• Pediatric Infection and Vaccine
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• v.12 no.2
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• pp.166-177
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• 2005

Purpose : The purpose of this study was to examine the molecular epidemiology and genetic variability of adenovirus(Ad) serotypes Ad1, Ad2, and Ad5 over 14 years in Korea. Methods : A total of 382 adenoviral strains isolated from the nasopharyngeal aspirates of children with lower respiratory tract infections in Seoul, Korea from November 1990 to February 2003 were serotyped by neutralization assay with type-specific antisera. Viral DNAs were extracted from infected cell lysates by the modified Hirt procedure. Genome type(GT) was determined by DNA restriction analysis with 12 restriction enzymess(BamHI, BclI, BglI, BglII, BstEII, EcoRI, HindIII, HpaI, SalI, SmaI, XbaI, and XhoI). To evaluate the genetic relatedness, pairwise comigrating restriction fragments(PCRF) analysis was performed. Results : Of 382 strains, 33 strains(9%) were Ad1, 45 strains(12%) were Ad2, and 24 strains(6%) were Ad5. Eighteen GTs(Ad1p1-Ad1p7, Ad1a, Ad1b, Ad1b1-Ad1b3, Ad1c, Ad1d, Ad1e, Ad1e1, Ad1e2, Ad1f) among Ad1, 24(Ad2p1-Ad2p11, Ad2a, Ad2a1-Ad2a6, Ad2b, Ad2c, Ad2d, Ad2e, Ad2e1-Ad2e3) among Ad2, and 10(Ad5p1, Ad5p2, Ad5a, Ad5a1-Ad5a7) among Ad5 strains were identified. One or two strains of the vast majority of GTs were isolated during the study period while a few GTs were identified sporadically with more than 2 strains. It is notable that some GTs such as Ad1p5 and Ad5a1 appeared in cluster during a short period. In analysis of genetic relatedness, the degree of PCRFs(pairwise comigrating restriction fragments) for Ad1 varied from 79 to 99%, for Ad2, 82 to 99%, and for Ad5, 85 to 99%. Conclusion : This study established the comprehensive nomenclature systems of Ad1, Ad2, and Ad5. Diverse GTs identified in this study have crucial implications in the genomic diversity and epidemiological characteristics of Ad1, Ad2, and Ad5.

• Journal of Chest Surgery
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• v.38 no.8 s.253
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• pp.538-544
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• 2005

Background: Pulmonary artery banding (PAB) is an initial palliative procedure for a diverse group of patients with congenital cardiac anomalies and unrestricted pulmonary blood flow. We proved the usefulness of PAB through retrospective investigation of the surgical indication and risk analysis retrospectively. Material and Method: One hundred and fifty four consecutive patients (99 males and 55 females) who underwent PAB between January 1986 and December 2003 were included. We analysed the risk factors for early mortality and actuarial survival rate. Mean age was $2.5\pm12.8\;(0.2\sim92.7)$ months and mean weight was $4.5\pm2.7\;(0.9\sim18.0)\;kg$. Preoperative diagnosis included functional single ventricle $(88,\;57.1\%)$, double outlet right ventricle $(22,\;14.2\%)$, transposition of the great arteries $(26,\;16.8\%)$, and atrioventricular septal defect $(11,\;7.1\%)$. Coarctation of the aorta or interrupted aortic arch $(32,\;20.7\%)$, subaortic stenosis $(13,\;8.4\%)$ and total anomalous pulmonary venous connection $(13,\;8.4\%)$ were associated. Result: The overall early mortality was $22.1\%\;(34\;of\;154)$, The recent series from 1996 include patients with lower age $(3.8\pm15.9\;vs.\;1.5\pm12.7,\;p=0.04)$ and lower body weight $(4.8\pm3.1\;vs.\;4.0\pm2.7,\;p=0.02)$. The early mortality was lower in the recent group $(17.5\%;\;16/75)$ than the earlier group $(28.5\%;\;18/45)$. Aortic arch anomaly (p=0.004), subaortic stenosis (p=0.004), operation for subaortic stenosis (p=0.007), and cardiopulmonary bypass (p=0.007) were proven to be risk factors for early death in univariate analysis, while time of surgery (<1996) (p=0.026) was the only significant risk factor in multivariate analysis. The mean time interval from PAB to the second-stage operation was $12.8\pm10.9$ months. Among 96 patients who survived PAB, 40 patients completed Fontan operation, 21 patients underwent bidirectional cavopulmonary shunt, and 35 patients underwent biventricular repair including 25 arterial switch operations. Median follow-up was $40.1\pm48.9$ months. Overall survival rates at 1 year, 5 years and 10 years were $81.2\%\;65.0\%,\;and\;63.5\%$ respectively. Conclusion: Although it improved in recent series, early mortality was still high despite the advances in perioperative management. As for conventional indications, early primary repair may be more beneficial. However, PA banding still has a role in the initial palliative step in selective groups.

