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The Current Status of Multidrug-resistant Tuberculosis in Korea (국내 다제내성 결핵의 실태)

  • Kim, Byoung-Ju;Lee, In-Hee;Lee, Duk-Hyung;Bai, Gill-Han;Kong, Suk-Jun;Lee, Sun-Hwa;Moon, Hae-Ran;Lee, Kyoung-Ryul;Lee, Jun-Young;Park, Seung-Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.4
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    • pp.404-411
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    • 2006
  • Purpose : Multidrug-resistant tuberculosis (MDR-TB) is an emerging threat to human beings. However, there is little data on the current status of MDR-TB in Korea. This study investigated the current status of MDR-TB in Korea using a survey of all the data from drug susceptibility tests (DST) performed across the country over the last three years. Method : The DST results between Jan. 2000 and Dec. 2002 from 7 laboratories, which were in charge of all antituberculous DSTs across the country as of March 2002, were collected and analyzed to determine the actual number of drug-resistant or MDR-TB patients, annual trend, degree and pattern of resistance against anti-TB drugs, etc. Results : Six laboratories used the absolute concentration method for DST and one used the proportional method. 59, 940 tests had been performed over the 3 year study period. The number of DST performed annually was 18,071, 19,950, and 21,919 in 2000-2002, respectively. The number of resistant tuberculosis patients (resistant against at least one anti-TB drug) had increased by 16.9% from 6,338 in 2000 to 7,409 in 2002. The rate of resistant tuberculosis among all DST results was 35.1% in 2000, 34.5% in 2001, and 33.8% in 2002. The number of MDR-TB patients (resistant against at least both isoniazid and rifampin) showed an increasing trend (14.5%) from 3,708 in 2000 to 4,245 in 2002. Conclusion : Approximately 4,000 MDR-TB cases are newly identified by DST annually and the number is showing an increasing trend. This study suggests that in order to cope with the current MDR-TB situation, the DST methods will need to be standardized and more aggressive measures will be required.

Clinical Evaluation of Surgical Resection on Pulmonary Tuberculosis -Multiple Drug Resistent Pulmonary Tuberculosis (폐결핵 환자에 적용된 폐절제술의 임상적 연구 -다제약제내성 결핵환자를 중심으로-)

  • 전희재;한동기
    • Journal of Chest Surgery
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    • v.30 no.8
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    • pp.786-792
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    • 1997
  • A clinical study of 71 cases of pulmonary tuberculosis that had had surgical resection during the period of 7 years and 6months from January 1989 to June 1996 in National Masan Tuberculosis Hospital. The results were as follows. 1. The ratio of male to female was 3.7:1 and in the age incidence the fourth decade was 22%, the third decade 15%. Although medical treatment was performed for more than 3 to 6 months, preoHeratively the conversion failure rate of positive sputum to negative state was 66.2%(47 cases). Of the failure cases, multiple-drug-resistant(MDR) patients were 41 cases(87.2%), 3. In MDR group, preoperatively conversion failure rate was 71.9%. 4. From the view of indica ion for lung resection on the radiographic finding, cavitary lesions were 43 cases(60.6%), destroyed lung lesions were 24 cases(33.8%). 5. The incidence of postoperative complication was 28.2%(20 cases). All cases were MDR 6. group and the most common of complication was tuberculosis spreading. In bilateral lesion, incidence of postoperative tuberculosis spreading was 25%(7 cases). Of the 7 cases, there was the cavitary lesion in 6 cases(86.7%). Total conversion rate of AFB positive sputum to negative state related to resectional sugery was 76.6% and in MDR group conversion rate of AFB positive sputum to negative state was 73.2% Conversion rate of MDR group with bilateral lesion was the lowest(60%). Conversion rate of drug-sensitivity group was 100% regardeless of lesions Slt to. In conclusion, despite of long-standing medical treatment, it is difficult to converse sputum-positive to negative state in multiple-drug resistance patients and that increases postoperative complications su h as tuberculosis relapse as a lack of appropriate drugs postoperatively. Postoperative conversion rate of sputum-positive to negative state was decreased in multiple-drug resistance patients. Because multiple-drug resistance patients have inireased due to several factors in Korea, it is important to prevent spreading of multiple-drug resistnce patients through the aggressive operative treatment. When the first medical therapy is fail or drug-resistance is found, operative treatment should be considered with the secondary medical therapy. The operation should be aggressively attempted even though at first medical treatment if indicated.

