• Nuclear Medicine and Molecular Imaging
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• v.42 no.5
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• pp.383-393
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• 2008

Purpose: Cancer specific killing can be achieved by therapeutic gene activated by cancer specific promotor. Expression of sodium iodide symporter (NIS) gene causes transportation and concentration of iodide into the cell, therefore radioiodine treatment after NIS gene transfer to cancer cell could be a form of radionuclide gene therapy. luciferase (Luc) gene transfected cancer cell can be monitored by in vivo optical imaging after D-luciferin injection. Aims of the study are to make vector with both therapeutic NIS gene driven by AFP promoter and reporter Luc gene driven by CMV promoter, to perform hepatocellular carcinoma specific radiodiodine gene therapy by the vector, and assessment of the therapy effect by optical imaging using luciferase expression. Materials and Methods: A Vector with AFP promoter driven NIS gene and CMV promoter driven Luc gene (AFP-NIS-CMV-Luc) was constructed. Liver cancer cell (HepG2, Huh-7) and non liver cancer cell (HCT-15) were transfected with the vector using liposome. Expression of the NIS gene at mRNA level was elucidated by RT-PCR. Radioiodide uptake, perchlorate blockade, and washout tests were performed and bioluminescence also measured by luminometer in these cells. In vitro clonogenic assay with 1-131 was performed. In vivo nuclear imaging was obtained with gamma camera after 1-131 intraperitoneal injection. Results: A Vector with AFP-NIS-CMV-Luc was constructed and successfully transfected into HepG2, Huh-7 and HCT-15 cells. HepG2 and Huh-7 cells with AFP-NIS-CMV-Luc gene showed higher iodide uptake than non transfected cells and the higher iodide uptake was totally blocked by addition of perchlorate. HCT-15 cell did not showed any change of iodide uptake by the gene transfection. Transfected cells had higher light output than control cells. In vitro clonogenic assay, transfected HepG2 and Huh-7 cells showed lower colony count than non transfected HepG2 and Huh-7 cells, but transfected HCT-15 cell did not showed any difference than non transfected HCT-15 cell. Number of Huh-7 cells with AFP-NIS-CMV-Luc gene transfection was positively correlated with radioidine accumulation and luciferase activity. In vivo nuclear imaging with 1-131 was successful in AFP-NIS-CMV-Luc gene transfected Huh-7 cell xenograft on nude mouse. Conclusion: A Vector with AFP promoter driven NIS and CMV promoter driven Luc gene was constructed. Transfection of the vector showed liver cancer cell specific enhancement of 1-131 cytotoxicity by AFP promoter, and the effect of the radioiodine therapy can be successfully assessed by non-invasive luminescence measurement.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.294-308
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• 2002