• Journal of Chest Surgery
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• v.36 no.9
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• pp.651-658
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• 2003

Since the first implanted in September 1997, the use of On-X prosthetic heart valve has been increasing around in the world. This study was designed to assess the feasibility, safety, and the postoperative hemodynamics with this new valve in clinical setting. Material and Method: The current study was carried out on 52 patients undergoing aortic valve replacement with this prosthesis between April 1999 to August 2002 at Chonnam National University Hospital to evaluate the surgical results. 52％ of the patients were male and the average age at implant was 50$\pm$13 years. The study followed the guidelines of the AATS/STS. Preoperatively, 32(61.5％) patients were in NYHA functional class III or IV and 2 patients had previous aortic valve surgery. Concomitant cardiac surgery was performed in 71.1％. The implanted valve sizes were 19 mm in 13 patients, 21 mm in 26, 23 mm in 10 and 25 mm in 3, respectively. Mean follow-up was 16.6$\pm$10.5 months (1∼39 months). Echocardiographic assessment was performed pre- and immediate postoperatively, as well as 3, 6, 12 months after surgery, evaluating pressure loss and regression of left ventricular hypertrophy. Result: Mean cardiopulmonary bypass time was 191$\pm$94.7 minutes with an aortic cross-clamp time of 142$\pm$51.7 minutes. There was no early and late mortality, Freedom from adverse events at 1 year in the study were as follows: thromboembolism, 95.6$\pm$6％; bleeding events, 90.2$\pm$4％; paravalvular leakage 92.3$\pm$4％; and overall valve-related morbidity at 1 year was 76.6$\pm$3％. There were no cases of valve thrombosis, prosthetic valve endocarditis and structural or non-structural failure. Left ventricular function at 12 months after surgery (EF=62.7$\pm$9.8％) revealed a statistically significant improvement compared to preoperative investigation (EF=55.8$\pm$15.9％, p=0.006). Left ventricular mass index was 247.3$\pm$122.3 g/$m^2$ on preoperative echocardiographic study, but regressed to 155.5$\pm$58.2 g/$m^2$ at postoperative 1 year (p=0.002). Over the follow-up period a further decrease of peak transvalvular gradients was observed in all patients: 62.5$\pm$38.0 mmHg on preoperative assessment, 18.2$\pm$6.8 mmHg at immediate postoperative period (p < 0.0001), 7.6$\pm$5.09 mmHg (p<0.0001) at 6 month, 18.0$\pm$10.8 mmHg (p<0.0001) at 1 year. Conclusion: The On-X prosthetic heart valve performs satisfactorily in the first 1 year period. Clinical outcome by examining NYHA functional classification revealed especially good results. Effective regression of left ventricular hypertrophy and statistically significant decrease of transvalvular gradient were observed over the first year, but longer-term follow-up of this patient group is needed to establish the expected rates for late valve-related events as well as the long-term clinical efficacy of this valve.

• Journal of Chest Surgery
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• v.35 no.12
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• pp.847-853
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• 2002

