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Association of Genetic Variations with Pemetrexed-Induced Cytotoxicity in Non-Small Cell Lung Cancer Cells (비소세포폐암 세포주에서 pemetrexed의 세포독성과 유전학적 다형성과의 상관성 조사)

  • Yoon, Seong-Ae;Choi, Jung-Ran;Kim, Jeong-Oh;Shin, Jung-Young;Zhang, XiangHua;Kang, Jin-Hyoung
    • Journal of Life Science
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    • v.20 no.1
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    • pp.103-112
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    • 2010
  • Pemetrexed has demonstrated clinical activity in non-small cell lung cancer (NSCLC) as well as other solid tumors. It transports into the cells via reduced folate carrier (RFC) and is polyglutamated by folypolyglutamate synthetase (FPGS). Pemetrexed directly inhibits several folate-dependent enzymes such as thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). We investigated the effects of genetic variations and the expression of RFC, FPGS, TS and DHFR enzymes on drug sensitivity to pemetrexed in NSCLC cells. Polymorphisms in RFC, FPGS, and DHFR were genotyped in four NSCLC cells - A549, PC14, HCC-1588, and H226. Real-time RT-PCR and Western blot was performed to evaluate mRNA transcripts and protein of these genes. The cytotoxicity of pemetrexed was measured by SRB assay. In PC14 and H226 cells, increased mRNA expressions of RFC and FPGS were associated with higher cytotoxicity to pemetrexed. 2R/2R genotype of TS and its increased mRNA expression were associated with drug resistance to pemetrexed in A549 cells, whereas 3R/3R genotype in TS with decreased mRNA expression was associated with higher sensitivity in H226 cells. After pemetrexed treatment, an inverse change of DHFR mRNA and protein expression was found. The strongest linkage disequilibrium (LD) was discovered between-1726C>T and -1188A>C SNP of DHFR gene. Our findings suggest the cytotoxic effect of pemetrexed may be associated with genetic polymorphisms and the expression level of genes involved in pemetrexed metabolisms in NSCLC cells.

Respiratory Failure of Acute Organophosphate Insecticide Intoxication (유기인제 중독에 의한 호흡부전)

  • Shin, Kyeong-Cheol;Lee, Kwan-Ho;Park, Hye-Jung;Shin, Chang-Jin;Lee, Choong-Ki;Chung, Jin-Hong;Lee, Hyun-Woo
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.3
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    • pp.363-371
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    • 1999
  • Background: Because of the widespread use and availability of agricultural insecticides, acute organophosphate poisoning as a suicide or an accident is becoming the most common type of poisoning and serious problem in Korea. The mortality of organophosphate poisoning varied from 10 to 86 percent. The cause of death was thought to be a combination of excessive bronchial secretion, bronchospasm, respiratory muscle paralysis and depression of respiratory center, summarily respiratory failure. We evaluated the respiratory complications in patients with acute organophosphate intoxication to determine the predisposing, factors to respiratory failure and to reduce the incidence of respiratory failure or mortality. Method: We conducted a retrospective study of 111 patients with the discharge diagnosis of organophosphate poisoning who were hospitalized at Yenugnam University Hospital during the 5 years. The diagnosis of organophosphate poisoning has based on the followings (1) a history of exposure to an organophosphate compounds. (2) the characteristic clinical signs and symptoms. (3) decrease in the cholinesterase activity in the serum. Results: Respiratory failure developed in 31(28%) of 111 patients with acute organophosphate poisoning. All cases of respiratory failure developed within 96 hours after poisoning and within 24 hours in 23 patients. The 80 patients who did not develop respiratory failure survived. In 31 patients with respiratory failure, 15(44%) patients were dead. The patients with respiratory failure had more severe poisoning, that is, the lower level of serum cholinesterase activity on arrival, the higher mean dosage of atropine administered within first 24 hours. In 16 patients with pneumonia, 14 patients developed respiratory failure. In 5 patients with cardiovascular collapse, 2 patients developed respiratory failure. There was no correlation to between age, sex, the use of pralidoxime and respiratory failure. The serum cholinesterase level in survivors at time of respiratory failure and weaning was $66.05{\pm}85.48U/L$, $441{\pm}167.49U/L$, respectively. Conclusion: All the respiratory failure complications of acute organophosphate poisoning occurred during the first 96 hours after exposure. The severity of poisoning and pneumonia were the predisposing factors to respiratory failure. Aggressive treatment and prevention of the above factors will reduce the incidence of respiratory failure.

