생체분해성 고분자를 이용한 사시수술용 제형개발 및 효용성에 대한 연구

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

A new device, muscle clamping system was developed to facilitate exact quatifying technique A strabismus surgery, and reduce the risk of complications. The device is composed of a lower fixing body with three jaws and an upper supporting body. They are used to clip an extraocular muscle and fix it to the sclera with a single bite. Superior rectus recession on 16 rabbit eyes were performed with this new device. Conjunctival injection, muscle adhesion strength, and light microscopic findings were examined at 1, 2, 4 and 8 weeks postoperatively. The Conjunctival injection were minimal, adhesion power ranged from 420 to 600 gram gravity, which is sufficient in withstand the normal pull of human extraocular muscle. In microscopic exam, some Inflammatory cells and fibrosis were found. The new device was technically easy, fast, and accurate, so it may be useful in stabismus surgery.

생체분해성 망막압정을 이용한 망막고정에 대한 실험적 연구

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

Biodegradable retinal fixation devices obtain mechnical fixation of the retina with desirable chorioretinal scarring and with the potential for local, sustained release of antimetabolites and steroids to inhibit proliferative vitreoretinopathy. We manufactured a biodegradable retinal tack with barb that was designed in order to prevent intrusion from implantation of retinal tacks. This study was carried to evaluate the efficacy for retinal fixation and the capability for sustained release of drugs with a newly designed biodegradable retinal tack Biodegradable retinal tacks were made of polymers of glycolic acids and were designed with barbs in a shape to prevent the disinsertion. Biodegradale retinal tacks are divided into 3 parts, a conical portion that is inserted into the sclera, a cylinder portion that remains in the vitreous, and a neck portion between the pin and the cylinder. The tapered conical end was manufactured to allow easy insertion through the retina and choroid into the sclera. A cylinder portion was manufactured with a tapered angle that fixes firmly into the orifice of 19 gauge spinal needle. A neck portion, 0.4 mm in diameter, was designed to prevent disinsertion from following implantation of retinal tack. The applicator was a 19 gauge spinal needle and its orifice was prepared to 15°angle to accept the tapered cylinder portion of the retinal tack. The retinal tacks, secured in the needles, were passed through the formed vitreous and inserted into the retina, choroid, and sclera and were released by pushing the internal needle, usually within 2-3mm of the medullary ray of the posterior rabbit retina A retinal tack was placed in each of 8 pigmented rabbit eyes. Slit-lamp biomicroscopy, indirect ophthalmoscopy and fundus photography were performed periodically from 1 day to 8 weeks after surgery. Eight eyes were enucleated and studied by light microscopy at 8 weeks. Biomicroscopic evaluation of the animals revealed edemas adjacent to the retinal surfaces immediately after insertion of the biodegradable retinal tacks in all the animals. These edemas disappeared after 1 week. The first noticeable change in the size of retinal tacks was shown after 2weeks. The size of the retinal tacks gradually got smaller, decreasing to about one-half at 4 weeks and about one-third at 8 weeks. All retinal tacks remained in inserted places without any movement for an 8 week period. On light microscopy, epiretinal proliferations were seen to extend into the vitreous cavity. Cellular capsules that lined the inner aspect of the scleral defect caused by tack insertion were found. However the adjacent retina had a normal cytologic appearance and architecture in all specimens. We manufactured a biodegradable retinal tack that is designed to prevent intrusion from implantation of retinal tacks. All biodegradable retinal tacks reduce in size with time, but no retinal tacks extruded from the inserted place. The newly designed biodegradable retinal tack can be used for retinal fixation and may be used as a vehicle for the introduction of pharmacologic agents to prevent the cellular events that promote proliferative vitreoretinopathy.