We previously published the data that proved the safety of retrograde cerebral perfusion for 120 minutes. At this time, we planned to check the neuron-specific enolase and S100-$\beta$ in serum and urine to assess the possibility of early detection of cerebral injury. Material and Method: We used pigs(Landrace species) weighing 35 kg and performed RCP for 120 minutes. After the weaning of cardiopulmonary bypass, we observed the pigs for another 120 minutes. Systemic arterial pressure, central venous pressure, and serum and urine levels of neuron-specific enolose (NSE) and S100$\beta$ protein were checked. Central venous pressure during RCP was maintained in the range of 20 to 25 mmHg. Result: Serum levels of NSE(ng/$m\ell$) were 0.67$\pm$0.18(induction of anesthesia), 0.53$\pm$0.47(soon after CPB), 0.44$\pm$0.27(20min alter CPB), 0.24$\pm$0.09(RCP 20min), 0.37$\pm$0.35(RCP 40min), 0.33$\pm$0.21 (RCP 60min), 0.37$\pm$0.22(RCP 80min), 0.41$\pm$0.23(RCP 100 min), 0.48$\pm$0.26(RCP 120min), 0.42$\pm$0.29(30min after rewarming), 0.35 $\pm$0.32(60min after rewarming, 0.42$\pm$0.37(CPBoff 30min), 0.47$\pm$0.34(CPBOff 60min), 0.47$\pm$0.28(CPBOff 90min), and 0.57$\pm$0.29(CPBOff 120min). There was no statistically significant difference in levels between before and after RCP(ANOVA, p＞0.05). Urine levels of NSE also showed no statistically significant difference in levels between before and after RCP. There was no correlation between urine and serum levels of NSE(Pearson correlation, p＞0.05). Serum levels of S100$\beta$ protein(ng/$m\ell$) during the same time frames were 0.14$\pm$0.08, 0.15$\pm$0.07, 0.22$\pm$0.15, 0.23$\pm$0.07, 0.28$\pm$0.10, 0.40$\pm$0.05, 0.47$\pm$0.03, 0.49$\pm$0.12, 0.43$\pm$0.11, 0.46$\pm$0.15, 0.62$\pm$0.17, 0.77$\pm$0.21, 0.78$\pm$0.23, 0.77$\pm$0.23, and 0.82$\pm$0.33. There was statistically significant difference in levels between before and after RCP(ANOVA, p＜0.05). Urine levels of NSE also showed statistically significant difference in levels between before and after RCP(ANOVA, p＜0.05). There was significant correlation between urine and serum levels of NSE(Pearson correlation, p＜0.05). Conclusion: The author observed the increase in serum and urine levels of S100$\beta$ after 120 minutes of RCP. Significant correlation between serum and urine levels was observed. The results were considered to be the fundamental data that could correlate this study with human-based study.

• Atmosphere
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• v.24 no.3
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• pp.303-315
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• 2014

Terrestrial ecosystem plays the important role as carbon sink in the global carbon cycle. Understanding of interactions of terrestrial carbon cycle with climate is important for better prediction of future climate change. In this paper, terrestrial carbon cycle is investigated by Hadley Centre Global Environmental Model, version 2, Carbon Cycle (HadGEM2-CC) that considers vegetation dynamics and an interactive carbon cycle with climate. The simulation for future projection is based on the three (8.5/4.5/2.6) representative concentration pathways (RCPs) from 2006 to 2100 and compared with historical land carbon uptake from 1979 to 2005. Projected changes in ecological features such as production, respiration, net ecosystem exchange and climate condition show similar pattern in three RCPs, while the response amplitude in each RCPs are different. For all RCP scenarios, temperature and precipitation increase with rising of the atmospheric $CO_2$. Such climate conditions are favorable for vegetation growth and extension, causing future increase of terrestrial carbon uptakes in all RCPs. At the end of 21st century, the global average of gross and net primary productions and respiration increase in all RCPs and terrestrial ecosystem remains as carbon sink. This enhancement of land $CO_2$ uptake is attributed by the vegetated area expansion, increasing LAI, and early onset of growing season. After mid-21st century, temperature rising leads to excessive increase of soil respiration than net primary production and thus the terrestrial carbon uptake begins to fall since that time. Regionally the NEE average value of East-Asia ($90^{\circ}E-140^{\circ}E$, $20^{\circ}N{\sim}60^{\circ}N$) area is bigger than that of the same latitude band. In the end-$21^{st}$ the NEE mean values in East-Asia area are $-2.09PgC\;yr^{-1}$, $-1.12PgC\;yr^{-1}$, $-0.47PgC\;yr^{-1}$ and zonal mean NEEs of the same latitude region are $-1.12PgC\;yr^{-1}$, $-0.55PgC\;yr^{-1}$, $-0.17PgC\;yr^{-1}$ for RCP 8.5, 4.5, 2.6.