Background : The cell-mediated immune response plays an important role in tuberculosis. After being activated by mycobacterial antigens, T lymphocytes express a high affinity receptor (IL-2R) for interleukin-2 (IL-2) on their own surface and release a soluble fraction of the IL-2 receptor (sIL-2R) from the cell membrane into the circulation. Neopterin is a metabolite of guanosine-triphosphate, which is produced by stimulated macrophages under the influence of IFN-$\gamma$ with a T lymphocyte origin. Therefore, the utility of sIL-2R, IFN-$\gamma$ and the neopterin levels as immunologic indices of the cell-mediated immune response and severity of disease in patients with pulmonary tuberculosis was assessed. Methods : The serum sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 39 patients with pulmonary tuberculosis, 6 patients with tuberculous lymphadenitis prior to treatment and 10 healthy subjects. The serum and pleural sIL-2R, neopterin and ADA levels were measured in 22 patients with tuberculous pleurisy. The patients with pulmonary tuberculosis were divided into a mild, moderate and severe group according to the severity by ATS guidelines. To compare the results from these patients with those of the pretreatment levels, the sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 36 of the 39 patients(1 patient, expired; 2 patients were referred to a sanitarium) with pulmonary tuberculosis after 2 months of treatment. Results : 1) the serum sIL-2R and IFN-$\gamma$ levels were elevated in patients with tuberculosis when compared to those of healthy subjects (p>0.05). The neopterin concentration in the serum was significantly lower in patients with pulmonary tuberculosis($2967{\pm}2132.8$ pg/ml) than in healthy controls($4949{\pm}1242.1$ pg/ml)(p<0.05). 2) In the pulmonary tuberculosis group, the serum sIL-2R and IFN-$\gamma$ levels were higher in patients with severe disease than those in patients with mild and moderate disease. However, the neopterin levels declined as the pulmonary tuberculosis became more severe (p<0.01). 3) The mean serum sIL-2R and IFN-$\gamma$ levels declined from $1071{\pm}1139.4$ U/ml to $1023{\pm}1920.9$ U/ml(p>0.05), $41{\pm}52.8$ pg/ml to $22{\pm}23.9$ gm/ml(p<0.05), respectively, after 2 month of treatment. The mean serum neopterin levels increased from $3158{\pm}2272.6$ pg/ml to $3737{\pm}2307.5$ pg/ml(p>0.05) after a 2 month of treatment. These findings were remarkable in the severe group of pulmonary tuberculosis with a clinical correlation. 4) In the patients with tuberculous pleurisy, the serum sIL-2R and ADA were significantly higher than those in the pleural fluid, However, the neopterin levels in the sera and pleural effusion were similar. Conclusion : On the basis of this study, sIL-2R, IFN-$\gamma$ and neopterin measurements may not only provide an insight into the present state of the cell-mediated immune response, but also serve as parameters monitoring of the prognosis of the disease, particularly in patients with severe pulmonary tuberculosis. In addition, an assay of the pleural sIL-2R levels might signal a stimulated local immunity including T cell activation in the tuberculous pleural effusion.

• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.71-79
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• 2003

Background : A bronchoalveolar lavage(BAL) is useful in diagnosing the etiology of bilateral pulmonary infiltrations, but may worsen the oxygenation and clinical status in severely hypoxemic patients. This study assessed the safety and efficacy of the continuous positive airway pressure(CPAP) using a conventional mechanical ventilator via a face mask as a tool for maintaining the oxygenation level during BAL. Methods : Seven consecutive patients with the bilateral pulmonary infiltrates and severe hypoxemia ($PaO_2/FIO_2$ ratio ${\leq}200$ on oxygen 10 L/min via mask with reservoir bag) were enrolled. The CPAP 5-6 $cmH_2O(F_IO_2\;1.0)$ was delivered through an inflatable face mask using a conventional mechanical ventilator. The CPAP began 10 min before starting the BAL and continued for 30 min after the procedure was completed. A bronchoscope was passed through a T-adapter and advanced through the mouth. BAL was performed using the conventional method. The vital signs, pulse oxymetry values, and arterial blood gases were monitored during the study. Results : (1) Median age was 56 years(male:female=4:3). (2) The baseline $PaO_2$ was $78{\pm}16mmHg$, which increased significantly to $269{\pm}116mmHg$(p=0.018) with CPAP. After the BAL, the $PaO_2$ did not decrease significantly but returned to the baseline level after the CPAP was discontinued. The $SpO_2$ showed a similar trend with the $PaO_2$ and did not decrease to below 90 % during the duration of the study. (3) The $PaCO_2$ increased and the pH decreased significantly after the BAL but returned to the baseline level within 30 min after the BAL. (5) No complications directly related to the BAL procedure were encountered. However, intubation was necessary in 3 patients(43 %) due to the progression of the underlying diseases. Conclusion : In severe hypoxemic patients, CPAP using a face mask and conventional mechanical ventilator during a BAL might allow minimal alterations in oxygenation and prevent subsequent respiratory failure.

