그레이브스 병에서 항갑상성제 투여중 발생한 갑상성기능저하증의 치료

송기호(Ki Ho Song),김병수(Byung Su Kim),장상아(Sang A Jang),안유배(Yu Bae Ahn),한제호(Je Ho Han),유순집(Soon Jip Yoo),이종민(Jong Min Lee),손현식(Hyun Sik Son),윤건호(Kun Ho Yoon),감무일(Moo Il Kang),차봉연(Bong Yun Cha),이광우(Kwang Wo 대한내과학회 1996 대한내과학회지 Vol.51 No.3

N/A Objectives : Antithyroid drug is highly effective and safe in the treatment of Graves` disease. However, some patients may be rendered hypothyroid by large dosage of andithyroid drug : at this point reduction of dosage is common but often difficult to quantitate. Alternatively, combination therapy of antithyroid drug with L-thyroxine is often used, but there are few reports on its long-term effectiveness. Methods : 43 patients with Graves` disease who developed hypothyroidism during methimazole treatment were studied. They received combination therapy of 100mg methimazole with 50 ㎍(group 1, n=16) or 100 ㎍(group 2, n=27) L-thyroxine per day. Hypothyroidism was defined as elevation of seruum thyroid-stimulating hormone (TSH) concentrations above normal ranges. Results : 1) Hypothyroidism occurred within 5.8±3.7(mean ± SD) months after methimazole treatment and mean doses of methimazole were 22,1±8.4mg per day. 2) Serum total thyroxine concentrations increased significantly from 3.7±2,4㎍/dl in the hypothyroid stage to 9.4+3.0 ㎍/dl after 2 months of combination therapy(p<0.0001). 3) Serum TSH concentrations decreased significantly from 34.1+30.6μU/ml in the hypothyroid stage to 3.4+5.2 μU/ml after 2 months of combination therapy(p<0.0001). 4) After 6 months of combination therapy, 74.2Yo of patients became euthyroid. 5) There was no significant difference in the frequency of euthyroid patients after combination therapy betwen group 1 and group 2. Conclusion: These results suggest that long- term combination therapy of antithyroid drug with L-thyroxine in small fixed doses could be effective and convenient to maintain euthyroidism in patients with Graves' disease who developed hypothyroidism during antithyroid drug treatment.

제2형 당뇨병환자에서 족부병변의 발생률 및 위험인자 분석: 5년 관찰연구

박신애 ( Shin Ae Park ),고승현 ( Seung Hyun Ko ),이승환 ( Seung Hwan Lee ),조재형 ( Jae Hyoung Cho ),문성대 ( Sung Dae Moon ),장상아 ( Sang A Jang ),손현식 ( Hyun Shik Son ),송기호 ( Ki Ho Song ),차봉연 ( Bong Yun Cha ),손호영 ( H 대한당뇨병학회 2009 Diabetes and Metabolism Journal Vol.33 No.4