• Korean Journal of Poultry Science
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• v.33 no.3
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• pp.171-179
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• 2006

Changes in the chicken testis from hatching to adulthood were studied in Korean native chickens of 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, 28, 32, 44, 52 and 64 weeks (n=13 chickens per group) of age. The present study was to investigate in more detail the post-hatching development of testis in Korean native chickens. Testes of chickens were fixed by whole body perfusion using a fixative containing 2.5% glutaraldehyde in cacodylate buffer, processed and embedded in Epon-araldite. Using $1{\mu}m$ sections stained with methylene blue-azure II, qualitative and quantitative(stereological) morphological studies were performed. Sperm production was measured by routine technique. The average volume of a testis of 1 week old Korean native chickens was determined as 0.015 g and the parameter increased linearly from 1 week to 21 weeks days (28.9 g), and did not change from 21 weeks to 64 weeks. The volume density of the seminiferous tubules increased with age from 32.6% at week 1 to 92.89% at week 64. The volume density of the interstitium represents 67.4% of the testicular parenchyma at week 1. This proportion progressively diminished during development to reach a value of 7.11% at week 64. Total sperm production per testis increased significantly from 18 weeks to 28 weeks and remained unchanged. Sperm production per 1 g testis increased significantly from 18 weeks to 28 weeks, did not change significantly from 28 weeks to 52 weeks, and declined significantly at 64 weeks of age. The average diameter of the seminiferous tubules gradually increased with age from 1 week $(42.4{\mu}m)$ to 21 weeks $(412.8{\mu}m)$. The length of the seminiferous tubules was 0.34 m at 1 week, increased significantly in subsequent age groups and reached 72.2 m by weeks 64. The stage of germ cell development in seminiferous tubules was classified as 1) spermatogonia $(1\sim8\;weeks)$, 2) spermatogonia and spermatocytes $(10\sim12\;weeks)$, 3) spermatogonia, spermatocytes and round spermatids $(14\sim16\;weeks)$, and 4) speramatogonia, spermatocytes, spermatids and spermatozoa $(18\sim64\;weeks)$. These results clarified the pattern of changes in the testicular development in Korean native chickens from hatching to adulthood as 1) neonatal-prepubertal $(1\sim12\;weeks)$, 2) puberty$(14\sim18\;weeks)$, and adult$(21\sim64\;weeks)$.

• Investigative Magnetic Resonance Imaging
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• v.8 no.1
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• pp.32-41
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• 2004

Purpose : To measure the NMR relaxation properties of MnPC, to observe the characteristics of liver enhancement patterns on MR images in experimentally implanted rabbit VX2 tumor model, and to estimate the possibility of tissue specific contrast agent for MnPC in comparison with the hepatobiliary agent. Materials and Methods : Phthalocyanine (PC) was chelated with paramagnetic ions, manganese (Mn). 2.01 g (5.2 mmol) of phthalocyanine was mixed with 0.37 g (1.4 nlmol) of Mn chloride at $310^{\circ}C$ for 36 hours and then purified by chromatography ($CHCl_3:\;CH_3OH=98:2$, volume ratio) to obtain 1.04 g $(46\%)$ of MnPC (molecular weight = 2000 daltons). The T1/T2 relaxivity (R1/R2) for MnPC were determined at a 1.5 T (64 MHz) MR spectrometer. VX2 tumor model was experimentally implanted in the liver parenchyma of rabbits. All MR studies were performed on 1.5 T. The human extremity radio frequency coil of a bird cage type was employed. MR images were acquired at 17 to 24 days after VX2 carcinoma implantation.4 mmol/kg MnPC and 0.01 mmol/kg Mn-DPDP were injected via the ear vein of rabbits. T1-weighted images were obtained with spin-echo (TR/TE=516/14 msec) and fast multiplanar spoiled gradient recalled (TR/TE : 80/4 msec, $60^{\circ}$ flip angle) pulse sequence. Fast spin-echo (TR/TE=1200/85 msec) was used to obtain the T2-weighted images. Results : The value of T1/T2 relaxivity (R1/R2) of MnPC was $7.28\;mM^{-1}S^{-1}$ and $55.56\;mM^{-1}S^{-1}$ respectively at 1.5 T (64 MHz). Because the T2 relaxivity of MnPC that bonded strongly, covalently manganese with phthalocyanine was very high, the signal intensity of liver parenchyma was decreased on postcontrast T2-weighted images and we could easily distinguish the VX2 carcinoma within the liver parenchyma. When MnPC was administrated intravenously, the tumor margin delineation was more remarkable than Mn-DPDP-enhanced images. The enhancement of liver parenchyma with MnPC persisted at relatively high levels over at least one hour after injection of the contrast agents. Conclusion : The hepatic uptake and biliary excretion of MnPC, which are similar to Mn-DPDP, suggest that this agent is a new liver-specific agent. Also, MnPC seems to be used as a dual contrast agent (T1 and T2) with high T2 relaxivity. However, it is warranted that MnPC needs further investigation as a potential contrast agent for MR imaging of the liver. That is, further characterizations of MnPC are needed in vivo and in vitro before clinical trials. The diagnostic potential of MnPC will also have to be examined more in the animal models of additional types.