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The Usefulness of Pleural IFN-$\gamma$ Level in Differential Diagnosis of Tuberculous Pleural Effusion and Malignant Pleural Effusion (결핵성 흉막염과 악성 흉수의 감별진단에 있어서 흉수 IFN-$\gamma$ 측정의 유용성)

  • Kim, Myung-Sun;Yang, Sung-Eun;Chi, Hyun-Sook;Kim, Woo-Sung;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.2
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    • pp.280-289
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    • 1998
  • Background: It is sometimes difficult to differentiate tuberculous pleural effusion from malignant pleural effusion by clinical symptoms, signs, by routine tests of pleural fluid, and by pathologic studies. And recently, it was discovered that cytokines such as IL-2, IFN-$\gamma$, TNF-$\alpha$ are elevated in tuberculous pleural fluid, and there have been several attempts to diagnose tuberculous pleural effusion by using these immunological mediators. There are several studies regarding the diagnostic value of IFN-$\gamma$, and there are two studies in Korea. But the diagnostic values of IFN-$\gamma$ in these studies were slightly lower than those in other countries. To compare the diagnostic value of IFN-$\gamma$ with those of CEA and ADA, and to determine the sensitivity and specificity of IFN-$\gamma$ in Korean, we mesured IFN-$\gamma$, CEA level and ADA activity in pleural effusions. Methods: ADA activity, IFN-$\gamma$ level and CEA level as well as cell count, differential count, and biochemical assays such as protein content and lactate dehydrogenase were measured in 40 cases of tuberculous pleuritis and 42 cases of malignant pleural effusion. Results: Tuberculous pleural fluid showed higher levels of IFN-$\gamma$ and ADA ($832.6{\pm}357.2$ pg/ml and $82.5{\pm}25.9$ U/L, respectively) than those of malignant pleural effusion ($2.6{\pm}8.0$ pg/ml and $19.2{\pm}10.9$ U/L, respectively) (p<0.01). Malignant pleural effusions showed higher median value (102.2 ng/ml) than tubercalous pleural effusions (1.8 ng/ml) (p<0.01). The sensitivities of IFN-$\gamma$, ADA, CEA were 0.97, 0.87, 0.67 and the specificities of IFN-$\gamma$, ADA, CEA were 1.0, 0.97, 1.0, respectively. There was no significant correlation between ADA activity and IFN-$\gamma$ level. Conclusion: This study showed that IFN-$\gamma$ test would be a very useful clinical test for differential diagnosis of tuberculous pleuritis and malignant pleural effusion because it is very sensitive and specific, although it is an expensive test.

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A Simple Isolating Method of Preantral Follicles from Mouse Ovaries (생쥐 난소에서 Preantral Follice의 단순 분리법)