위암 환자의 복강내 투여를 위한 Activated Charcoal-Alginate Bead 제형으로부터 Mitomycin C의 용출 거동

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

Locoregional recurrence is the most common type of recurrence in surgical operation of gastric adenocarcinoma, and peritoneal dissemination is one of the most difficult problems in advanced gastric adenocarcinoma treatment. Because the peritoneal cavity is the most common site of the first recurrence after gastric cancer resection, intraperitoneal chemotherapy seems a logical choice for cancer chemotherapy. In this study, Mitomycin C (MMC)-activated charcoal (CH)-alginate (ALG) beads were prepared by the mixtures of CH particles adsorbed with MMC as an anti-cancer drug and aqueous alginate solution. The alginate is recognized as biodegradable, nontoxic, and biocompatible. The release of MMC from the beads in 0.1 M Tris buffer was stable and continuous until about 1 week. The MMC-CH-ALG beads can be applied in the peritoneal cavity for intraperitoneal chemotherapy since they provide a good adhesiveness on the tissue and controlled release pattern of the drugs.

위암환자의 복강내에 투여한 Mitomycin C-Carbon Particle의 Mitomycin 용출에 관한 연구

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

Locoregional recurrence is the most common type of recurrence in surgical operation of gastric adenocarcinoma, and peritoneal dissemination is one of the most difficult problems in advanced gastric adenocarcinoma treatment. Because the peritoneal cavity is the most common site of the first recurrence after gastric cancer resection, intraperitoneal chemotherpy seems a logical choice for cancer chemotherapy. The Mitomycin C(MMC) adsorbed by the activated charcoal particles(CH) is relatively released when the drug concentration surrounding the carbon particles becomes low in the peritoneum of the peritoneal cavity. For the intraperitoneal chemotherapy on the advanced gastric adenocarcnoma, mitomycin C adsorbed on activated carbon particles was administered in the peritoneal cavity just before abdominal wall closure. The closed drainage tubes were inserted in the peritoneal cavity and clamped for tuo hours after completion of operation. MMC concentrations were serially measured in peritoneal fluid, plasma and urine at 2hour, 48 hour, 72 hour and 168 hour following its administration in order to study the efficacy of the MMC-CH as a drug delivery system. There were minimal toxicities in born marrow, liver, and gastrointestinal system after intraperitoneal MMC-CH administration. The data of this study suggested that MMC-CH may have a somewhat more beneficial effect than surgery alone when administered in optimal dose and schedules, but the MMC concentration of the peritoneal fluid was not sufficient to eradicate remnant cancer cells, and effective duration of maintenance was only below 24 hours in the peritoneal fluid and plasma.

Effects of Regular Exercise and L-Arginine Intake on Abdominal Fat, GH/IGF-1 Axis, and Circulating Inflammatory Markers in the High Fat Diet-Induced Obese Aged Rat

Sok Park(박석),Ki Woon Sung(성기운),Jin Lee(이진),Cheon Ho Lee(이천호),Young Jun Lee(이영준),Young June Yoo(유영준),Kyoung Shil Park(박경실),Byung Jin Min(민병진),Yong Sub Shin(신용업),Jung Suk Kim(김정석),Hun Jung(정훈) 한국생명과학회 2012 생명과학회지 Vol.22 No.4