• Journal of the East Asian Society of Dietary Life
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• v.19 no.6
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• pp.891-908
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• 2009

This study was performed to investigate the dietary habits, body weight satisfaction and eating disorder tendencies of female university students in Kyungnam province. Anthropometric measurements, dietary habits, body weight satisfaction, food preferences, disordered eating, and nutrient intakes were assessed in 132 female students at Kaya University. The results were analyzed with $x^2$- and ANOVA tests using the SPSS package program. The average age of the subjects was 20.1 years and average body mass index (BMI) were $21.1\;kg/m^2$. According to BMI, the percentages of students who were underweight, normal weight and overweight by BMI were 21.2, 55.3, and 23.5, respectively. Duration of exercise was significantly different by BMI. Index scores for a mini dietary assessment were significantly higher in the normal and overweight groups than in the underweight group. Scores for sweet, salty, and meat preferences were highest and scores for bean and vegetable preferences were lowest, in the underweight group. Satisfaction for present body weight was lowest, and self-perception of body image and weight control experiences were highest in the overweight group. All subjects in the overweight group wanted to be slim, and those in the normal and underweight groups, preferred to be more slim despite their current body weight being in the normal or below normal range. The percentage of the subjects who were at risk for eating disorders (based on scores from the Eating Attitude Test-26, EAT-$26{\geqq}20$) was 11.3%. Scores for EAT-26 were higher in the overweight group than in the underweight and normal weight groups. Nutrient intakes were not different among the groups. Therefore, dietary habits, taste and food preferences, satisfaction for present body weight, and disordered eating were significantly different according to BMI. These results suggest that overweight female university students need help correcting disordered eating, and nutrition counseling should be established to aid desirable weight control methods. Those who are underweight and normal weight need help establishing proper perceptions of their normal body weight and body image as well as nutrition counseling for health.

• Radiation Oncology Journal
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• v.28 no.4
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• pp.193-204
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• 2010

Purpose: To analyze the treatment outcomes, complications, prognostic factors after a long-term follow-up of patients with nasopharyngeal carcinoma treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Materials and Methods: Between December 1981 and December 2006, 190 eligible patients with non-metastatic nasopharyngeal carcinoma were treated at our department with a curative intent. Of these patients, 103 were treated with RT alone and 87 patients received CCRT. The median age was 49 years (range, 8~78 years). The distributions of clinical stage according to the AJCC 6th edition included I: 7 (3.6%), IIA: 8 (4.2%), IIB: 33 (17.4%), III: 82 (43.2%), IVA: 31 (16.3%), IVB: 29 (15.3%). The accumulated radiation doses to the primary tumor ranged from 66.6~87.0 Gy (median, 72 Gy). Treatment outcomes and prognostic factors were retrospectively analyzed. Acute and late toxicities were assessed using the RTOG criteria. Results: A total of 96.8% (184/190) of patients completed the planned treatment. With a mean follow-up of 73 months (range, 2~278 months; median, 52 months), 93 (48.9%) patients had relapses that were local 44 (23.2%), nodal 13 (6.8%), or distant 49 (25.8%). The 5- and 10-year overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) rates were 55.6% and 44.5%, 54.8% and 51.3%, in addition to 65.3% and 57.4%, respectively. Multivariate analyses revealed that CCRT, age, gender, and stage were significant prognostic factors for OS. The CCRT and gender were independent prognostic factors for both DFS and DSS. There was no grade 4 or 5 acute toxicity, but grade 3 mucositis and hematologic toxicity were present in 42 patients (22.1%) and 18 patients (9.5%), respectively. During follow-up, grade 3 hearing loss in 9 patients and trismus in 6 patients were reported. Conclusion: The results of our study were in accordance with findings of previous studies and we confirmed that CCRT, low stage, female gender, and young age were related to improvement in OS. However, there are limitations in the locoregional control that can be achieved by CCRT with 20 conventional radiation therapy. This observation has led to further studies on clarifying the efficacy of concurrent chemotherapy by intensity modulated radiation therapy.