  • Kim, Ju-Hwan;Park, Kee-Sang;Song, Hai-Bum;Chun, Sang-Sik
    • Clinical and Experimental Reproductive Medicine
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    • v.27 no.3
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    • pp.235-243
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    • 2000
  • Objective: Our present studies were conducted to examine more effective isolating method of preantral follicles from mouse ovaries. Methods: ICR mice (3-6 weeks old) were sacrificed through cervical dislocation and their ovaries were removed and put into watch glasses containing Hams F-10 supplemented with 10% fetal bovine serum (FBS). Preantral follicles were isolated by three different methods; 1) enzymatical method and 2) mincing method, and 3) scraping method. Enzymatical method was carried out as following. Ovaries were bisected with a pair of fine 30G needles. Bisected ovaries were incubated at $37^{\circ}C$ and 5% $CO_2$ incubator in 2-well dish containing Hams F-10 supplemented with collagenase 600 lU/ml and DNAse 20 lU/ml. After 20 min., follicles were isolated by repeated pipetting. Isolated preantral follicles were collected, and the remnant of tissues was placed in incubator and previous procedure was repeated. Mincing method was carried out with a pair of fine 30G needles attached to 1 ml syringes and minced ovary. Scraping method was carried out with a pair of fine 30G needles and scratched to surface of ovary. The differences between isolating methods were analyzed using Student's t-test and Chi-square. Results were considered statistically significant when ${\rho}$ value was less than 0.05. Results: In handling time, mincing or scraping method ($28{\pm}3.42$ min or $16{\pm}1.58$ min) were significantly (p<0.00001) shorter than enzymatical method ($72{\pm}1.69$ min), and scraping method was significantly (p<0.01) shorter than mincing method. Total number of isolated follicles was significantly (p<0.0001) higher in enzymatical method ($49.8{\pm}3.91$) than in mincing or scraping method ($25.3{\pm}2.33$ or $20.5{\pm}1.75$). Isolated follicles in ${\leq}$90${\mu}m$ were significantly (p<0.005) higher in enzymatical method ($15{\pm}1.71$) than in mincing or scraping method ($7.8{\pm}0.98$ or $8.1{\pm}1.31$). In 91~130 ${\mu}m$, isolated follicles were significantly (p<0.0005) higher in enzymatical method ($33{\pm}3.27$) than in mincing or scraping method ($16.3{\pm}1.82$ or $10.7{\pm}1.38$). In ${\geq}$ 131 ${\mu}m$, isolated follicles were not significantly differences between all groups. In equal sizes, the rate of isolated follicles in ${\leq}$ 90 ${\mu}m$ was highest in scraping method (39.6% vs. enzymatical method: 30.1%, p<0.05; mincing method: 30.9%, p=0.11719, NS). Rate of follicles in $91{\sim}130$ ${\mu}m$ was significantly (p<0.05) lower in scraping method (52.7%) than in enzymatical or mincing method (66.3% or 64.5%). Rate of follicles in ${\geq}$131 ${\mu}m$ was highest in scraping method (8.3% vs. enzymatical or scraping method: 3.6%, p<0.05 or 4.6%, p=0.19053, NS). Conclusions: This study suggests that scraping method is simple and useful for isolation of preantral follicles, because this method reduced handling time and recovered enough follicles. The recovered rate of isolated follicles in diameter of 91 ~ 130 ${\mu}m$ was highest in all methods.

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Correlations of Leptin, Adiponectin and Leptin/Adiponectin Ratio with Metabolic Disorders in the Childhood Obesity (소아 비만에서 Leptin, Adiponectin 및 Leptin/Adiponectin Ratio와 대사 장애의 연관성에 관한 연구)

  • Cho, Sung Jong;Kim, Eun Young;Moon, Kyung Rye
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.9 no.1
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    • pp.48-57
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    • 2006
  • Purpose: To investigate the correlation of the serum leptin, adiponectin, and leptin/adiponectin ratio with metabolic disorders in the childhood obesity. Methods: Fifty children (25 obese and 25 non-obese) were recruited in the pediatric outpatient clinic of Chosun University Hospital from January 1st to June 30th 2005. Adiponectin, leptin, anthropometric parameters, glucose, LDL-cholesterol, HDL-cholesterol, total cholesterol, triglyceride, and insulin levels were measured. The correlations of leptin and adiponectin levels with anthropometric parameters, glucose, insulin and lipids were analyzed by Pearson's correlation coefficients. Results: Insulin and leptin levels of the obese group were significantly higher than those of the non-obese group (p<0.05, p<0.001 respectively). HDL-cholesterol and adiponectin levels of the obese group were significantly lower than those of the non-obese group (p<0.005, p<0.05 respectively). In the obese group, leptin level was positively correlated with BMI and the percentage of body fat, but negatively correlated with adiponectin level. Moreover, adiponectin level of the obese group was negatively correlated with BMI and the percentage of body fat, but positively correlated with leptin level. In the non-obese group, only insulin level was positively correlated with adiponectin. In the obese group, leptin/adiponectin ratio was positively correlated with the percentage of body fat and leptin level. Also, leptin/adiponectin ratio was positively correlated with BMI and the percentage of body fat in the non-obese group. Conclusion: Leptin, adiponectin, and leptin/adiponectin ratio did not appear to have a major role linking various metabolic disorders in the childhood obesity, even though they were strongly associated with obesity indices. Also, leptin/adiponectin ratio was associated with obesity indices even in non-obese children.