• Investigative Magnetic Resonance Imaging
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• v.8 no.2
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• pp.79-85
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• 2004

Purpose : To evaluate the usefulness and reproducibility of $^1H$ MRS in different 1.5 T MR machines with different coils to compare the SNR, scan time and the spectral patterns in different brain regions in normal volunteers. Materials and Methods : Localized $^1H$ MR spectroscopy ($^1H$ MRS) was performed in a total of 10 normal volunteers (age; 20-45 years) with spectral parameters adjusted by the autoprescan routine (PROBE package). In all volunteers, MRS was performed in a three times using conventional MRS (Signa Horizon) with 1 channel coil and upgraded MRS (Echospeed plus with EXCITE) with both 1 channel and 8 channel coil. Using these three different machines and coils, SNRs of the spectra in both phantom and volunteers and (pre)scan time of MRS were compared. Two regions of the human brain (basal ganglia and deep white matter) were examined and relative metabolite ratios (NAA/Cr, Cho/Cr, and mI/Cr ratios) were measured in all volunteers. For all spectra, a STEAM localization sequence with three-pulse CHESS $H_2O$ suppression was used, with the following acquisition parameters: TR=3.0/2.0 sec, TE=30 msec, TM=13.7 msec, SW=2500 Hz, SI=2048 pts, AVG : 64/128, and NEX=2/8 (Signa/Echospeed). Results : The SNR was about over $30\%$ higher in Echospeed machine and time for prescan and scan was almost same in different machines and coils. Reliable spectra were obtained on both MRS systems and there were no significant differences in spectral patterns and relative metabolite ratios in two brain regions (p>0.05). Conclusion : Both conventional and new MRI systems are highly reliable and reproducible for $^1H$ MR spectroscopic examinations in human brains and there are no significant differences in applications for $^1H$ MRS between two different MRI systems.

• Journal of Preventive Medicine and Public Health
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• v.31 no.4 s.63
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• pp.751-769
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• 1998

This study was conducted to assess the attitude of pregnant women toward delivery method, understanding of the reason for determining her own delivery method, participation in decision-making process and satisfaction with delivery method after labor. Study subjects were 693 pregnant women who had visited obstetric clinic for prenatal care in the last month of pregnancy in one general hospital and one obstetrics-gynecology specialty hospital in Taegu city from February 1 to March 31 in 1998. A questionnaire was administered before and after labor and a telephone interview was done one month after labor. Proportion of women who had health education and/or counselling about delivery method during prenatal care was 24.0% and this proportion was higher for women who had previous c-section(35.5%) than others. Women thought vaginal delivery is better than c-section for both maternal and baby's health regardless of previous delivery method. About 90% of primipara and multiparous women who had previous vaginal delivery wanted vaginal delivery for the index birth, while 85.6% of multiparous women who had previous c-section wanted repeat c-section. Reasons for choosing c-section in pregnant women who preferred vaginal delivery before labor were recommendation of doctors(81.9%), recommendation of husband (0.8%), agreement between doctor and pregnant woman(4.7%), and mother's demand (12.6%). Reasons for choosing vaginal delivery were mother's demand(30.6%) and no indication for c-section(67.2%). Reasons for choosing c-section in pregnant women who preferred c-section before labor were recommendation of doctors(76.2%), mother's demand(20.0%), recommendation of husband(1.3%), and agreement between doctor and pregnant woman(2.5%). Of the pregnant women who had c-section, by doctor's recommendation, the proportion of women who had heard detailed explanation about reason for c-section by doctor was 55.1%. Mother's statement about the reason for c-section was consistent with the medical record in 75.9% . However, over 5% points disparities were shown between mother's statement and medical record in cases of the repeat c-section and mother's demand. In primipara and multiparous women who had previous vaginal delivery, the delivery method for index birth had statistically significant association with the preference of delivery method before labor(p<0.05). All of the women who had previous c-section had delivered the index baby by c-section. Among mothers who had delivered the index baby vaginally, 84.9% of them were satisfied with their delivery method immediately after labor and 85.1% at 1 month after labor. However, mothers who had c-section stated that they are satisfied with c-section in 44.6% immediately after labor and 42.0% at 1 month after labor. Preferred delivery method for the next birth had statistically significant association with delivery method for the index birth both immediately after labor and in 1 month after labor. The proportion of mothers who prefer vaginal delivery for the next birth increased with the degree of satisfaction with the vaginal delivery for the index birth but the proportion of mothers who prefer c-section for the next birth was high and they did not change significantly with the degree of satisfaction with the c-section for the index birth. These results suggest that the current high technology-based, physician-centered prenatal and partritional cares need to be reoriented to the basic preventive and promotive technology-based, and mother-fetus-centered care. It is also suggested that active involvement of pregnant woman in decision-making process for the delivery method will increase the rate of vaginal birth after c-section and decrease c-section rate and improve the degree of maternal satisfaction after delivery.

