신이식후 갑상선 기능변화에 대한 장기간 추적관찰

류미숙(Mee Sook Ryu),홍성표(Seong Pyo Hong),이태원(Tae Won Lee),임천규(Chun Gyoo Ihm),김명재(Myung Jae Kim) 대한내과학회 1997 대한내과학회지 Vol.53 No.4

N/A Background: Thyroid status in uremia is still inconclusive due to the complexicity of the system. No single pathogenetic event may explain the thyroid function abnormalities in end stage renal disease (ESRD). Defects at all levels of the hypothalamic-pituitary-thyroid axis have been identified. Regarding the thyroid dysfunction in ESRD it is well recognized that the TSH response to TRH is blunted and serum concentrations of thyroid hormones are decreased in patients with ESRD. Whether or not on maintenance hemodialysis. Restoration of renal function with renal transplantation resulted in normalization of all parameters of thyroid function with exception of blunted TSH response to TRH. We evaluated the long-term changes of the thyroid function in 10 patients to know whether the thyroid function and the hypothalamo-pituitary axis were improved with the recovery of the renal function under maintenance low-dosage steroid administration after renal transplantation. Methods: These tests were performed during the morning in the fasting state in 10 ESRD patients before, 1 month and 6 years after renal transplantation (RT). Thyroid function tests. Serum T3, T4 were measured by RIA kit and serum TSH was measured by IRMA kit. TRH stimulation test. Serum blood samples were obtained 0, 30, 60, 90, 120 min after TRH (400㎍) administration. Statistical analysis. All grouped data were expressed as mean±SD. Student t-test was used to assess the statistical difference between any two means. Results: 1) The mean basal level of serum T3 was reduced in ESRD patients (53.6±33.2ng/dL) and increased to the low normal level 1 month after RT (87.8±25.4ng/dL), improved to the normal level 6 years after RT (116.3±28.8ng/dL). 2) The mean basal level of T4 was within normal range before RT (5.9±1.1㎍/dL), after 1 month (6.2±1.2㎍/dL) and after 6 years (6.5±1.4㎍/dL) of RT. 3) The mean basal level of TSH was within normal range before RT (2.0±1.2μU/mL), after 1 month (1.1±0.7μU/mL), and after 6 years (0.7±0.5μU/mL) of RT. Rut the mean TSH level of 6 years of RT was significantly decreased within the normal range. 4) In ESRD the TSH response to TRH was blunted, had a diminished peak and delayed fall before RT. After 1 month of RT, the TSH response to TRH was persistently blunted, however showed more rapid fall of TSH. After 6 years of RT, the TSH response to TRH normalized, but the absolute level of TSH and the peak level of TSH to TRH were less than before and after 1 month of RT. Conclusions: The abnormalities of thyroid hormones in uremic patients were improved partially after 1 month of RT and almost completely after 6 years of RT. But the level of T3H and the peak level of TSH to TRH were low within normal range, these results may be a direct consequence of low-dosage and long-term glucorcorticoid administration.

당뇨병성 신병증환자에서 Lipoprotein ( a ) 농도

은연기(Yeon Ki Eun),류미숙(Mee Sook Ryu),홍성표(Sung Pyo Hong),이태원(Tae Won Lee),임천규(Chun Gyoo Ihm),김명재(Myung Jae Kim) 대한내과학회 1997 대한내과학회지 Vol.53 No.5

