백서의 복강내에 투여한 Mitomycin-C-Polyglycolic acid 제형이 장기에 미치는 영향에 관한 연구

송규상,강대영,최정목,노승무,정경수,오정연,김진향,양준목,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

To evaluate the in-vivo effects of mitomycin-C-polyglycolic acid composite(MMC-PGA) the disk: shaped composite were implanted into the peritoneal cavity of the Sprague-Dawley rats. The pathologic changes were examined at various time points up to 12 weeks. Initially the soft tissue around the inserted disks showed capillary congestion at 3 days. Inflammatory infiltrates with foreign body giant cells appeared from the 2nd week and reached peak response at 6-8 weeks. These reaction diminished prominently at 12 weeks. No specific pathologic change was found in the liver, the kidneys, and the heart. The above results suggest that the MMC-PGA composite can serve as a new device for intraperitoneal chemotherapy of various types of cancers.

간생검조직의 병리조직학적 연구

송규상,강대영 충남대학교 의과대학 지역사회의학연구소 1986 충남의대잡지 Vol.13 No.2

A histopathologic study was performed on 158 liver biopsies submitted to the department of pathology, Chungnam National University College of Medicine, during the period from Jan. 1982 to Oct. 1986, and the results were as follows : 1. Amont 158 liver biopsies, the hepatitis is the most frequent(98 cases, 62.0%), followed by fatty liver(24 cases, 15.2%) liver cirrhosis(20 cases, 12.7%), and hepatoma(6 cases, 3.8%) The overall sex ratio was 3.4:1. 2. Among 98 cases of hepatitis, chronic hepatitis was 74 cases, nonspecific reactive hepatitis 12 cases, alcoholic hepatitis 5 cases, acute hepatitis 5 cases, and neonatal hepatitis 2 cases. The sex ratio of chronic hepatitis was 4.7 : 1 with the average age of 37.1 year-old and the prevalent age in the fourth decade. Chronic active hepatitis was to times more than chronicc persistant hepatitis. 3. The sex ratio of fatty liver was 2:1, the average age 37 year old, and the prevalent age was the fourth decable. 4. Liver cirrhosis was encountered in 20 cases with the sex ratio of 4:1, the average age of 35.5 year-old, and the prevalent age in the fifth decade. 5. The average age of hepatoma was 42.8 years old and the sex ratio was 2:1.

말기 신부전 환자에서 투여 경로에 따른 유전자 재조합 인 Erythropoietin(Epokine^(�))의 효과와 안정성에 대한 연구 : 제 4상 연구 A Phase 4 Single Center Study

송현용,윤향숙,강신욱,최규헌,하성규,이호영,한대석 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.2