• Tuberculosis and Respiratory Diseases
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• v.43 no.3
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• pp.367-376
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• 1996

Background : The diagnosis of emphysema during life is based on a combination of clinical, functional, and radiographic findings, but this combination is relatively insensitive and nonspecific. The development of rapid, high-resolution third and fourth generation CT scanners has enabled us to resolve pulmonary parenchymal abnormalities with great precision. We compared the chest HRCT findings to the pulmonary function test and arterial blood gas analysis in pulmonary emphysema patients to test the ability of HRCT to quantify the degree of pulmonary emphysema. Methods : From october 1994 to october 1995, the study group consisted of 20 subjects in whom HRCT of the thorax and pulmonary function studies had been obtained at St. Mary's hospital. The analysis was from scans at preselected anatomic levels and incorporated both lungs. On each HRCT slice the lung parenchyma was assessed for two aspects of emphysema: severity and extent. The five levels were graded and scored separately for the left and right lung giving a total of 10 lung fields. A combination of severity and extent gave the degree of emphysema. We compared the HRCT quantitation of emphysema, pulmonary function tests, ABGA, CBC, and patients characteristics(age, sex, height, weight, smoking amounts etc.) in 20 patients. Results : 1) There was a significant inverse correlation between HRCT scores for emphysema and percentage predicted values of DLco(r = -0.68, p < 0.05), DLco/VA(r = -0.49, p < 0.05), FEV1(r = -0.53, p < 0.05), and FVC(r = -0.47, p < 0.05). 2) There was a significant correlation between the HRCT scores and percentage predicted values of TLC(r = 0.50, p < 0.05), RV(r = 0.64, p < 0.05). 3) There was a significant inverse correlation between the HRCT scores and PaO2(r = -0.48, p < 0.05) and significant correlation with D(A-a)O2(r = -0.48, p < 0.05) but no significant correlation between the HRCT scores and PaCO2. 4) There was no significant correlation between the HRCT scores and age, sex, height, weight, smoking amounts in patients, hemoglobin, hematocrit, and wbc counts. Conclusion : High-Resolution CT provides a useful method for early detection and quantitating emphysema in life and correlates significantly with pulmonary function tests and arterial blood gas analysis.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.2
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• pp.99-110
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• 2008

Objectives: Preimplantation genetic diagnosis (PGD) has become an assisted reproductive technique for couples carrying genetic conditions that may affect their offspring. Osteogenesis imperfecta (OI) is an autosomal dominant disorder of connective tissue characterized by bone fragility and low bone mass. At least 95% of cases are caused by dominant mutations in the COL1A1 or COL1A2. In this study, we report on our experience clinical outcomes with 5 PGD cycles for OI in two couples. Methods: Before clinical PGD, we assessed the amplification rate and allele drop-out (ADO) rate of alkaline lysis and nested PCR protocol using heterozygous patient's single lymphocytes in the pre-clinical diagnostic tests for OI. We performed 5 cycles of PGD for OI by nested PCR for the causative mutation loci, COL1A1 c.2452G>A and c.3226G>A, in case 1 and case 2, respectively. The PCR products were analyzed by agarose gel electrophoresis, restriction fragment length polymorphism (RFLP) analysis with HaeIII restriction enzyme in the case 1 and direct DNA sequencing. Results: We confirmed the causative mutation loci, COL1A1 c.2452G>A in case 1 and c.3226G>A in case 2. In the pre-clinical tests, the amplification rate was 94.2% and ADO rate was 22.5% in case 1, while 98.1% and 1.9% in case 2, respectively. In case 1, a total of 34 embryos were analyzed and 31 embryos (91.2%) were successfully diagnosed in 3 PGD cycles. Eight out of 19 embryos diagnosed as unaffected embryos were transferred in all 3 cycles, and in the third cycle, pregnancy was achieved and a healthy baby was delivered without any complications in July, 2005. In case 2, all 19 embryos (100.0%) were successfully diagnosed and 4 out of 11 unaffected embryos were transferred in 2 cycles. Pregnancy was achieved in the second cycle and the healthy baby was delivered in March, 2008. The causative locus was confirmed as a normal by amniocentesis and postnatal diagnosis. Conclusions: To our knowledge, these two cases are the first successful PGD for OI in Korea. Our experience provides a further demonstration that PGD is a reliable and effective clinical techniques and a useful option for many couples with a high risk of transmitting a genetic disease.