N/A Background: Lipoprotein(a)[Lp(a)] is a subspecies of low-density lipoprotein and has been shown to be associated with pathogenesis of thrombosis-related disease. It is already known that patients with diabetic nephropathy are usually complicated by vascular complications such as coronary artery diseases and cerebrovascular accidents. According to the recent data, Lp(a) level tends to be increased as the proteinuria is increased and renal function are decreased. We evaluated the Lp(a) level to know whether its level is correlated to the severity of diabetic nephropathy. Methods: We investigated Lp(a) levels in eighty-one patients with Type 2 (non-insulin-dependent) diabetic patients. They were divided into four groups according to the level of urinary albumin excretion and serum creatinine level: Group 1 (n=30): normal renal function + urine microalbumin ≤20㎍/min, Group 2 (n=20): normal renal function + protein on urinalysis + urine microalbumin 20-200㎍/min, Group 3 (n=14): urine protein (+) on urinalysis + normal renal function, Group 4 (n=15): urine protein (+) on urinalysis + serum creatinine leve1≥1.5㎎/dL. Blood samples were obtained during the morning in the fasting state and separated serum from the it and reserved at -70℃. Lp(a) concentration was checked by one-step sandwich ELISA test. All grouped data were expressed as mean±SD. ANOVA and unpaired t-test was used to assess the statistical difference between any two means. Results: Lp(a) levels were 30.2±4.6㎎/dL in Group 1, 42.7±8.2㎎/dL in group 2, 73.4±19.7㎎/dL in group 3, and 80.7±14.8㎎/dL in group 4. The level of Lp(a) in group4, group 3, and group 2 was significantly higher than that of group 1 respectively (P=0.009, 0.001, 0.038). However, no significant correlation was observed between the level of Lp(a) and that of total cholesterol, triglyceride and total lipid in all groups. Conclusions: these results indicate that Lp(a) concentrations are increased in the patients with diabetic nephropathy with microalbuminuria or overt proteinuria. So, the presence of albuminuria may be the important determinant for the elevated Lp(a) level in diabetic nephropathy.

고콜레스테롤혈증 성인환자에서 무증상 갑상선 기능저하증의 빈도와 혈청 콜레스테롤 치에 대한 혈청 TSH 의 영향

정원제(Won Jea Jeong),박병헌(Byeong Heon Park),박철영(Cheol Young Park),류미숙(Mee Sook Ryu),오승준(Seung Joon Oh),우정택(Jeong Tack Woo),김성운(Sung Woon Kim),양인명(In Myoung Yang),김진우(Jin Woo Kim),최영길(Young Kil Choi),팽정령( 대한내과학회 2002 대한내과학회지 Vol.62 No.2

N/A Background: Subclinical hypothyroidism is frequently discovered from hypercholesterolemic adults. It is defined as an asymptomatic state which characterized by normal free thyroxine (FT4) and elevated thyroid stimulating hormone (TSH) level. Hypercholesterolemia is a major risk factor for coronary heart disease, however hypercholesterolemia caused by hypothyroidism can be easily managed by thyroid hormone replacement. The screening of thyroid disease in hypercholesterolemia patient must be emphasized in order to find out correctable hypothyroidism. So we screened the prevalence of overt and subclinical hypothyroidism at different hypercholesterol levels in middle-aged men and women and also analyzed the correlation between TSH and total cholesterol level. Methods: We measured serum TSH levels and FT4 by radioimmunoassay from 491 patients with hypercholesterolemia. The subjects were divided into two groups according to serum cholesterol level. Group I was serum cholesterol ≥240 -〈300 mg/dL and group II was ≥300 mg/dL. Subclinical hypothyroidism was defined as TSH levels higher than 4 mU/L, in the presence of normal FT4 concentration. Results: The overall prevalence of subclinical and overt hypothyroidism was 3.4% and 2.5% in men and 4.7% and 3.5% in women of middle age. In men the prevalence of overt and subclinical hypothyroidism increased from 2.3% of group I to 16.1% in the group II (p<0.05). In women that increased from 5.2 % to 12.9 % (p<0.05). After age correction, an increase of 1 mU/L TSH in men was associated with an increase of 3.2 mg/dL total cholesterol (p<0.01). A similar trend was also found in women (2.1 mg/dL p=0.052). Conclusion: In this population, the prevalence of hypothyroidism is up to 16.1% in middle-aged men, 12.9% in middle-aged women with high total cholesterol and it may justify screening of thyroid disease in hypercholesterolemic patients especially in clinical practice.(Korean J Med 62:187-193, 2002)