목 적 : 국내 독자적 기술로 첫 개발된 유전자 재조합 인 에리트로포에틴(Epokineⓡ)의 투여방법에 따른 유효성과 안정성을 알아보고자 하였다. 방 법 : Epokineⓡ을 주당 100-150 U/kg, 주 2회, 12주간 피하 주사하여 목표 또는 안정된 혈색소치 유지 후 무작위로 피하 및 정맥 주사군으로 나누어 12주간 혈액투석 및 복막투석 환자13명, 28명에서 유효성, 안정성을 분석하였다. 결 과 : 양군에서 혈색소치와 헤마토크릿은 Epokineⓡ 투여 2주 후부터 증가, 혈색소치가 혈액투석 환자는 투여 전 7.3 g/dL, 투여 12주 9.5 g/dL, 24주 10.6 g/dL로, 복막투석 환자는 6.8g/dL에서 12주 10.2 g/dL, 24주 10.8 g/dL로 증가하였다. 양군에서 교정 망상적혈구수(%)는투여 1주 후부터 전 기간동안 증가하였다. 혈청 내 철분, ferritin치는 양군에서 투여 2주 후부터감소, 총 철분 결합능은 투여 2주 후부터 증가하였다. 12주째 혈액투석 환자에서 많은 Epokineⓡ용량이 필요했으나(142.2±20.5 vs 117.3±33.6 U/kg/wk, p<0.001) 24주 후 양군의 용량차이는 없었다(123.6±41.5 vs 99.2±49.3 U/kg/wk, p>0.05). 혈액투석 환자에서 피하 주사가Epokineⓡ 투여용량이 더 적었으나(97.4±15.4 vs 145.4±2.9 U/kg/wk, p<0.002) 복막투석 환자는 차이가 없었다(93.0±60.2 vs 105.4±9.7 U/kg/wk, p>0.05) 연구기간 중 9명(18.8%)에서혈압강하제 추가가 필요한 혈압상승, 근육통 동반 상기도 감염 유사증상 및 두통 등의 부작용이 있었다. 대부분 자연소실 혹은 대증요법으로 치유되었고 2명이 부작용으로 탈락하였다. 결 론 : 말기 신부전 환자의 빈혈 개선에 사용하는 Epokineⓡ의 효과는 복막투석 환자에서 더 좋았으며 투여 경로는 정맥주사보다 피하주사가 높음을 알 수 있었다. Background : We evaluated the clinical efficacy and safety of recombinant human erythropoietin(Epokine^(ⓡ)). Methods : A comparative prospective study of intravenously and subcutaneously administrated Epokine^(ⓡ) conducted 13 patients performing hemodialysis and 28 patients performing continuous ambulatory peritoneal dialysis with end-stage renal disease. Epokine^(ⓡ) was given initially at a dosage of 100 unit/kg, subcutaneously, two times a week. The patients had achieved stable or more than 10 g/dL of hemoglobin level for 12 weeks and then we randomized switching intravenously or subcutaneously administrated Epokine^(ⓡ) for another 12 weeks. Results : Hemoglobin(g/dL) and hematocrit(%) increased significantly from baseline levels beginning from 2 weeks after Epokine^(ⓡ) administration. In HD patients, hemoglobin increased significantly from 7.3 to 9.5 after 12 weeks and to 10.6 after 24 weeks. In CAPD patients, hemoglobin increased significantly from 6.8 to 10.2 after 12 weeks and then 10.8 after 24 weeks(p<0.05). Corrected reticulocyte count(%) was significantly increased from baseline levels beginning from 1 week after Epokine^(ⓡ) administration and continuously increased during study period in both group. Serum ferritin and serum iron decreased significantly and total iron binding capacity increased significantly after 2 weeks. At 12 weeks, HD patients were significantly needed more dosage of Epokine^(ⓡ) than CAPD patients(142.2±20.5 vs 117.3±33.6 U/kg/wk, p<0.001), but at 24 weeks, the dosage was not different(123.6±41.5 vs 99.2±49.3 U/kg/wk, p> 0.05). In HD patients, intravenously administrated Epokine^(ⓡ) group was more dosage than subcutaneously group(97.4±15.4 vs 145.4±2.9 U/kg/wk, p< 0.002), but CAPD patients were not different by administration method(93.0±60.2 vs 105.4±9.7 U/kg/ wk, p>0.05). The 9 cases(18.8%) were suffered from headache and flu-like syndrome, but these side effects were not severe and disappeared from conventional therapy. Conclusion : Epokine^(ⓡ) administration is safe and effective in treating anemia of ESRD patients and subcutaneously administration is significantly more effective than intravenously. (Korean J Nephrol 2002;21(2):190-198)

지속성 외래 복막투석 환자에서 염증 지표와 고해상도 B 모드 경동맥 초음파 소견의 연관성에 관한 연구

송현용,송영수,안철우,강신욱,최규헌,하성규,이현철,이호영,한대석 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.2