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A Study on Effective Information Delivery of Digital Sign Systems in General Hospitals (종합병원 디지털 정보안내사인의 효과적 정보전달을 위한 연구)

  • Kim, Hwa Sil;Paik, Jin Kyung
    • Korea Science and Art Forum
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    • v.19
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    • pp.281-292
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    • 2015
  • For this study, I conducted a survey investigating current situation, user preference, and field experiment. Hospitals utilizing digital sign systems at least five years were selected, which are connected with visual elements (layout, typo, color) used in waiting areas and elements of the systems (time, video time line). The results obtained from the field survey showed that digital sign systems used the color of typo and background contrasted to one another to increase explicitness and to ensure easy understanding of contents. In addition, the Gothic typo with relatively high legibility was adopted. Time and video timeline, which characterize digital sign systems, showed the advertising screens of the hospitals and the guidance of medical treatment at regular intervals. Moreover, survey results on user satisfaction showed that a majority of respondents indicated they had difficulty in understanding digital information conveyed from digital sign systems due to time setting for rotational speed or the small size of typo although most of the users had previous experience with digital sign systems. The highest proportion of respondents (n=86, 86%) answered that information related to medical departments was what they sought most frequently and that this kind of information should be importantly considered in digital sign systems. For the experiment, new samples with restructured contents of current digital sign systems were created and tested while keeping its design unchanged as well as applying these new samples. Study participants were in their 20s through 50s. When the size of typo was larger under the same conditions for all age groups, study participants found the desired information approximately 3.5 seconds faster. In addition, those in their 20-30s and 40-50s showed the time difference of 4.7 seconds for small typo and 6 seconds for large typo, which suggested that there was a difference by age in the amount of time taken in the experiment to find the desired information from the rotating digital sign system regardless of age and the size of typo.

Effect of the Ayres Sensory Integration Intervention on the Motor Skills and Occupation Participation of Preschool Children with Attention-Deficit/Hyperactivity Disorder (Ayres의 감각통합중재가 학령전기 주의력결핍 과잉행동장애(ADHD) 성향 아동의 운동기능 및 작업참여에 미치는 영향)

  • Jung, Yun-Jin;Kang, Je-wook;Chang, Moon-young;Kim, Kyeong-Mi
    • The Journal of Korean Academy of Sensory Integration
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    • v.22 no.1
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    • pp.1-14
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    • 2024
  • Objective : This study aimed to investigate the impact of Ayres' sensory integration (ASI) intervention on motor skills and occupational participation of preschool children with attention-deficit/hyperactivity disorder (ADHD). Method : Children with ADHD aged between 4 and 6 years who met the inclusion and exclusion criteria were randomly recruited through screening tests. The subjects were divided into an experimental group (10 subjects) and a control group (8 subjects). The instruments used were the Bruininks-Oseretsky test of motor proficiency-2 (BOT-2), Pediatric Evaluation of Disability Inventory (PEDI), and Goal Attainment Scale (GAS) to evaluate occupational participation. The subjects in the experimental group underwent individual sensory integration therapy according to the ASI principles for 40 minutes twice a week in a total of 16 sessions over eight weeks. The control group did not receive the ASI intervention. Data analysis was performed using the Mann-Whitney U test, chi-squared test, Wilcoxon signed-rank test, and Cohen's d test in SPSS 20.0. Results : The ASI experimental group had significantly higher scores in total motor composite, manual coordination, body coordination, strength, and agility in motor function than the control group (p<.05). The two groups did not differ significantly in terms of occupational participation (PEDI), but GAS scores for individual target activities were significantly higher in the experimental group than in the control group (p<.05). Conclusion : This study shows that the ASI intervention has positive effects on motor skills and occupation participation among preschool children with ADHD.

