지난 2년간의 학회지 "신경정신의학" 심사 평가보고

김찬형,김세주,김도관,김성곤,박원명,송동호,박용천,이영문,오강섭,정영철,이상열,김주한,이동영,이헌정,함병주,김율리,김문두,김정진,이강욱,천근아,김재진,홍진표,홍승철 大韓神經精神醫學會 2007 신경정신의학 Vol.46 No.6

한국인 갑상선 수질암 환자에서 RET 원종양유전자 점돌연변이 양상

김형훈,김현진,정윤재,민용기,이명식,이문규,김광원,기창석,김종원,정재훈 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.4

연구배경: 갑상선 수질암의 25∼30%는 유전성으로 발현되는데, MEN 2A, MEN 2B 또는 가족성 수질암의 형태로 나타난다. RET 원종양유전자의 점돌연변이가 유전성 갑상선 수질암의 발생에 중요한 역할을 하므로, 진단 당시의 연령이나 가족력 유무에 관계없이 모든 갑상선 수질암 환자나 또는 RET 변이가 발견된 수질암 환자의 가족 구성원들에서 RET 변이 검색을 하여야 한다. 또한 일부 문헌에서 RET 변이의 양상에따라 임상상이 다르게 표현됨이 보고된 바 있다. 이에 저자들은 한국인 갑상선 수질암 환자에서 RET 원종양유전자의 점돌연변이의 양성률을 알아보고, 변이 양상에 따른 임상상의 차이가 있는지를 알아보고자 본 연구를 시행하였다. 방법: 치근 7년간 본원에서 갑상선절제술을 통해 갑상선 수질암으로 진단받은 29예에서 RET 원종양유전자의 점돌연변이 검사를 시행하였다. 29예의 평균연령은 39세(20∼60세)이었고, 남자 7예, 여자 22예 이었다. 이들의 말초혈액에서 genomic DNA를 분리하고, 특이 시발차를 이용하여 RET 원종양유전자의 exon10, 11, 13, 14, 16부위를 증폭하였다. 증폭된 부위를 자동염기서열분석기를 이용하여 직접 분석하였다. 양성으로 나온 경우는 모든 가족 구성원을 대상으로 RET 변이 유무를 검색하였다. 결과: 대상 환자 29예 중 9예 (31%)에서 RET 원종양유전자 점돌연변이가 발견되었다 RET 변이가 발견된 9예 (남자 3예, 여자 6예)의 평균 연령은 33세 (20∼51세)로 RET 변이가 발견되지 않은 20예의 평균연령 42세(24∼60세)보다 의미 있게 적었다. RET 변이가 발견된 9예 중 MEN 2A가 5예, 가족성 수질암이 1예, 그리고 산발성 수질암이 3예이었고, MEN 2B는단 1예도 진단되지 않았다. MEN 2A 5예 중 4예는 exon 11의 codon 634번(C634R 2예, C634Y 2예)에서, 그리고 나머지 1예는exon 10의 codon 618번 (C618R)에서 변이가 각각 발견되었다. 가족성 수질암 1아는 codon 634번(C634W)에서, 산발성 수질암 3예도 모두 codon 634번 (C634y 2예, C634s 1예)에서 각각 변이가 발견되었다. RET변이 양상 또는 위치에 따른 임상상의 차이는 발견할 수 없었다. 결론: 갑상선 수질암 환자 31%에서 RET 원종양유전자의 점돌연변이를 발견할 수 있었다. 유전성 수질암 중 가족성 수질암 1예를 제외하고 나머지 5예는MEN 2A이었다. 저자들의 5예와 지금까지 국내에서 보고 된 7예를 합친 국내 MEN 2A 12예 중 75% (9/12)는 exon 11의codon 634번(C634R 4예, C634y 4예, C634w 1예)에서, 그리고 나머지 25% (3/12)는 exon 10의 codon618번(C618R 2예, C618s 1예)에서 변이가 발견되었다. 국내에서는 codon 634과 codon 618 두 곳에만 국한된 양상이었고, codon 634에서의 C634R 변이는 1/3에서만 나타났다. 비록 본 연구에서는 제한된 환자 수 때문에 변이 양상과 임상상의 관계를 규명할 수 없었지만, 향후 많은 수의 환자를 대상으로 전향적인 연구를 시행하여 genotype-phenotype 관계 규명을 하는 것이 필요하다. Background: Medullary thyroid carcinomas (MTC) have been reported as hereditary in about 25 -30% of cases. The identification of germline mutation in RET proto-oncogene is important in the diagnosis of hereditary MTC, and occurs in three forms: MEN 2A, MEN 2B and familial MTC (FMTC). To evaluate the prevalence of the relationship of RET proto-oncogene mutation and genotype-phenotype was studied in Korean patients with MTC. Methods: Genomic DNA was obtained from 29 patients, with MTC, who underwent a total thyroidectomy, between 1997 and 2003, at the Samsung Medical Center. There were 7 male and 22 female patients, with an average age of 39, ranging from 20 to 60 years. Exon 10, 11, 13, 14 and 16 of the RET proto-oncogene were amplified, with specific primers, using PCR. A sequencing analysis was performed on the PCR product using an automatic sequencing analyzer. Results: Nine of the 29 patients (31%) were identified as having RET mutations. The average age of these 9 patients was 33 years, ranging from 20 to 51, with a female to male ratio of 2. Five patients had MEN 2A and one had FMTC, with the other 3 thought to have non-hereditary (sporadic) MTC. The 4 patients with MEN 2A had RET mutations on codon 634 of exon 11 (2 patients, C634R; 2 patients, C634Y) and the other patient on codon 618 of exon 10 (C618R). One patient with FMTC had a mutation on codon 634 (C634W). Three patients with sporadic MTC had RET mutations on codon 634 (2 patients, C634Y; 1 patient, C634S). However, no genotype- phenotype relationship could be found, due to the limited number of patients. Conclusion: Thirty-one percent (9/29) of the patients with MTC had RET proto-oncogene mutations. Three-quarters (9/12) of the Korean patients with MEN 2A, including another 7 patients reported in 3 papers in Korea, had RET mutations on codon 634 of exon 11 (4 patients, C634R; 4 patients, C634Y; 1 patient, C634W), but a quarter (3/12) had mutations on codon 618 of exon 10 (2 patients, C618R; 1 patient, C618S). Although no relations could be found between the genotypes and phenotypes, extensive prospective studies will be required to verify this (J Kor SOC Endocrinol 18:360-370, 2003).