성장호르몬 분비성 뇌하수체 선종에서 소마토스타틴 수용체 (제2아형, 제5아형), G_i2α 및 Pit-1 유전자 발현

류미숙,양인명,박철영,우정택,김성운,김진우,김영설,최영길,김은희,박승준,김국기 대한내분비학회 2002 Endocrinology and metabolism Vol.17 No.2

Background: Mutation of Gs protein subunit (gsp oncogene), detected in about 30∼40% of growth hormone (GH)-secreting pituitary tumors, is associated with an increased long-acting somatostatin analog octreotide sensitivity. However, the mRNA expression of somatostatin receptor (sst) was not changed in the GH-secreting pituitary tumor, regardless of whether they were gsp oncogene positive or negative. This suggests that the expression of genes coding for G_i2α, Pit-1 and the other factors involved in the regulation of secretory activity in somatotrophs is likely to be altered in gsp oncogene positive tumors. We observed the impact of the gsp oncogene on the expression of the genes coding for Gi2, Pit-1 and sst (2&5) in GH-secreting pituitary tumors. Methods: The GH response to octreotide was examined in 13 acromegalic patients before transsphenoidal adenomectomy. Genomic DNA and RNA were extracted from fresh frozen tumor tissues. PCR was performed to amplify and sequence the region between codon 184 and 251 that includes exons 8 and 9 of the Gs gene. Sst2, sst5, G_i2α and Pit-1 mRNA levels were measured by semi-quantitative RT-PCR. Results: Sst2 and sst5 mRNA transcripts were detected in all tumors (7 gsp +, 6 gsp-). The amount of sst transcripts varied considerably varied between the tumors. There were no significant differences in sex, age, tumor size, grade or basal GH levels. Pit-1 and sst2 mRNA levels were not different. In contrast, G_i2 mRNA levels were significantly higher in gsp (+) while sst5 mRNA levels were higher in gsp (-). Conclusion: These data suggests that gsp oncogene may increase Gi2α levels but decrease sst5 mRNA levels. However, Pit-1 and sst2 mRNA expression may not be affected by gsp oncogene. The increased expression of the G_i2α gene might be an inhibitory compensatory response to the action of gsp oncogene

