• Title/Summary/Keyword: Blind Area

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Variability in Drug Interaction According to Genetic Polymorph isms in Drug Metabolizing Enzymes

  • Jang, In-Jin;Yu, Kyung-Sang;Cho, Joo-Youn;Chung, Jae-Yong;Kim, Jung-Ryul;Lim, Hyeong-Seok;Shin, Sang-Goo
    • Environmental Mutagens and Carcinogens
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    • v.23 no.4
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    • pp.131-134
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    • 2003
  • There are significant differences in the extent of drug interactions between subjects. The influence of the genetic make up of drug metabolizing enzyme activities (CYP3A5, CYP2C19 and UDP-glucuronosyl transferase) on the pharmacokinetic drug interaction potential were studied in vivo. Nineteen healthy volunteers were grouped with regard to the $CYP3A5^{*}3$ allele, into homozygous wild-type (CYP3A5^{*}1/1^{*}1$, n=6), heterozygous $(CYP3A5^{*}1/^{*}3$, n=6), and homozygous variant-type $(CYP3A5^{*}3/^{*}3$, n=7) subject groups. The pharmacokinetic profile of intravenous midazolam was characterized before and after itraconazole administration (200 mg once daily for 4 days), and also following rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. For omeprazole and moclobemide pharmacokinetic interaction study 16 healthy volunteers were recruited. The volunteer group comprised 8 extensive metabolizers and 8 poor metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were randomly allocated into two sequence groups, and a single-blind, placebo-controlled, two-period crossover study was performed. In study I, a placebo was orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and 40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic study was performed. During study n, 40 mg of omeprazole was given each morning instead of placebo, and pharmacokinetic studies were performed on the first and eighth day with 300 mg of moclobemide coadministration. In the UGT study pharmacokinetics and dynamics of 2 mg intravenous lorazepam were evaluated before and after rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. The subjective and objective pharmacodynamic tests were done before and 1, 2, 4, 6, 8, and 12 hrs after lorazepam administration. The pharmacokinetic profiles of midazolam and of its hydroxy metabolites did not show differences between the genotype groups under basal and induced metabolic conditions. However, during the inhibited metabolic state, the $CYP3A5^{*}3/^{*}3$ group showed a greater decrease in systemic clearance than the $CYP3A5^{*}1/^{*}1$ group $(8.5\pm3.8$ L/h/70 kg vs. $13.5\pm2.7$ L/h/70 kg, P=0.027). The 1'-hydroxymidazolam to midazolam AUC ratio was also significantly lower in the $CYP3A5^{*}3/^{*}3$,/TEX> group $(0.58\pm0.35,$ vs. $1.09\pm0.37$ for the homozygous wild-type group, P=0.026). The inhibition of moclo-bemide metabolism was significant in extensive metabolizers even after a single dose of omeprazole. After daily administration of omeprazole for 1 week, the pharmacokinetic parameters of moclobemide and its metabolites in extensive metabolizers changed to values similar to those in poor metabolizers. In poor meta-bolizers, no remarkable changes in the pharmacokinetic parameters were observed. The area under the time-effect curves of visual analog scale(VAS), choice reaction time, and continuous line tracking test results of lorazepam was reduced by 20%, 7%, 23% respectively in induced state, and in spite of large interindividual variablity, significant statistical difference was shown in VAS(repeated measures ANOVA, p=0.0027).

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Interobserver Reproducibility of Segmental Scoring of $^{99m}Tc$-MIBI Myocardial SPECT ($^{99m}Tc$-MIBI 심근 SPECT의 분절 육안 분석시 판독자간의 일치도)

  • Yeo, Jeong-Seok;Lee, Dong-Soo;Lee, Kyung-Han;Kim, Jong-Ho;Shon, Kyung-Soo;Cho, Sung-Wook;Kwark, Cheol-Eun;Chung, June-Key;Lee, Myung-Chul;Seo, Jeong-Don;Koh, Chang-Soon
    • The Korean Journal of Nuclear Medicine
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    • v.28 no.3
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    • pp.317-325
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    • 1994
  • The accuracy of dipyridamole stress/rest $^{99m}Tc$-MIBI myocardial imaging for detection of ischemia depends on reproducible image interpretation. To evaluate the reproducibility of visual assessment, agreement in interpretation among two independent observers, blind-ed to clinical data, was evaluated in SPECT images of 131 patients (94 males, 38 females; mean age $58{\pm}7yr$) with suspected coronary artery disease who underwent both dipyridamole stress/rest $^{99m}Tc$-MIBI myocardial SPECT and coronary angiography. The left ventricle was divided into twenty-nine segments in stress and rest SPECT images and each segment was visually graded according to a five-point scale (segmental score : 0=normal, 1=equivocal, 2=mild decrease, 3=severe decrease and 4=absent uptake). Overall concordance of segmental scoring between the two observers was 80%. The Pear-son's correlation coefficient (r) of the segmental scores for stress and rest images were 0.67 and 0.65, respectively, while the difference in score between the two images showed a correlation of 0.45 (all p<0.001). Agreement between two observers in final SPECT diagnosis as absence or presence of disease was 93%. The degree of agreement in segmental scoring showed no difference between patients with or without agreement as to the presence of disease. Therefore it appeared that cases with inconcordant diagnosis between the 2 observers were mainly due to a difference in individual threshold for interpretating the significance of a particular decreased uptake area rather than to a difference in perceiving the degree of the hypoactivity Thus, establishment of individual optimum thresholds in visual interpretation of myocardial SPECT may be helpful to improve reproducibility and accuracy of scan diagnosis.