• Tuberculosis and Respiratory Diseases
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• v.49 no.6
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• pp.724-732
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• 2000

Background : In patients with severe chronic lung diseases even a small pneumothorax can result in life-threatening respiratory distress. It is important to treat the attack by chest tube drainage until the lung expands. Pneumothorax with a persistent air leak that does not resolve under prolonged tube thoracostomy suction is usually treated by open operation to excise or oversew a bulla or cluster of blebs to stop the air leak. Pleurodesis by the instillation of chemical agents is used for the patient who has persistent air leak and is not good candidate for surgical treatment. When the primary trial of pleurodesis with common agent fails, it is uncertain which agent should be used f or stopping the air leak by pleurodesis. It is well known that inappropriate drainage of hemothorax results in severe pleural adhesion and thickening. Based on this idea, some reports described a successful treatment with autologous blood instillation for pneumothorax patients with or without residual pleural space. We tried pleurodesis with autologous bood for pneumothorax with persistent air leak and then we evaluated the efficacy and safety. Methods : Fifteen patients who had persistent air leak in the pneumothorax complicated from the severe chronic lung disease were enrolled. They were not good candidates for surgical treatment and doxycycline pleurodesis failed to stop up their air leaks. We used a mixture of autologous blood and 50% dextrose for pleurodesis. Effect and complications were assessed by clinical out∞me, chest radiography and pulmonary function tests. Results : The mean duration of air leak was 18.4${\pm}$6.16 days before ABP (autologous blood and dextrose pleurodesis) and $5.2{\pm}1.68$ days after ABP. The mean severity of pain was $2.3{\pm}0.70$ for DP(doxycycline pleurodesis) and $1.7{\pm}0.59$ for ABDP (p<0.05). There was no other complication except mild fever. Pleural adhesion grade was a mean of $0.6{\pm}0.63$. The mean dyspnea scale was $1.7{\pm}0.46$ before pneumothrax and $2.0{\pm}0.59$ after ABDP (p>0.05). The mean $FEV_1$ was $1.47{\pm}1.01$ before pneumothorax and $1.44{\pm}1.00$ after ABDP (p>0.05). Except in 1 patient, 14 patients had no recurrent pneumothorax. Conclusion : Autologous blood pleurodesis (ABP) was successful for treatment of persistent air leak in the pneumothorax. It was easy and inexpensive and involved less pain than doxycycline pleurodesis. It did not cause complications and severe pleural adhesion. We report that ABP can be considered as a useful treatment for persistent air leak in the pneumothorax complicated from the severe chronic lung disease.

• Sleep Medicine and Psychophysiology
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• v.5 no.1
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• pp.54-70
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• 1998