간세포암과 감별이 어려웠던 악성중피종 치험 1예

김선문,허원석,채경훈,강윤세,정재훈,김연수,박기오,문희석,이엄석,김석현,성재규,이병석,이헌영,신경숙,조준식,송인상,강대영 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

Malignant peritoneal mesothelioma is a rare neoplasm that arises from the mesothelium of a serosal cavity and is a rapidly fatal disease with a median survival of 4 to 12 months for untreated cases. Recently, we experienced a case with malignant peritoneal mesothelioma who was suspected hepatocelluar carcioma by abdominal CT scan and was confirmed by biopsy including immunohistochemical stain(calretinin) after surgery. We performed tumor excisions and wedge resection of the liver(segment Ⅷ)and inserted Tencoff catheter in abdominal cavity at 25th day of post-operation. We treated with intraperitoneal paclitaxel(25mg/m^(2)/day for 5 days) six courses monthly. She was well tolerable and is still living without any evidence of recurrence for 14th month of post-operation.

서울의 PPNG 발생 빈도(1991-1992)

김재홍,윤기범,박평원,김영진,전경민,김영태,김중환,곽호,구상완,송민석,유옥,지혜구,김동원,문상은,박영립,정승호,성범진,성순제,엄주용,황정열,이기홍,이주협,전태진 대한화학요법학회 1994 대한화학요법학회지 Vol.12 No.1

The prevalence of PPNG among pretreated gonorrhea cases isolated at the STD clinic of Choong-Ku Public Health Center in Seoul has been studied and reported annually since 1981. In 1991, 123 strains of N.gonorrhoeae were isolated, among which 58(47.1%) were PPNG. In 1992, 98 starains of N.gonorrhoeae were isolated, among which 51(52.0%) were PPNG. In all, 109(49.3%) strains were found to be PPNG among 221 strains isolated between 1991-1992. The prevalence of PPNG in Seoul showed increased tendency till 1989, thereafter, it has been stationary or slightly decreasing.