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Effect of hyperglycemia on mortality rates in critically ill children (소아 중환자에서 고혈당과 사망률과의 관계)

  • Kim, Seonguk;Kim, Bo Eun;Ha, Eun Ju;Moon, Mi Young;Park, Seong Jong
    • Clinical and Experimental Pediatrics
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    • v.53 no.3
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    • pp.323-328
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    • 2010
  • Purpose : To verify the effect of hyperglycemia on mortality rates in critically ill children and to identify the blood glucose level that influences prognosis. Methods : From July 2006 to June 2008, a total of 206 patients who were admitted to the pediatric intensive care unit (PICU) at Asan Medical Center and who survived for more than 7 days were retrospectively reviewed. We analyzed the maximum glucose value within 7 days in PICU, PRISM-III score and SOFA score within 24 hours, and mortality. We did not perform an adjustment analysis of drugs affecting glucose level. Results : The maximum glucose level within 7 days in PICU was higher in the nonsurvival group than in the survival group. Using 4 cutoff values (125, 150, 175, and 200 mg/dL), the mortality of patients with hyperglycemia was found to be 13.0 %, 14.4%, 19.8%, and 21.1%, respectively, and the cutoff values of 175 and 200 mg/dL revealed significant differences in mortalities between the hyperglycemic and normoglycemic groups. The PRISM-III score was not significantly different between the hyperglycemic and normoglycemic groups under a glucose cutoff value of 175 mg/dL, but the SOFA score was higher in the hyperglycemic group. Under a glucose cutoff value of 200 mg/dL, the PRISM-III score was higher in the hyperglycemic group, and the SOFA score did not differ between the 2 groups. Conclusion : Hyperglycemia with a maximal glucose value ${\geq}175\;mg/dL$ during the first 7 days after PICU admission was associated with increased mortality in critically ill children.

Enhancement of Sensitivity of Human Lung Cancer Cell Line to TRAIL and Gefitinib by IGF-1R Blockade (폐암세포주에서 IGF-1R 억제를 이용한 TRAIL 및 gefitinib에 대한 감수성 증가를 위한 연구)

  • Lee, Yoon-Jin;Park, Mi-Young;Kang, Young-Ae;Kwon, Sung-Youn;Yoon, Ho-Il;Lee, Jae-Ho;Lee, Choon-Taek
    • Tuberculosis and Respiratory Diseases
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    • v.63 no.1
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    • pp.42-51
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    • 2007
  • Background: TRAIL is a cytokine that selectively induces apoptosis in various cancer cell lines. Gefitinib is new targeted drug applied in lung cancer that selectively inhibits EGFR tyrosine kinase. However, lung cancers have shown an initial or acquired resistance to these drugs. This study examined the effect of IGF-1R and its blockade on enhancing the sensitivity of lung cancer cell lines to TRAIL and gefitinib. Methods: Two lung cancer cell lines were used in this study. NCI H460 is very sensitive to TRAIL and gefitinib. On the other hand, A549 shows moderate resistance to TRAIL and gefitinib. The IGF-1R blockade was performed using adenoviruses expressing the dominant negative IGF-1R and shRNA to IGF-1R and AG1024 (IGF-1R tyrosine kinase inhibitor). Results: The adenovirus expressing dominant negative IGF-1R(950st) induced the increased expression of defective IGF-1R on the lung cancer cell surface, and the adenovirus-shIGF-1R effectively decreased the level of IGF-1R expression on cell surface. The genetic blockade of IGF-1R by the adenovirus-dnIGF-1R and AG1024 increased the sensitivity of A549 cells to TRAIL. The reduction of IGF-1R by transduction with ad-shIGF-1R also increased the sensitivity of the A549 cells to gefitinib. Conclusion: The blockade of IGF-1R through various mechanisms increased the sensitivity of the lung cancer cell line that was resistant to TRAIL and gefitinib. However, further studies using other cell lines showing acquired resistance as well as in vivo animal experiments will be needed.

