대장 및 직장의 악성 폐색 환자에서 자가확장형인공관 삽입술에 대한 연구

유창범 ( Chang Beom Ryu ),김환열 ( Hwan Yeol Kim ),권강안 ( Kang An Kwon ),정인섭 ( In Sup Jung ),홍수진 ( Su Jin Hong ),김진오 ( Jin Oh Kim ),조주영 ( Joo Young Cho ),이준성 ( Joon Sung Lee ),이문성 ( Moon Sung Lee ),심찬섭 ( Cha 대한장연구학회 2003 Intestinal Research Vol.1 No.1

Background/Aims: The optimal palliative treatment of unresectable colorectal malignant obstruction is still debated. Recently, successful short-term palliation of malignant colorectal obstruction using self-expandable metal stents has been reported by several groups of investigators. Aims: The aim of this study was to evaluate the clinical usefulness of these self-expandable metal stents (SEMS) through the scope for the treatment of malignant colorectal cancer. Methods: Between May 1999 and December 2002, 35 patients (M:F=19:16) with malignant colorectal obstruction were treated for relief from the obstruction with endoscopically guided intubation of a SEMS through the working channel of an endoscope. Uncovered stents were intserted in 29 patients and covered stents in 6 patients. The technical and clinical success rates and complication were evaluated. Results: The sites of obstructions were on the rectum (n=3), sigmoid colon (n=9), descending colon (n=9), transverse colon (n=8) and ascending colon (n=6). SEMS insertion was successful in 34 of 35 patients (97%). In 31 of 34 patients with successful placement of the stent, symptoms of obstruction resolved within 72 hours. Two patients underwent the formal bowel preparation and elective single-stage surgery without complication 10 and 60 days after stent placement. Perforation occurred in 1 patients during stent placement and died. The mean follow up was 144 days (5-610 days). Stent migration occurred in 7 patients during follow-up who were 2 (33.3%) of 6 patients with covered stent and 5 (17.8%) of 28 patients with uncovered stent. After migration of stents, another stent was reinserted in 3 of 7 patients. Obstruction of the stent because of tumor ingrowth and overgrowth was observed in 4 patients with uncovered stent. Conclusions: SEMS placement through the working channel of an endoscope provide not only palliative decompression in cases with inoperable malignant colorectal obstruction but preoperative decompression to undergo the one-step surgery in patients with malignant colorectal obstruction. (Intestinal Research 2003;1:45-50)

위 편평선종 및 조기위암에서 내시경적 점막절제술 후 절제부위에서 발생한 융기형 병변에 관한 임상적 고찰

천영국,유창범,고봉민,김진오,조주영,이준성,이문성,진소영,심찬섭,Cheon Young Koog,Ryu Chang Beom,Ko Bong Min,Kim Jin Oh,Cho Joo Young,Lee Joon Seong,Lee Moon Sung,Jin So Young,Shim Chan Sup 대한위암학회 2001 대한위암학회지 Vol.1 No.1

Purpose: Several studies of an endoscopic mucosal resection(EMR) have been reported, but reports about benign protruding lesions that arise at the scar of EMR for early gastric cancer (EGC) or a gastric adenoma are rare. The purpose of this study was to elucidate endoscopic and histological characteristics of benign protruding lesions which arise at the scar of an EMR for EGC and a gastric flat adenoma. Materials and Methods: In 101 lesions (73 gastric flat adenomas and 28 EGCs) from 96 patients, 16 lesions developed new protruding lesions that arose at the scar of the EMR. We retrospectively analyzed the endoscopic findings of initial and protruding lesions, and several other clinical factors (H. pylori infection, eradication therapy, and proton pump inhibitor (PPI) or H2-blocker use). Results: 1. The mean duration until detection of the protruding lesion was 8.9 months ($1.5\∼27$). Protruding lesions arose at the scar of the EMR in 1 of 28 EGCs ($3.6\%$) and from 15 of 73 gastric flat adenomas ($20.5\%$). All of the patients were men. 2. With respect to the endoscopic findings, the shapes of the protruding lesions were as follows: 10 Yamada (Y) I, 4 Y-II, 1 Y-III, and 1 flat lesion. Histological examination of the protruding lesions revealed regenerating hyperplasia in 5 lesions, intestinal metaplasia in 5, and both in 6. 3. The incidence of these lesions was higher in cases of tubular adenomas with focal high-grade dysplasia than in cases of tubular adenomas without dysplasia (p<0.05). 4. The incidence of H. pylori infection was higher in patients ($81.7\%$) who developed a protruding lesion than in those ($51.8\%$) who did not develop (p=0.029); also, the incidence of use of PPI was higher in those patients (p=0.045). However, eradication therapy for H. pylori and duration of use of PPI or H2-blocker showed no difference between groups. Conclusions: It may be possible that the potential hyperplasia that may reside in normal mucosa surrounding EGC or a gastric adenoma might awaken during the healing process of the EMR ulcer and develop to benign protruding lesions. And, H. pylori and PPI might also be related to the development of the protruding lesions.

