• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.215-228
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• 1999

Background: Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology often involving the lungs and intrathoracic lymph nodes. The natural course of sarcoidosis is variable from spontaneous remission to significant morbidity or death. But, the mechanisms causing the variable clinical outcomes or any single parameter to predict the prognosis was not known. In sarcoidosis, the number and the activity of CD4 + lymphocytes are significantly increased at the loci of disease and their oligoclonality suggests that the CD4 + lymphocytes hyperreactivity may be caused by persistent antigenic stimulus. Recently, it has been known that CD4+ lymphocytes can be subdivided into 2 distinct population(Th1 and Th2) defined by the spectrum of cytokines produced by these cells. Th1 cells promote cellular immunity associated with delayed type hypersensitivity reactions by generating IL-2 and IFN-$\gamma$. Th2 cells playa role in allergic responses and immediate hypersensitivity reactions by secreting IL-4, IL-5, and IL-10. CD4+ lymphocytes in pulmonary sarcoidosis were reported to be mainly Th1 cells. IL-12 has been known to play an important role in differentiation of undifferentiated naive T cells to Th1 cells. And, Moller et al. observed increased IL-12 in bronchoalveolar lavage fluid(BALF) in patients with sarcoidosis. So it is possible that the elevated level of IL-12 is necessary for the continuous progression of the disease in active sarcoidosis. This study was performed to test the assumption that IL-12 can be a marker of active pulmonary sarcoidosis. Methods: We measured the concentration of IL-12 in BALF and in conditioned medium of alveolar macrophage(AM) using ELISA(enzyme-linked immunosorbent assay) method in 26 patients with pulmonary sarcoidosis(10 males, 16 females, mean age: $39.8{\pm}2.1$ years) and 11 normal control. Clinically, 14 patients had active sarcoidosis and 12 patients had inactive. Results: Total cells counts, percentage and number of lymhocytes, number of AM and CD4/CD8 lymphocyte ratio in BALF were significantly higher in patients with sarcoidosis than in control group. But none of these parameters could differentiate active sarcoidosis from inactive disease. The concentration of IL-12 in BALF was significantly increased in sarcoidosis patients ($49.3{\pm}9.2$ pg/ml) than in normal control ($2.5{\pm}0.4$ pg/ml) (p<0.001). Moreover it was significantly higher in patients with active sarcoidosis ($70.3{\pm}14.8$ pg/ml) than in inactive disease ($24.8{\pm}3.l$ pg/ml) (p=0.001). Also, the concentration of IL-12 in BALF showed significant correlation with the percentage of AM(p<0.001), percentage(p<0.001) and number of lymphocyte(p<0.001) in BALF, suggesting the close relationship between the level of IL-12 in BALF and the inflammatory cell infiltration in the lungs. Furthermore, we found a significant correlation between the level of IL-12 and the concentration of soluble ICAM-1 : in serum(p<0.001) and BALF (p=0.001), and also between IL-12 level and ICAM-1 expression of AM(p<0.001). The AM from patients with pulmonary sarcoidosis secreted significantly larger amount of IL-12 ($206.2{\pm}61.9$ pg/ml) than those of control ($68.3{\pm}43.7$ pg/ml) (p<0.008), but, there was no difference between inactive and active disease group. Conclusion : Our data suggest that the BALF IL-12 level can be used as a marker of the activity of pulmonary sarcoidosis.

• Journal of Radiation Protection and Research
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• v.32 no.3
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• pp.105-110
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• 2007

