• Journal of Chest Surgery
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• v.13 no.2
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• pp.85-91
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• 1980

Extracorporeal circulation by hemodilution technique has been currently used with its clinical safety and good peripheral tissue perfusion in open heart surgery. There is no doubt that $O_{2}$ carrying capacity of the blood is disturbed by decreased hemoglobin level resulting from hemodilution of the circulating blood. From the view point of the blood gas exchange, these experimental studies were undertaken to determined the sate limit of hemodilution in the condition of cardiopulmonary bypass with a constant perfusion flow rate. Twelve adult mongrel dogs weighing 10 to 13 Kg. were anesthetized with pentobarbital and then respiration was controlled with Harvard volume respirator using room air. The cardiopulmonary by pass was performed by use of Sarns heart lung machine (console 5000, 5 head and 2 roller pumps) and Travenol pediatric bubble oxygenator. The perfusion rate during bypass was maintained at a constant rate of 80 ml/min/Kg of body weight. The ratio of oxygen gas flow to blood flow was kept in 3 to 1 constantly. International hemodilution was attained by serial blood withdrawals and immediate infusion of equal volumes of diluants composed of Ringer's lactate, 5% dextrose in water and 25% mannitol solution, proportionally 60%, 30%, and 10%. Arterial and venous blood samples were obtained between 15 and 20 minutes following each hemodilution. Hematocrits and hemoglobin values, $PO_{2}$, $PCO_{2}$ and pH were measured. Oxygen and carbon dioxide contents oxygen consumption and carbon dioxide elimination were calculated groups according to different hematocrit values and the correlations were evaluated. Result were as follows. 1. the arterial $O_{2}$ tension and $O_{2}$ saturation were maintained at the physiological level irrespective of the hematocrit value. 2. The venous $O_{2}$ tension and $O_{2}$ saturation showed a tendency to decline with the decrease in hematocrit value and positive correlation between them (r = +0.49, r = +0.76), The mean values of venous $O_{2}$ tension and $O_{2}$ saturation, however, were not decreased when the hematocrit levels were lower than 20%. 3. The arterial $O_{2}$ content declined lineally in proportion to the fall of hematocrit level with a positive correlation between them (r = +0.95). 4. The venous $O_{2}$ contents were decreased gradually as the hematocrit value decreased with positive correlation between them ( r =+0.89). The trend of diminution of venous $O_{2}$ content, however, was became low according to progressive decrease of hematocrit level. 5. Systemic oxygen consumption was in higher range than $O_{2}$ requirement of basal metabolism when the hematocrit value was above 20%, but abruptly decreased when the hematocrit value became to below 20%. 6. The arterial $CO_{2}$ tension and $CO_{2}$ content showed trend of increasing with progressive decrease of hematocrit value but exhibited a rather broad range and there was no relationship between those value and the hematocrit value. 7. The venous $CO_{2}$ tension and $CO_{2}$ content have also no correlation with change of Ht. value but related directly to those value of arterial blood with positive correlation between them (r = +0.78, r = +0.95_. 8. A-V difference of $CO_{2}$ content and $CO_{2}$ elimination wasnot significantly influenced by Ht. value. From the results, we obtained that feasible limit in inteneional hemodilution is above the hematocrit value of 20% under the given experimental condition.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.5
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• pp.362-368
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• 2008

Purpose: It is well known that lung to heart ratio (LHR) is one of the high risk findings in TI- 201 myocardial perfusion SPECT. We evaluated the clinical efficacy of LHR to identify severe coronary artery disease in adenosine stress Tc-99m tetrofosmin gated myocardial perfusion SPECT (gSPECT). Materials and Methods: The study population was 157 patients who underwent both adenosine stress Tc-99m gSPECT and coronary angiography (CAG) within one month. According to the results of CAG and gSPECT LHR and the incidence of increased LHR were compared. Results: Among 53 patients with normal coronary arteries increased LHR was found in 2 patients (3.8%) and 0 in 44 patients (0%) with one vessel disease, 2 in 27 with two vessel disease (7.4%) and 8 in 33 with triple vessel disease (24.2%). Significant differences were found in LHR between subgroups of summed stress score, summed rest score and LV ejection fraction (LVEF). There were weak negative correlation between LHR and LVEF and weak positive correlation between LHR and SSS and SRS. Conclusion: Increased LHR had higher incidence in patients with triple vessel disease, severe LV dysfunction and/or extensive perfusion defect than those of normal group. Although its sensitivity might be low to identify severe coronary artery disease, LHR could be helpful in abnormal myocardial perfusion SPECT to stratify risk and prognosis.