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Improvement of Personal Information Protection Laws in the era of the 4th industrial revolution (4차 산업혁명 시대의 개인정보보호법제 개선방안)

  • Choi, Kyoung-jin
    • Journal of Legislation Research
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    • no.53
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    • pp.177-211
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    • 2017
  • In the course of the emergence and development of new ICT technologies and services such as Big Data, Internet of Things and Artificial Intelligence, the future will change by these new innovations in the Fourth Industrial Revolution. The future of this fourth industrial revolution will change and our future will be data-based society or economy. Since there is personal information at the center of it, the development of the economy through the utilization of personal information will depend on how to make the personal information protection laws. In Korea, which is trying to lead the 4th industrial revolution, it is a legal interest that can not give up the use of personal information, and also it is an important legal benefit that can not give up the personal interests of individuals who want to protect from personal information. Therefore, it is necessary to change the law on personal information protection in a rational way to harmonize the two. In this regard, this article discusses the problems of duplication and incompatibility of the personal information protection law, the scope of application of the personal information protection law and the uncertainty of the judgment standard, the lack of flexibility responding to the demand for the use of reasonable personal information, And there is a problem of reverse discrimination against domestic area compared to the regulated blind spot in foreign countries. In order to solve these problems and to improve the legislation of personal information protection in the era of the fourth industrial revolution, we proposed to consider both personal information protection and safe use by improving the purpose and regulation direction of the personal information protection law. The balance and harmony between the systematical maintenance of the personal information protection legislation and laws and regulations were also set as important directions. It is pointed out that the establishment of rational judgment criteria and the legislative review to clarify it are necessary for the constantly controversial personal information definition regulation and the method of allowing anonymization information as the intermediate domain. In addition to the legislative review for the legitimate and non-invasive use of personal information, there is a need to improve the collective consent system for collecting personal information to differentiate the subject and to improve the legislation to ensure the effectiveness of the regulation on the movement of personal information between countries. In addition to the issues discussed in this article, there may be a number of challenges, but overall, the protection and use of personal information should be harmonized while maintaining the direction indicated above.

A Study on Damage factor Analysis of Slope Anchor based on 3D Numerical Model Combining UAS Image and Terrestrial LiDAR (UAS 영상 및 지상 LiDAR 조합한 3D 수치모형 기반 비탈면 앵커의 손상인자 분석에 관한 연구)

  • Lee, Chul-Hee;Lee, Jong-Hyun;Kim, Dal-Joo;Kang, Joon-Oh;Kwon, Young-Hun
    • Journal of the Korean Geotechnical Society
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    • v.38 no.7
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    • pp.5-24
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    • 2022
  • The current performance evaluation of slope anchors qualitatively determines the physical bonding between the anchor head and ground as well as cracks or breakage of the anchor head. However, such performance evaluation does not measure these primary factors quantitatively. Therefore, the time-dependent management of the anchors is almost impossible. This study is an evaluation of the 3D numerical model by SfM which combines UAS images with terrestrial LiDAR to collect numerical data on the damage factors. It also utilizes the data for the quantitative maintenance of the anchor system once it is installed on slopes. The UAS 3D model, which often shows relatively low precision in the z-coordinate for vertical objects such as slopes, is combined with terrestrial LiDAR scan data to improve the accuracy of the z-coordinate measurement. After validating the system, a field test is conducted with ten anchors installed on a slope with arbitrarily damaged heads. The damages (such as cracks, breakages, and rotational displacements) are detected and numerically evaluated through the orthogonal projection of the measurement system. The results show that the introduced system at the resolution of 8K can detect cracks less than 0.3 mm in any aperture with an error range of 0.05 mm. Also, the system can successfully detect the volume of the damaged part, showing that the maximum damage area of the anchor head was within 3% of the original design guideline. Originally, the ground adhesion to the anchor head, where the z-coordinate is highly relevant, was almost impossible to measure with the UAS 3D numerical model alone because of its blind spots. However, by applying the combined system, elevation differences between the anchor bottom and the irregular ground surface was identified so that the average value at 20 various locations was calculated for the ground adhesion. Additionally, rotation angle and displacement of the anchor head less than 1" were detected. From the observations, the validity of the 3D numerical model can obtain quantitative data on anchor damage. Such data collection can potentially create a database that could be used as a fundamental resource for quantitative anchor damage evaluation in the future.