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The Measurement of Sensitivity and Comparative Analysis of Simplified Quantitation Methods to Measure Dopamine Transporters Using [I-123]IPT Pharmacokinetic Computer Simulations ([I-123]IPT 약역학 컴퓨터시뮬레이션을 이용한 민감도 측정 및 간편화된 운반체 정량분석 방법들의 비교분석 연구)

  • Son, Hye-Kyung;Nha, Sang-Kyun;Lee, Hee-Kyung;Kim, Hee-Joung
    • The Korean Journal of Nuclear Medicine
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    • v.31 no.1
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    • pp.19-29
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    • 1997
  • Recently, [I-123]IPT SPECT has been used for early diagnosis of Parkinson's patients(PP) by imaging dopamine transporters. The dynamic time activity curves in basal ganglia(BG) and occipital cortex(OCC) without blood samples were obtained for 2 hours. These data were then used to measure dopamine transporters by operationally defined ratio methods of (BG-OCC)/OCC at 2 hrs, binding potential $R_v=k_3/k_4$ using graphic method or $R_A$= (ABBG-ABOCC)/ABOCC for 2 hrs, where ABBG represents accumulated binding activity in basal ganglia(${\int}^{120min}_0$ BG(t)dt) and ABOCC represents accumulated binding activity in occipital cortex(${\int}^{120min}_0$ OCC(t)dt). The purpose of this study was to examine the IPT pharmacokinetics and investigate the usefulness of simplified methods of (BG-OCC)/OCC, $R_A$, and $R_v$ which are often assumed that these values reflect the true values of $k_3/k_4$. The rate constants $K_1,\;k_2\;k_3$ and $k_4$ to be used for simulations were derived using [I-123]IPT SPECT and aterialized blood data with a standard three compartmental model. The sensitivities and time activity curves in BG and OCC were computed by changing $K_l$ and $k_3$(only BG) for every 5min over 2 hours. The values (BG-OCC)/OCC, $R_A$, and $R_v$ were then computed from the time activity curves and the linear regression analysis was used to measure the accuracies of these methods. The late constants $K_l,\;k_2\;k_3\;k_4$ at BG and OCC were $1.26{\pm}5.41%,\;0.044{\pm}19.58%,\;0.031{\pm}24.36%,\;0.008{\pm}22.78%$ and $1.36{\pm}4.76%,\;0.170{\pm}6.89%,\;0.007{\pm}23.89%,\;0.007{\pm}45.09%$, respectively. The Sensitivities for ((${\Delta}S/S$)/(${\Delta}k_3/k_3$)) and ((${\Delta}S/S$)/(${\Delta}K_l/K_l$)) at 30min and 120min were measured as (0.19, 0.50) and (0.61, 0,23), respectively. The correlation coefficients and slopes of ((BG-OCC)/OCC, $R_A$, and $R_v$) with $k_3/k_4$ were (0.98, 1.00, 0.99) and (1.76, 0.47, 1.25), respectively. These simulation results indicate that a late [I-123]IPT SPECT image may represent the distribution of the dopamine transporters. Good correlations were shown between (3G-OCC)/OCC, $R_A$ or $R_v$ and true $k_3/k_4$, although the slopes between them were not unity. Pharmacokinetic computer simulations may be a very useful technique in studying dopamine transporter systems.

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Effect of Verapamil on Cellular Uptake of Tc-99m MIBI and Tetrofosmin on Several Cancer Cells (수종의 암세포에서 Verapamil이 Tc-99m MIBI와 Tetrofosmin의 섭취에 미치는 영향)

  • Kim, Dae-Hyun;Yoo, Jung-Ah;Suh, Myung-Rang;Bae, Jin-Ho;Jeong, Shin-Young;Ahn, Byeong-Cheol;Lee, Kyu-Bo;Lee, Jae-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.1
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    • pp.85-98
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    • 2004
  • Purpose: Cellular uptake of $^{99}mTc$-sestamibi (MIBI) and $^{99}mTc$-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Materials and Methods: Celluar uptakes of Tc-99m MIBI and TF were measured in erythroleukermia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto $200{\mu}M\;at\;1{\times}10^6\;cells/ml\;at\;37^{\circ}C$. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Results: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of $100{\mu}M$ and the maximal increase at $50{\mu}M$ was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over $1{\mu}M$. With a concentration of $200{\mu}M$ verapamil, MIBI and TF uptakes un K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with $10{\mu}M$, but were also decreased with verapamil higher than $10{\mu}M$, resulting 40% and 5% of baseline at $50{\mu}M$. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at $200{\mu}M$. Conclusion: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.