Study for the Synthesis of $[^{123}I]$Idoxifene and Its Uptake in the Breast Cancer Cell ($[^{123}I]$Idoxifene 합성과 유방암의 세포섭취에 관한 연구)

  • Cho, Young-Sub;Yang, Seung-Dae;Suh, Yong-Sup;Chun, Kwon-Soo;Ahn, Soon-Hyuk;Lim, Soo-Jung;Lim, Sang-Moo;Yu, Kook-Hyun
    • The Korean Journal of Nuclear Medicine
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    • v.34 no.5
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    • pp.410-417
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    • 2000
  • Purpose: Idoxifene is currently entering phase II clinical trials for the treatment of advanced breast cancer. The radiolabeled idoxifene using $[^{123}I]$ provides an opportunity for clinical pharmacology with single photon emission computed tomography (SPECT). The purpose of this study was to prepare radiolabeled idoxifene using $[^{123}I]$ and to determine its cell uptake of breast cancer cell line. Materials and Methods: With a view to evaluating new anticancer drugs, we are investigating the novel antiestrogen pyrrolidino-4-iodotamoxifen (idoxifene). $[^{123}I]$Idoxifene has been prepared in no-carrier-added form using a tributyl stannylated precursor which has been synthesized by means of (2-chloroethoxy)benzene with (${\pm}$)-2-phenylbutanoic acid on the basis of previously reported standard methods. The biodistribution and dynamic behavior of the compound were investigated using the comparative breast cancer cell line, MCF-7 (estrogen receptor-positive) and MDA-MB-468 (non-estrogen receptor). Results and Conclusion: Acylation of (2-chloroethoxy)benzene with (${\pm}$)-2-phenylbutanoic acid gave the versatile ketone (81%) which reacted with 1,4-diiodobenzene to give triphenylethylene as a mixture of E and Z geometric isomers, which were separated by the recrystallization in ethanol. The E-isomer was treated with pyrrolidine to give idoxifene (67%). In order to incorporate radioactive iodine into the 4-position, the 4-stannylated precursor was prepared (30%). The yield of radioiodination was 90-92% with a high radiochemical purity greater than 98%. The ratio of tumor uptake of the breast cancer cell line between MCF-7 and MDA-MB-468 was about 1.7.

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Socio-medical Study on Gonorrhoea with Special References of Prevalence, PPNG and Antibiotic Resistance (임질환자(淋疾患者)에 관(關)한 사회의학적(社會醫學的) 연구(硏究) -유병률(有病率), PPNG 및 항균제내성(抗菌劑耐性)을 중심(中心)으로-)

  • Lee, Seong-Ho;Hwang, In-Dam;Park, Young-Soo;Koh, Dai-Ha
    • Journal of Preventive Medicine and Public Health
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    • v.16 no.1
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    • pp.41-50
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    • 1983
  • The incidence of sexually transmitted disease, especially gonorrhoea has risen despite the progress in its diagnosis and treatment. For the effective control programs of sexually transmitted disease, it should be required socio-medical approaches. A study on gonorrhoea and penicillinase-producing Neisseria gonorrhoeae(PPNG) was conducted in Jeonju and Kunsan area from March, 1982 through August, 1982. The 221 entertrainers were studied in order to determine the prevalences of gonorhoea and PPNG. Socio-demographic informations of the entertainers were obtained by interviewing them. Gonococci were cultured on Thayer-Martin enrichment media for isolation, and PPNG was confirmed using beta-lactamase reagent ($PADAC^{tm}$ Beta-Lactamase Test Strips, Galbiochem-Behring). The results of the study are summarized as follows; 1. The average age of the entertainers studied was $26.1{\pm}4.7$ years. 2. The average years of working in entertaining business was $2.4{\pm}1.4$ years, and the average income per month was $239,592{\pm}90,480$ won. On the education level, 70.6% of the entertainers were middle or high school graduates 3. 47.5% of the entertainers were using contraceptives. 90.5% have experienced artificial abortion. 4. 37(16.7%) out of 221 entertainers were revealed to gonorrhoea, and 13 (35.1%) of gonorrhoea patients were by PPNG. 5. The prevalence rates of gonorrhoea and the proportion of PPNG by age were not significant statistically. Meanwhile, the colelations between the rates of gonorrhoea and education, frequency of love-making with customers and type of sexual partner were highly significant statistically. 6. 37 strains of gonococci isolated were almostly resistant to several antimicrobial agents, especially amikacin, clindamycin and chloramphenicol. Furthermore PPNG strains were completely resistant to not only above drugs but also penicillin.