진단 및 치료 대장 내시경의 합병증으로 발생한 대장 천공의 치료에 대한 임상적 고찰순천향대학교 의과대학 내과학교실 소화기 연구소, 대전 속편한 내과

정성원 ( Song Won Jung ),유창범 ( Chang Beom Ryu ),송민수 ( Yon Soo Kim ),김연수 ( Min Soo Song ),고봉민 ( Bong Min Ko ),차상우 ( Sang Woo Cha ),류권호 ( Kwon Ho You ),홍수진 ( Soo Jin Hong ),김영석 ( Young Seok Kim ),문종호 ( Jon 대한장연구학회 2004 Intestinal Research Vol.2 No.1

Colonoscopy is used increasingly because the indication for therapeutic colonoscopy has been increased and the technique has been developed continuously as well as colonosopy is useful for diagnosis of colonic disease. Therefore, It is important understanding precisely about the complication of colonoscopy and managing the complication immediately and properly. In particular, colon perforation is the most fatal, emergency case and have needed surgical treatment, generally. Recently, the case treated with endoscopic clipping and conservative management has been reported. but until now, when perforated, wheather the endoscopic clipping or the surgical management at each other case is beneficial is not confirmed.

위종양성 병변에 대한 내시경 절개 점막하 박리법의 임상적 유용성

정윤호,은수훈,조수영,정인섭,유창범,이준성,이문성,김부성,심찬섭,Jung, Yoon-Ho,Eun, Soo-Hoon,Cho, Joo-Young,Jung, In-Seop,Ryu, Chang-Beom,Lee, Joon-Seong,Lee, Moon-Sung,Kim, Boo-Sung,Shim, Chan-Sup 대한위암학회 2006 대한위암학회지 Vol.6 No.2

목적: 최근 위선종 및 조기위암에 대해 새로운 내시경적 치료법인 내시경 절개 점막하 박리법은 기존의 내시경적 점막절제술 보다 더 넓은 적응증을 가지고 있지만 시술의 난이도가 높고 합병증의 위험이 있어 보편적으로 시술되고 있지 않다. 이에 내시경 절개 점막하 박리법으로 치료한 위의 종양성 병변의 치료 성적을 바탕으로 그 임상적 유용성을 알아보고자 하였다. 대상 및 방법: 내시경 절개 점막하 박리법을 시행한 164명의 환자들의 179개의 위종양성 병변에 대하여 완전절제 및 일괄절제 여부, 합병증, 재발 여부 등을 분석하였다. 결과: 179개의 병변은 조기위암 126예(70.3%), 선종 42예 (23.4%)였다. 병변의 침윤 깊이를 확인할 수 있었던 조기위암 420예는 각각 점막1층(sm1) 0.8% (1/120), 점막2층(m2) 38.3% (46/120), 점막3층(m3) 25% (57/120), 점막하1층(sm1) 11.7% (14/120), 점막하2층(sm2) 1.6% (2/120)이었다. 종양의 일괄절제율과 완전절제율은 각각 96.0%, 85.2%였다. 합병증은 천공 8예(4.4%), 출혈 38예(21.2%)가 발생하였으나, 천공 1예를 제외한 나머지는 비수술적으로 치료가 가능하였다. 결론: 본 연구에서 내시경 절개 점막하 박리법은 위종양성 병변의 근치적 치료에 비교적 안전하고 효과적인 술기이고, 향후 보다 장기간의 추적관찰을 통해 그 유용성이 검증되어야 할 것으로 생각한다. Purpose: Endoscopic incision and submucosal dissection (EISD) is a technique that is being implemented for the resection of gastric adenomas and early gastric cancer (EGC). Since EISD requires a high degree of skill and experience, and due to its association with a moderate risk of gastrointestinal bleeding, its use has been limited. The objective of this study is to investigate the clinical benefits of EISD based upon clinical data on the EISD procedure. Materials and Methods: This study was conducted at Soonchunhyang University Hospital and it included 179 gastric adenoma and early gastric carcinoma lesions from 164 patients who had undergone an EISD from February 2003 to May 2005. Results: Among the total of 179 lesions, the distributions of EGC and adenomas were 70.3% (126/179) and 23.4% (42/179) respectively. The sizes of lesions were divided into 10 mm or less, $11{\sim}20\;mm,\;21{\sim}30\;mm$ and greater than 31 mm and each rates are 10.0% (18/179), 46.3% (83/179), 30% (50/179) and 15.0% (28/179). Among 120 cases which could be measured depth of lesion in according to pathologic findings, m1 (0.8%, 1/120), m2 (38.3%, 46/120), m3 (25%, 57/120), sm1 (11.7%, 14/120), sm2 (1.6%, 2/120) were diagnosed as early stages of gastric cancer. The complete resection rate was 85.2% (150/176) and en-bloc resection rate was 96.0% (169/176). Complications as such as perforation and bleeding developed in 4.4%(8/179) and 21.2% (38/179), respectively. Conclusion: EISD is an effective in the endoscopic treatment for gastric adenoma and early gastric cancers. However, further evaluation of this method and long-term follow-up will be necessary for an evaluation of the recurrence rate after resection of a tumor.