Performance Characteristics of 3D GSO PET/CT Scanner (Philips GEMINI PET/DT) (3차원 GSO PET/CT 스캐너(Philips GEMINI PET/CT의 특성 평가)

  • Kim, Jin-Su;Lee, Jae-Sung;Lee, Byeong-Il;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.4
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    • pp.318-324
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    • 2004
  • Purpose: Philips GEMINI is a newly introduced whole-body GSO PET/CT scanner. In this study, performance of the scanner including spatial resolution, sensitivity, scatter fraction, noise equivalent count ratio (NECR) was measured utilizing NEMA NU2-2001 standard protocol and compared with performance of LSO, BGO crystal scanner. Methods: GEMINI is composed of the Philips ALLEGRO PET and MX8000 D multi-slice CT scanners. The PET scanner has 28 detector segments which have an array of 29 by 22 GSO crystals ($4{\times}6{\times}20$ mm), covering axial FOV of 18 cm. PET data to measure spatial resolution, sensitivity, scatter fraction, and NECR were acquired in 3D mode according to the NEMA NU2 protocols (coincidence window: 8 ns, energy window: $409[\sim}664$ keV). For the measurement of spatial resolution, images were reconstructed with FBP using ramp filter and an iterative reconstruction algorithm, 3D RAMLA. Data for sensitivity measurement were acquired using NEMA sensitivity phantom filled with F-18 solution and surrounded by $1{\sim}5$ aluminum sleeves after we confirmed that dead time loss did not exceed 1%. To measure NECR and scatter fraction, 1110 MBq of F-18 solution was injected into a NEMA scatter phantom with a length of 70 cm and dynamic scan with 20-min frame duration was acquired for 7 half-lives. Oblique sinograms were collapsed into transaxial slices using single slice rebinning method, and true to background (scatter+random) ratio for each slice and frame was estimated. Scatter fraction was determined by averaging the true to background ratio of last 3 frames in which the dead time loss was below 1%. Results: Transverse and axial resolutions at 1cm radius were (1) 5.3 and 6.5 mm (FBP), (2) 5.1 and 5.9 mm (3D RAMLA). Transverse radial, transverse tangential, and axial resolution at 10 cm were (1) 5.7, 5.7, and 7.0 mm (FBP), (2) 5.4, 5.4, and 6.4 mm (3D RAMLA). Attenuation free values of sensitivity were 3,620 counts/sec/MBq at the center of transaxial FOV and 4,324 counts/sec/MBq at 10 cm offset from the center. Scatter fraction was 40.6%, and peak true count rate and NECR were 88.9 kcps @ 12.9 kBq/mL and 34.3 kcps @ 8.84 kBq/mL. These characteristics are better than that of ECAT EXACT PET scanner with BGO crystal. Conclusion: The results of this field test demonstrate high resolution, sensitivity and count rate performance of the 3D PET/CT scanner with GSO crystal. The data provided here will be useful for the comparative study with other 3D PET/CT scanners using BGO or LSO crystals.

A Novel in Vitro Method for the Metabolism Studies of Radiotracers Using Mouse Liver S9 Fraction (생쥐 간 S9 분획을 이용한 방사성추적자 대사물질의 새로운 체외 측정방법)

  • Ryu, Eun-Kyoung;Choe, Yearn-Seong;Kim, Dong-Hyun;Lee, Sang-Yoon;Choi, Yong;Lee, Kyung-Han;Kim, Byung-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.4
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    • pp.325-329
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    • 2004
  • Purpose: Usefulness of mouse liver S9 fraction was evaluated for the measurement of the metabolites in the in vitro metabolism study of $^{18}F$-labeled radiotracers. Materials and Methods: Mouse liver S9 fraction was isolated at au early step in the course of microsome preparation. The in vitro metabolism studies were tarried out by incubating a mixture containing the radiotracer, S9 fraction and NADPH at $37^{\ciirc}C$, and an aliquot of the mixture was analyzed at the indicated time points by radio-TLC. Metabolic defluorination was further confirmed by the incubation with calcium phosphate, a bone mimic. Results: The radiotracer $[^{18}F]1$ underwent metabolic defluorination within 15 min, which was consistent with the results of the in vivo method and the in vitro method using microsome. Radiotracer $[^{18}F]2$ was metabolized to three metabolites including $4-[^{18}F]fluorobenzoic$ acid within 60 min. It is likely that the one of these metabolites at the origin of radio-TLC was identical with the one that obtained from the in vivo and in vitro (microsome) method. Compared with the in vitro method using microsome, the method using S9 fraction gave a similar pattern of the metabolites but with a different ratio, which can be explained by the presence of cytosol in the S9 fraction. Conclusion: These results suggest that the findings of the in vitro metabolism studies using S9 fraction can reflect the in vivo metabolism of novel radiotracers in the liver. Moreover, this method can be used as a tool to determine metabolic defluorination along with calcium phosphate absorption method.