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The Prognostic Factors Affecting the Occurrence of Subsequent Unprovoked Seizure in Patients Who Present with Febrile Seizure after 6 Years of Age (6세 이후 열경련 환자의 비열성발작으로 진행되는 위험 인자)

  • Lee, Hyeon Ju;Kim, Seung Hyo
    • Journal of the Korean Child Neurology Society
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    • v.26 no.4
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    • pp.215-220
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    • 2018
  • Purpose: Few reports have described the prognostic factors affecting the occurrence of subsequent unprovoked seizure in patients who present with febrile seizure (FS) after 6 years of age. We investigated the prognostic factors affecting the development of unprovoked seizures after FS among patients from Jeju Island. Methods: We included patients who developed FS after 6 years of age, who presented to our outpatient clinic between January, 2011 and June, 2017. Clinical data were obtained through chart reviews and phone call interviews. We used logistic regression analysis to analyze the risk factors associated with the occurrence of subsequent unprovoked seizure. Results: Of the 895 patients who presented to our hospital due to their febrile seizure, 83 developed FS after 6 years of age. Among them, 3 patients were prescribed antiepileptic drugs before the onset of the unprovoked seizure, and 4 patients developed an unprovoked seizure before 6 years of age. Thus, overall, 76 patients were included in the study. 51 patients developed first FS before 6 years of age. In the remaining patients, the first FS developed after 6 years of age. The mean observational period since the last outpatient follow-up visit was 3.2 years (median 3.04 years, range: 1.42-4.71 years). Among them, 21% developed an unprovoked seizure. Logistic regression analysis showed that electroencephalographic (EEG) abnormalities served as an independent risk factor for a subsequent unprovoked seizure. Conclusion: EEG is the proper diagnostic tool to predict the risk of a subsequent unprovoked seizure in patients with FS after 6 years of age.

Pediatric Endoscopic Sedation in Korea: A Survey of the Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition (소아청소년 진정내시경: 대한소아소화기영양학회 학술위원회 조사 보고)

  • Ryoo, Eell;Kim, Kyung-Mo
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.11 no.1
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    • pp.21-27
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    • 2008
  • Purpose: The aim of this survey was to analyze the choice of sedative drugs and their side effects during pediatric endoscopic sedation in Korea. We also evaluated doctors, caretakers and patient satisfaction with the procedures. Methods: Between June 2006 and July 2006, a 16-item survey regarding current sedation practices, during one month, was mailed to 28 hospitals in Korea. The results of the survey responses were then analyzed. Results: Endoscopy performed under conscious sedation was reported in 89.0% of the responders and endoscopy under general anesthesia in 0.9% of 465 endoscopic procedures. Endoscopy under conscious sedation was performed in 89.1% for upper gastrointestinal endoscopy (GFS) and 88.1% for lower GFS. Midazolam was used for conscious sedation during the endoscopy in 84.5% of cases and propofol was used in two cases (0.5%). In addition, a bezodiazepine/opioid combination was used iin 84.6% (44 cases) for lower GFS. Patients were monitored with pulse oxymetry, EKG (91.4%) as well as automatic BP (5.1%). Transient hypoxia was the only side effect noted and was treated with supplemental oxygen (4.6%). Flumazenil was used in 2.71% of cases. The choice of sedation was made by the endoscopist (84%). The satisfaction rate for endoscopists was 68%, and for the patients and caretakers was 84% (as reported by the endoscopists). Conclusion: Midazolam was used only for the upper GFS and benzodiazepine/opioid combination was used for the lower GFS in Korea. The rate of satisfaction was relatively high and there were no significant side effects noted during the endoscopy under conscious sedation.