서울의 Penicillinase Producing Neisseria gonorrhoeae 발생빈도(1997)

김재홍,문득곤,김정수,김용준,임동진,박상훈,김희성,이민수,송기훈,김갑형,김형석,성소영,이인섭,김석우,황지환,조창근,김경문,부태성 대한화학요법학회 2000 대한화학요법학회지 Vol.18 No.3

Background : In recent years, gonorrhea has been pandemic and remains one of the most common STDs in the world, especially in developing countries. Objective & Methods : For the detection of a more effective therapeutic regimen and assessing the prevalence of PPNG, we have been trying to study the patients who have visited the Venereal Disease Clinic of Choong-Ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. Results : In 1997. 99 strains of N. gonorrhoeae were isolated, among which 45(45.5%) were PPNG. Conclusion : The prevalence of PPNG in Seoul, which had been decreased to 39% in 1996 after a peak of 74.3% in 1993, is increased to 45.5% in 1997.

담낭절제술 후 발현된 간, 신장 및 복막을 침범한 유전분증 1예

김성연,김덕영,김경아,송준호,이승우,한지영,김문재 대한내과학회 2003 대한내과학회지 Vol.65 No.1

저자 등은 최근 담낭절제술을 시행받은 후에 발생된 간기능 이상과 조절되지 않는 복수를 주소로 내원한 환자에서 진단된 유전분증 1예를 경험하였기에 보고하는 바이다. Amyloidosis is a heterogenous group of often fatal disorders characterized by extracellular deposition of a proteinaceous material with a unique fibrillar form in various tissues and organs. Deposition of amyloid may cause widespread dysfunction of the involved organs. Recently, we experienced a case of 40-year-old male patient with nephrotic syndrome, uncontrolled ascites and jaundice, which developed after cholecystectomy. We confirmed systemic amyloidosis involving kidney, liver and peritoneum by kidney and liver and peritoneum biopsy. The case that, having about a month of incubation period after cholecystectomy, amyloidosis occurred in a healthy man before the operation, and that amyloid was deposited in the peritoneum site incised during the operation provides grounds that amyloidosis may be triggered by cholecystectomy. Given the rarity of this case, the following is a report of this case and a review of the relevant literatures.

서울의 Penicillinase Producing Neisseria gonorrhoeae 발생빈도(1998)

김재홍,김준호,반재용,이정우,황성주,정준규,정성태,강진문,조흔정,홍창의,정혜신,이한승,김이선,이봉길,이종호,선영우,한기덕,윤성필,이성훈,안종성,박석범,문승현,조항래,김형섭,류지호,황재영,박준홍,손상욱 한양대학교 의과대학 2001 한양의대 학술지 Vol.21 No.1

In recent years, gonorrhea has been pandemic and remains one of the most common STDs in the world, especially in developing countries. For the detection of a more effective therapeutic regimen and assessing the prevalence of Penicillinase Producing Neisseria gonorrhoeae(PPNG), we have been trying to study the patients who have visited the Venereal Disease Clinic of Choong-Ku Public Health Center in Seoul since 1980 by menas of the chromogenic cephalosporin method. In 1998, 93 strians of N. genorrhoeae were isolated, among which 60(64.5%) were PPNG. The prevalence of PPNG in Seoul, which had been decreased to 39% in 1996 after a peak of 74.3% in 1993, is increased to 64.5% in 1998.

