Helicobacter pylori 감염에서 CagA 및 VacA 발현과 위 상피세포 증식과의 관계

김남일(Nam Il Kim),이중현(Jung Hyun Lee),이영실(Yeoung Sil Lee),이재욱(Jae Uk Lee),이구(Goo Lee),서정일(Jeong Ill Suh),양창현(Chang Heon Yang),이창우(Chang Woo Lee),윤환중(Hwan Jung Yun),장태정(Tae Jung Jang),김정란(Jung Ran Kim),하경 대한내과학회 2000 대한내과학회지 Vol.58 No.5

N/A Background : Infection with Helicobacter pylori (H. pylori) has been associated with an increased risk for developing gastric cancer. This risk is further enhanced with CagA positive H. pylori strains. Increased epithelial cell proliferation is associated with an increased risk for gastric cancer. The aim of the study was to investigate whether the gastric epithelial cell proliferation was related to the expression of CagA and VacA in H. pylori infection. Methods : The subjects were 77 patients who had undergone diagnostic esophagogastroduodenoscopy with biopsy; 18 gastritis, 18 gastric ulcer, 17 duodenal ulcer and 24 gastric cancer. The expression of cytotoxic genes was determined indirectly by assaying serum IgG antibodies to specific antigens of H. pylori. Gastric epithelial cell proliferation was assessed using immunohistochemical method using Ki-67 monoclonal antibody. Acute and chronic inflammation, intestinal metaplasia and glandular atrophy were scored according to the updated Sydney system. Results : Ki-67 labeling index, acute and chronic inflammation were significantly higher in H. pylori infected persons (n=70, 90.9%) than in uninfected persons (n=7, 9.1%) (p<0.05), but the difference in intestinal metaplasia and glandular atrophy between the two groups was not statistically significant. Ki-67 labeling indices in persons infected with CagA positive strains (n=56, 80.0%) were significantly higher than in persons infected with CagA negative strains (n=14, 20%) (0.55±0.13 vs 0.37±0.17, p<0.05), but the differences in acute and chronic inflammation, intestinal metaplasia and glandular atrophy between the two groups were not statistically significant. No significant difference was found in Ki-67 labeling index, acute and chronic inflammation, intestinal metaplasia and glandular atrophy according to expression of VacA. Conclusion : Gastric mucosal cell proliferation, which might be closely involved in the pathogenesis of gastric carcinoma, was significantly higher in CagA positive H. pylori infected persons.(Korean J Med 58:516-525, 2000)

소세포폐암의 임상경과 및 예후인자

장대영(Dae Young Zang),이정신(Jung Shin Lee),김태원(Tae Won Kim),정병학(Byung Hak Jung),윤환중(Hwan Jung Yun),최종수(Jong Soo Choi),박진희(Jin Hee Park),이동숙(Dong Sook Lee),이제환(Je Hwan Lee),김성배(Sung Bae Kim),김상위(Sang We Ki 대한내과학회 1998 대한내과학회지 Vol.54 No.1

N/A Background: Although small cell lung cancer is a chemosensitive disease, it grows rapidly and relapses frequently. Even with optimum treatment, only small portion of patients have experienced long-term survival. The objective of this study was to describe the clinical characteristics and therapeutic features, and to analyze the prognosis in small cell lung cancer. Methods: We analyzed retrospectively 151 evaluable patients with histologically confirmed small cell lung cancer from August 1989 to June 1995 at our institution. Of 151 patients, 3 had surgery and chemotherapy, 59 had chemotherapy and chest irradiation, and 89 had chemotherapy only. Results: Most patients(82.1%) were men, and the median age was 62 years. Of all patients, 49% had performance status of 0.1 and 59.6% had limited disease. The overall response rate was 67.8% : complete response 23.8%, partial response 44.4%. Complete responses were documented in all of three patients who had surgery and chemotherapy, 49.2% of those who had chemotherapy and radiotherapy, and 4.5% of those who had chemotherapy only. The median follow-up duration was 309 days. The median progression-free survival and overall survival were 256 days and 354 days, respectively: patients who had surgery and chemotherapy were 1631 days and 1631 days, those who had chemotherapy and radiotherapy were 344 days and 450 days, and those who had chemotherapy only were 186 days and 278 days, respectively; complete responders were 580 days and 710 days, partial responders were 231 days and 364 days, non-responders were 132 days and 151 days, respectively. Of 151 patients, 11.3% survived more than two years(long-term survival). Most long-term survivors had limited disease(82.4%) and good performance(76.5%). Long-term survival ocurred in two patients of those who had surgery and chemotherapy, 16.9% of those who had chemotherapy and radiotherapy, and 5.6% of those who had chemotherapy only. Most long-term survivors(70.6%) had complete response. Twenty of 36 complete responders and 8 of 17 long-term survivors had disease relapses or progressions. Patients with limited disease, those with good performance, and those with normal alkaline phosphatase had a significantly higher complete response rate and longer progression-free survival and overall survival than their counterparts. Of pretreatment characteristics, stage and performance status were correlated complete response and survival, independently. Complete response outcome was significant independent variable for survival. Conclusion: The disappointing results in this disease support the need for both new treatment strategies to improve complete response rate and to decrease relapse rate and large-scaled prospective studies to know natural history of long-term survivors.