배 경 : 저알부민혈증 및 C-반응 단백(C-reactive protein, CRP)이 증가된 지속성 외래 복막투석 환자의 사망률이 높은 정확한 이유는 밝혀져 않다. 혈액투석 환자에서처럼 복막투석 환자에서 저알부민혈증 및 염증반응이 심혈관계 질환 위험인자 인지 알아보고자 하였다. 방 법: 비당뇨병성 말기 신부전, 지속성 외래 복막투석 환자 93명의 심혈관계 질환 위험인자들과 복막 투과 특성 및 알부민, CRP 등의 염증지표에 따라 고해상도 초음파를 이용한 경동맥내막-중간막 두께, 내막-중간막 면적, 플라크의 유무 등을 단면적으로 비교하였다. 결 과: 복막 투과 특성은 고투과막군 14명, 중간 고투과막군 38명, 중간 저투과막군 31명, 저투과막군 10명으로 각 군간의 경동맥 내막-중간막 두께, 플라크 유무 및 내막-중간막 면적의 차이는 없었다. 기존 관상동맥 질환 환자는 8예(8.6%)로 내막-중간막 두께는 관상동맥 질환이 없는 환자보다 증가되었고(0.79±0.21 vs 0.60±0.11 mm, p<0.05) 플라크 형성은 더 많이 보이나 통계적 유의성은 없었다(75.0 vs 63.5%, p>0.05). 혈청 알부민치와 경동맥 내막-중간막 면적은 역상관관계를 보였다(r=-0.27, p<0.05). 저알부민혈증 환자(혈청 알부민 <3.5 g/dL)는 정상 알부민혈증 환자보다 내막-중간막 두께가 증가되었고(0.67±0.15 vs 0.61±0.12 mm, p<0.05), 플라크도 유의하게 많았다(68.0 vs 55.8%, p<0.05). 혈청 CRP치와 경동맥 내막-중간막 면적은 양의 상관관계가 있었으며(r=0.21, p<0.05) CRP가 높은 환자(≥0.8 mg/dL, n=18)에서플라크가 많이 관찰되었으나(65.8 vs 50.0%, p<0.05) 경동맥 내막-중간막 두께 및 내막-중간막면적은 양군간에 차이가 없었다. 다변량 회귀 분석상 경동맥 내막-중간막 두께에 영향을 미치는 인자는 고령, 높은 CRP, 기존 심혈관계질환, 낮은 혈청 알부민 순이였다. 결 론 : 복막투석 환자에서 고해상도 초음파를 이용한 경동맥 내막-중간막 두께 측정은 심혈관계 질환 유무 예측의 비침습적 검사가 될 수 있고 저알부민혈증 및 높은 CRP과 같은 만성염증 지속상태가 복막투석 환자에서 죽상 동맥 경화증의 발생을 증가시킨다고 가정할 수 있다. Background : Continuous ambulatory peritoneal dialysis(CAPD) patients with low albumin(LA) and signs of inflammation reflected by increased C-reactive protein(CRP) level have an increased mortality, but the mechanism of this phenomenon is not clear yet. Methods : To answer whether LA and inflammation also enhance cardiovascular risk in CAPD patients, we performed cross sectional study measuring carotid artery intima-media thickness(IMT), calculated intima-media area(cIM area) and the presence of plaque by high-resolution B-mode ultrasonography in 93 non-diabetic CAPD patients. Results : Patients with coronary artery disease (CAD, n=8) had significantly increased IMT(0.79± 0.21 mm vs. 0.60±0.11 mm, p<0.05) and higher prevalence of carotid plaques(75.0% vs. 63.5%) compared to the non-CAD patients. Significant inverse correlation was observed between serum albumin (SA) level and cIM area(r=-0.27, p<0.05). Those patients with LA(SA <3.5 g/dL) had significantly increased IMT compared to non-LA patients(0.67±0.15 mm vs 0.61±0.12 mm, p<0.05). Prevalence of carotid plaques was also significantly higher in LA patients (68.0% vs. 55.8%, p<0.05). CRP level revealed a significant positive correlation with cIM area(r=0.21, p< 0.05). Patients with high CRP(≥0.8 mg/dL, n=18) had higher prevalence of carotid plaques (65.8% vs. 50.0%, p<0.05) compared to those patients with CRP <0.8 mg/dL, but IMT and cIMT area were not different. By multivariate logistic regression analysis, old age, high CRP, history of CAD and low SA were the independent risk factors affecting IMT. Conclusion : Our study strongly suggests that low albumin and chronic inflammatory state of CAPD patients could be associated with increasing atherosclerotic cardiovascular disease. (Korean J Nephrol 2002;21(2):285-294)