연구배경: 제 2형 당뇨병환자에서 당뇨병성 족부병변에 의한 하지절단은 지속적으로 증가하고 있다. 또한 당뇨병성 족부궤양 단계에서의 적절한 예방과 치료가 하지절단의 위험성을 50%나 감소시킨다고 보고된 바 있다. 본 연구는 당뇨병성 족부병변의 발생률과 임상양상 그리고 위험인자들을 살펴보고자 하였다. 방법: 2003년 1월부터 12월까지 가톨릭대학교 성빈센트병원에 내원한 제2형 당뇨병환자를 2008년까지 5년간 관찰하였다. 족부병변의 위험인자를 확인하기 위해 6개월 마다당화혈색소를 반복 측정하였고, 당뇨병성 합병증을 조사하였다. 자율신경병증은 Ewing 방법에 따라 반복적인 심호흡호기와 흡기 시 (E/I 비), 체위 변화 시(30:15 비), 발살바 수기 시 심박동수의 변화를 측정하였다. 신기능 저하를 확인하기 위해 단백뇨 여부와 MDRD GFR를 이용하였다. 결과: 총 646명의 대상 환자 중에서 연구기간을 완료한 환자는 508명(82.9%)이었고, 이 중 32명(6.3%)에서 당뇨병성 족부병변이 발생하였다. 당뇨병성 족부병변이 발생한 군에서는 당뇨병 유병기간이 길었고, 고혈압 동반률이 높았으며, 망막병증 동반율도 높았다. 연구기간 동안의 평균 당화혈색소도 발생군에서 높게 측정되었다. Lipoprotein (a)가 증가되거나 신기능이 저하된 경우 당뇨병성 족부병변의 발생이 증가함을 확인하였다. 무엇보다 심혈관계 자율신경병증의 동반은 당뇨병성 족부병변의 발생을 4배 가까이 증가시킴을 확인하였고, 이는 말초신경병증 못지않게 중요함을 알 수 있었다. 결론: 당뇨병성 족부병변의 발생과 가장 밀접한 관련이 있는 것은 평균 당화혈색소임을 확인하였다. 또한 신기능의 저하와 심혈관계 자율신경병증이 중요한 유발인자임을 확인하였다. 따라서 당뇨병성 족부병변의 발생을 예방하기 위해서는 엄격한 혈당조절뿐만 아니라 정기적인 신기능과 자율신경병증에 대한 정기적인 평가가 이뤄져야 할 것이다. Background: The frequency of lower extremity amputation due to diabetic foot has been increasing in type 2 diabetic patients. The aim of this study was to observe the incidence, clinical aspects and associated risk factors for diabetic foot. Methods: We evaluated the incidence of diabetic foot through a five-year observation of type 2 diabetic patients who presented to St. vincent`s Hospital between January and December 2003. To identify the risk factors for diabetic foot, we evaluated mean glycosylated hemoglobin A1c (HbA1c) every six months and assessed renal function based on the existence of proteinuria and estimated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) equation. Patients were also evaluated for retinopathy, peripheral neuropathy and autonomic neuropathy using Ewing`s method. Results: From an initial pool of 613 patients, the observational study of 508 patients (82.9%) was completed. The mean age, duration of diabetes and HbA1c were 50.3±10.6 yrs, 7.2±6.5 yrs and 8.8±2.1%, respectively. Diabetic foot occurred in 32 patients (6.3%). The incidence of diabetic foot increased when diabetic retinopathy (OR=6.707, 2.314~19.439), peripheral neuropathy (OR=2.949, 1.075~8.090), and autonomic neuropathy (OR=3.967, 1.476~10.660) were present and when the MDRD GFR (OR=5.089, 1.712~15.130) decreased. Mean HbA1c (OR=12.013, 1.470~98.179) was found to be an independent risk factor for diabetic foot. Conclusion: The present study confirmed the importance of intensive glycemic control and the role of autonomic dysfunction in the development of diabetic foot. In addition, diabetic retinopathy and impaired renal function proved to be factors associated with the occurrence of diabetic foot. Therefore, intensive glycemic control, as well as periodic examination of renal function, are essential for the prevention of diabetic foot. (Korean Diabetes J 33:315-323, 2009)

제2형 당뇨병 입원 환자에서 혈당변동성 지표인 Average Daily Risk Range와 관련된 인자

박신애 ( Shin Ae Park ),고승현 ( Seung Hyun Ko ),이승환 ( Seung Hwan Lee ),조재형 ( Jae Hyung Cho ),문성대 ( Sung Dae Moon ),장상아 ( Sang A Jang ),송기호 ( Ki Ho Song ),손현식 ( Hyun Shik Son ),윤건호 ( Kun Ho Yoon ),차봉연 ( Bon 대한당뇨병학회 2009 Diabetes and Metabolism Journal Vol.33 No.1

원위부 신세뇨관성 산증으로 발현한 Sjo¨gren Syndrome 1예

장상아,한제호,손현식,윤건호,조철수,차봉연,김호연,이광우,손호영,강성구 대한내과학회 1993 대한내과학회지 Vol.44 No.6

저자들은 저칼륨혈증을 주증상으로 내원한 환자에서, 원위부 신세뇨관성 산증으로 발현된 Sjo¨gren's 증후군 1예를 경험하였기에 문헌고찰과 함께 보고하는 바이다. Distal renal tubular acidosis is a condition characterized by an inability of the distal nephron to acidify the urine, causing hyperchloremic metabolic acidosis, hypercalciuria, hypokalemia, nephrocalcinosis, and nephrolithiasis. Both hereditary and aquired forms have been described, the latter commonly associated with immune-mediated disorders. It has recently been noted that diseases characterized by hyperglobulinemia are occasionally complicated by renal tubular acidosis, and this combination of hyperglobulinemia and renal tubular acidosis has been reported in Sjo¨gren's syndrome and other immune-mediated disorders. Recently we experienced a case of Sjo¨gren's syndrome of which manifestations were severe hypokalemia, and other features of distal renal tubular acidosis. We presents a case of Sjo¨gren's syndrome complicated by renal tubular acidosis with literature review.