Objectives : The purpose of this study is to evaluate the role of structural and functional changes of the brain in the pathophysiology of schizophrenia. Methods : The authors measured the regions of interest on the magnetic resonance imaging of the brain in 20 patients with paranoid schizophrenia(15 men and 5 women) and 23 control subjects(15 men and 8 women). We also assessed the neurocognitive functions with the Wisconsin Card Sorting Test, the Benton Neuropsychological Assessment, and the Weschler IQ test-Korean version, soft neurologic signs, and psychiatric symptoms in the patient group. Results : In the patient group, all ventricles and basal ganglia including caudate nucleus and globus pallidus were significantly enlarged. Although there were no significant differences between the two groups in the values of right frontal lobe and left temporal lobe, there was a tendency of decrease in the values of right frontal lobe and left temporal lobe. There were significant positive correlations between the values of ventricles and the frequency of previous hospitalization. However, there were no significant correlations between other values of regions of interest and clinical data. The value of the right frontal lobe was significantly correlated with the score of soft neurologic signs, which is suggestive of the neurodevelopmental abnormalities. There were significant correlations between the value of frontal lobe and the scores of the various subscales of Benton Neuropsychiatric Inventory. In contrast, the value of left amygdala and putamen showed significant correlation with the score of verbal IQ on the Weschler IQ test. Structural changes of the temporal lobe areas were related with the positive and general symptom scores on PANSS, while those of the basal ganglia were related with the negative symptom scores. Conclusions : These results suggest that the structural changes of the brain in the patients with schizophrenia show the dual process, which is suggestive that the enlarged ventricle show the neurodegenerative process, while enlarged basal ganglia, and shrinked right frontal and left temporal lobe show the neurodevelopmental abnormalities. Among these changes, structural changes of the frontal lobe related with various neuropsychological deficits, while those of left temporal lobe related with language abnormality. Relative to the relation between structural changes and psychiatric symptoms, structural changes of the temporal lobe areas were related with the positive and general symptoms, while those of the basal ganglia were related with the negative symptoms.

• Tuberculosis and Respiratory Diseases
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• v.58 no.6
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• pp.562-569
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• 2005

Background : The severity scoring system is useful for predicting the outcome of critically ill patients. However, the system is quite complicated and cost-ineffective. Simple serologic markers have been proposed to predict the outcome, which include troponin-I, lactate and C-reactive protein(CRP). The aim of this study was to evaluate the prognostic values of troponin-I, lactate and CRP in critically ill non-cardiac patients. Methods : From September 2003 to June 2004, 139 patients(Age: $63.3{\pm}14.7$, M:F = 88:51), who were admitted to the MICU with non-cardiac critical illness at Gyeongsang National University Hospital, were enrolled in this study. This study evaluated the severity of the illness and the multi-organ failure score (Acute Physiologic and Chronic Health EvaluationII, Simplified Acute Physiologic ScoreII and Sequential Organ Failure Assessment) and measured the troponin-I, lactate and CRP within 24 hours after admission in the MICU. Each value in the survivors and non-survivors was compared at the 10th and 30th day after ICU admission. The mortality rate was compared at 10th and 30th day in normal and abnormal group. In addition, the correlations between each value and the severity score were assessed. Results : There were significantly higher troponin-I and CRP levels, not lactate, in the non-survivors than in the survivors at 10th day($1.018{\pm}2.58ng/ml$, $98.48{\pm}69.24mg/L$ vs. $4.208{\pm}10.23ng/ml$, $137.69{\pm}70.18mg/L$) (p<0.05). There were significantly higher troponin-I, lactate and CRP levels in the non-survivors than in the survivors on the 30th day ($0.99{\pm}2.66ng/ml$, $8.02{\pm}9.54ng/dl$, $96.87{\pm}68.83mg/L$ vs. $3.36{\pm}8.74ng/ml$, $15.42{\pm}20.57ng/dl$, $131.28{\pm}71.23mg/L$) (p<0.05). The mortality rate was significantly higher in the abnormal group of troponin-I, lactate and CRP than in the normal group of troponin-I, lactate and CRP at 10th day(28.1%, 31.6%, 18.9% vs. 11.0%, 15.8 %, 0%) and 30th day(38.6%, 47.4%, 25.8% vs. 15.9%, 21.7%, 14.3%) (p<0.05). Troponin-I and lactate were significantly correlated with the SAPS II score($r^2=0.254$, 0.365, p<0.05). Conclusion : Measuring the troponin-I, lactate and CRP levels upon admission may be useful for predicting the outcome of critically ill non-cardiac patients.