Purpose : In spite of recent remarkable improvement of diagnostic imaging modalities such as CT, MRI, and PET and radiation therapy planing systems, ICR plan of uterine cervix cancer, based on recommendation of ICRU38(2D film-based) such as Point A, is still used widely. A 3-dimensional ICR plan based on CT image provides dose-volume histogram(DVH) information of the tumor and normal tissue. In this study, we compared tumor-dose, rectal-dose and bladder-dose through an analysis of DVH between CTV plan and ICRU38 plan based on CT image. Method and Material : We analyzed 11 patients with a cervix cancer who received the ICR of Ir-192 HDR. After 40Gy of external beam radiation therapy, ICR plan was established using PLATO(Nucletron) v.14.2 planing system. CT scan was done to all the patients using CT-simulator(Ultra Z, Philips). We contoured CTV, rectum and bladder on the CT image and established CTV plan which delivers the 100% dose to CTV and ICRU plan which delivers the 100% dose to the point A. Result : The volume$(average{\pm}SD)$ of CTV, rectum and bladder in all of 11 patients is $21.8{\pm}6.6cm^3,\;60.9{\pm}25.0cm^3,\;111.6{\pm}40.1cm^3$ respectively. The volume covered by 100% isodose curve is $126.7{\pm}18.9cm^3$ in ICRU plan and $98.2{\pm}74.5cm^3$ in CTV plan(p=0.0001), respectively. In (On) ICRU planning, $22.0cm^3$ of CTV volume was not covered by 100% isodose curve in one patient whose residual tumor size is greater than 4cm, while more than 100% dose was irradiated unnecessarily to the normal organ of $62.2{\pm}4.8cm^3$ other than the tumor in the remaining 10 patients with a residual tumor less than 4cm in size. Bladder dose recommended by ICRU 38 was $90.1{\pm}21.3%$ and $68.7{\pm}26.6%$ in ICRU plan and in CTV plan respectively(p=0.001) while rectal dose recommended by ICRU 38 was $86.4{\pm}18.3%$ and $76.9{\pm}15.6%$ in ICRU plan and in CTV plan, respectively(p=0.08). Bladder and rectum maximum dose was $137.2{\pm}50.1%,\;101.1{\pm}41.8%$ in ICRU plan and $107.6{\pm}47.9%,\;86.9{\pm}30.8%$ in CTV plan, respectively. Therefore, the radiation dose to normal organ was lower in CTV plan than in ICRU plan. But the normal tissue dose was remarkably higher than a recommended dose in CTV plan in one patient whose residual tumor size was greater than 4cm. The volume of rectum receiving more than 80% isodose (V80rec) was $1.8{\pm}2.4cm^3$ in ICRU plan and $0.7{\pm}1.0cm^3$ in CTV plan(p=0.02). The volume of bladder receiving more than 80% isodose(V80bla) was $12.2{\pm}8.9cm^3$ in ICRU plan and $3.5{\pm}4.1cm^3$ in CTV plan(p=0.005). According to these parameters, CTV plan could also save more normal tissue compared to ICRU38 plan. Conclusion : An unnecessary excessive radiation dose is irradiated to normal tissues within 100% isodose area in the traditional ICRU plan in case of a small size of cervix cancer, but if we use CTV plan based on CT image, the normal tissue dose could be reduced remarkably without a compromise of tumor dose. However, in a large tumor case, we need more research on an effective 3D-planing to reduce the normal tissue dose.

• Journal of Internet Computing and Services
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• v.14 no.5
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• pp.69-76
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• 2013