근치적 목적의 절제술 후 II , IIIA 기 비소세포폐암의 Mitomycin - C , Vinblastine , Cisplatin ( MVP ) 복합항암화학요법과 방사선요법의 병용 치료

김태원 ( Tae Won Kim ),이정신 ( Jung Shin Lee ),정병학 ( Byung Hak Jung ),윤환중 ( Hwan Jung Yun ),장대영 ( Dae Young Zang ),이제환 ( Je Hwan Lee ),김성배 ( Sung Bae Kim ),김상위 ( Sang We Kim ),서철원 ( Cheol Won Suh ),이규형 ( K 대한내과학회 1998 대한내과학회지 Vol.54 No.5

Objectives: The poor survival rates among patients receiving surgery alone for stages II and III non-small cell lung cancer prompted several trials of adjuvant therapy after resection. We performed a prospective phase II study in patients with stage II-IIIA non-small cell lung cancer after resection to evaluate the feasibility, activity and toxicity of the postoperative sequential MVP chemotherapy and radiotherapy. Methods: Between February 1991 and May 1995, 60 patients with resected stage II, IIIA non-small cell lung cancer received 2 cycles of MVP combination chemotherapy (Mitomycin-C 6 mg/m², Vinblastine 6 mg/m², Cisplatin 60 mg/m) within 3 weeks after surgery, followed by thoracic irradiation (5,040 cGy after complete resection and 900 cGy booster to microscopically positive resection margin at 1.8 Gy per fraction) within 3-4 weeks after chemotherapy. Results: Forty nine men and 11 women with a median age of 60.5 years (range 33-81 years) were included. During the median follow-up period of 828 days (61-2,015 days), 25 patients had developed recurrence. Among the 25 failures, 3 were local relapse only and 20 were distant metastasis only and 2 had both local and distant sites of recurrence. Three-year overall survival and event-free survival were 43% and 37%, respectively. Neutropenia of grade I-II was observed only in 13 patients. Eleven patient showed grade I-II radiation pneumonitis and 32 had grade I-II radiation esophagitis, Conclusion: Postoperative sequential MVP chemotherapy and radiotherapy in resected stage II-IIIA non-small cell lung cancer is well-tolerated and shows interesting activity,

암환자의 통증치료에 대한 $Ultracet^{(R)}$의 유효성과 안전성

이효진,진선아,윤각원,양영준,박남환,천재민,박남숙,윤환중,조덕연,김삼용,Lee, Hyo-Jin,Jin, Sun-Ah,Yun, Gak-Won,Yang, Yung-Joon,Park, Nam-Whan,Chun, Jae-Min,Park, Nam-Sook,Yun, Hwan-Jung,Jo, Deog-Yeon,Kim, Sam-Yong 한국호스피스완화의료학회 2006 한국호스피스.완화의료학회지 Vol.9 No.2

