작용이 있고, 자발성 반복성 경련의 발생과 태상 섬유 발아의 발생은 NMDA 수용체 활성화와 관련이 있으며, NMDA 수용체 활성화는 간질 발생에 중요한 역할을 할 것으로 사료된다. Purpose: We investigated the effect on MK 801 on the development on brain damage, spontaneous recurrent seizures and mossy fiber sprouting in the pilocarpine induced status epilepticus animal model. Methods: Fifty two adult Sprague Dawley male rats(180-240gm) were studied under ketamine/xylazine(87㎎/13㎎/㎏, IP) anesthesia and were implanted at the F3, P3, F4, P4 areas for recording EEG. With a single intraperitoneal(IP) administration of pilocarpine hydrochloride(360㎎/㎏), 70% developed status epilepticus(SE). When SE was not induced within 1 hour after injection of pilocarpine, the second dose of pilocarpine(175㎎/㎏, IP) was injected, with 86.6% of success. Results: All studied animals were divided into two large groups, one group was treated with NMDA receptor antagonist, the other was control group. The mean duration of SE was 62.00±6.80 minutes in the MK 801(1㎎/㎏, IP, 30 minutes after SE) treated group, and 61.10±7.37 minutes in the control group without any signigicant differences(P>0.05). Neuronal loss(necrosis dominantly) was observed at CA1 and CA3 areas in the control group, with more loss after 6 weeks than 24 or 72 hrs specimens. However, there was no neuronal loss in MK 801 treated group. The protective effect of MK 801 for neuronal injury suggested the glutamate receptor activation was involved in the neuronal injury induced by repeated seizure attack. Spontaneous recurrent seizures(SRS) were observed 70% of animals in the control group, but there were no SRS observed in the MK 801 treated group. The mean scores of mossy fiber sprouting were significantly higher in the control group(2.05±0.47) than MK 801 treated group(0.4±0.32)(P<0.05). Conclusion: These results suggested that SRS and mossy fiber sprouting were associated with NMDA receptor activation, and NMDA receptor activation had a key role in the epilepsy development.