포타슘과 소디움이 白鼠腎臟 動脈에 미치는 影響에 對한 病理學的 硏究

宋圭祥,姜大榮 충남대학교 의과대학 지역사회의학연구소 1986 충남의대잡지 Vol.13 No.1

There are experimental and epidemiological data which indicate that high sodium intake is a major factor in the genesis of hypertension and that potassium moderates salt induced hypertension. To study the effect on blood pressure and morphologic change of sodium and potassium intake, the male Sprague-Dawley rats were fed diets containing different amount of sodium(4%, 8%) and potassium(1%, 2%, 4%) for six months. The systolic blood pressure was measured monthly from the first month, and the size and morphologic change of renal arteries were also investigated monthly from the second month of feeding. The results were as follows: 1. High sodium intake induces hypertension, and in the case of feeding the same sodium concentration, hypertensinogenic effect is greater in the rats receiving less dietary potassium intake than high potassium intake. 2. There is more statistically significant increase of ED/LD ratio in the high sodium and potassium fed groups than those of the control group (P<0.05). Medium sodium and potassium fed groups also reveal statistical significance(P<0.05). 3. Hyperplasia of endothelial cells and hypertrophy of media are more prominent in the high sodium fed groups than those of the control group, and these changes are more evident in the high sodium intake groups than those of the medium sodium intake groups. In the groups receiving the same sodium concentration, each blood vessel reveals the decrease of ED/LD ratio with increment of potassium concentration, but there is no statistical significance (P>0.05).

Rat의 복강내에 투여한 5-fluorouracil-polyglycolic acid 제형이 장기에 미치는 영향에 관한 연구

강대영,송규상,최정목,노승무,정경수,오정연,김진향,양준묵,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

For more effective intraperitoneal chemotherapy, the authers made 5-fluorouracil-polyglycolic acid composite disks(FU-PGA disks) with 5-fluorouracil and polyglycolic acid, a biodegradable polymer. We inserted the FU-PGA disk into the peritoneal cavites of Sprague-Dawley male rats, the control and three experimental groups; one FU-PGA disk insert group(300mg/kg), two FU-PGA disk insert group(600mg/kg), and three FU-PGA disk insert group(900mg/kg). The control group received a similar number of PGA disk inserts. A pharmacokinetic study was performed to measure the 5-fluorouracil concentration in the peritoneal fluid, blood, and tissues(liver, kidney and heart) at 24 hours, 72hours and 168 hours after insertion of the FU-PGA disk. Light and electron microscopic studies were done. The results were as follows: 1) The number of white blood cells and platelets decreased after FU-PGA insertion. The degree was proportional to the duration and amounts inserted. The change in the number of red blood cells varied slightly. 2) Light microscopically, slight changes were noted at 168 hours in the 3 disk insert group (900mg/kg). Mild fatty change and hepatocyte degeneration around the central veins of the liver were noted, with vacuolar degeneration in the proximal convoluted tubules of the kidney. 3) Electron microscopically,the liver showed focal increases of lipid droplets in the hepatocytes, and irregular nuclear membrane with focal nucleolar segregation of the fibrillar and granular elements. Also the double membranous structure of the hepatocytes and Kupffer cells was widened with bleb formation. The kidney showed wide separation of the nuclear double membrane in the proximal convoluted tubular cells and mesangial cells, with vacuolation and myelin figure formation in the mitochondria of the proximal convoluted tubular cells, at 72 hours and 168 hours in the 2 to 3 FU-PGA insert groups. The heart showed focal loss of cristae,vacuolation and myelin figure formation in the mitochondria of the 2 to 3 FU-PGA insert groups. In conclusion, despite the large amont of FU-PGA inserted, the histopathological changes in the liver, kidney and heart were slight, and consonant with the very low amount of 5-fluorouracil concentrations detected in the liver, kidney and heart. The above results suggest that the FU-PGA composite can serve as a new device for releasing drugs in a controlled manner and easily targeted to intraperitoneal organs. This device can improve the efficacy of intraperitoneal chemotherapy for gastric cancer.

복막유착의 원인 규명과 예방을 위한 실험적 연구

강대영,송규상,노승무,조준식,이태용 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.1

Postoperative peritoneal adhesion is the most common cause of intestinal obstruction, and intestinal obstruction is one of the most difficult problems in abdominal surgery. In this experimental study for developing peritoneal adhesion model and its prevention, we divided rats into 5 groups; the talc powder treated group, the cotton-fluff treated group, the talc+fluff treated group, the ischemia group and the control group. There were 16 rats in each group. We made incisions on the midabdomen of the rats and administered talc powder, cotton fluff and talc powder+fluff into the peritoneal cavity respectively. In the ischemia group, we clamped the root of superior mesenteric artery for two minutes to induce ischemia on the small bowel of the rat. We counted the number of the peritoneal adhesive sites in peritoneal cavity on the 7th, 14th , 21st and 42nd postoperative day after peritoneal adhesion induced operation, and observed the characters of the adhesion state. The average number of the peritoneal adhesions were 1.25 per one rat in the talc powder group, 1.44 in the fluff group, 1.31 in the talc+fluff group and 1.31 in the ischemia group compared with 0.94 per one rat in the control group performed sham operation. 91.6% of the all adhesions were observed on the peritoneum of the previous incision sites and only 8.4% of the adhesions were adhered to the peritoneal surface of non-incision sites. The data of this study suggest that peritoneal injury and inflammatory reaction is the major cause of peritoneal adhesion. Also this study indicates that foreign bodies can develop peritoneal adhesion, but the effect is much lower than that of peritoneal injury with inflammatoty reaction.