목적: 외래에 내원하는 암환자들을 대상으로 암성통증의 조절에 있어서 $Ultracet^{(R)}$의 효과와 안전성에 대해 알아보고자 하였다. 방법: 암으로 진단을 받고 통증 조절을 목적으로 $Ultracet^{(R)}$을 투여한 61명의 환자를 대상으로 통증조절의 정도와 통증이 환자의 삶의 질에 미치는 영향에 대한 평가를 위해 Korean version of Brief Pain Inventory를 이용하였다. 약물의 안전성은 복용 후 나타나는 부작용 정도에 의하여 평가하였다. 결과: 대상환자의 평균연령은 59.9세였고 성별분포는 남자가 34명, 여자가 27명이었다. 환자의 진단은 폐암, 위암, 육종, 대장암, 췌장암, 자궁 경부암, 두경부암, 그리고 림프종 등의 순이었다. 대상환자에서 가장 심했을 때의 통증 정도는 $Ultracet^{(R)}$을 사용하기 전후에 유의한 감소를 보이지 않았으나($5.18{\pm}1.41\;vs.\;4.82{\pm}1.94$; P=0.113), 가장 약했을 때의 통증 정도($1.2{\pm}1.05\;vs.\;0.87{\pm}1.35$; P=0.038), 환자가 느끼는 통증의 평균 정도($3.65{\pm}1.01\;vs.\;3.13{\pm}1.73$: P=0.022)와 바로 지금 느끼는 통증정도($3.63{\pm}1.25\;vs.\;2.85{\pm}1.94$; P=0.003)는 유의하게 감소되었다. $Ultracet^{(R)}$의 사용으로 인한 부작용은 전반적으로 경미하여 2도의 오심과 구토 각 1예와 1도의 변비, 소양증, 안면 홍조가 각각 1예씩 관찰되었으나 3도나 4도의 독성은 관찰되지 않았다. 결론: $Ultracet^{(R)}$은 외래환경에서 암환자의 통증조절에 있어서 안전하게 사용할 수 있는 비교적 효과적인 약물로 생각된다. Purpose: We aimed to investigate the efficacy and side effects of $Ultracet^{(R)}$ in relieving cancer pain in setting. Methods: Sixty-one cancer patients over 18 years old, who had cancer pain with or without medication, were enrolled. Pain and other variables were evaluated before and after treatment with $Ultracet^{(R)}$ for 2 weeks, using Korean version of Brief Pain Inventory. Results: Of 61 patients with assessable efficacy data, the maximum pain intensity(PI) experienced in a day were $5.18{\pm}1.41\;and\;4.82{\pm}1.94$, before and after treatment with$Ultracet^{(R)}$ respectively (P=0.113). The minimum PI experienced in a day were $1.2{\pm}1.05\;and\;0.87{\pm}1.35$, before and after treatment with $Ultracet^{(R)}$, respectively (P=0.038). The average PI experienced in a day were $3.61{\pm}1.01\;and\;3.15{\pm}1.73$, before and after treatment with $Ultracet^{(R)}$, respectively (P=0.022). The current PI were $3.63{\pm}1.25\;and\;2.85{\pm}1.94$, before and after treatment with $Ultracet^{(R)}$, respectively (P=0.003). Regarding the quality of life, only mood changed for the better in 49 patients who were treated with $Ultracet^{(R)}$ alone ($1.98{\pm}1.73\;and\;1.35{\pm}1.15$, before and after treatment respectively; P=0.046). There were five (8.2%) adverse events associated with $Ultracet^{(R)}$ treatment. Conclusion: $Ultracet^{(R)}$ seems effective and safe in ambulatory patients with cancer pain.

소화기암 세포주에 대한 Interferon 의 항암제 세포독성 증강 효과

김성철(Sung Chul Kim),길준영(Jun Young Kil),전의건(Eui Gun Chun),윤환중(Hwan Jung Yun),조덕연(Deog Yeon Jo),김삼용(Sam Yong Kim),김영건(Young Kun Kim) 대한내과학회 1992 대한내과학회지 Vol.43 No.5