Intratypic Variants of HPV-16 E6jE7 Oncogene Isolated from Sexually High-Risk Women in Busan. (부산지역 유흥업소 종사여성으로부터 분리된 HPV16형의 발암유전자(E6/E7) 돌연변이 유형 분석)

  • Min, Sang-Kee;Kim, Sung-Soon;Choi, Byeong-Sun;Jang, Dai-Ho;Lee, Mee-Ok;Choi, Seung-Hwa;Kim, Nam-Ho;Park, Yon-Koung;Jeong, Yeong-A;Kim, Seong-Joon;Bin, Jae-Hun;Park, Ho-Kuk
    • Journal of Life Science
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    • v.19 no.6
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    • pp.765-769
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    • 2009
  • Recent studies have reported that the distribution of HPV-16 sequence variation differs geographically, and more specifically that HPV-16 E6/E7 intratypic variants might carry a high risk for development of ICC (invasive cervical cancer) and CIN (cervical intraepithelial neoplasia) in a given population. To investigate the genetic diversities of HPV-16 E6/E7 oncogene by region, we collected nineteen HPV-16 isolates from sexually high-risk women in Busan, and analyzed the HPV-16 E6/E7 coding regions (nt 34 to 880) with HPV-16 E6/E7 specific PCR amplification. At the nucleotide levet eleven variants of the E6 genes and nine variants of the E7 genes were identified as follows: E6 T178G (n=l1), E6 T178A (n=l), E6 T350G (n=3), E6 A442C (n=2), E6 AI04T, E6 All1G, E6 C116T, E6 G145T, E6 T183G, E6 C335T, E6 G522C and E7 A647G (n=12), E7 A645C, E7 A777C, E7 G663A, E7 T732C, E7 T760C, E7 A775T, E7 T789C and E7 T795G, respectively. At the amino acid levet the isolated HPV-16 E6 and E7 genes showed eleven E6 variants: E6 D25E (n=12), E6 L83V (n=4), E6 E113D (n=2), E6 MIL, E6 Q3R, E6 P5S, E6 Q14H, E6 D25N, E6 127R, E6 H78Y, E6 C140S and three E7 variants: N29S (n=12), L28F, T72S. HPV16 E6 L83V, the dominant variant in the Caucasian population, showed relatively low frequencies in our study population. We elucidated that the dominant HPV-16 E6/E7 variants were HPV-16 E6 D25E (63.2%) and HPV-16 E7 N29S (63.2%), which were phylogenetically included in Asian lineage. Further study is needed to evaluate the risk of cervical cancer related HPV-16 E6/E7 intratypic variants in the Korean population.

The study of food habit and degree of depression in nursing home and privite home living elderly (시설노인과 재가노인의 식습관과 정신건강 상태에 관한 실태조사)

  • Han, Myung-Joo;Koo, Sung-Ja;Lee, Young-Soon
    • Journal of the Korean Society of Food Culture
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    • v.13 no.5
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    • pp.475-486
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    • 1998
  • The dietary habit, health condition and the cognition concerning the health food have been surveyed with the help of the 151 old people living in In-Cheon and Seoul. In this study, the old are classified as an institution for the aged and the old in their own home. The preference and mental health condition influenced on dietary habits have been surveyed as wall. Their dietary habits such s three meals a day and a regular meal time have show) that they have generally good eating habits. Psychologically, the old in an institution for the aged think their health condition is not so good in comparison with the old in their own home. The old in their own home have good condition in that they can go up the stairs, exercise often and walk relatively well. Moreover, men's health condition is better than women. The old generally like meats(especially beef) and prefer sesame oil, perilla oil, soy been oil to Western oil. They like sweat flavor the most and hot, salty taste in order. Thier favorite cooking method is a pot stew, soup and season. The difference between dietary habit and mental health based on an academic career, an allowance and a residential condition shows that the old who live alon have relatively terrible eating habit and the more learned, the better. The more pocket money they have, the better dietary habits they have. The old feel glommy in general and the old in an institution are more depressed and it is statistically significant.