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Contractile Response of Methylene Blue on Vascular Smooth Muscles - Rabbit Thoracic Aorta and Porcine Mesenteric Artery - (혈관평활근에 대한 Methylene Blue의 수축작용 - 가토흉부대동맥근과 돼지장간막동맥근 -)

  • Baik, Yung-Hong;Choi, Soo-Yong;Kim, Jae-Ha;Cho, Nam-Kee
    • The Korean Journal of Pharmacology
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    • v.26 no.1
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    • pp.13-23
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    • 1990
  • Methylene Blue (MeB) and gentian violet $(10^{-6}{\sim}10^{-4}\;M)$ produced contractions in isolated thoracic aortic preparations of rabbits in a dose-dependent fashion, while other dyes, evans blue and eosine yellowish, did not affect the basal tension in the same range of doses. Porcine mesenteric arterial rings also responded to MeB with dose-dependent contractions. Single dose of $10^{-4}$ M MeB produced a biphasic response: contraction followed by relaxation. The contraction developed slowly within $2{\sim}4$ min and peaked in about 20 minutes and then slowly relaxed to the basal level. Tyramine $(10^{-4}\;M)$ also induced contraction but it developed faster and was more persistent than that of MeB. While the tyramine-induced tension was reproducible, the MeB-induced one wat not reiterable until 3 to 5 hours after washing out the MeB. Adding $10^{-4}$ M MeB further potentiated the contraction induced by $10^{-4}$ M tyramine. However, the MeB contraction was not affected by further addition or tyramine. Both tyramine- and MeB-induced tensions were abolished or significantly inhibited by pretreatment with various drugs acting on the sympathetic nervous system. The tyramine-induced tension was more sensitive to guanethidine and 6-hydroxydopamine than the MeB-induced tension, while the latter was more sensitive to $Ca^{2+}-free$ PSS and reserpine. But they have similar sensitivity to prazosin. The MeB-induced tension was significantly inhibited but not abolished by 6-hydroxydopamine pretreatment. However, either tyramine or 6-hydroxydopamine could not affect the basal tension of the ring that MeB once had been tested. These results suggest that MeB-induced contractions of rabbit thoracic aorta and porcine mesenteric artery result from a release of endogenous norepinephrine from adrenergic nerve endings and are dependent in part on extracellular calcium, and that the potency of MeB to release or to deplete norepinephrine is greater than that of either tyramine or 6-hydroxydopamine.

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Cross-resistance Between Rifampicin and Rifabutin and Its Relationship with rpoB Gene Mutations in Clinically Isolated MDR-TB Strains (다제내성 결핵 균주에서 리팜핀과 리파부틴간의 교차내성률 및 rpoB 유전자 돌연변이와의 연관성)

  • Kim, Byoung Ju;Oh, Seung Hwan;Cho, Eun Jin;Park, Seung Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.2
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    • pp.171-179
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    • 2006
  • Background : Despite the emerging danger of MDR-TB to human beings, there have only been a limited number of drugs developed to treat MDR-TB since 1970. This study investigated the cross-resistance rate between rifampicin (RFP) and rifabutin (RBU) in order to determine the efficacy of rifabutin in treating MDR-TB. In addition, the results of rifabutin were correlated with the rpoB mutations, which are believed to be markers for MDR-TB and RFP resistance. Methods : The MICs of RBU were tested against 126 clinical isolates of MDR-TB submitted to the clinical laboratory of National Masan TB Hospital in 2004. Five different concentrations ($10-160{\mu}g/ml$) were used for the MICs. The detection of the rpoB mutations was performed using a RFP resistance detection kit with a line probe assay(LiPA), which contains the oligonucleotide probes for 5 wide type and 3 specific mutations (513CCA, 516GTC, and 531TTG) The rpoB mutation was determined by direct sequencing. Results : The rate of cross-resistance between RFP and RBU was 70.5%(74/105) at $20{\mu}g/ml$ RBU(ed note: How much RFP?) Most mutations (86.3%) occurred in the 524~534 codons. The His526Gln, His526Leu, Leu533Pro, Gln513Glu, and Leu511Pro mutations(Ed note: Is this correct?) were associated with the susceptibilty to RBU. Conclusion : Based on the cross-resistance rate between RFP and RBU, RBU may be used effectively in some MDR-TB patients. Therefore, a conventional drug susceptibility test for RBU and a determination of the critical concentration are needed. However, rpoB gene mutation test may be have limited clinical applications in detecting RBU resistance.