N/A Background: 1nterferons (IFN) have antiproliferative activity and immune moduiatory function. Interferons and cytotoxic drugs have different mechanism of action on cancer cells. To investigate the interaction of interferons with cytotoxic drugs, we treated human gastrointestinal cancer cells with combinations of anti- cancer drugs and interferons. Methods: Using the colorimetric [3-(4, 5-dimethlyth- iazo1-2-yl)-2, 5-diphenyltetraxolium bromide] (MTT) assay, we evaluated the chemosensitivity of anticancer drugs (5-fluorouracil, adriamycin), and the inhibitory effects of alpha interferon and gamma interferon, and the cytotoxic effects of the combination of interferons and anticancer drugs against the human gastric cancer cell line SNU-5 and the colon cancer cell line SNU-C. Results : Both 5-FU and adriamycin produced dosedependent inhibition of cancer cell growth; the alpha interferon and the gamma interferon had 12% and 18% inhibitory effects against SNU-5 cells respectively, and they showed 29% and 30% inhibitory effects against SNU-C1 cells respectively. Cytotoxicity of anticancer drugs was markedly augmented by the addition of alpha or gamma interferons. The II4 values of 5-FU and adriamycin decreased to 1/ 37 and 1/33, respectively, when alpha interferon was added to these drugs, and ID50 values of 5-FU and adriamycin decreased to 1/7 and 1/5.4, respectively, when the gamma interferon was added. Conclusions: The results indicate that interferons, when used concomitantly with the cytotoxic drug 5-FU or adriamycin, can augment the cytotoxicity of the latter drugs. A clinical trial incorporating interferons with anticancer drugs in gastrointestinal malignancies should be warranted.

재생불량성 빈혈의 임상적 고찰

길준영 ( Gil Jun Yeong ),전의건 ( Jeon Ui Geon ),윤환중 ( Yun Hwan Jung ),김백수 ( Kim Baeg Su ),최용석 ( Choe Yong Seog ),조덕연 ( Jo Deog Yeon ),김삼용 ( Kim Sam Yong ) 대한내과학회 1993 대한내과학회지 Vol.44 No.3