한국인 제1형 당뇨병에서 체도 세포질 항체의 양성률 : 항GAD항체, 항ICA512항체, 항phogrin항체의 조합 측정으로의 대체 가능성 Possible Replacement with Combined Measurement of Anti-GAD, Anti-ICA512, and Anti-phogrin Antibodies

김경아,김동준,정재훈,민용기,이문규,김광원,진동규,고경수,김상진,이명식 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.6

연구배경:최근 당뇨병의 분류를 새로 제정함에 있어 자가항체가 양성이면 임상형에 상관없이 제1형 당뇨병으로 분류하자는 제안이 나옴으로써 자가항체의 중요성은 더욱 커질 것으로 예상된다. 특히 우리나라와 같이 비비만형인 제2형 당뇨병이 많은 나라에서는 당뇨병의 병인 규명에 자가항체가 중요한 위치를 차지할 것으로 사료된다. 자가항체 중에서 전통적으로 측정되어온 췌도 세포질 항체(ICA)는 표준화하기 어렵고 기술적으로 제한점이 많으며 현실적으로도 췌장 공여자가 적은 점 등이 문제로 알려져 있다. ICA의 대응 항원들로는 GAD(glutamic acid decarboxylase), IA­2(islet­associaated antigen­2;ICA512), IA­2β(phogrin)등이 있다. 이러한 대응 항원에 대한 특이적인 자가항체의 측정은 ICA에 비해 표준화되었으며 최근에는 방사면역측정법(radioimmunoassay;RIA)키드까지 등장하여 손쉽고 정확히 이를 측정할 수 있게 되었다. 연구자들은 한국인 제1형 당뇨병에서 측정법이 표준화 되어 있는 항GAD항체 및 항ICA512항체 조합(combimation)의 조합으로 ICA의 측정을 대신할 수 있는지를 조사하였고 더 나아가 항phogrin항체의 조합 측정으로 임상적 유용성이 있는지 보고자 하였다. 방법: ICA는 면역조직화학 염색법을 이용하였다. 항 GAD항체는 상업화 된 키드(RSR??, United Kingdom)를 이용하였다. 항 ICA512항체와 항phogrin항체의 측정은 in vitro transcription&translation한 후 이를 이용해 방사면역 침전법을 이용하였다. 대상 환자로는 전형적 제1형 당뇨병 76명, 지진형 제1형 당뇨병 22명, 제2형 당뇨병 39명이었으며 각 군간의 연령은 각각 22.8±14.0, 37.9±13.9, 45.3±12.3세였다. 결과:1)전형적인 제1형 당뇨병에서는 ICA의 양성률이 30%, RIA조합만의(항GAD항체 또는 항 ICA512항체 또는 항phgrin항체 한가지에라도 양성인 경우)양성률이 57%이었다. 지진형 제1형 당뇨병에서는 각각 18%, 50%이었다. 제2형 당뇨병에서는 각각 7.7%, 5.1%이었다. 2)각 군에서 ICA가 양성인 군에서 RIA조합 양성률을 보면 전형적 제1형 당뇨병에서는 96%, 지진형 제1형 당뇨병에서는 100%에서 양성이었고 제2형 당뇨병에서는 RIA 조합 양성이 없었다. 각 군에서 ICA가 음성인 군에서도 RIA 조합시 전형적 제1형 당뇨병에서는 40%, 지진형 제1형 당뇨병에서는 39%에서 양성이었고, 제2형 당뇨병에서는 5.6%에서 양성이었다. 3)전형적 제1형 당뇨병에서 ICA가 양성인 군(n=23)에서 96%가 RIA조합 양성이었는데 이때 각각의 RIA유형을 보면 항GAD항체 양성이 87%였다. 한편 항 ICA512항체 양성이 48%, 항phogrin항체 양성이 44%이고 항GAD항체 도는 항ICA512항체 양성이 96%를 차지한다. 지진형 제1형 당뇨병에서는 ICA가 양성인 군(n=4)에서는 항 GAD항체 양성이 3명, 항ICA512항체 양성이 1명이었다. 따라서 기존의 ICA를 RIA조합으로 대체할 수 있을 것으로 사료되었는데 이때 항GAD항체와 항ICA512항체의 조합이 도움이 되겠고 항phogrin항체의 추가적인 검사는 일부의 환자에서만 도움이 되리라 사료된다. 4)이환 기간에 따라 ICA와 RIA조합을 비교시 ICA는 차이가 없었으나 RIA조합의 양성률은 지진형 제1형 당뇨병에서 4년 이상의 이환 기간이 지나면 그 이전보다 떨어졌다. 5)발병 연령에 따라 ICA와 RIA조합을 비교시 ICA 양성률이 전형적 제1형 당뇨병에서 15세 이전에 발병한 그룹에서 그 이후에 발병한 그룹보다 유의하게 높았다. 결론:이상의 결과를 요약하면 항GAD항체 및 항ICA512항체 측정의 조합은 ICA보다 민감도가 높아 기존의 ICA를 대체함은 물론 임상적 이용에서 현격한 우월성을 보이며, 성인에서 발병한 비전형적인 당뇨병의 분류에도 도움이 될 것으로 사료되었다. 추가적인 항phogrin항체의 측정은 임상적 유용성이 없었다. Background : Type 1 diabetes includes all forms of autoimmune-mediated and idiopathic beta-cell destruction leading to an absolute insulin deficiency. Evidence of an autoimune pathogenesis was assessed by studying cytoplasmic islet cell antibodies (ICA), antibodies to glutamic acid decarboxylase (GADA), antibodies reacting with an islet tyrosine phosphatase-related molecule referred to as ICA 512 (ICA 512A), or its homologue phogrin (phogrin-A). In comparison with ICA, the best validation to assess the risk of type 1 diabetes, shows that a combination of antibodies to GADA with ICA 512A has the power to detect a majority of ICA and 97 ~ 100% of subjects who progressed to overt diabetes. These findings suggest the possibility of replacing the laborious ICA test in the screening programs to identify subjects at risk of progressing to type 1 diabetes or for classifying the stage of diabetes at the