HBeAg 음성 만성 B형 간질환에서 Lamivudine의 치료 효과

정인두,박능화,김병철,박지현,서광원,김대현,주광로,김도하 대한간학회 2003 Clinical and Molecular Hepatology(대한간학회지) Vol.9 No.2

목적: HBeAg 음성 만성 B형 간질환 환자에서 라미부딘 치료 효과, 내성 발생률, 치료 종료 후 재발률 및 각각의 예측 인자를 알아보고자 하였다. 대상과방법: HBeAg 음성, anti-HBe 양성이나 HBV DNA가 양성인 HBeAg 음성 만성 B형 간질환으로 진단 받은 환자 중에서 혈청 ALT치가 상승되어 있는 59명을 대상으로 라미부딘을 1일 100mg씩 6개월(평균 14개월)이상 투여하였다. 평균 연령은 42.1세였고 남녀 비는 52:7이였다. 치료 전 혈청 ALT평균치는 368 IU/L, HBV DNA평균치는 494 pg/mL였다. 치료 전, 치료 개시 후 및 종료후 1-2개월 간격으로 간기능 검사, HBeAg, anti-HBe, HBV DNA를 측정하였다. 치료 반응군은 반응이 일어난 시점을 기준으로 1-2개월 간격으로 2번 이상 반응이 유지되는 것을 확인한 후 투약을 중지하고 재발 유무를 추적 관찰하였다. 결과: 라미부딘 투여 후 50명 중 56명(94.9%)에서 혈청 HBV DNA가 음전되었으며 누적 음전율은 1개월후 27%, 2개월 후 71%, 3개월 후 90%, 5개월 후 95%였다. 혈청 ALT치는 52명(88.2%)에서 정상으로 회복되었으며 대부분 6개월 내에 이루어졌다. 혈청 ALT치의 누적 정상화율은 2개월 후 30%, 3개월 후 47%, 6개월 후 78%, 10개월 후 86%였다. 혈청 HBV DNA가 음전되고 혈청 ALT치가 정상으로 유지된 치료 반응은 52예(88.1%)에서 일어났으며, 누적 치료반응률은 2개월 후 10%, 4개월 후 49%, 6개월 후 66%, 10개월 후 80%, 18개월 후 88%였다. 라미부딘 총 투여 기간이 유일한 치료 반응 예측 인자였다(p=0.000). 변이형의 출현은 5예(8.5%)에서 일어났고 누적 발생률은 10개월 후 8%, 16개월 후 13%였다. Breakthrough발생 예측인자와 관련된 유의한 인자는 없었다. 치료 반응군중 투여 중지한 34명 중 17명(50%)에서 재발하였으며(평균추적기간: 6개월, 범위: 1-22개월) 대부분 투여중지 6개월 내에 재발하였다. 누적 재발률은 3개월 후 24%, 6개월 후 47%, 10개월 후 66%였다. 재발과 관련된 예측 인자는 치료 반응후 추가적인 라미부딘 누여만이 유의한 인자였다(p=0.019). 특히 12개월 이상 유지한 7명 모두에서 재발하지 않았다. 결론: 라미부딘은 HBeAg 음성 만성 B형 간질환에서 높은 치료효과와 낮은 breakthrough를 보였으며 라미부딘 투여 기간만이 유일한 치료 반응 예측 인자이었다. 그러나 치료 종료 후 많은 예에서 재발하였으며 치료 반응 후 추가적인 라미부딘 투여 기간만이 유일한 재발 예측 인자였으며 재발을 막기 위해서는 장기간의 추가적인 라미부딘 투여가 필요할 것으로 사료된다. Background/Aims: Lamivudine therapy is effective in inhibiting HBV replications in patients with HBeAg-negative chronic liver disease. However, the sustained response rate appears to be particularly poor, because the vast majority of patients relapse soon after cessation of therapy. The aim of this study was to evaluate the efficacy of lamivudine, the breakthrough rate, and the relapse rate of discontinuing therapy after response in patients with HBeAg-negative chronic liver disease. Methods: Fifty-nine patients with HBeAg-negative chronic liver disease who have received lamivudine for at least 6 months, were studied. The mean duration of treatment was 14 months. Complete response was defined as undetectable serum HBV DNA by bDNA and normalization of ALT levels. Once HBV DNA disappearance and ALT normalization were observed, lamivudine therapy was continued for at least two additional months. The mean follow-up after cessation of treatment was 6 (1-22) months. Results: Fifty-six patients were undetectable HBV DNA. The cumulative HBV DNA loss rates at 3 months and 5 months were 90% and 95%, respectively. The ALT normalization was observed in 52 patients. The cumulative ALT normalization rates at 6 months and 10 months were 78% and 86%, respectively. The complete response was observed in 52 patients. The cumulative rates of complete response at 10 months and 18 months were 80% and 88%, respectively. A predictive factor for complete response was only the duration of lamivudine treatment. Virological breakthrough was observed in 5 (8.5%). Thirty-four patients stopped taking lamivudine after 7.7 (2-15) months of the additional therapy. Seventeen of those patients (50%) experienced relapse. The cumulative relapse rates at 3 months, 6 months and 10 months were 24%, 47% and 66%, respectively. The only predictive factor for relapse was the duration of additional lamivudine treatment after response. Conclusions: Lamivudine was an effective treatment of HBeAg negative chronic liver disease. Relapse, however, was usually observed after cessation of lamivudine. Our results showed that long-term lamivudine therapy is required in order to decrease the high relapse rates in patients with HBeAg-negative chronic liver disease.