B 형 간염바이러스 양성인 간경변환자에서 간 이식시 Immunoprophylaxis 후 1 년이상 HBV DNA 및 HBsAg 소실을 보인 1 예

김인철,김동구,김부성,박두호,이창돈,고용복,장상아,윤승규,정재열,신제현,오승택 대한내과학회 1995 대한내과학회지 Vol.49 No.1

Orthotopic liver transplantation(OLT) in hepatitis B virus(HBV) associated liver diseases remains controversial because of the high recurrence of HBV reinfection. To prevent this reinfection a passive immunoprophylaxis with Hepatitis B immunoglobulin(HBIG), HBV vaccine and interferon have been attempted. In our report, serum HBsAg and HBV DNA of the patient were positive before OLT. We administered intravenously 10,000 IU HBIG during the anhepatic phase, followed by 1,000 IU daily for the first postoperative week. Circulating HBsAg by radioimmunoassay(RIA) and HBV DNA or HCV RNA by polymerase chain reaction(PCR) were not detected to postopertive 53th weeks. In conclusion, passive immunoprophylaxis was able to reduce risk of recurrent HBV infection in HBV DNA positive patient before OLT. Therefore, patients with end stage liver diseases associated HBV infection cannot be considered a relative contraindication to DLT.

인슐린비의존형 당뇨병 환자에서 Metformin 단독요법

이광우,손호영,차봉연,강무일,윤건호,강성구,이종민,장상아,문성대,손현식,안유배 대한당뇨병학회 1997 Diabetes and Metabolism Journal Vol.21 No.2

적혈구 막단백 4.2 결핍에 의한 유전성 구상 적혈구증 1 예

김승호,이종우,이영석,최황,한남익,장상아,강성구,진종률,이현승,정용학,지영희 대한내과학회 1994 대한내과학회지 Vol.46 No.6

Hereditary spherocytosis is the most common form of congenital hemolytic anemia, which is characterized by spheroidal red blood cells, increased osmotic fragility and splenomegaly. The development of protein research revealed various primary defect resides in the erythrocyte membrane proteins of the spherocyte. Recently, we studied a 36-year-old male hereditary spherocytosis patient with anemia and splenomegaly, Analysis of the erythrocyte membrane proteins by SDS-PAGE showed a deficiency of protein 4.2.

소의 대동맥 내피세포에서 산화 저밀도지단백이 인슐린 결합 및 인슐린수용체의 내재화와 재순환에 미치는 영향

김혜수,송기호,강무일,윤건호,유순집,장상아,안유배,문성대,이광우,차봉연,한제호,손호영,허갑법 대한당뇨병학회 1999 Diabetes and Metabolism Journal Vol.23 No.3

Background: Endothelial dysfunction is perhaps one of the earliest manifestations of atherosclerosis. This abnormality is in part due to altered membrane signal transduction in endothelial cells. Oxidized LDL that is atherogenic may induce endothelial dysfunction, and its presence has been documented in atherosclerotic vessels. Many studies have shown that oxidized LDL inhibits signaling pathways mediated by inhibitory GTP-binding proteins (Gi- protein). It is also known that G-protein is involved in insulin recycling on cultured human umbilical vein endothelial cells. Therefore, to determine the effect of oxidized LDL on endothelial cells: insulin binding, internalization, and the recycling of insulin receptors were assessed in cultured bovine aortic endothelial cells treated with native LDL, oxidized LDL, and in some cells pretreated with pertussis toxin before the incubation with oxidized LDL. Method: Native LDL (density 1.019 1.063 g/mL) was obtained from using the rapid single discontinuous density gradient ultracentrifugation of plasma samples from a single donor. Oxidized LDL was prepared by exposing samples of native LDL to CuSO4 (5 uM) at 37't for 24 hours. Endothelial cells at 80% confluence were treated with the indicated concentrations of native LDL, oxidized LDL, and some cells were pretreated with pertussis toxin for 6 hrs before the incubation with oxidized LDL. These cells were incubated for 24 72 hours. Results: 1. Binding of (125)I-insulin(0.17nM) to endothelial cells treated with increasing concen- trations of oxidized LDL shows dose-dependent decrease. There were significant differences in insulin binding between native LDL and oxidized LDL-treated cells (p$lt;0.05). Binding of 'I-insulin (0.17 nM) to endothelial cells treated with increasing culture time of oxidized LDL shows more decreased than that of native LDL significantly (p$lt;0.05). And oxidized LDL had additive effect, but not significant, with pertussis toxin on the specific (125)I-insulin binding to bovine aortic endothelial cells. 2. Internalization of insulin receptors reached rapidly to its maximal level around 30min at 37'C. At 60 min, oxidized-LDL treated cells was less increased in internalization of insulin receptors than that of native LDL treated cells [59.1+1.9% of total cell associated insulin (mean+SE) vs. 67.5+1.1%, p$lt;0.05]. There were additive effects, but not significant differences, between oxidized LDL and pretreated with pertussis toxin before the incubation with oxidized LDL. 3. After 30 min of incubation with unlabeled insulin (33 nM), insulin binding in oxidized LDL treated cells was significantly higher compared to native LDL treated cells (69.0+2.5% of control values vs. 63.7+1.2%, p$lt;0.05), suggesting that oxidized-LDL decreased internalization of insulin receptors. And during the process of recycling, there were significant differences in insulin receptor recycling between the oxidized LDL and native LDL treated cells, but oxidized LDL had an additive effect, but not significant, with pertussis toxin on insulin receptor recycling to the bovine aortic endothelial cells. Conclusion: 1. The findings in this study suggest that oxidized LDL may play a causative role to produce the insulin resistance by inhibiting insulin binding, internalization and recycling of insulin receptor in cultured bovine aortic endothelial cells 2. This study suggests that the effect of oxidized LDL to the bovine aortic endothelial cells in insulin binding and receptor-mediated transcytosis is caused by inhibiting pertussis toxin sensitive Gi-protein. $quot;