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Studies on the Organo-mercury Residues in Rice Grain -I. Mercury residues in rice seeds treated with organo-mercury fungicide- (수도(水稻)에 처리(處理)된 유기수은제(有機水銀劑)의 잔류성(殘留性)에 관(關)한 연구(硏究) -제1보(第1報) 침지용유기수은제(浸漬用有機水銀劑)로 처리(處理)된 수도종자중(水稻種子中)의 수은잔류량(水銀殘留量)에 관(關)하여-)

  • Lee, Dong-Suk
    • Applied Biological Chemistry
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    • v.8
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    • pp.87-93
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    • 1967
  • 1) For the micro-analysis of mercury in plant materials, the method of Furutani was shown to be the simplest and most efficient way and the recovery of the assay was about 98%. 2) When the rice grain was soaked in 1/1000 diluted solution of organo-mercury fungicide for 8 hours at the end of March, the amounts of mercury residues in the brown rice and unhulled rice were 8.8 to $9.5\;{\mu}g/g$ seeds and 10.1 to $10.7\;{\mu}g/g$ seeds, respectively. 3) By washing the treated rice seeds with running water for three days, tile residual mercury concentration was reduced to 1/4 to 1/5; thus the mercury residues were 1.86 to $1.92\;{\mu}g/g$ for brown rice and 1.96 to $2.93\;{\mu}g/g$ for unhulled rice. 4) The residual mercury was present more in the unhulled rice than in the brown rice, either before or after washing of the treated seeds. 5) Among the different rice varieties, no difference was observed in mercury residues by seed treatment and washing.

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Ultrasonic Assessment of Gastric Emptying According to Feeding Types and Postprandial Postures (수유 종류 및 수유 후 자세에 따른 위 배출 시간의 초음파적 연구)

  • Park, Jae-Ock;Kim, Jong-Bock
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.2 no.1
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    • pp.65-73
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    • 1999
  • Purpose: Regurgitation, vomiting and feeding intolerance are frequent in the neonates. Esophageal function and gastric peristalsis are not fully developed in the neonates, so we should give attention to reduce the incidence of regurgitation and vomiting after feeding. It is necessary to shorten the gastric emptying by change of feeding types and postprandial postures. Gastric emptying time was measured by ultrasound in the neonates to evaluate the effect of feeding types and postprandial postures. Method: We measured gastric antral cross sectional area along the abdominal aorta at the level of the superior mesenteric artery in longitudinal section at NPO state (4 hours after feeding), 0 and every 30 min. after feeding until the value goes below or back to the NPO state. Fifteen neonates were examined in each breast-fed and formula-fed group in supine position. Eighteen and 15 neonates were examined in supine and prone posture after formula feeding, respectively. We used 5 MHz convex prove with Aloka Echo Camera SSD-650. Result: 1) Gastric emptying time of breast-fed infants was $76.0{\pm}20.02$ min. which was significantly shorter than $96.0{\pm}20.28$ min. of formula-fed infants. 2) Gastric emptying time on postprandial prone posture was $85.0{\pm}22.43$ min. which was not significantly different from $96.0{\pm}20.28$ min. on postprandial supine posture. Conclusion: Breast feeding is strongly recommended to the neonates to shorten gastric emptying time. So we can expect to reduce the incidence of regurgitation, vomiting and feeding intolerance. The postprandial posture depends on the traditional trend which is safe and comfortable to the mothers.

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Neonatal Sepsis and Antimicrobial Susceptibilities in the Neonatal Intensive Care Unit and Nursery (신생아 패혈증의 원인 및 항생제 감수성)