연구배경 : 재생불량성 빈혈은 우리나라를 비롯하여 극동지역에서 호발하는 중요한 질환이며 우리나라 재생불량성빈혈 환자의 임상상은 서양과 차이가 있는 것으로 알려져 있다. 재생불량성 빈혈 환자를 임상적으로 관찰하여 생존기간과 예후인자등을 알아보고자 1985년 8월부터 1991년 7월까지 6년동안 충남대학교병원 내과에서 입원가료를 받은 재생불량성 빈혈 환자 32예에 대하여 분석하였다. 방법 : 모든 대상환자에 일차적으로 oxymetholone(50~100mg/d)을 경구 투여하였고 필요에 따라 prednisolone (5~10 mg/d)을 추가하였다. Androgen 요법에 반응이 없는 20예중 9예에 antilymphocyte globulin (20mg/kg/d)을 4일간 정맥주사 하였으며 동시에 methylprednisolone (20mg/kg/d)을 5일간 정맥주사 하였다. 결과 : 1) 연령별로는 21~30세가 12예 (37.5%)로서 가장 많았으며 40세 이하가 25예(78.2%)였다. 2) 원인을 추정할 수 없는 경우가 26예(81.2%)로 대부분을 차지하였고 원인을 추정할 수 있는 경우가 6예 (18.8%)였는데 한약제 2예(6.3%), benzene 2예 (6.3%), 항진균제 1예(3.1%), 급성간염 B형 1예(3.1%) 였다. 3) Androgen을 중심으로 한 치료에 31예 중 5예(16.1%)에서 완전방응을, 6예(19.4%)에서 부분반응을 보여 반응율은 35.5%이였다. Androgen 치료에 반응이 없었던 20예중 9예에 2차적으로 시행한 antilymphocyte globulin 면역조절요법에 2예(22.2%)에서 완전방응을 보여 전체 42%의 반응율을 보였다. 4) 초진시 중증 재생불량성 빈혈 환자 20예(64.5%)의 72개월 생존율은 79.3%, 중앙생존기간은 32(2~72+)개월이었다. 중등도의 재생불량성 빈혈 11예(37.5%)의 72개월 생존율은 90%, 중앙생존기간은 37(13~72+)개월이었다. 50 남자 환자에서 여자 환자보다 반응율이 더 높았고 (61.5% vs 27.8%, p<0.05). 원인추정이 가능했던 예에서 원인을 알수 없었던 예보다 더 높은 반응율을 보였다(66.7% vs 28%, p<0.05). 그러나 초진시의 혈소판수, 과립구수, 또는 교정 망상적혈구수는 치료반응에 영향을 미치지 못하였다(p>0.05). 결론 : 재생불량성 빈혈 환자 32예중 31예에서 androgendmf 중심으로한 고식적치료와 면역억제요법만으로도 72개월 생존율이 83.1%였으며 서양환자에서의 예후보다 훨씬 양호한 것으로 판단된다. 따라서 골수이식은 초진시 중증 재생불량성 빈혈 진단을 받은 환자 중에에서도 고위험군을 선정하여 시행하는 것이 바람직하다고 생각되며 중등도 이하의 재생불량성 빈혈에서는 면역조절요법(항림프구 혈청 치료)과 고식적치료가 우선적으로 권장되어야 할 것으로 사료된다. Background : It is well konwn that aplastic anemia is more prevalent in the Far East than elsewhere in the world. There have been many suggestions that the clinical features of the patients with aplastic anemia in Korea would be somewhat different from that of western countries. Analysis of clinical data of 32 cases of aplastic anemia diagnosed at Chungnam National University Hospital from August 1985 to July 1991 was done. Methods : Initially all patients were treated with oxymetholone (50-100mg/d) with or without prednisolone (5-10mg/d) and supportive care. The patients who did not respond to androgen therapy were treated with antilymphocyte globulin (ALG) (20mg/kg/d for 4 days) plus methylprednisolne (methyl PD) (20mg/kg/d for 5 days). Analysis of reponse to therapy was done in 31 patients who could be followed for more than 3 months. Results : 12 patients (37.5%) were in their third decade and 25 cases of patients (78.2%) were below 40 years of age. The incidence decreased in older age groups. Exposure to possible toxic agents were seen in 6 cases (18.8%) ; benzene was counted in 2 cases (6.3%), herb drug in 2 cases (6.3%), antifungal agent in 1 case (3.1%). One case of aplastic anemia occured after acute viral hepatitis infection (type B) (3.1%), Eleven (35.5%) out of thity-one patients responded to androgen therapy (CR : 16.1%, PR : 19.4%). Nine out of the twenty patients who did not respond to androgen therapy were treated with ALG plus methyl PD. Two patients (22.2%) out of 9 showed complete responses. Overall response of present series of patients was 42% (oxymetholone±prednisolone therapy : 35.5%, ALG+methyl PD : 22.2%). By Kaplan-Meier product limit estimation, median survival time of 31cases was 36 months and the actuarial survival at 72 months was 83.1%. The median survival time of 31 cases was 36 months and the actuarial survival at 72 months was 83.1%. The median survival time of severe aplastic anemia (32 months) was similiar with that of moderately severe aplastic anemia (37 months). Factors associated with favourable survival were male sex and presence of etiological factor (p<0.05). Conclusions : In the present series, the survival rate of patients with aplastic anemia were somewhat different from that of western countries. Since the prognosis of patients with aplastic anemia in Korea is more favourable. A randomized controlled study would be needed to define the therapeutic role of bone marrow transplantation in patients with severe aplastic anemia in Korea.

귀밑샘 점액표피양암종의 폐 전이에 연관된 비후성 골관절증의

송승택 ( Seung Taek Song ),유인설 ( In Seol Yoo ),김영 ( Young Kim ),박찬걸 ( Chan Keol Park ),윤환중 ( Hwan Jung Yun ),강성욱 ( Seong Wook Kang ),김진현 ( Jin Hyun Kim ) 대한류마티스학회 2014 대한류마티스학회지 Vol.21 No.5

Hypertrophic osteoarthropathy is a syndrome characterized by periosteal new bone formation, arthritis, and clubbing of the fingers and toes. The majority of cases occur secondarily to the conditions associated with pulmonary, cardiac, gastrointestinal disorders or other systemic diseases. There are many cases with malignancy worldwide. We report the first patient who had hypertrophic osteoarthropathy due to metastatic cancer after surgical removal for mucoepidermoid carcinoma of the parotid gland.