time of diagnosis. Up to now, it is unclear whether these results are applicable to the slowly progressive type 1 diabetes that appears to be more prevalent in Asian than in western countries. The prevalence of combined autoantibody testing (1≥ of GADA, ICA512A, or phogrin-A) was investigated in the patients with type 1 diabetes (typical and slowly progressive) and type 2 diabetes, and compared with that of ICA which is a more laborious and insensitive test. Methods : The ICA assay was performed using immunoenzymatic staining of frozen human (blood group O) pancreatic sections with serial dilutions of serum samples with peroxidase-labeled protein A. For the GADA determination, commercially available GADA radiommunoassay kits utilizing the ^125I-labeled recombinant GAD65 (RSR®, United Kingdom) as an antigen was used. Either ICA512A or phogrin-A were detected by a radioligand-binding assay after in vitro transcription and translation using the clone ICA512bdc or phogrin c DNA. Serum was obtained from 76 patients with type 1 diabetes(mean age 45.3± 12.3 years). Typical and slowly progressive type 1 diabetes patients had the disease for between 4.0±4.6 and 10.1±9.5 years, respectively at the earliest serum sampling. Results: 1) In typicaltype 1 diabetes, 30% of patients tested positive for ICA and 57% for the combined autoantibody test. In type 2 diabetes, 7.7% and 5.1% tested positive, respectively. 2) Ninety-six percent of ICA-positive patients expressed one or more of the 3 auto-antibody specificities in typicaltype 1 diabetes. Among the 53 ICA-negative patients with typicaltype 1 diabetes, 40% had one or more of these auto-antibodies. In the slowly pregressive type 1 diabetes, 100% of the ICA-positive and 39% of the ICA-negative patients expressed one or more of the 3 autoantibody specificities. 3) Of the 23 patients with ICA-positive typical type 1 diabetes patients, 87% had a positive result for GADA, 48% FOR ICA512A, 44% for phogrin-A, and 96% for GADA or ICA512A. Of the 4 patients with ICA-positive slowly progressive type 1 diabetes, three had a positive result for GADA, and 1 for ICA512A. 4) When the prevalence of combined autoantibody testing was analyzed according to the duration of diabetes, the prevalence in patients tested within 4 years after the diagnosis and more than 4 years after the diagnosis was 61% and 52%, respectively in typical type 1 diabetes. Furthermore, that for the ICA was 37% and 21%, respectively. In the slowly progressive type 1 diabetes, the prevalence of combined auto-antibody testing was 88% and 25%, respectively (p<0.05), while that of ICA was 25% and 13%, respectively. 5) In typical type 1 diabetes, ICA were detected more frequently in patients younger than 15 years of age (48%) than in older patients (23%) (p<0.05), while the prevalence of combined auto-antibody testing -was not different according to the onset age(65% vs 53%). Conclusion : Combined autoantibody testing for GADA and ICA512A is more sensitive that ICA in type 1 diabetes. Therefore, it could replace the laborious ICA measurement and may be useful for discriminating the etiology of adult onset a typical diabetes(J Kor Diabetes Asso 25 :430~445, 2001).