The incidence of globally infectious and pathogenic diseases such as H1N1 (swine flu) and Avian Influenza (AI) has recently increased. An infectious disease is a pathogen-caused disease, which can be passed from the infected person to the susceptible host. Pathogens of infectious diseases, which are bacillus, spirochaeta, rickettsia, virus, fungus, and parasite, etc., cause various symptoms such as respiratory disease, gastrointestinal disease, liver disease, and acute febrile illness. They can be spread through various means such as food, water, insect, breathing and contact with other persons. Recently, most countries around the world use a mathematical model to predict and prepare for the spread of infectious diseases. In a modern society, however, infectious diseases are spread in a fast and complicated manner because of rapid development of transportation (both ground and underground). Therefore, we do not have enough time to predict the fast spreading and complicated infectious diseases. Therefore, new system, which can prevent the spread of infectious diseases by predicting its pathway, needs to be developed. In this study, to solve this kind of problem, an integrated monitoring system, which can track and predict the pathway of infectious diseases for its realtime monitoring and control, is developed. This system is implemented based on the conventional mathematical model called by 'Susceptible-Infectious-Recovered (SIR) Model.' The proposed model has characteristics that both inter- and intra-city modes of transportation to express interpersonal contact (i.e., migration flow) are considered. They include the means of transportation such as bus, train, car and airplane. Also, modified real data according to the geographical characteristics of Korea are employed to reflect realistic circumstances of possible disease spreading in Korea. We can predict where and when vaccination needs to be performed by parameters control in this model. The simulation includes several assumptions and scenarios. Using the data of Statistics Korea, five major cities, which are assumed to have the most population migration have been chosen; Seoul, Incheon (Incheon International Airport), Gangneung, Pyeongchang and Wonju. It was assumed that the cities were connected in one network, and infectious disease was spread through denoted transportation methods only. In terms of traffic volume, daily traffic volume was obtained from Korean Statistical Information Service (KOSIS). In addition, the population of each city was acquired from Statistics Korea. Moreover, data on H1N1 (swine flu) were provided by Korea Centers for Disease Control and Prevention, and air transport statistics were obtained from Aeronautical Information Portal System. As mentioned above, daily traffic volume, population statistics, H1N1 (swine flu) and air transport statistics data have been adjusted in consideration of the current conditions in Korea and several realistic assumptions and scenarios. Three scenarios (occurrence of H1N1 in Incheon International Airport, not-vaccinated in all cities and vaccinated in Seoul and Pyeongchang respectively) were simulated, and the number of days taken for the number of the infected to reach its peak and proportion of Infectious (I) were compared. According to the simulation, the number of days was the fastest in Seoul with 37 days and the slowest in Pyeongchang with 43 days when vaccination was not considered. In terms of the proportion of I, Seoul was the highest while Pyeongchang was the lowest. When they were vaccinated in Seoul, the number of days taken for the number of the infected to reach at its peak was the fastest in Seoul with 37 days and the slowest in Pyeongchang with 43 days. In terms of the proportion of I, Gangneung was the highest while Pyeongchang was the lowest. When they were vaccinated in Pyeongchang, the number of days was the fastest in Seoul with 37 days and the slowest in Pyeongchang with 43 days. In terms of the proportion of I, Gangneung was the highest while Pyeongchang was the lowest. Based on the results above, it has been confirmed that H1N1, upon the first occurrence, is proportionally spread by the traffic volume in each city. Because the infection pathway is different by the traffic volume in each city, therefore, it is possible to come up with a preventive measurement against infectious disease by tracking and predicting its pathway through the analysis of traffic volume.

• Tuberculosis and Respiratory Diseases
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• v.43 no.3
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• pp.308-322
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• 1996

Background : Neutrophils are considered to play critical roles in the development of acute respiratory distress syndrome. Histamine, which is distributed abundantly in lung tissue, increases the rolling of neutrophills via increase of P-selectin expression on the surface of endothelial cells and is known to have some interrelationships with IL-1, IL-8 and TNF-$\alpha$. We studied to investigate the effect of the histamine on the acute lung injury of the rats induced by intratracheal insufflation of TNF-$\alpha$ which has less potency to cause lung injury compared to IL-1 in rats. Methods : We intratracheally instilled saline or TNF(R&D, 500ng), IL-1(R&D, 50ng)or histamine of varius dose(1.1, 11 and $55\;{\mu}g/kg$) with and without TNF separately in Sprague-Dawley rats weighing 270-370 grams. We also intratracheally treated IL-1(50ng) along with histamine($55\;{\mu}g/kg$). In cases, there were synergistic effects induced by histamine on the parameters of TNF-induced acute lung injury, antihistamines(Sigma, mepyramine as a $H_1$ receptor blockade and ranitidine as a $H_2$ receptor blockade, 10 mg/kg in each)were co-administered intravenously to the rats treated TNF along with histamine($1.1\;{\mu}g/kg$) intratraeheally. Then after 5 h we measured lung lavage neutrophil numbers, lavage cytokine-induced neutrophil chemoattractants(CINC), lung myeloperoxidase activity(MPO) and lung leak. We also intratracheally insufflated TNF with/without histamine($11\;{\mu}g/kg$), then after 24 h measured lung leak in rats. Statistical analyses were done by Kruskal-Wallis nonparametric ANOVA test with Dunn's multiple comparison test or by Mann-Whitney U test. Results : We found that rats given TNF, histamine alone(11 and $55\;{\mu}g/kg$), and TNF with histamine(l.1, 11, and $55\;{\mu}g/kg$) intratracheally had increased (p<0.05) lung MPO activity compared with saline-treated control rats. TNF with histamine $11\;{\mu}g/kg$ had increased MPO activity (P=0.0251) compared with TNF-treated rats. TNF and TNF with histamine(1.1, 11, and $55\;{\mu}g/kg$) intratracheally had all increased (p<0.05) lung leak, lavage neutophil numbers and lavage CINC activities compared with saline. TNF with histamine $1.1\;{\mu}g/kg$ had increased (p=0.0367) lavage neutrophil numbers compared with TNF treated rats. But there were no additive effect of histamine with TNF compared with TNF alone in acute lung leak on 5 h and 24 h in rats. Treatment of rats with the $H_1$ and $H_2$ antagonists resulted in inhibitions of lavage neutrophil accumulations and lavage CINC activity elevations elicited by co-treated histamine in TNF-induced acute lung injury intratracheally in rats. We also found that rats given IL-1 along with histamine intratracheally did not have increase in lung leak compared with IL-1 treated rats. Conclusion : Histamine administered intratracheally did not have synergistic effects on TNF-induced acute lung leak inspite of additive effects on increase in MPO activity and lavage neutrophil numbers in rats. These observations suggest that instilling histamine intratracheally would not play synergistic roles in neutrophil-mediated acute lung injury in rats.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.479-492
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• 1997

