The Frequency and the Course of the Adverse Effects of Azathioprine/6-Mercaptopurine Treatment in Patients with Inflammatory Bowel Disease.

BACKGROUND/AIMS: This study was to evaluate the frequency and the course of the adverse effects of AZA/6-MP in Korean patients with inflammatory bowel disease (IBD). METHODS: Medical records of the patients with IBD treated with AZA/6-MP at Severance hospital from June 1996 to September 2006 were retrospectively analyzed. RESULTS: A total of 133 patients were studied. Male to female ratio was 1.3:1. The mean age was 31.7+/-10.9 year. Adverse effects included leukopenia occurred in 75 cases (56.4%), nausea/vomiting in 32 cases (24.1%), arthralgia in 6 cases (4.5%), hepatitis in 6 cases (4.5%), skin rash in 4 cases (3.0%), herpes zoster in 3 cases (2.3%), and headache in 1 case (0.8%). Most of leucopenia (58.7%) developed within 3 months after maximal tolerated dose of AZA/6-MP and nausea/vomiting frequently occurred within 3 months after start of AZA/6-MP treatment. Thirty-eight patients (28.6%) required the discontinuation of medication due to adverse effects. CONCLUSIONS: Leukopenia was the most common adverse effect of AZA/6-MP treatment. Leukopenia and nausea/vomiting developed frequently in the early period of treatment of AZA/6-MP in patients with IBD. AZA/6-MP should be used cautiously to scrutinize bone marrow suppressionope

A Case of Crohn`s Disease with Iliac Arterio-Enteric Fistulae

Arterioenteric fistula is rare but can cause life-threatening bleeding. A case of Crohn`s disease with severe gastrointestinal hemorrhage caused by iliac arterioenteric fistula is presented. A 36-year-old male with Crohn`s disease was admitted because of massive lower gastrointestinal bleeding, which required transfusion of 16 units of packed RBCs over 2 days. Radioisotope RBC scan revealed intestinal bleeding directly from the right iliac artery. Emergent operation confirmed iliac arterioenteric fistulae with active bleeding, There was no further intestinal bleeding after surgery. Remission had been maintained for 3 years with mesalazineope

Pulmonary Inflammatory Pseudotumor: A report of 28 cases

BACKGROUND: Pulmonary inflammatory pseudotumor is an uncommon benign lesion of the lung. In Korea, most literature of the pulmonary inflammatory pseudotumor was case reports. METHODS: We collected 28 cases of pulmonary inflammatory pseudotumor in Korea. This collective series included 4 cases from our hospital and 24 cases were reviewed from the literature since 1977. The analysis involved the age, sex, chief complaint, hematologic examination, size and location of the lesion, cavity formation, presence of calcification and treatment method. RESULTS: Male was more prevalent (81.5%) than female and mean age was 37.9 years old (6~63 yrs). Chief complaints were cough (44.4%), chest pain (29.6%), fever (22.2%), hemoptysis (15%), sputum (15%) and dyspnea (11.1%). There were asymptomatic cases in 11.1%. Hematologic examination revealed normal finding (53.3%) and anemia (20%). The mean size of the lesion was 4.76 cm (1.5~14 cm) and the locations were parenchymal (85.7%), endobronchial (10.7%) and endotracheal (3.6%). Except the endotracheal case, the lesions were in the right (46.4%), the left (42.8%) and bilateral (7.1%). Calcifications (18.5%) and cavitations (11.1%) were present. Diagnostic methods were open thoracotomy (82.1%), bronchoscopy (3.6%), needle aspiration biopsy (7.1%) and core needle gun biopsy (7.1%). Treatments were surgery (85.2%), steroid therapy (7.4%), rigid bronchoscopic removal (3.7%) and observation (3.7%). Postoperative recurrence occurred in only 1 case (4.3%). CONCLUSION: Pulmonary inflammatory pseudotumor was more prevalent in the male, and patients presented with the respiratory symptoms were common. It was necessary to do surgery in most cases for diagnosis and/or treatment.ope