혈당측정기 GlucoDr™ System의 평가

박철영,류미숙,우정택,김성운,김진우,김영설,안규정 대한당뇨병학회 2002 임상당뇨병 Vol.3 No.2

연구배경: 당뇨병 환자에서 엄격한 혈당조절은 환자의 예후와 밀접한 관련이 있다. 혈당조절을 철저히 하기 위해서는 자가 혈당 측정기의 사용이 필수적이라 할 수 있다. 또한 저혈당이 빈번하게 발생하거나, 위험요소가 있는 환자들에게도 유용하게 사용될 수 있다. 이에 저자들은 전기화학감지법의 원리를 이용하여 국내에서 처음 생산된 자가혈당측정기인 GlucoDr™ blood Glucose Testing System(ALL Medicus, Co, Korea)를 현재 국내에서 시판되고 있는 다른 제품과 비교, 평가하여 임상적 유용성을 살펴보고자 하였다 방법: 혈당측정기준장비는 YSI 2300 STAT Plus(YSI Incorporated, USA)를 사용하였으며 GlucoDr™외에 Glucocard(KDK, Japan), Precision QID(Abbott Laboratories, Co, USA), Glucotrend(Roche, USA), Surestep(Lifescan, USA)의 다른 혈당측정기를 같이 평가하였다. 정밀도, 직선성, 비교방법과의 상관관계 평가, 검체량에 따른 영향, 헤마토크리트에 따른 영향, 검사자에 따른 영향, 항응고제에 따른 영향들을 평가하였다. 결과: 본 연구에서의 주된 평가대상인 GlucoDr™의 평가결과, 정밀도를 나타내는 검사 내, 검사 간 변이계수는 8%이내였으며, 45~500mg/dL 범위에서 R²=0.9906, 0.9984 정도의 직선성을 나타내었다. 본 연구에 있어 비교방법으로 이용한 YSI 2300 STAT Plus와의 상관관계 및 정확도는 y = 1.0058x + 0.453, R = 0.9853인 것으로 나타났다. 검체량이나 검사자 및 항응고제에 따른 측정값에는 유의할만한 차이가 없는 것으로 나타났으나, 헤마토크리트가 증가 또는 감소함에 따라 최소 10%에서 최대 26% 가량의 영향을 받는 것으로 관찰되었다. 결론: GlucoDrTM는 국내 사용되는 다른 혈당측정기와 비교하여 유용할 것으로 생각된다. Background: Self-monitoing blood glucose devices are sidely used in monitoring and point-of-care testing for the management of diabetic patients. We performed the present study to evaluate the performance of the GlucoDr™ blood glucose testing system using an electrochemical technique. Method: The GlucoDr™ was evaluated for linearity, precision, comparison of method, the effect of sample volume, hematocrit concentration, reapplication, operator and application methods. Results: The GlucoDr™ showed good linearity for glucose concentrations ranging from 52mg/dl to 475mg/dl(r²=0.971). The single day, and day-to-day, CV were within 8%. Excellent correlation was found between the GlucoDr™ and YSI 2300 STAT Plus(y=1.0058x + 0.453, r²=0.9710). The sample volume, reapplication, operator and application method produced no significant effect on the test result. An overestimation in the glucose values was found with low hematocrit concentrations. There was no significant effect by the anticoagulants, with the exception of citrate. Conclusion: The GlucoDr™ showed good linearity, precision and correlation with the reference method and provided rapid and reliable result for blood glucose levels. Therefore, the GlucoDr™ seems appropriate for clinical use in the management of diabetic patients.

폐농양 및 복부농양을 일으킨 Eikenella corrodens 감염 2예 : Two Case Reports and Review

정용희,류미숙,김영식,이우인,이희주,서환조 대한화학요법학회 2000 대한화학요법학회지 Vol.18 No.1

Eikenella corrodens is a slowly growing, facultative anaerobic gram-negative bacillus. It is a normal inhabitant of the human upper respiratory tract, and it is recognized as an infrequent cause of invasive disease. To date, a few cases of E. corrodens infection were noted from all other organ. We report herein two cases of E. corrodens infection. In one case E. corrodens was isolated in the lung abscess and in the other case it was in the appendiceal abscess. The patients were treated empirically with penicillin G. The results of the bacterial culture and sensitivity test were available with it. The patients were discharged 15 days later with marked improvement after treatment. Our report clearly demonstrates that E. corrodens can be the pathogen of lung abscess and intraabdominal abscess. We reviewed descriptions from the literature of infections caused by E. corrodens.