후복막섬유증 5례의 임상적 고찰

정충식,김수현,안병수,심대성,박도영,김철성,장대수 조선대학교 1994 The Medical Journal of Chosun University Vol.19 No.1

Retroperitoneal fibrosis is a fibrotic process of the retroperitoneum that frequently produces ureteral obstruction. It can occur as an idiopathic disease or in association with various non-malignant and malignant condition. In the early phase of the retroperitoneal fibrosis ; symptoms originate from the disease process itself, while in the late state the clinical features represent the effect of obstructive uropathy and renal failure. Treatment consist of steroid therapy, urinary diversion and ureterolysis with jntraperitonealization or lateralization or wrapping with omentum. Herein we present 5 cases of retroperitoneal fibrosis.

광 산란 실험방법을 이용하여 액정 네마틱-스멕틱 A 상전이 근처의 임계현상 연구

金斗哲,高正大 제주대학교 1989 논문집 Vol.28 No.-

A electrical oven that was able to controle a millidegree was made and it's tempearature stability was investigated. The temperature gradient of electrical oven was ±2.5m℃. In a light scattering experiment, The temperature dependence of sattering light intensity near nematic to smectic-A phase transition of 80CB was measured. The intensity of scattered light from 80CB was continuous at T?? and it proved that nematic to smectic-A phase transition is second order. The longitudinal correlation length ?? diverges with critical exponent ?=0.66 ±0.02. This result is consistent with de Gennes' prediction.

기업물류경쟁력확보를 위한 물류용기 풀시스템 도입성과 분석

김대기,김상철,김정혁 한국로지스틱스학회 2002 로지스틱스연구 Vol.10 No.1

본 연구의 목적은 물류용기 풀시스템 도입효과에 대한 이론적이고도 계량적인 근거를 제시함으로써 기존의 물류용기 사용 관행에서 오는 낭비요인을 찾아 제거하고, 이를 통해 물류표준화 및 공동화의 필요성을 강조하고자 함에 있다. 물류용기표준화 및 공동화의 도입효과를 분석하기 위하여, 국내의 한 완성 차 업계의 실 데이터를 이용한 Box Pool System 시뮬레이션 모델을 구축하였다. 평균 상차시간, box 보유량, 평균 box 체류시간 등의 성과척도를 중심으로 BPS도입효과를 분석한 결과, 평균 상차시간은 62%, 시스템 내 box 체류시간은 38% 감소하였으며, 기존의 약 1/3수준의 box보유만으로도 시스템을 효율적으로 운영할 수 있다는 긍정적인 결론을 도출하였다. 즉, 물류용기 표준화 및 공동화 작업은 물류비용절감과 물류서비스 개선을 통한 기업물류경쟁력 확보의 가장 기초적이고도 필수적인 조건이다. The purpose of the study is to provide theoretical and qualitative grounds to the introduction of container pool system. By finding our and eliminating wastes from our everyday routine practices, we emphasize the importance of joint utilization and standardization of containers. In order to qualitatively measure the effects of joint utilization and standardization of containers, we constructed BPS : 62% reduction in average loading time, 38% reduction in system queue time, and 68% reduction in box inventories in the system. That is, standardization and joint utilization of containers is the most fundamental and requisite condition to secure business logistics competitiveness, which is realized by logistics cost reduction as well as logistics service improvement.