Patterns of Recurrence and Prognosis in Patients with Intestinal Behcet’s Disease Who Underwent a Bowel Resection

PURPOSE: We aim to analyze the clinical course and the recurrence patterns after surgical treatment in patients with intestinal Behcet's disease and to determine the prognostic factors. METHODS: Thirty-eight patients with intestinal Behcet's disease who had undergone operations between 1979 and 2007 were analyzed. Clinical characteristics between the recurrent group (n=24) and the non-recurrent group (n=14) were compared. The cumulative recurrence rates were calculated by using the Kaplan-Meier method, and the results were compared by using the log-rank test. RESULTS: The median follow-up was 120 months. The median age of the 38 patients was 36.5 years, and the patients included 26 males and 12 females. Recurrences after surgical treatment were observed in 24 patients, and reoperations were performed in 21 patients. The mean age at operation was 35.7 years in the recurrent group and was less than 43.4 years in the non-recurrent group (P=0.030). Clinical subtypes of Behcet's disease (complete or incomplete vs. suspicious) and the cause of operation (presence vs. absence of a perforation or fistula) were different between the recurrent and the non-recurrent groups (P=0.048, P=0.014, respectively). The 5-year cumulative recurrence rate and reoperation rate for all patients with intestinal Behcet's disease who underwent operations were 52.7% and 36.0%, respectively the clinical subtypes and the cause of the operation were significant factors affecting the cumulative recurrence and the reoperation rates. CONCLUSIONS: Intestinal Behcet's disease demonstrates high recurrence and reoperation rates after surgical treatment. More careful follow up is needed to these surgical patients with high risk of recurrence and reoperationope

선박용 일체형 원자로에서의 자연대류 특성에 대한 연구

Thesis (doctoral)--서울대학교 대학원 :원자핵공학과,2000.Docto

대장암 미세환경에서 S100A8/A9 유도와 골수세포 분화에 대한 근섬유모세포의 역할

Dept. of Medicine/박사The overexpression of S100A8/A9 is associated with inflammatory and neoplastic conditions. S100A8/A9 proteins and myeloid cells in the tumor microenvironment play important roles in cancer invasion and progression. S100A8/A9 are involved in the metastatic processes and act as chemo-attractant to facilitate the homing of tumor cells to premetastatic niches. Most studies have focused on the interactions between tumor cells and inflammatory cells and between tumor cells and myofibroblasts in tumor microenvironments. The effect of tumor-infiltrated myofibroblasts on myeloid cells in the tumor microenvironment is relatively unknown. Therefore, the aim of this study was to investigate the role of myofibroblasts in the induction of S100A8/A9 as well as in the differentiation of myeloid cells in the colorectal cancer (CRC) microenvironment.To investigate the interactions among cancer cells, myofibroblasts, and inflammatory cells in CRC microenvironment, a series of 10 CRC cell lines, 18CO cells (colonic myofibroblasts) and THP-1 cells (inflammatory myeloid cells), which were co-cultured with each other or cultured in conditioned medium (CM) from other cells were used. Expression of S100A8/A9 was evaluated by Western blot, immunohistochemical staining and immunofluorescence. The secreted factors from the cell lines were analyzed using cytokine antibody array. Flow cytometry analysis was performed to analyze the differentiation markers of myeloid cells.CM from 18CO cells induced increased expression of S100A8/A9 in THP-1 cells. 18CO CM induced differentiation of THP-1 cells into myeloid-derived suppressor cells (CD33 and arginase-1) or M2 macrophages (CD163 and CD206) expressing S100A8/A9. IL-6 and IL-8 were increased in 18CO CM, compared to those in both controls and THP-1 CM. Neutralizing antibodies to IL-6 and IL-8 attenuated 18CO CM-induced increased expression of S100A8/A9. Increased expression of S100A8/A9 was noted in inflammatory cells along with myofibroblasts in human CRC tissues. S100A8 expressing cells exhibited CD68 expression and tumor-infiltrated myofibroblasts expressed IL-8 in human CRC tissues. In conclusion, it was demonstrated that the release of IL-6 and IL-8 from myofibroblasts induced the expression of S100A8/A9 in tumor-infiltrating myeloid cells, and myofibroblasts induced the differentiation of myeloid cells into myeloid-derived suppressor cells or M2 macrophages expressing S100A8/9 in vitro.prohibitio

Simultaneous Removal of So₂and NOx by Pulsed Corona Discharge Process

Maste

염증성 장질환 환자에서 thiopurine methyltransferase 유전자 검사의 임상적 유용성.