  • Moon, Jin Hwa;Oh, Sung Hee;Kim, Hak Won;Moon, Su Jee;Choi, Tae Yeol
    • Pediatric Infection and Vaccine
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    • v.9 no.2
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    • pp.163-174
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    • 2002
  • Background : To delineate the changes in the causative agents of neonatal sepsis and their antimicrobial susceptibilities in the neonatal intensive care unit and nursery of Hanyang University Hospital during the past 10 years. Methods : Hospital records of 15,144 patients hospitalized at the NICU and nursery of Hanyang University Hospital from 1989 to 1998 were reviewed and neonates diagnosed of neonatal sepsis were sorted and included in the study. The study period was divided into Period A(the first 5 years) and Period B(the second 5 years) to analyse causative agents and their antimicrobial susceptibilities. Results : Neonatal sepsis was diagnosed in 170 patients(1.1%{Period A 1.2%, Period B 1.0%}) among the total of 15,144 inpatients. Two hundred isolates(Period A 109 isolates, Period B 91 isolates) were identified in 186 blood cultures(Period A 99 cultures, Period B 87 cultures) from 170 patients(Period A 91 patients, Period B 79 patients). The average age at the onset of the disease, when the initial blood culture was drawn, was 12.3 days old(Period A 8.8 days, Period B 16.3 days), and the proportion of the early onset disease was 34.7% in Period A and 23.0% in Period B, indicating that neonatal sepsis developed earlier during Period A. Among the isolated organisms including Gram positive bacteria[132(66.0%)], Gram negative bacteria [60(30.0%)], and fungi[8(4.0%)], coagulase negative Staphylococcus(CNS) was the most common organism(69/34.5%), followed by Staphylococcus aureus(36/18.0%), Klebsiella pneumoniae(17/8.5%), Enterococcus(12/6.0%), Enterobacter cloacae(8/4.0%), Escherichia coli(6/3.0%), and Pseudomonas aeruginosae(5/2.5%). The isolated fungi were Candida parapsilosis, Candida albicans, and Trichosporon pullulans. CNS, S. aureus and Acinetobacter baumannii were isolated more frequently in Period A compared to Period B. Antimicrobial susceptibilities of CNS and S. aureus to methicillin and the first generation cephalo sporins were decreased in Period B compare to Period A, those to aminoglycosides were increased in Period B, and vancomycin resistant strains were not identified. K. pneumoniae, Enterococcus, E. coli, and P. aeruginosa were isolated less frequently in Period B, compared to Period A. For K. pneumoniae, antimicrobial susceptibilities to the first generation cephalosporins were low in both Periods A and B, those to tobramycin and gentamicin were increased in Period B, and those to amikacin, ceftriaxone, and trimethoprim-sulfamethoxazole were high in both Periods A and B. Antimicrobial susceptibilities of Enterococcous to ampicillin, penicillin, and the first generation cephalosporins were decreased in Period B, but vancomycin resistant strains were not identified. Conclusion : The occurrence rate of neonatal sepsis during the past 10 years in the NICU and nursery of the Hanyang University hospital was 1.1%, and the most common causitive agents were CNS and S. aureus, to which the antimicrobial susceptibilities to the first line drugs decreased in the later half of the study period with no vancomycin resistant isolates identified. Group B Streptococcus known to be the most common agent causing neonatal sepsis was not identified, and K. pneumoniae was isolated more commonly during the later half of the study period without decreased antimicrobial susceptibilities.

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Clinical Analysis of Influenza in Children and Rapid Antigen Detection Test on First Half of the Year 2004 in Busan (2004 상반기 부산 지역에서 유행한 인플루엔자의 임상 역학적 분석 및 인플루엔자 진단에 있어서의 신속 항원 검사법)

  • Choi, So Young;Lee, Na Young;Kim, Sung Mi;Kim, Gil Heun;Jung, Jin Hwa;Choi, Im Jung;Cho, Kyung Soon
    • Pediatric Infection and Vaccine
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    • v.11 no.2
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    • pp.158-169
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    • 2004
  • Purpose : Although influenza is one of the most important cause of acute respiratory tract infections in children, virus isolation is not popular and there are only a few clinical studies on influenza and diagnostic methods. We evaluated the epidemiological and clinical features of influenza in children and rapid antigen detection test(QuickVue influenza test) on fist half of the year 2004 in Busan. Methods : From January 2004 to June 2004, throat swab and nasal secretion were obtained and cultured for the isolation of influenza virus and tested by rapid antigen detection test(QuickVue influenza test) in children with suspected influenza infections. The medical records of patients with influenza virus infection were reviewed retrospectively. Results : Influenza viruses were isolated in 79(17.2%) out of 621 patients examined. Influenza virus was isolated mainly from March to April 2004. The ratio of male and female with influenza virus infection was 1.2 : 1 with median age of 4 years 6month. The most common clinical diagnosis of influenza virus infection was bronchitis. There was no difference between influenza A and B infection in clinical diagnosis and symptoms. All patients recovered without severe complication. The sensitivity obtained for rapid antigen detection test (QuickVue influenza test) was 93.6% and the specificity was 80.2%, the positive predictive value 40.8%, the negative predictive value 98.8%. Conclusion : With rapid antigen detection test, it is possible early detection of influenza in children. reduction in use of antimicrobial agent and early use of antiviral agent.

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