망간 노출 근로자의 정신 ·신경행동 양상에 영향을 주는 요인

문영한,권기련,김은아,김규상,김양호,김재우,노재훈,양정선,진영우 大韓産業醫學會 1999 대한직업환경의학회지 Vol.11 No.2

The risk posed to human health by environmental manganese (Mn) exposure is unknown. The purpose of this study is to establish if subclinical effects related to Mn exposure and examine the factors influencing psychoneurobehaviral outcomes of Mn exposed workers. This study involved 121 male workers of welding, alloy furnace, and manufacturing of welding stick. Study investigations include: a questionnaire covering demographic characteristics, job and exposure history and medical symptoms and conditions, monitoring workplace air for personal exposure to respirable and inhalable manganese, analysis of blood and urine samples, psychoneurobehaviral test(neurobehaviral core test battery(NCTB), signal change on magnetic resonance imaging (MRI) scans, minimental state and neurological examination). The main results of this study were as follows; 1. Preliminary results showed that, with increasing manganese exposure, neurobehaviral performance was poorer and signal change on MRI scans increased. 2. The results of examination revealed significant relations on psychoneurobehaviral outcomes (neurobehaviral performance, signal change on MRI scans, and neurological features). 3. In multiple regression, age and educational status as demographic variables and exposure level were significantly related to neurobehaviral test. Also exposure level and serum Mn concentrations were positively related to signal change on MRI scans and neurological features affected by Mn on the brain (signal change). 4. Psychoneurobehaviral outcomes from Mn exposure were related to neurobehaviral performance, signal change on MRI scans, neurological features and profile of mood states (POMS), and influenced positively with age, alcohol and smoking history, and duration of Mn exposure, negatively with educational status. Serum Mn concentrations in combination with brain MRI scans, and perhaps a battery of neurobehaviral tests, appear to be the best way to monitor excessive exposure to Mn. These results are consistent with our knowledge on Mn action on the brain and are similar to the type of neurobehaviral dysfunction. They suggest that there may be age, educational status, and life style (alcohol and drinking history) differences with chronic environmental exposure. These findings suggest further evaluation, particularly on relationships between Mn exposure, aging, and susceptibility factors.

급성심근경색후 발생한 심실중격결손 2례

김태희,이재호,김애란,허민영,문치숙,정수룡,김대경,김두일,김동수 인제대학교 백병원 2002 仁濟醫學 Vol.23 No.4

Ventricular septal defect remains an infrequent but devastating complication of acute MI. Approximately 1∼3% of cases of acute myocardial infarction are complicated by ventricular septal rupture in the prethrombolytic era and the incidence has decreased to 0.2% with reperfusion therapy. This mechanical complication usually occurs within the first 10 to 14 days when necrotic tissue is most abundant and the collateral coronary circulation is not well developed. This lesion is generally associated with complete coronary obstruction rather than severe stenosis. Rupture of the ventricular septum is a severe mechanical complication of acute myocardial infarction, usually resulting in death unless surgical repair is performed. The bad prognosis of this event within the first 2 weeks indicates the need for early surgical rapair. This complication is more frequent after the first acute myocardial infarction in the elderly and secondary to a transmural myocardial infarction. We report two cases of ventricular septal rupture after acute myocardial infarction.