• Biotechnology and Bioprocess Engineering:BBE
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• v.7 no.3
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• pp.163-170
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• 2002

This report describes the use of a transtubular bioreactor to study the relative effects of diffusion versus perfusion of medium on antibody production by a hybridoma cell line. The study was performed with a high-density cell culture maintained in a serum-free, low-protein medium for 77 days. It was determined that the reactor possessed a macro-mixing pattern residence time distribution similar to a continuous stirred tank reactor (CSTR), However, due to the arrangement of the medium lines in the reactor, the flow patterns for nutrient distribution consist of largely independent medium path lengths ranging from short to long. When operated with cyclic, reversing, transtubular medium flow, some regions of the reactor (with short residence times) are more accessible to medium than others (with long residence times). From this standpoint, the reactor can be divided into three regions: a captive volume, which consists of medium primarily delivered via diffusion; a lapped volume, which provides nutrients through unilateral convection; and a swept volume, which operates through bilateral convection. The relative sizes of these three volumes were modified experimentally by changing the period over which the direction of medium flow was reversed from 15 min (larger captive volume) to 9 h (larger swept volume). The results suggest that antibody concentration increases as the size of the diffusion-limited (captive) volume is increased to a maximum at around 30 min with a sharp decrease thereafter. As reflected by changes in measured consumption of glucose and production of lactate, no significant difference in cellular metabolism occurred as the reactor was moved between these different states. These results indicate that the mode of operation of the transtubular bioreactor may influence antibody productivity under serum-free, low-protein conditions with minimal effects on cellular metabolism.

• KSBB Journal
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• v.30 no.3
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• pp.103-108
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• 2015

Production of foreign proteins by transgenic plant cell cultures has several advantages such as post-translational modification, low risk of product contamination and low-cost production and purification. However, target proteins are degraded by extracellular proteases existing in the media. A solution to this problem is the use of perfusion culture and ion exchange chromatography for the application of integrated bioprocess using in situ recovery. With this method, production of human granulocyte-macrophage colony-stimulating factor (hGM-CSF) was investigated in this study. First, optimization of cell concentration during the induction phase for the production of hGM-CSF was examined. As cell concentration increased, the level of hGM-CSF was decreased due to the presence of extracellular proteases. Induction using sugarfree media produced 33% more hGM-CSF. The effects of pH on the binding of hGM-CSF to cationic and anionic exchange resins were also investigated. In terms of stability, optimal pH was found to be 5~7. In the case of using buffer exchange when CM-Sepharose was used as a cationic exchange resin, optimal pH for binding was 4.8 and adsorption yield was 77%. When DEAE-Sepharose was used as an anionic exchange resin, it was 5.5 (74%). Without buffer exchange, optimal pH was 4.6 (84%). From these results, an integrated bioprocess using in situ recovery with simultaneous production and separation of foreign protein in transgenic plant cell suspension cultures was found to be feasible.

• The Korean Journal of Nuclear Medicine
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• v.39 no.6
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• pp.430-437
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• 2005

Purpose: The objectives of this study were - First, to determine the normal range of left ventricular end diastolic volume (EDV), end systolic volume (ESV) and election fraction (EF) from gated myocardial perfusion SPECT for Quantitative Gated SPECT (QGS) and 4D-MSPECT (4DM), respectively. Second, to evaluate the relationships between values produced by both software packages. Materials & Methods: Tc-99m MIBI gated myocardial perfusion SPECT were performed for 77 patients (mean age: $49.6{\pm}13.7y$, n=37(M), 40(F)) with a low likelihood (<10%) of coronary artery disease (CAD) using dual head gamma camera (E.CAM, Siemens, USA). Left ventricular EDV, ESV and EF were automatically measured by means of QGS and 4DM, respectively. Results: in QGS, the mean EDV, ESV and EF for all patients were $78.2{\pm}25.2ml,\;27.4{\pm}12.9ml\;and\;66.6{\pm}8.0%$ at stress test respectively, not different from rest test (p>0.05). In 4DM, the mean EDV, ESV and EF for all patients were $89.1{\pm}26.4ml,\;29.1{\pm}12.8ml\;and\;68.5{\pm}6.7%$ at stress test. Most cases in 4DM, there was no significant difference statistically between stress and rest test (p>0.05). But statistically significant difference was found in EF ($68.5{\pm}6.7%$ at stress vs $70.9{\pm}8.0%$ at rest, p<0.05). Correlation coefficients between the methods for EDV, ESV and EF were comparatively high (0.95, 0.93, 0.71 at stress test and 0.95, 0.90, 0.69 at rest test, respectively). However, Bland-Altman plots showed a large range of the limit value of agreement for EDV, ESV and EF between both methods ($-30ml{\sim}10ml,\;-12ml{\sim}8ml,\;-14%{\sim}11%$ at stress test and $-32ml{\sim}5ml,\;-13ml{\sim}13ml,\;-18%{\sim}12%$ at rest test). Conclusion: We found the normal ranges of EDV, ESV and EF for patients with a low likelihood of CAD in both methods. We expect these values will be a good reference to interpret gated myocardial perfusion SPECT. Although good correlation was observed between both methods, they should not be used interchangeably. Therefore, when both programs are used at the same site, it will be important to apply normal limits specific to each method.