A Preliminary Epidemiologic Study on Korean Veterans Exposed to Herbicides in Vietnam War (파월국군장병의 고엽제 위해에 관한 예비적 역학조사)

  • Kim, Joung-Soon;Lee, Hyun-Sul;Lee, Hong-Bok;Lee, Won-Young;Park, Young-Joo;Kim, Sung-Soo
    • Journal of Preventive Medicine and Public Health
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    • v.27 no.4 s.48
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    • pp.711-734
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    • 1994
  • Among chemical agents in herbicides, dioxin (2, 3, 7, 8-tetrachloro dibenzo-$\rho$-dioxin : TCDD), a chemical contaminant in herbicides sprayed during the Vietnam War has been known to be the major agent causing toxic effects. Approximately 320,000 korean soldiers participated the Vietnam War from 1964 to 1974. Although the potential hazards of the herbicides among Korean veterans exposed were implicated, the problem had not been a public issue until 1991 when Korean veterans were informed U.S. companies, the herbicides manufacturer payed fund, from which a trust fund for New Zealand and Australian Class members were established in 1985. After a series of appeals and demonstration by the Korean Veterans demanding medical care and compensation for their serious health damages, a bill of medical care and compensation for herbicides victims was promulgated in March 1993 and become effective from May 1993, This study was carried out with two major objectives : the first to understand the health problems caused from the herbicides by reviewing literatures published, and the second to examine the nature and extent of health impacts among Korean veterans exposed and to develop valid study methods for the major study by interviewing and reviewing records on a part of veterans (638 persons) registered and completed medical examination in Seoul Veterans Administration Hospital from June to October 1993. The results obtained are as followings: 1. The literature review of 107 papers revealed that 1) Dioxin is teratogenic, carcinogenic and affects almost all organs including nervous, endocrine, and reproductive systems in animal experiments. 2) The diseases showing evidence of causal association were Hodgkin's disease, non-Hodgkin's disease, lung cancer, lymphoma, soft tissue sarcoma, chloroacne and polyneuropathy when judged on the basis of consistency in study results and biological plausibility. 2. Interview and medical record review study on 638 veterans, though limited validity owing to lack of control group, crude estimates of dioxin exposure levels (no biomarkers measurable), and uncertainty of diagnosis, showed that: 1) Most of the study subject's were in their 40's of age and had been dispatched to Vietnam during the period from $1965{\sim}1970$ around one year. 2) Most frequently complained symptoms in medical examination were motor weakness (32%), sensory abnormalities in extremities (23%), skin diseases (22%), and pain in extremities (20%) whereas in Interview they were more frequent in order of skin problem (44%), motor weakness (38%), sensory abnormalities and pain in extremities(17% and 19% each). Kappa indices on the same category of complaints between two sources of information were variable and relatively low. 3) On medical examination, only a part of the 638 subjects had initial impression (442 pts) and final diagnosis (218 pts) suggesting decision making on diagnosis appeared to be difficult even with all available modern medical technologies: in initial impression disorders from peripheral and central neuropathy were predominant whereas in final diagnosis various types of skin disorder were most frequent 4) When dose-response relationship between several conditions (from questionnaire) and arbitrary exposure scores were examined by CMH linear trend test, spontaneous abortion, sexual problems and health problem of offsprings showed statistically significant linear trends. However, pregnancy, accident and suicidal attempts did not show any relationship in this study capacity. 5) Among complaints, psychosis and neurosis (anxiety, phobia) in interview study, and memory disorder and psychosis in medical record study revealed linear trend. 6) Skin disorder was the only condition showing linear trend in initial impression and none in final diagnosis on medical examination. Even though objective to select out dioxin-related disease or group of diseases from this study was not achieved the research experiences provided firm basis for developing various methodological approaches. 3. From this preliminary study we concluded that a larger scale major epidemiologic study on health impacts of herbicides among Korean veterans exposed is not only Indispensible but also well designed study with more valid exposure information and diagnosis may be able to establish causal relationship between certain groups of diseases and exposure to the herbicides among Korean veterans.