Dept. of Medicine/석사[한글] 염증성 장질환 환자의 치료에서 스테로이드는 매우 중요한 치료제이다. 그러나, 부작용이 나타나거나 치료에 불응하는 경우가 나타나므로 azathioprine (AZA)이나 6-mercaptopurine (6-MP)과 같은 면역 조절제를 사용하게 된다. Thiopurine methyltransferase (TPMT)는 이들 약제의 대사에 중요한 효소로 6-MP가 6-thioguanine nucleotides (TGN)로 대사되는데 경쟁적으로 작용하게 된다. TPMT 활성도는 유전적 다양성과 연관되는데 대략 90%의 서양인에서 고활성도를 갖는 동종 접합체를 갖고, 약 10% 는 중등도의 활성도를 보이는 이형 접합체를 보이며, 약 300명 중 1명이 저활성도를 갖는 동형접합체를 갖는 것으로 알려져 있다. TMPT의 유전형과 표현형은 95%이상 일치하는 것으로 보고 된다. 이에 연구자는 polymerase chain reaction (PCR)을 이용하여 정상인 100명과 염증성 장질환 환자 300명을 대상으로 TPMT 유전자 검사를 통하여 면역 조절제에 의한 골수 기능 억제와의 상관 관계를 알아보고자 하였다. G238C 다형성, G460A 다형성, 그리고 A719G 다형성은 정상인(0/200 alleles)과 환자군(0/600 alleles) 모두에서 발견되지 않았다 (0/200 alleles). 본 연구에서 흔한 TPMT 다형성은 극히 드무나, AZA 또는 6-MP사용에 따른 골수 기능 억제의 빈도가 이전의 연구 결과 보다 높은 것으로 보아 향후 드문 TPMT 다형성에 관한 연구와 TPMT 효소의 활성도 및 TGN의 농도 측정이 필요할 것으로 생각한다. 핵심 되는 말: 염증성 장질환, TPMT 유전자 검사, Azathioprine, 6-mercaptopurine, 골수 기능 억제 [영문] The metabolic pathway catalyzed by thiopurine methyltransferase (TPMT) is in competition with a pathway that leads from 6-mercaptopurine to 6-thioguanine nucleotides. TPMT activity exhibits genetic polymorphism. Approximately 90% of Caucasian subjects was reported as homozygous for an allele for high RBC TPMT activity, about 10% was heterozygous and had intermediate activity, and about one of every 300 subjects was homozygous for an allele for low RBC TPMT and lacked detectable enzyme activity. The correlations between phenotype and genotype of TPMT have been reported greater than 95%. Using polymerase chain reaction (PCR) method, common TPMT genotypes in one hundred subjects with no disease and three hundred subjects with inflammatory bowel disease (IBD) were studied. The correlations between the genotype of TPMT and bone marrow suppression during the treatment with AZA or 6-MP were made. G238C, G460A, and A719G polymorphism was not detected in normal subjects (0/200 alleles) and in the patients with IBD (0/600 alleles. But the frequency of bone marrow suppression during the treatment with AZA or 6-MP was considerably higher (31.3%) than what was reported in previous studies (5%). There was no correlation between thiopurine- induced bone marrow suppression and TPMT genotype.ope

요동조건하에서의 원자로 열수력 특성 파악을 위한 RETRAN-03 코드 개선

학위논문(석사)--서울대학교 대학원 :원자핵공학과,1996.Maste