• Journal of radiological science and technology
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• v.32 no.4
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• pp.461-469
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• 2009

To predict the tumor grading, various imaging modalities have been applied clinically. This study determines clinical usefulness of perfusion MRI, using relative cerebral blood volume in grading of the gliomas. We did a retrospective review of 17 patients (mean age, 57.5 years; 11 male, 6 female) who underwent perfusion MR and conventional MRI, and then correlated pathologically after operation. Statistical analysis of regional cerebral blood volume and relative cerebral blood volume(rCBV) was performed by using softwares such as PAT by SIEMENS and Xmap ver 2.0 developed by ourselves. Six patients out of 13 were low-grade gliomas while eleven patients were the high-grade gliomas. Mean relative CBV (m_rCBV/white matter) in the low-grade gliomas was 1.62, and mean relative CBV(m_rCBV/cortex) was 0.12. In the high-grade gliomas, mean relative CBV(m_rCBV/white matter) and mean relative CBV(m_rCBV/cortex) were 33.53 and 0.96. Mean relative CBV of gliomas were elevated with a statistical difference(P<.05), compared with contralateral white matter(P=.019) or cortex(P=.025). Furthermore mean relative CBV(m_rCBV/white matter) was much higher than mean relative CBV(m_rCBV/cortex). Perfusion MRI using regional cerebral blood volume and rCBV is very useful imaging modality for grading the glioma.

• The Korean Journal of Nuclear Medicine
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• v.39 no.2
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• pp.141-145
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• 2005

Hypoxia (decreased tissue oxygen tension) is a component of many diseases such as tumors, cerebrovascular diseases and ischemic heart diseases. Although hypoxia can be secondary to a low inspired $pO_2$ or a variety of lung disorders, the most common cause is ischemia due to an oxygen demand greater than the local oxygen supply. In the heart tissue, hypoxia is often observed in persistent low-flow states, such as hibernating myocardium. Direct "hot spot" imaging of myocardial tissue hypoxia is potentially of great clinical importance because it may provide a means of identifying dysfunctional chronically ischemic but viable hibernating myocardium. A series of radiopharmaceuticals that incorporate nitroimidazole moieties have been synthesized to detect decreased local tissue pO2. In contrast to agents that localize in proportion to perfusion, these agents concentrate in hypoxic tissue. However, the ideal agents are not developed yet and the progress is very slow. Furthermore, the research focus is on tumor hypoxia nowadays. This review introduces the myocardial hypoxia imaging with summarizing the development of radiopharmaceuticals.

• The Korean Journal of Nuclear Medicine
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• v.34 no.3
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• pp.199-206
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• 2000

Purpose: Myocardial perfusion scintigraphy is a useful technique to diagnose and to predict prognosis in patients with suspected or known coronary artery disease. The purpose of the present study is to evaluate the prognostic value of normal exercise $^{99m}Tc$-MIBI myocardial perfusion single photon emission computed tomography (SPECT) and to analyze results with regard to those of exercise electrocardiography or coronary angiography. Materials and Methods: We evaluated 301 patients (mean age $52{\pm}10$ years, 166 males and 135 females) with normal exercise $^{99m}Tc$-MIBI myocardial perfusion SPECT performed for suspected coronary artery disease. Subject were evaluated for cardiac events and followed for 8-55 months (mean $19{\pm}10$ months) after imaging. Results: During the follow-up period, there was no cardiac death but only one non-fatal myocardial infarction (event rate 0.21% per year). In addition, only one patient underwent coronary revascularization. There was no significant difference in cardiac event rate between patients with positive (n=27) and negative (n=235) exercise electrocardiography (p:NS). There was no cardiac event in 17 patients who underwent coronary angiography (4 patients with >50% luminal narrowing, 2 patients with vasospasm and 11 patients with no significant lesion). Conclusion: Patients with normal exercise $^{99m}Tc$-MIBI myocardial perfusion SPECT has a very low risk for cardiac events regardless of exercise electrocardiographic and coronary angiographic findings.