Background : Isoniazid(INH) and rifampicin(RFP) are potent antituberculous drugs which have made tuberculous disease become decreasing. In Korea, prescribed doses of INH and RFP have been different from those recommended by American Thoracic Society. In fact they were determined by clinical experience rather than by scientific basis. Even there has been. few reports about pharmacokintic parameters of INH and RFP in healthy Koreans. Method : Oral pharmacokinetics of INH were studied in 22 healthy native Koreans after administration of 300 mg and 400mg of INH to each same person successively at least 2 weeks apart. After an overnight fast, subjects received medication and blood samples were drawn at scheduled times over a 24-hour period. Urine collection was also done for 24 hours. Pharmacokinetics of RFP were studied in 20 subjects in a same fashion with 450mg and 600mg of RFP. Plasma and urinary concentrations of INH and RFP were determined by high-performance liquid chromatography(HPLC). Results : Time to reach peak serum concentration (Tmax) of INH was $1.05{\pm}0.34\;hrs$ at 300mg dose and $0.98{\pm}0.59\;hrs$ at 400mg dose. Half-life was $2.49{\pm}0.88\;hrs$ and $2.80{\pm}0.75\;hrs$, respectively. They were not different significantly(p > 0.05). Peak serum concentration(Cmax) after administration of 400mg of INH was $7.14{\pm}1.95mcg/mL$ which was significantly higher than Cmax ($4.37{\pm}1.28mcg/mL$) by 300mg of INH(p < 0.01). Total clearance(CLtot) of INH at 300mg dose was $26.76{\pm}11.80mL/hr$. At 400mg dose it was $21.09{\pm}8.31mL/hr$ which was significantly lower(p < 0.01) than by 300mg dose. While renal clearance(CLr) was not different among two groups, nonrenal clearance(CLnr) at 400mg dose ($18.18{\pm}8.36mL/hr$) was significantly lower than CLnr ($23.71{\pm}11.52mL/hr$) by 300mg dose(p < 0.01). Tmax of RFP was $1.11{\pm}0.41\;hrs$ at 450mg dose and $1.15{\pm}0.43\;hrs$ at 600mg dose. Half-life was $4.20{\pm}0.73\;hrs$ and $4.95{\pm}2.25\;hrs$, respectively. They were not different significantly(p > 0.05). Cmax after administration of 600mg of RFP was $13.61{\pm}3.43mcg/mL$ which was significantly higher than Cmax($10.12{\pm}2.25mcg/mL$) by 450mg of RFP(p < 0.01). CLtot of RFP at 450mg dose was $7.60{\pm}1.34mL/hr$. At 600mg dose it was $7.05{\pm}1.20mL/hr$ which was significantly lower(p < 0.05) than by 450mg dose. While CLr was not different among two groups, CLnr at 600 mg dose($5.36{\pm}1.20mL/hr$) was significantly lower than CLnr($6.19{\pm}1.56mL/hr$) by 450mg dose(p < 0.01). Conclusion : Considering Cmax and CLnr, 300mg, of INH and 450mg RFP might be sufficient doses for the treatment of tuberculosis in Koreans. But it remains to be clarified in the patients with tuberculosis.