상부소화관의 확대 내시경

이상호 ( Sang Ho Lee ),유창범 ( Chang Beom Ryu ),장재영 ( Jae Young Jang ),조주영 ( Joo Young Cho ) 대한소화기학회 2006 대한소화기학회지 Vol.48 No.3

For the diagnosis of upper gastrointestinal (GI) lesions, magnification method is usually used in conjunction with chromoscopy, enabling the endoscopist to view subtle mucosal patterns in exquisite detail. Recently published datas have shown that magnifying endoscopy might be a valuable adjunct for the diagnosis, detection, and characterization of inflammatory and neoplastic lesions of the upper GI tract. It is also proven to be an useful surveillance protocol in identifying dysplastic epithelium or early cancer within a segment of Barrett`s esophagus. Possible indications for magnifying endoscopy in upper GI tract include screening and surveillance of Barrett`s esophagus, defining the extent of esophageal and gastric adenocarcinoma, detecting synchronous/metachronous gastric and esophageal cancers, diagnosing Helicobacter pylori infection, and recognizing minimal mucosal changes in gastroesophageal reflux disease. By grading the quality of evidence for the currently published trials, it is clear that the majority are case series, case reports, and/or observational studies without randomization, control, or blinding. Moreover, other evidence-based criteria such as independent, blind comparisons of magnifying endoscopy with a standard method which evaluates this technology in an appropriate spectrum of patients to whom the test may be applicable, and standardizing methodology would be crucial before magnifying endoscopy becomes a standard procedure in clinical practice. In the future, a uniform classification system for staining and magnifying patterns should be devised and observer agreement should be tested. Futher studies then could be performed based upon consistent, validated, and standardized terminologies and criteria. (Korean J Gastroenterol 2006;48:145-155)

간경변증 환자의 말초혈액단핵구에서 중합효소연쇄반응법을 이용한 Cytomegalovirus DNA 의 검출

문종호(Jong Ho Moon),유창범(Chang Beom Ryu),박철호(Cheol Ho Park),류권호(Kwon Ho Ryu),박찬욱(Chan Wook Park),이준성(Joon Sung Lee),이문성(Moon Sung Lee),조성원(Sung Won Cho),황승덕(Seung Deok Hwang),심찬섭(Chan Sup Shim),이희발(Hi Ba 대한내과학회 1995 대한내과학회지 Vol.49 No.6