본 연구는 비만과 노화가 동시에 유발된 흰쥐에서 12주간의 트레드밀 운동과 L-arginine의 투여가 복부지방량, GH, IGF-Ⅰ, somatostatin, fibrinogen, PAI-1에 미치는 영향을 관찰하고 이를 개선하는데 더욱 효과적인 방법을 제시하는데 그 목적이 있다. 이를 위해 단독 처치 군과 복합 처치 군으로 나누어 실험하여 그 효과를 비교, 분석한 결과 다음과 같은 결론을 얻었다. 1. 복부지방량은 통제집단에 비해 모든 집단에서 유의하게 감소하였다(p<0.01). 2. AG+EX, AG+LA+EX집단에서 통제집단에 비해 GH의 혈중 농도가 유의하게 높게 나타났다(p<0.1). 3. AG+EX, AG+LA+EX집단에서 통제집단에 비해 IGF-Ⅰ의 혈중 농도가 유의하게 증가하였다(p<0.01). The purpose of this study was to investigate the effect of exercise and/or L-arginine on abdominal fat, IGF-1 on GH/IGF-1 axis, fibrinogen, and PAI-1 in aged and obese rats. Male Sprague-Dawley rats were treated with a D-galactose aging inducing agent (50 mg/kg) given intraperitoneally for 12 weeks. Thirty-two male Sprague-Dawley rats were treated and divided into four groups: aging-high fat diet group (AG+HF), AG+HF with L-arginine intake group (AG+LA), AG+HF with exercise group (AG+EX), and AG+EX with L-arginine intake group (AG+LA+EX). The experimental rats underwent treadmill training (60 min/day, 6 days/week at 0% gradient) for 12 weeks. L-arginine was given orally (150 mg/kg/day) for 12 weeks. After the experiment, blood was collected from the left ventricle and abdominal fat was extracted. The results showed that GH was significantly increased in AG+EX and AG+AL+EX. IGF-1 was significantly increased in both the AG+AL+EX and AG+EX group (p<0.05), while fibrinogen and PAI-1 were not significantly different among the groups. Abdominal fat was significantly decreased in the AG+LA, AG+EX, and AG+LA+EX groups (p<0.05) compared with the AG+HF group. In conclusion, this study suggests that exercise alone or L-arginine alone or a combination not only increases the GH and IGF-1 concentration, but also decreases the abdominal fat mass.

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.

Rat의 복강에 삽입한 Fluorouracil-Polyglycolic acid 제형의 Fluorouracil 용출에 관한 연구

노승무,정경수,오정연,김진향,양준묵,강대영,송규상,최정목,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 忠南大學校 癌共同硏究所 1998 癌共同硏究所 硏究誌 Vol.2 No.1

A common form of relapse in adenocarcinoma of the stomach is intraperitoneal dissemination, in fact, among gastric adenocarcinoma patients who have undergone surgery intended to cure, approximately 50% of the patients develope initial recurrence in the peritoneal cavity regardless of the anatomic site of the primary tumor within the stomach. The efficacy of systemic postoperative chemotherapy to prevent peritoneal recurrence of gastrric adcnocarcinoma is not satisfactory. There is still a great need for improved therapeutic strategies on the disseminated microscopic disease and small miliary nodules remaining on the peritoneal surface or lymphatics after operation. The authers have made fluorouracil-polyglycolic acid composite disks(Fu-PGA disks) with fluorouracil and biodegradable polymer: polyglycolic acid for more effective intraperitoneal chemotherapy. We inserted the Fu-PGA disk(s) in the peritoneal cavity of rat and pharmacokinetic study was performed to measure fluorouracil concentration in the peritoneal fluid, plasma, liver, kidney and heart tissue at 24 hour, 72 hour and 168 hour after insertion of Fu-PGA disk(s). Myelosuppressive action of this composite also was determined following its administration. The data of this study suggested that Fu-PGA composite will be a new device releasing drugs in a controlled manner and having targetability to peritoneum, and this device will be improving the efficacy of intraperitoneal chemotherapy for gastric adenocarcinoma.

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.

Rat의 복강에 삽입한 Filorouracil-Polyglycolic acid제형의 Fluorouracil용출에 관한 연구

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

A common form of relapse in adenocarcinoma of the stomach is intraperitioneal dissemination, in fact, among gastric adenocarcinoma patients who have undergone surgery intended to cure, approximately 50% of the patients develope initial recurrence in the peritoneal cavity regardless of the anatomic site of the primary tumor within the stomach. The efficacy of systemic postoperative chemotherapy to prevent peritoneal recurrence of gastrric adenocarcinoma is not satisfactory. There is still a great need for improved therapeutic strategies on the disseminated microscopic disease and small miliary nodules remaining on the peritoneal surface or lymphatics after operation. The authers have made fluorouracil-polyglycolic acid composite disks(Fu-PGA disks) with fluorouracil and biodegradable polymer: polyglycolic acid for more effective intraperitoneal chemotherapy. We inserted the Fu-PGA disk(s) in the peritoneal cavity of rat and pharmacokinetic study was performed to measure fluorouracil concentration in the peritoneal fluid, plasma, liver, kidney and heart tissue at 24 hour, 72 hour and 168 hour after insertion of Fu-PGA disk(s). Myelosuppressive action of this composite also was determined following its administration. The data of this study suggested that Fu-PGA composite will be a new device releasing drugs in a controlled manner and having targetability to peritoneum, and this device will be improving the efficacy of intraperitoneal chemotherapy for gastric adenocarcinoma.