류마티스 : 전신홍반루푸스로 오인된 혈관내B대세포림프종 1예

박찬걸 ( Chan Keol Park ),이정찬 ( Jeong Chan Lee ),강성욱 ( Seong Wook Kang ),심승철 ( Seung Cheol Shim ),윤환중 ( Hwan Jung Yun ),김진만 ( Jin Man Kim ),유인설 ( In Seol Yoo ) 대한내과학회 2015 대한내과학회지 Vol.89 No.6

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin’s lymphoma (NHL) and that progresses rapidly and is usually fatal. Because it usually presents with nonspecific symptoms, such as fever, the early diagnosis of IVLBCL is very difficult and it is often misdiagnosed as another disease. Systemic lupus erythematosus (SLE) is an autoimmune disease that affects various organs. The clinical manifestation of SLE ranges from rash and arthritis through anemia and thrombocytopenia to serositis, nephritis, seizures, and psychosis. Thus, it can be easily confused with many other disorders. We report a case of IVLBCL mimicking SLE in the initial diagnosis. (Korean J Med 2015;89:746-751)

급성골수백혈병에 대한 관해유도화학요법 후의 Granulocyte Colony-stimulating Factor의 효과

윤환중,최지영,전의건,길준영,조덕연,김삼용 충남대학교 의과대학 지역사회의학연구소 1993 충남의대잡지 Vol.20 No.2

Granulocyte colony-stimulating factor(G-CSF) have been shown to hasten the recovery of neutropenia following anti-cancer chemotherapy. There are controversial opinions on the use of G-CSF in acute myelogenous leukemia(AML) because clonogenic studies have shown that G-CSF stimulates leukemic colonies as well as granulocyte colonies. In this study, we evaluated the effectiveness and safety of recombinant human G-CSF after induction chemotherapy with DAV regimen(Ara-C 100mg/㎡ day 1-8, Doxorubicin 45mg/㎡ day 3-5, VP-16 100mg/㎡ day 6-8) in 9 patients with AML. G-CSF therapy(200 ㎍/㎡/day) was begun 2 days after the end of chemotherapy and continued for 10 days. 17 AML patients who recieved the same chemotherapy before the onset of this study were used as historical control. G-CSF shortened the duration of granulocytopenia (less than 500/㎣) significantly (13 vs 23 days, p<0.001), but it had no effect on platelet recovery. Although the incidence of febrile episodes was almost the same, the duration of febrile episodes was shorter in the group treated with G-CSF( 5 vs 12 days, p=0.03). There was no evidence that G-CSF accelerated the regrowth of leukemic cells and the complete remission rates between the 2 groups were not different. These results show that G-CSF accelerates the recovery of granulocytopenia and shortens the febrile days after chemotherpy in patients with AML, without affecting the regrowth of leukemic cells.

진행암 환자에서 Cisplatin 병용화학요법 시 Ondansetron의 오심 구토 조절 효과

조문준,윤환중,전의건,길준영,조덕연,김삼용 충남대학교 의과대학 지역사회의학연구소 1993 충남의대잡지 Vol.20 No.2

Ondansetron is a novel agent that selectively binds to the 5-hydroxytryptamine_3 receptor, and has been reported to have a prominent effect in the prevention of anti-neoplastic agent induced nausea and vomiting. Twenty solid tumor patients who were scheduled to receive cisplatin containing combination chemotherapy participated in a prospectively open-labeled study to evaluate the antiernetic efficacy and safety of ondansetron. The male to female ratio was 11 : 9 and median age was 49(16-70). The sites of primary neoplasms and number of patients were as following : head and neck 4, metastatic carcinoma of unknown primary site 3, stomach 3, osteosarcoma 2, ovary 2, esophagus 1, melanoma 1, penile 1, bladder 1, cervix 1, and extragonadal germ cell 1. Ondansetron was given as an 8mg loading dose IV before chemotherapy followed by 8mg IV every 8 hours until 24 hours after chemotherapy completion. Complete or major control(0 to 2 emetic episodes) of emesis was achieved in 17 of 20 patients(85%;complete 50%, major 35%) receiving ondansetron during the first 24hrs of chemotherapy. During the period of day 2 through clay 5 of chemotherapy, 14 of 20(75%) patients had complete or major control of emesis(complete 35%, major 35%). No severe side reactions were recorded in ondansetron treated patients, while mild to moderate headache was noted in 20% of patients. These results show that ondansetron is effective in the control of cisplatin induced nausea and emesis, and can be administered safely with minimal side effects.