N/A Objectives: Human cytomegalovirus(CMV) infections are common and usually asymptomatic, but fatal infections occur frequently in immunocompromised patients. In Korea, CMV infection is common and patients with liver cirrhosis are frequently in a condition of immunosuppression, may predispose to the frequent occurrence of CMV infections. The purpose of this study was to investigate the prevalence of CMV infection in patients with liver cirrhosis and to evaluate the relationship between the status of C3:IV infection and liver function. Methods, The subjects of this study were 36patients with liver cirrhosis, 4patients with non A, non B, non C(NANRNC) hepatitis, and 13normal controls. IgG and IgKI antibodies to CMV were measured using a microparticle enzyme immunoassay(MEIA). Specimens of urine were cultured for CMV using shell vial culture method. Peripheral blood mononuclear cells(PBMC) were investigated for the presence of CMV-DNA using PCR. Rusults: In CMU antibody test, IgM and IgG antibodies were detected in 7(19.4%) of 36patients with liver cirrhosis, IgG antibody was detected in the other 29patients and all control subjects. In shell vial culture, CMV was cultured in 1(2.8%) of 36patients with liver cirrhosis(IgM and IgG positive). CMV DNA was detected by PCR in 19(52.8%) of 36patients with liver cirrhosis, but 1(7.7%) of 13 control subjects (p<0.05). CMV DNA was detected in 6(85.7%) of 7cirrhotic patients with IgM and IgG antibodies positive, 13(44.8%) of 29cirrhotic patients with IgG antibody positive. CMV DNA positive cirrhotic patients show 5(26.3%) in Child A, 6(31.6%) in Child H, 8(42.1%) in Child C. CMV DNA negative cirrhotic patients show 4(23.5%) in Child A, 12(70.6%) in Child B, 1(5.9%) in Child C(p<0.05). CMV DY:A positive cirrhotic patients showed the tendency of more frequent detection of HBsAg and HBeAg than CMU DNA negative cirrhotic patients(p<0.05). Conclusion: These results suggest that CMV infection is common in cirrhotic patients and the CMV DNA positive patients with liver cirrhosis have more impairment of liver function than the CMV DNA negative patients with liver cirrhosis.

대장 아메바종 1예

김환열 ( Hwan Yeol Kim ),고봉민 ( Bong Min Ko ),권계원 ( Kye Won Kwon ),홍수진 ( Soo Jin Hong ),유창범 ( Chang Beom Ryu ),김진오 ( Jin Oh Kim ),조주영 ( Joo Young Cho ),이준성 ( Joon Sung Lee ),이문성 ( Moon Sung Lee ),심찬섭 ( Ch 대한장연구학회 2003 Intestinal Research Vol.1 No.1

Amebiasis is observed worldwide. Usual symptoms of amebiasis include bloody stool, diarrhea, abdominal pain, fever and weight loss. Severe form of amebiasis is associated with perforation, pseudopolyp, peritonitis, toxic megacolon and ameboma. An ameboma represents a localized amebic infection with organized granulation tissue and is almost found in cecum and rectum. We report a case of ameboma of rectum detected incidentally without specific symptom, with review of relevant literature. (Intestinal Research 2003;1:68-71)

대장점막암의 내시경적 완전 절제술 후 재발암 1예

김환열 ( Hwan Yeol Kim ),고봉민 ( Bong Min Ko ),권계원 ( Kye Won Kwon ),홍수진 ( Soo Jin Hong ),유창범 ( Chang Beom Ryu ),김영석 ( Young Seok Kim ),이문성 ( Moon Sung Lee ),심찬섭 ( Chan Sup Shim ),김부성 ( Boo Sung Kim ) 대한장연구학회 2003 Intestinal Research Vol.1 No.2

Early colon cancers were resected endoscopically in many cases. But problems with recurrences and remnants of tumors have occured. We reported a case of recurrent cancer on 9 months after endoscopic resection for mucosal cancer of colon, with review of relevant literature. (Intestinal Research 2003;2:201-204)

대장의 측방발육형 종양에서 내시경적 분할점막절제술 후 추적 대장내시경의 유용성

김환열 ( Hwan Yeol Kim ),고봉민 ( Bong Min Ko ),차상우 ( Sang Woo Cha ),권계원 ( Kye Won Kwon ),홍수진 ( Soo Jin Hong ),유창범 ( Chang Beom Ryu ),김영석 ( Young Seok Kim ),문종호 ( Jong Ho Moon ),김진오 ( Jin Oh Kim ),조주영 ( Joo 대한장연구학회 2003 Intestinal Research Vol.1 No.2