• Journal of Chest Surgery
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• v.31 no.3
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• pp.233-241
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• 1998

To define the risk factors affecting the early major morbidity and mortality after multiple- valve operations, the preoperative, intraoperative and postoperative informations were retrospectively collected on 124 consecutive patients undergoing a multiple-valve operation between October 1985 and July 1996 at the department of Thoracic and Cardiovascular Surgery of Pusan Paik Hospital. The study population consists of 53 men and 71 women whose mean age was 37.9$\pm$11.5(mean$\pm$SD) years. Using the New York Heart Association(NYHA) classification, 41 patients(33.1%) were in functional class II, 60(48.4%) in class III, and 20(16.1%) in class IV preoperatively. Seven patients(5.6%) had undergone previous cardiac operations. Atrial fibrillations were present in 76 patients(61.3%), a history of cerebral embolism in 5(4.0%), and left atrial thrombus in 13(10.5%). The overall early mortality rate and postoperative morbidity was 8.1% and 21.8% respectively. Among the 124 cases of multiple-valve operation, there were 57(46.0%) of combined mitral valve replacement(MVR) and aortic valve replacement(AVR), 48(38.7%) of combined MVR and tricuspid annuloplasty(TVA), 12(9.7%) of combined MVR, AVR and TVA, 3(2.4%) of combined MVR and aortic valvuloplasty, 2(1.6%) of combined MVR and tricuspid valve replacement, and others. The patients were classified according to the postoperative outcomes; Group A(27 cases) included the patients who had early death or major morbidity such as low cardiac output syndrome, mediastinitis, cardiac rupture, ventricular arrhythmia, sepsis, and others; Group B(97 cases) included the patients who had the good postoperative outcomes. The patients were also classified into group of early death and survivor. In comparison of group A and group B, there were significant differences in aortic cross-clamping time(ACT, group A:153.4$\pm$42.4 minutes, group B:134.0$\pm$43.7 minutes, p=0.042), total bypass time(TBT, group A:187.4$\pm$65.5 minutes, group B:158.1$\pm$50.6 minutes, p=0.038), and NYHA functional class(I:33.3%, II:9.7%, III:20%, IV:50%, p=0.004). In comparison of early death(n=10) and survivor(n=114), there were significant differences in age(early death:45.2$\pm$8.7 years, survivor:37.2$\pm$11.6 years, p=0.036), sex(female:12.7%, male:1.9%, p=0.043), ACT(early death:167.1$\pm$38.4 minutes, survivor:135.7$\pm$43.7 minutes, p=0.030), and NYHA functional class(I:0%, II:4.9%, III:1.7%, IV:35%, p=0.001). In conclusion, the early major morbidity and mortality were influenced by the preoperative clinical status and therefore the earlier surgical intervention should be recommended whenever possible. Also, improved methods of myocardial protection and operative techniques may reduce the risk in patients with multiple-valve operation.