다단토양층을 이용한 하수처리에 관한 연구

손대희,정윤철,신정훈,정진영,안대희 한국물환경학회 2004 한국물환경학회지 Vol.20 No.3

The sewages produced from small villages, rural community, drinking water reservation area and park which doesn't have sewage piping system can be caused a serious water pollution at the restricted areas. The objective of this research was to suggest an economical and effective sewage treatment method by investigating the removal of the organics, nitrogen, and phosphorus in the multi-soil-layering reactor. Soil, natural zeolite, and iron slag were used as a supporting media of multi-soil-layering in this research. The purpose of natural zeolite addition was to maintain the consistent ammonium exchange capacity by providing a sequential environment, and that of iron slag addition was to remove phosphorus by adsorption. Continuous experiment of lab-scale single-soil-layering (S-1), multi-soil-layering (S-2), and mixed-soil-layering (S-3) methods were studied to compare and optimize three different types of the reactors. The organic removal efficiencies showed more than 90% in all three reactors. While S-1 and S-3 reactors showed about T-N removal of 31%, 45%, respectively, the average T-N removal efficiency of the S-2 reactor represented an 87%. In conclusion, that results suggest that the multi-soil-layering reactor could be effectively utilized as a plant for treatment of small village sewage.

말기신부전 환자에서 혈액투석 전후의 QT간격분산 비교

강대웅,정지용,윤나라,안치용,김종오,신병철,정종훈,김현리 朝鮮大學校 附設 醫學硏究所 2006 The Medical Journal of Chosun University Vol.31 No.2

Background: Some cases of QT interval, corrected QT interval (QTc), QT dispersion (QTd) and corrected QT dispersion (QTcd) have been reported in ESRD, but these results are variable and the influence of a hemodialysis is still controversial, In this study, we investigated the effect of hemodialysis on QT and QTc interval and QT and QTc dispersion in patients with ESRD 15 min before and 15 minute after each hemodialysis. Methods: Sixty-seven patients with ESRD (men 33 & women 34) on three-times stable hemodialysis (>3 months) were randomly enrolled. Fifty control subjects with a similar age and normal renal function were enrolled from this hospital. Routine biochemical studies were measured pre- and post dialysis, at the time of the ECG. Plasma Na+, K+, BUN, creatinine, ionized calcium and phosphate were checked. Twelve-lead electrocardiographs were performed at 10㎜/mv and 50㎜/s using a HewIett-Packard Pagewriter 100, before and after a single hemodialysis session.The QT interval was measured from the onset of the QRS complex to the end of the T wave. If the end of the T wave was not clear in a particular lead then it was excluded from analysis. When U waves were present, the end of the T wave was taken as the nadir between the T and U waves. Each QT interval was corrected for heart rate using Bazett's formula (QTc==QT/√(RR)) (ms). The difference between maximal and minimal QT interval duration was defined as QT dispersion (QTd) in each of the 12 leads. Result: This study demonstrates that QT, QTd, QTcd is higher in hemodialysis patients compared with control subjects, and QT and QTd rise postdialysis to levels comparable to those seen acutely following myocardial infarction, when patients are at greatly increased risk of potentially fatal ventricular arrhythmias, Conclusions: QT interval and QT dispersion, markers of risk for arrhythmias and sudden death, are elevated in hemodialysis patients, and rise postdialysis. QT interval and QT dispersion is an easily obtainable, noninvasive, simple, inexpensive, and widely available method of risk stratification in uremic patients receiving chronic dialysis. Additional studies are needed to clarity whether increased postdialysis QT dispersion results in an increased occurrence of arrhythmias.