원발성 간암종의 조직 발생에 대한 면역조직학적 연구

강대영,최정목,송규상,이헌영 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

To assess the utility of cytokeratin(CK) profile in the differential diagnosis of primary liver carcinomas(PLCs),we evaluated a series of needle biopsied specimens and surgically resected PLCs, comprising 30 pure hepatocellular carcinomas(HCCs) and 20 cholangiocarcinomas(CCs). The results are summarized as follows: 1) The pure hepatocellular carcinomas showed intense cytoplasmic expression of anti-cytokeratin (AE1/AE3);28/30 (93.3%). 2) The cholangiocarcinomas showed cytoplasmic expression of 2 types of CK(Anti-CK19,AE1/AE 3);14 of 20 (70.0%) of the CCs evidenced mature bile duct phenotype (CK 19), whereas 10 of 20 (50.0%) displayed the hepatocytic profile(AEl/AE3). 3) Nine of 30 HCCs also displayed the bile duct cell profile; high grade HCCs(8/20), and low grade HCCs(1/10). The above results show that a mixed biological phenotype can be found both among morphologically pure HCCs and peripheral CCs, suggesting that these two forms could share a common histogenesis.

乳房 疾患의 病理組織學的 硏究

姜大榮,宋圭祥 충남대학교 의과대학 지역사회의학연구소 1985 충남의대잡지 Vol.12 No.2

A histopathologic study was made on 844 cases of the breast lesions of female, which were collected, from Jan. 1980 to July 1985, at the Department of Pathology, School of Medicine, Chungnam National University. The results were as follows 1. Among 844 cases of the breast lesions of female the age distribution shows the highest frequency in the third decade(317 cases, 37.6%), followed by the 4th decade(260 cases, 30.8%), the 5th decade(147 cases, 17.4%), the 6th decade(53 cases, 6.3%), and the second decade(42 cases, 5.0%) in decreasing order of frequency. 2. The most: frequent breast lesion was the nonneoplastic lesion(345 cases, 40.9%), followed by benign tumor(326 cases, (38.6%), malignant tumor(130 cases, 15.4%), and inflammatory disease(43 cases, 5.1%). 3. Among inflammatory disease, acute mastitis and abscess was 21 cases and chronic mastitis and plasma cell mastitis was 20 cases. Seventeen cases of inflammatory disease were present in the third decade. 4. The most prevalent nonneoplastic lesion was fibrocystic disease(297 cases, 86.1%), which reveals the highest frequency in the fourth decade(129 cases), followed by third decade(93 cases) and the fifth decade(54 cases). The mean age of fibrocystic disease was 32.9 years. 5. Among benign tumor fibroadenoma was 269 cases (82.5%), intraductal papilloma and lactating adenoma, 17 cases, respectively, lipoma 7 cases, and tubular adenoma, cystosarcoma phyllodes, fibroma, 4 cases, each. The most prevalent age of fibroadenoma was the third decade(the mean age; 27.7 years). 6. Among 130 cases of malignant tumor infiltrating duct carcinoma shows the highe incidence(112 cases, 86.1%), followed by noninfiltrating duct carcinoma 10 cases, lobula carcinoma 4 cases, and sarcoma 3 cases, in decreasing order of frequency. The most frequen subtype of infiltrating duct carcinoma was simple type, followed by scirrhous, medullary, papillary, colloid, and infiltrating comedocarcinoma. The malignant tumor shows highest incidence in the fifth decade and the mean age was 47.6 years.

좌심실 수축기 기능장애를 동반한 양수색전증 1예

박대균,홍경순,두영철,한규록,오동진,유규형,임종윤,고영박,이광학,이영,송원근,김현태 대한순환기학회 1999 Korean Circulation Journal Vol.29 No.8