• The Korean Journal of Nuclear Medicine
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• v.32 no.3
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• pp.259-265
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• 1998

Purpose: We studied early rest/24 hour delay T1-201 perfusion SPECT for prediction of wall motion improvement after reperfusion in patients with acute myocardial infarction. Materials and Methods: Among 17 patients (male/female= 11/6, age: $59{\pm}13$) with acute myocardial infarction, 15 patients were treated with percutaneous transcoronary angioplasty (direct:2, delay: 11) and intravenous urokinase (2). Spontaneous resolution occurred in infarct-related arteries of 2 patients. We confirmed TIMI 3 flow of infarct-related artery after reperfusion in all patients with coronary angiography. We performed rest T1-201 perfusion SPECT less then 6 hours after reperfusion and delay T1-201 perfusion SPECT next day. T1-201 uptake was visually graded as 4 point score from normal (0) to severe defect (3). Rest T1-201 uptake ${\le}2$ or combination of rest T1-201 uptake ${\le}2$ or late reversibility were considered to be viable. Myocardial wall motion was graded as 5 point score from normal (1) to dyskinesia (5). Myocardial wall motion was considered to be improved when a segment showed an improvement ${\ge} 1$ grade in follow up echo compared with the baseline values. Results: Among 98 segments with wall motion abnormality, the severity of myocardial wall motion decrease was as follow: mild hypokinesia: 18/98 (18%), severe hypokinesia: 28/98 (29%), akinesia: 51/98 (52%), dyskinesia: 1/98 (1%). The wall motion improved in 85%. Redistribution (13%), and reverse redistribution (4%) were observed in 24 hour delay SPECT. Positive predictive value (PPV) and negative predictive value (NPV) of combination of late reversibility and rest T1-201 uptake were 99%, and 54%. PPV and NPV of rest T1-201 uptake were 100% and 52% respectively. Predictive values of combination of rest T1-201 uptake and late reversibility were not significantly different compared with predictive values of rest T1-201 uptake only. Conclusion: We conclude that early T1-201 perfusion SPECT predict myocardial wall motion improvement with excellent positive but relatively low negative predictive values in patients with acute myocardial infarction after reperfusion.

• Journal of Chest Surgery
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• v.23 no.6
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• pp.1049-1056
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• 1990

The OXYREX hollow fiber membrane oxygenator developed by joint work of KIST and Green Cross Medical company has been evaluated by experimental investigation and clinical application, In this oxygenator gas exchanges occur through small pores of 0.1pm size which are distributed on 70% of surface of polypropylene hollow fiber. The Oxyrex membrane oxygenator consists of 36 thousand hollow fibers and it has 3.3m2 of gas exchange surface. The Oxyrex membrane oxygenator has unique blood flow path: blood enters the oxygenator passes between the hollow fibers and exits through outlet ports, that provides low transmembrane pressure drop. In the animal experiment and in vitro investigations of Oxyrex oxygenator, it showed low transmembrane pressure difference, effective heat exchanger performance, stable gas transfer function and less blood trauma. The Oxyrex oxygenator been used from March, 1990, to October, 1990, in 40 patients undergoing open heart operations. In the clinical applications of Oxyrex, adequate oxygenation[PaO2, 283$\pm$70mmHg] and carbon dioxide removal[PaCO2, 27\ulcorner6mmHg]were maintained under the condition of FiO2: below 0.6, Hct; 25%, perfusion flow; 2.4 L/min, gas flow: 2.1 L/min. During maximum 365 minutes of cardiopulmonary bypass[CPB] time period, the Oxyrex oxygenator maintained stable condition of PaO2, PaCO2 respectively and it also kept low plasma hemoglobin level. The complement proteins C3 and CH50 were not significantly changed pre to post CPB. There were no complications related to the oxygenator during and after the CPB.