목적: 대장의 측방발육형 종양은 대장 벽을 따라 낮고 넓게 자라는 표면형 종양으로 악성변화율이 높고, 크기에 비하여 점막하 침윤의 빈도는 많지 않기 때문에 내시경적 점막절제술에 의한 치료가 시행되고 있다. 이에 본 연구에서는 내시경적 분할점막절제술후 추적 대장내시경의 시기 및 결과에 대하여 조사하였다. 대상 및 방법: 2001년 3월부터 2003년 8월까지 32개월간 순천향대학교 부천병원 소화기병 센터에서 대장내시경상 측방발육형 종양으로 진단받은 31예 중 크기가 20 mm 이상으로 내시경적 분할 점막절제술을 시행한 21예를 대상으로 하였다. 이중 추적검사 가 시행되지 않은 4예와 수술을 시행한 2예를 제외한 15예를 대상으로 조사하였다. 평균 추적기간은 10.3개월(2-18개월)이었다. 결과: 여자가 14예로 남자의 7예 에 비해 많았고, 평균 연령은 56.9세였다. 조직학적 소견에서 10예(47.6%)가 선암, 관상-융모상 선종이 7예(33.3%), 융모상 선종이 1예(4.8%), 관상 선종이 3예 (14.3%)였다. 내시경적 분할 점막절제술후 추적 대장내시경을 처음 시행한 시기는 평균 2.2개월(1-5개월)이었으며, 총 15예 중 5예(33.3%)에서 추적 기간중 절제 부위에서 재발이 관찰되었다. 선암 2예에서 2개월후 관상선종이, 관상-융모상 선종 1예에서 2개월후 조직검사상 고도 세포 이형성이, 관상 선종 1예에서 5개월후 조직 검사상 선종성 용종이, 국소적 고도 세포 이형성이 동반된 관상 선종 1예에서 4개월 후 조직검사상 관상 선종이 관찰되었다. 이 5예에서 추가적인 내시경적 치료를 시행하였고, 이후 추적 대장내시경상 현재까지 이상 소견은 관찰되지 않았다. 결론: 대장의 측방발육형 종양중 크기가 직경 20 mm 이상이어서 내시경적 분할점막 절제술을 시행한 경우에는 절제부위의 재발율이 높으므로 내시경적 절제술 이후에 도 주기적인 추적 대장 내시경의 시행이 필요하고 최소한 절제후 1년 이내에 시행해야 한다고 생각한다. Background/Aims: Laterally spreading tumors (LST) of the colon are defined as tumors over 10 mm in diameter that are low in height and grow superficially. These tumors are highly malignant and usually mucosal lesions, therefore endoscopic mucosal resection is desirable. We analysed retrospectively the result of endoscopic piecemeal mucosal resection (EPMR) in LSTs larger than 20 mm in diameter. Methods: 21 patients with LSTs larger than 20 mm in diameter were treated using EPMR. The resection sites were examined for residual or recurrent lesions by follow-up colonoscopy. Results: Of the 21 patients who underwent EPMR, 2 patients performed surgical resection and 4 patients were lost during follow-up period. Residual or recurrent lesions were detected in 5 of these 15 patients after EPMR. After additional endoscopic therapy, no more residual or recurrent lesions were detected. Conclusions: After EPMR for large LSTs, it is necessary to strictly follow-up at least within 1 year. (Intestinal Research 2003;2:186-191)

Helicobacter pylori 일차 및 이차 치료의 제균율 변화와 재감염률

나현식 ( Hyun Sik Na ),홍수진 ( Su Jin Hong ),윤효중 ( Hyo Joong Yoon ),맹주희 ( Joo Hee Maeng ),고봉민 ( Bong Min Ko ),정인섭 ( In Sup Jung ),유창범 ( Chang Beom Ryu ),김진오 ( Jin Oh Kim ),조주영 ( Joo Young Cho ),이준성 ( Joon 대한소화기학회 2007 대한소화기학회지 Vol.50 No.3