인슐린비의존형 당뇨병 환자에서 C-peptid의 장기적인 추적관찰

이광우,송기호,손호영,차봉연,한제호,윤건호,강성구,장상아,안유배,유순집 대한당뇨병학회 1996 Diabetes and Metabolism Journal Vol.20 No.4

조혈모세포이식술이 단기간의 골대사에 미치는 영향

이광우,송기호,손호영,강무일,윤건호,유순집,강성구,장상아,안유배,문성대,오기원,김춘추,최윤희,김혜수,차봉연 대한내분비학회 1999 Endocrinology and metabolism Vol.14 No.2

Background: The organ transplantation becomes the management of choice for many patients with chronic and life threatening heart, liver, kidney, bone marrow, and pancreatic diseases. A new set of side effects unique to this groups of patients has become recognized. Bone disease is one of these complications. It is well known that there is an interplay between the cells in the bone marrow and the surrounding bone tissue. Marrow stromal cells include the progenitors of the osteoblastic lineage are the sources of effector molecules that support and regulate both hematopoiesis and bone remodeling. But little is known about the effects of myeloablative treatment followed by bone marrow transplantation(BMT) on bone metabolism. Methods: We have investigated prospectively in 29 patients undergoing BMT(4 autologous, 25 allogenic) for hematologic diseases(19 leukemia, 9 severe aplastic anemia, 1 myelodyspoietic syndrome). Serum concentrations of calcium, phosphorus, creatinine, gonadotropins, sex hormones and biochemical markers of bone turnover(osteocalcin and carboxyterminal cross-linked telopeptide of type I collagen(ICTP)] were measured. The samples were collected before BMT and 1, 2, 3, 4, 12 weeks, 6 months and 1 year thereafter. Bone mineral density was measured with DEXA(Dual Energy X-ray Absorptiometry) before and after 1 year of BMT. Results: 1. ICIP was progressively increased until 4 weeks after BMT when peak values were reached. And then decreased thereafter and basal values were regained after 1 year. Osteocalcin was progressively decreased until 3 weeks after BMT when nadir values were reached. And then increased thereafter and basal values were regained after 3 months. No distinct differences were observed in serum biochemical turnover marker between both sexes and between patients who received total body irradiation and those who did not. 2. Lumbar BMD was 2.1% decreased from 1.113 +- 0.132 g/cm to 1.089 +- 0.137 g/cm, and femoral BMD was 6.2% decreased fiom 1.078 +- 0.156 g/cm to 1.011 +- 0.157 g/cm. 3. 92% of the women (11/12) became menopausal manifested by high gonadotropin and low estradiol levels immediately after BMT. In contrast to women, gonadotropins and testosterone levels were not changed significantly in men after BMT. Conclusion: The rapid impairment of bone formation and also increase in bone resorption, as mirrored by the biochemical markers in this study, might play a role for the post-BMT bone loss. Further studies over many patients with a longer follow up will be needed. (J Kor Soc Endocrinol 14:355-364, 1999)