뇌혈관질환을 동반한 당뇨병 환자에서 지속적 혈당측정의 유용성 평가

정성훈,강인구,박철영,류미숙,우정택,김성운,김진우,김영설 대한당뇨병학회 2002 임상당뇨병 Vol.3 No.2

연구배경: 뇌혈관질환을 동반한 고령의 당뇨병환자는 이들의 신경학적 결손으로 경고 증상없이 심한 저혈당에 노출될 가능성이 크다. 실제로 하루 4번 정도의 자가 혈당 측정으로는 이를 감지하기 어려울 뿐 아니라 검사에 따른 고통으로 적극적인 혈당 조절에 제한이 따르게 된다. 이에 저자들은 Mini Med사의 지속적 혈당측정기(CGMS, continuous glucose monitoring system)를 이용하여 뇌혈관질환을 동반한 당뇨병 환자에서 24시간 혈당의 변동양상을 알아보고 각기 다른 인슐린 치료방침에 따른 혈당조절의 효율성을 비교하고자 하였다. 방법: 2001년 1월부터 6월까지 경희대학교 부속병원에 입원해 있는 10명의 뇌혈관질환을 동반한 제 2형 당뇨병환자를 대상으로 하였다. 이 들은 모두 튜브식이를 받고 있엇고 최소 1개월 이상 인슐린 치료를 시행 받았다. 지속적 혈당측정기를 착용하고 3일간의 연속적인 혈당을 측정하였고, 치료 첫 날은 NPH, 둘째 날은 속효성 인슐린과 NPH, 마지막 날은 혼합형 인슐린제제로 치료하여 그 효과를 비교하였다. 이들 각기 다른 인슐린 제재의 하루 총량에 차이는 없었다. 혈당치가 3.3mmol/L 미만이거나 7.8mmol/L를 초과하는 경우 그 차이값의 총합을 시간으로 나누어 이 값(△Glu)이 적을수록 치료효과가 우수한 것으로 판정하였다. 또한 당 수치가 3.3mmol/L 미만인 경우를 저혈당 event, 16.7mmol/L 초과한 경우를 고혈당 event로 임의로 정의하였고, 이를 통해 지속적 혈당측정의 유용성을 간접적으로 평가하고자 하였다. 결과: 평균 △Glu값은 첫째 날이 0.93 ± 0.43mmol/Lㆍmin?¹, 둘째날이 0.71 ± 0.29mmol/Lㆍmin?¹ 마지막 날이 0.58 ± 0.29mmol/Lㆍmin?¹로서 서로 다른 3가지 치료방침사이에 통계학적으로 유의한 차이는 없었다(p=0.115). 10명의 환자들 중 자가 혈당측정기로는 1명에서 저혈당 event, 2명에서 고혈당 event를 인지하였으나 지속적 혈당측정기로는 각각 9명에서 event를 확인하였다. 결론: 지속적 혈당측정기를 이용한 각각의 인슐린 치료방침에 따른 혈당조절 효율성의 차이는 없었으나, 자가혈당 측정기로는 알 수 없었던 일 중 혈당 변동사항을 정확하게 알 수 있어, 뇌혈관질환을 동반한 당뇨병 환자에서 보다 적극적인 인슐린 치료 및 관리를 할 수 있을 것으로 생각된다. Background: Diabetic stroke patients are susceptible to hypoglycemia. However, there are many limitations in detecting hypoglycemic events, even though glucoses levels are checked 3 to 4 times per day using the fingerstick method. Therefore, we investigated the glycemic excursions and pattern in diabetic stroke patients using the continuous glucose monitoring system (CGMS, MiniMed) and its clinical utility. The other objective was to compare the treatment dfficacy between insulin regimens. Methods: From jan 2001 to jun 2001, 10 adult type 2 diabetic stroke patients wore CGMS for consecutive 3 days, which continuously checked the glucose level. NPH insulin, multiple daily injection of regular insulin ± NPH and the mixed type(Novolet 30/70, Novo Nordisk) were used on the first, second and third days of the study, respectively. If the mean delta glucose(△Glu = A+B/time, A=∑(hlucose-7.8), glucose > 7.8 mmol/l, B=∑(3.3-glucose) if, glucose < 3.3 mmol/l) was calculated in order to recognize the degree of individual glycemic changes and to compare the efficacy of each treatment diverse insulin regimen. We arbitrarily defined a glucose level less than 3.3mmol/l, as a hypoglycemic event, and more than 16.7mmol/l as a hyperglycemic event. Results: Variable patterns of glycemic changes were observed among patients with the same dosage, but a different insulin regimen. The mean △Glu was 0.93±0.43 on the first day, 0.71±0.29 on the second day and 0.58±0.29 on the third. There was no significant difference in treatment efficacy between the 3 different insulin modalities(p=0.115). Of the 10 patients, a hypoglycemic event was detected in 1 with the fingerstick method, in contrast to 9 with CGMS, with hyperglycemic events being detedted in 2 and 9, respectively. Conclusion: Continuous glucose monitoring maybe useful in providing the information necessary for optimal glycemic control in the diabetic stroke patients.