목적: H. pylori 제균율과 재감염률은 지역에 따라 다양하게 보고 되고 있다. 저자들은 최근 5년 동안 경기도 부천지역 주민을 대상으로 일차 및 이차 제균치료의 연도별 제균율 변화와 재감염률을 알아보고자 하였다. 대상 및 방법: 2001년 2월부터 2006년 8월까지 순천향대학교 부천병원 소화기내과 외래에 내원하여 상부위장관내시경 검사를 실시하여 위궤양 또는 십이지장 궤양을 진단받고 H. pylori 감염을 확인하여 일차 제균치료를 시행한 3,267명의 환자와 일차 제균치료에 실패하여 이차 제균치료를 시행한 317명의 환자를 대상으로 제균율을 조사하였다. 또한 성공적으로 제균 치료가 된 환자 중에서 3년 이상 추적 관찰한 167명을 대상으로 재감염률 및 소화성 궤양의 재발률을 조사하였다. H. pylori 감염은 내시경 검사를 통한 조직 검사와 신속요소 분해효소 검사로 판단하였고 일차 제균치료는 삼제요법, 이차 제균치료는 사제요법을 시행하였으며, 제균 판정은 제균요법을 시행하고 4-6주가 지난 후 신속요소분해효소 검사와 조직검사, 13C-요소호기검사를 통해 판정하였으며 이 후 추적 관찰 역시 내시경 검사와 함께 신속요소분해효소 검사나 13C-요소호기검사를 통해 판정하였다. 결과: 일차 치료 제균율은 PP 분석에서 2001년은 83.7%, 2002년은 83.4%, 2003년은 83.9%, 2004년은 85.9%, 2005년은 87.2%, 2006년은 81.8%로 나타났으며 각 연도별 제균율은 유의한 차이를 보이지 않았다. 이차 치료 제균율은 PP 분석에서 2002년은 80.0%, 2003년은 86.8%, 2004년은 89.7%, 2005년은 98.0%, 2006년은 78.8%로 나타났으며 각 연도별 제균율은 유의한 차이를 보이지 않았다. 재감염률은 3년 동안 추적 관찰한 167명 중 총 10명에서 재감염이 발견되어 총 누적 재감염률은 6.0%였고, 연간 재감염률은 2.0%로 나타났다. 궤양 재발은 재감염이 발생하지 않은 환자에서는 17.2%, 재감염 환자군에서는 50%로 나타났으며 이 두 군 간에 유의한 차이를 보였다. 결론: 경기도 부천지역에서 일차 제균치료로서 PPI를 기본으로 하는 삼제 병합요법과 이차 제균치료로서 사제 병합요법은 최근 5년 동안 제균율 변화 경향을 보이지 않아 아직까지 유용한 치료법으로 생각한다. H. pylori의 연간 재감염률은 2.0%였으며 재감염이 있는 환자군에서 궤양 재발이 유의하게 높아 성공적인 제균치료가 궤양의 재발 억제에 영향을 미침을 알 수 있었다. Background/Aims: The increasing trend of antibiotic resistance emphasizes the need for the assessment of eradication rate of first and second-line therapy for Helicobacter pylori (H. pylori) infection. The reinfection rate depends on the geographical, national, or socioeconomic status of the patients. The aim of this study was to evaluate the recent 5-year changes of eradication rates and the reinfection rates after the successful eradication of Helicobacter pylori infection for 3-years follow-up in Bucheon, Korea. Methods: From February 2001 to August 2006, 3,267 patients with H. pylori-positive peptic ulcer disease received the first-line therapy for 7 days. The 317 patients who failed to the first-line therapy received the second-line therapy for 7 days. The 167 patients with 3-years follow-up after the successful eradication were included. 13C-urea breath tests or rapid urease tests and histologies were assessed to determine the H. pylori status after the eradication. Results: The eradication rate of first-line therapy was 83.7% in 2001, 83.4% in 2002, 83.7% in 2003, 85.9% in 2004, 87.2% in 2005, and 81.8% in 2006 by per protocol analysis (PP), respectively. The eradication rate of second-line therapy was 80.0% in 2002, 86.8% in 2003, 89.7% in 2004, 98.0% in 2005, and 78.8% in 2006 by PP. The cumulative reinfection rate was 6.0%. The annual reinfection rate was 2.0%. The recurrence rate of peptic ulcer was 17.2% in the patients without reinfection and 50% with reinfection. Conclusions: The eradication rate for H. pylori have not changed in the recent 5-years. The annual reinfection rate was low. The successful eradication of H. pylori was effective for preventing the recurrence of peptic ulcers. (Korean J Gastroenterol 2007;50:170-175)