Mouse의 심폐이식에서 IL-2 Receptor의 역할에 관한 연구

김대원,조정희,한덕종,이인철 울산대학교 의과대학 1993 울산의대학술지 Vol.2 No.1

Improved graft survival after organ transplantation is relied upon the innumerable studies concerning the immunologic reactions following antigen exposure and the accompanying strategies against rejection response. Cellular immunity is known to act as a major role in organ transplantation. We performed heart-lung transplantation in mice in order to define cellular immune reactions. For that purpose we analysed the functional role of the immune cells by the cellular cytotoxicity and phenotypic reactions by the IL-2 receptor(R) positive immune cells in the spleen as well as in the graft. ·Mean graft survival after the allogenic heart-lung transplantation in mice(BALB/C to CBA) was 8.5±2.5 days. ·Splenocyte cytotoxicity was the highest on the postoperative day 6 and then decreased abruptly to even lower than that of control mouse. ·Immunohistochemical analysis of spleen harvested consecutively during the postoperative period showed that proportion of IL-2R positive lymphocyte was around 20% in white pulp and scarce in red pulp illustrating nonspecific pattern regardless of rejection. ·Quantitative assay of IL-2R positive splenocyte showed the peak level on the postoperative day 6. ·IL-2R analysis of transplanted heart showed that IL-2R positive lymphocyte infiltated the heart progressively from the epicardium toward the endocardium with the maximal cellular infiltrate progressively from the epicardium toward the endocardium with the maximal cellular infiltrate on the postoperative day 4. These results illustrate that cellular cytotoxicity and expression of IL-2R positive cells have the consistent finding in terms of roles and diagnostic aid graft rejection following heart-lung transplantation in mice.

企業 附設 硏究所 活動實態에 관한 硏究 : 釜山·慶南地域을 中心으로

河正鎭,黃圭完,申大赫,兪炳哲 동아대학교 공과대학 부설 한국자원개발연구소 1990 硏究報告 Vol.14 No.2

The research institute of an enterprise attaches have been enlarged in korea. This study grasps the status and the research activity in the research institute of an enterprise attached in the Pusan and Kyungnam. So, we find the important role in the research institute of a enterprise attached.

디클로페낙 프로드럭들의 흰쥐 피부 투과

도희정,조원제,용철순,이치호,김대덕 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-

Various alkyl ester prodrugs of diclofenac were synthesized in order to investigate the relationship between their skin permeation characteristics and physicochemical properties. Solubility in various vehicles was measured at room temperature. I -Octanol/water partition coefficients (Log P) and capacity factors (k') were measured to determine the lipophilicity of the prodrugs. Stability of prodrugs in the skin extract and homogenate was also investigated before conducting the skin permeation studies. Increases in the Log P and capacity factor values were observed when alkyl esters of diclofenac were prepared. Since the aqueous solubility of the prodrugs was not high enough, they were saturated in propylene glycol (PG) for skin permeation studies. Prodrugs were rapidly metabolized to diclofenac, both in skin homogenate and in dermal extract of skin. The skin permeation rate of alkyl ester prodrugs was significantly higher than diclofenac with shorter lag time. Moreover, a parabolic relationship was observed between the permeation rate and the log P values of prodrugs, and the maximum flux was achieved at a log P value of around 4.0.

디클로페낙 프로드럭들의 흰쥐 피부 투과

도희정,조원제,용철순,이치호,김대덕 영남대학교 약품개발연구소 2002 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

Various alkyl ester prodrugs of diclofenac were synthesized in order to investigate the relationship between their skin permeation characteristics and physicohemical properties. Solubility in various vehicles was meastured at room temperature. 1-Octanol/water partition coefficients (Log P) and capacity factors (k") were measured to detemine the lipophilicity of the prodrugs. Stability of prodrugs in the skin extract and homogenate was also investigated before conduction the skin permeation studies. Increases in the Log P and capacity factor values were observed when alkyl esters of diclofenac were perpared. Since the aqueous solubility of the prodrugs was not high enough, they were saturated in propylene glycol (PG) for skin permeation studies. Prodrugs were rapidly metabolized to diclofenac, both in skin homogenate and in dernal extract of skin. The skin permeation rate of alkyl ester prodrugs was significantly higher than diclofenac with shorter lag time. Morecover, a parabolic relationship was observed between the pemeation rate and the log P values of prodrugs, and the maximum flux was achieved at a log P value of around 4.0.