비만 환자의 치료 시 시부트라민 ( Reductil(R) ) 의 유효성 및 안전성 평가를 위한 제 3 상 다기관 공동 임상시험

박철영,김영철,류미숙,남수연,박혜순,김상만 대한비만학회 2001 The Korean journal of obesity Vol.10 No.4

Background: Sibutramine(ReductilR ) is a weight control drug that inhibits the reuptake of both serotonin and norepinephrine. This study was performed to evaluate the efficacy and safety of oral treatment with the sibutramine in obese patients. Methods: This study was 12-week, double blind, multi-center trial following a 2 weeks screening period. The study protocol included a screening visit to assess patient eligibility; a screening period of 2 weeks, a titration period of 4 weeks, and a subsequent 8-week maintenance period. Eligible patients had a body mass index (BMI) greater than 30kg/m2 or between 27 and 30 with controlled hypertension, diabetes and hyperlipidemia. Ninety-nine nine obese patients were randomized either to sibutramine (50 patients) or placebo(49 patients) at 4 participating centers. Results: After 12 weeks treatment, sibutramine resulted in significant reduction in weight. Among patients receiving sibutramine, 68.2% of patients lost 5% or more of body weight compared with 13.0% in the placebo group. Mean absolute weight change at 12 weeks was -5.9±3.8kg in the sibutramine group and -1.6±2.6kg in the placebo group. Sibutramine-induced weight loss was not associated with significant improvements in serum levels of lipid profile. Most adverse events were mild to moderate in severity and transient. The common adverse events were anorexia, headache, and constipation. Sibutramine group did not increase significantly mean Conclusion: Overall, the results showed that sibutramine is well tolerated and a useful, effective therapy for obesity in Korean.

G_Sα 돌연변이 유전자를 영구히 발현하는 GH3 세포주에서 소마토스타틴 수용체 유전자 및 G_i2α, pit-1α 유전자의 발현

박철영,양인명,김은희,손숙진,류미숙,우정택,김성운,김진우,김영설,최영길,박승준 대한내분비학회 2002 Endocrinology and metabolism Vol.17 No.2

Background: Cyclic AMP stimulates the expression of the somatostatin (SRIF) receptor (sst1-5) and human growth hormone (GH)-secreting pituitary tumors with the gsp oncogene which increases intracellular cAMP levels, and shows a good inhibitory response of the GH to SRIF. Taken together, we hypothesized that the gsp oncogene may increase the SRIF receptor expression or and factors related to the postreceptor signal transduction of the SRIF, in order to enhance its responsiveness to SRIF. To test this hypothesis, we investigated if the gsp oncogene could increase the sst1, sst2, G_i2α, and pit-1α gene expression in GH3 cells. Methods: GH3 cells were permanently transfected with the plasmid expressing Gsα gene, where the arginine of codon 201 was replaced with histidine. Intracellular cAMP levels and GH concentrations were measured by radioimmunoassays. Gene expressions of the sst1, sst2, G_i2α, and pit-1α were determined by RT-PCR. Results: Intracellular cAMP levels and medium GH release were increased by 1.7 and 2.7-fold in GH3 cells expressing the gsp oncogene, respectively. In GH3 cells expressing the gsp oncogene, the sst1 mRNA levels were decreased, whereas those of the sst2, Gi2α and pit-1α mRNA were increased. A 4-h forskolin (10 μM) stimulation remarkably increased the sst1 and sst2 mRNA levels in GH3 cells expressing wild and mutant Gsα. However, forskolin did not affect the G_i2α and pit-1α mRNA levels. In contrast, SRIF (1 μM, 2 h) decreased the sst2 mRNA levels only in GH3 cells expressing the gsp oncogene. Conclusion: These results suggest that higher expressions of sst2, G_i2α, and pit-1α, induced by the gsp oncogene may be a mechanism by which gsp-positive pituitary tumors show a greater response to SRIF. The discrepancy between these and in vivo results should be explored further

인슐린 비의존형 당뇨병에서의 베타 3 아드레날린 수용체 유전자 변이

최영길,양인명,우정택,김성운,류미숙,김영설,김진우,팽정령 대한당뇨병학회 1996 Diabetes and Metabolism Journal Vol.20 No.4