Impact of an Additional Chromosome on the Clinical Outcomes of Hematopoietic Stem Cell Transplantation in Philadelphia Chromosome–Positive Acute Myeloid Leukemia in Adults

Min, Gi June,Kim, Hee-Je,Yoon, Jae-Ho,Kwak, Dae-hun,Park, Sung-Soo,Jeon, Young-Woo,Lee, Sung-Eun,Cho, Byung-Sik,Eom, Ki-Seong,Kim, Yoo-Jin,Lee, Seok,Min, Chang-Ki,Cho, Seok-Goo,Kim, Dong-Wook,Lee, Jon Elsevier 2018 BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Vol.24 No.8

<P><B>Abstract</B></P> <P>The incidence of Philadelphia chromosome positivity (Ph<SUP>+</SUP>) in adults with acute myeloid leukemia (AML) is very low. Ph<SUP>+</SUP> AML is considered to be high risk for failure to attain remission or for early relapse after standard chemotherapy. Because of the low incidence of the disease, it has been difficult to determine the best treatment, including the effects of tyrosine kinase inhibitors. We retrospectively analyzed 29 patients with Ph<SUP>+</SUP> AML (median age, 45 years; range, 18 to 80) managed at our center between 2002 and 2016. Two patients were not treated at all, 3 received repeated low-dose cytarabine, and 24 were treated with 3 + 7 standard induction chemotherapy. All 27 treated patients also received interim imatinib 400 mg orally until the day of the next chemotherapy cycle began or as conditioning for allogeneic hematopoietic cell transplantation (HCT), which was performed in 17 patients. Of the 29 patients with Ph<SUP>+</SUP> AML, 7 (24.1%) had additional inv(16), 3 of whom had therapy-related AML. In the 7 with inv(16), the median age was younger (31 versus 44 years, <I>P</I> = .083) and the complete remission (CR) rate was relatively higher (85.7% versus 54.5%, <I>P</I> = .214) than in those without inv(16). Among the 27 treated patients, 20 (74.1%) achieved CR after standard chemotherapy with interim imatinib and 2 (7.4%) achieved CR after low-dose cytarabine with interim imatinib. After a median follow-up of 65.5 months (range, 13.4 to 156.6), the 5-year overall survival (OS) among all 27 treated patients was 43.1%. For the 17 patients who underwent HCT the 5-year OS of 17 patients (10 in subgroup without inv(16) and 7 in subgroup with inv(16)) treated with allogeneic HCT was 69.3%. All 7 with inv(16) were still alive at the end of the study. In contrast, all patients not treated with HCT died within a median of 6.25 months (range, .2 to 18.2). Interim imatinib combined with chemotherapy yielded an acceptable remission rate in adult patients with Ph<SUP>+</SUP> AML. Allogeneic HCT as a postremission therapy provided long-term disease control in two-thirds of those who underwent the transplant. We also demonstrated that inv(16) was related to a favorable outcome in Ph<SUP>+</SUP> AML, including therapy-related AML.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Philadelphia chromosome–positive AML patients can benefit from TKI interim therapy along with standard chemotherapy to achieve complete remission. </LI> <LI> Minimal residual disease negativity could be a predictor of better clinical outcome after allogeneic hematopoietic cell transplantation. </LI> <LI> The presence of inv(16) in patients with Ph<SUP>+</SUP> AML is associated with better survival outcome. </LI> </UL> </P>