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Clinical Results of Aortic Valve Replacement (대동맥판 치환술의 임상 성적)

  • Na, Guk-Ju;O, Jeong-U;An, Byeong-Hui;Kim, Sang-Hyeong
    • Journal of Chest Surgery
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    • v.30 no.2
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    • pp.152-157
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    • 1997
  • From August 1986 until June 1995, single aortic valve replacement was performed in 65 patients at the Chonnam National University Hospital. worthy-eight were male and 17 were female patients, ranging from 19 to 68 years of age(median : 43 years). The causes of the valve lesions were rheumatic in 29 patients (44.6%), bicuspid aortic valve in 6 patients (6.2%), endocarditis in 6 patients(6.2%), unknown in others. Concomitant surgical procedures were performed in 10 patients : repair of congenital defect in 5, pericardiectomy in 1, coronary artery bypass grafting in 1, noncoronary sinus plication in 1, Valsalva sinus aneurysmectomy in 1, subaortic membrane resection in 1 Used valves were 51. Jude-Medical valve in 42, Duromedics valve in 22, Bjork-Shiley valve in 2, Carpentier-Edward valve in 1. There were 3 hospital deaths (4.6%), and 2 late deaths (3.2%). Follow-up was 95.2% complete. The 10-year acturlal survival rate was 85.3%. Postoperative complications were low cardiac utput in 8, arrythmia in 5, valve related hemolysis in 1, cerebral infarction in 1, and gastrointestinal bleeding in 2. Reoperation was performed in 4 for surgical bleeding, in 3 for paravalvular leak. The mean improvement in New York Heart Association functional class is from 2.79 $\pm$ 0.66 preoperatively to 1.25 $\pm$ 0.49 postoperatively(p < 0.001) The change of cardiothoracic ratio from preoperative to postoperative is 0.57 $\pm$ 0.06 to 0.54 $\pm$ 0.05 (p < 0.05). The left ventricular ejection fraction change is not significant perioperatively. There are no mechanical failures. This early and intermediate-term follow-up suggests that in adults in whom valve repair is not possible, the mechanical valve is a reliable and durable prosthesis with good hemodynamic function and a low rate of thromboembolic event.

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Comparison of IVF Outcomes in Patients with Endometriosis According to Severity (자궁내막증이 있는 불임 여성에서 중등도에 따른 체외 수정의 결과 비교)

  • Kim, Hye Ok;Kang, Inn Soo
    • Clinical and Experimental Reproductive Medicine
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    • v.33 no.4
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    • pp.219-227
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    • 2006
  • Objective: To evaluate the impact of endometriosis on IVF-ET cycles and to compare IVF outcomes between stage I/II and stage III/IV endometriosis. Methods: We analyzed 697 patients (1,199 cycles) with endometriosis (stage I-II:638 cycles, stage III-IV: 561 cycles) and 325 pts (459 cycles) with tubal factor as controls between January 1994 and April 2004. Pts with endometriosis were diagnosed by laparoscopy and medical and surgical treatment were done in 353 cycles (55.3%) and 466 cycles (83.1%) of stage I-ll/stage III-IV endometriosis. Cycles with age>35 years or FSH>20 miU/mL or severe male factor infertility were excluded. Results: The number of retrieved oocytes ($9.97{\pm}7.2$ vs. $13.4{\pm}7.9$ (p<0.0001 )), total number of embryos ($6.5{\pm}4.8$ vs. $9.1{\pm}5.6$ (p<0.0001)), and good quality embryos ($2.43{\pm}1.6$ vs. $2.74{\pm}1.7$ (p=0.013)) significantly decreased in stage III-IV endometriosis than in control. But pregnancy rate of stage III-IV endometriosis was comparable with control (35.7% vs. 36.8%). Fertilization rate and number of total embryos were lower in stage I-II endometriosis than in control ($64.8{\pm}22.9$ vs. $70.8{\pm}20.8$ (p<0.0001), $7.6{\pm}5.0$ vs. $9.1{\pm}5.6$ (p<0.0001)). In patients with medical and surgical treatment of endometriosis, pregnancy rate and live birth rate was significantly lower in stage I-II than in stage III-IV endometriosis (29.2 vs. 36.2 (%), p=0.045, 23.9 vs. 31.5 (%), p=0.043). There was no difference in the mean age, but the duration of infertility was significantly longer ($56.5{\pm}26.3$ vs. $46.9{\pm}25.8$ (mon), p<0.0001) and fertilization rate was lower ($64.7{\pm}23.3$ vs. $70.5{\pm}22.7$ (%), p=0.001) in stage I-II than stage III-IV endometriosis. Conclusion: We suggest that IVF should be considered earlier in patients with minimal to mild endometriosis because of significantly decreased fertilization rates.