• Journal of Chest Surgery
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• 제24권3호
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• pp.253-260
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• 1991

The adequacy of anticoagulation with heparin during cardiopulmonary bypass, and precise neutralization with protamine at the conclusion of cardiopulmonary bypass, were important. In sixty children undergoing cardiopulmonary bypass, ACT and heparin dose-response curve were studied. Total dose of heparin before bypass were 2.80$\pm$0.74 mg/kg and the amount of protamine administered after bypass were 3.0$\pm$1.23 mg/kg. So protamine: heparin ratio was 1.07: l.c After administration of protamine which dose is calculated with heparin dose-response curve, ACTs were returned to normal range[mean 114.8 $\pm$13 second]. The heparin sensitivity and its half-life do not have relationship with age, weight, height, surface area and urine amount during operation. And there are too much individual variations in heparin sensitivity and its half-life. So conventional heparin protocols can overestimate or underestimate the amount of heparin and protamine. Heparin dose-response curve makes it possible to maintain anticoagulation in a safe range during bypass with adequate amount of heparin individually. At the conclusion of bypass, this curve can be used to predict the precise amount of protamine amount of protamine needed for neutralization of the heparin. But heparin dose-response curve to be used clinically, further studies will be needed about relationship between ACT and heparin level in the high range, influence of hemodilution and hypothermia to ACT and discrepancy between true adequate amount of protamine and calculated amount by heparin dose-response curve.

• Communications for Statistical Applications and Methods
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• 제29권3호
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• pp.287-299
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• 2022

In radiation epidemiology, the excess relative risk (ERR) model is used to determine the dose-response relationship. In general, the dose-response relationship for the ERR model is assumed to be linear, linear-quadratic, linear-threshold, quadratic, and so on. However, since none of these functions dominate other functions for expressing the dose-response relationship, a Bayesian semiparametric method using splines has recently been proposed. Thus, we improve the Bayesian semiparametric method for the selection of the tuning parameters for splines as the number and location of knots using a Bayesian knot selection method. Equally spaced knots cannot capture the characteristic of radiation exposed dose distribution which is highly skewed in general. Therefore, we propose a nonparametric Bayesian knot selection method based on a Dirichlet process mixture model. Inference of the spline coefficients after obtaining the number and location of knots is performed in the Bayesian framework. We apply this approach to the life span study cohort data from the radiation effects research foundation in Japan, and the results illustrate that the proposed method provides competitive curve estimates for the dose-response curve and relatively stable credible intervals for the curve.

• 한국방사선학회논문지
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• 제18권3호
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• pp.239-248
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• 2024

방사선치료는 고에너지를 사용함으로 인체에 부작용이 발생할 수 있다. 이에 따라 적정 선량의 설정과 발생장치에서 만들어진 방사선에 대한 신뢰도를 확보하는 것이 중요하다. EPR/알라닌 선량평가는 물 동등성, 선량 응답 선형성과 낮은 페이딩 등의 장점이 있으므로 방사선치료 장비의 품질관리에서 유용하게 사용될 것으로 생각한다. 따라서 본 연구에서는 선형가속기 6 MV 에너지를 활용하여 알라닌의 질량에 따른 EPR/알라닌 선량평가의 신호와 선량반응곡선을 비교하였다. 조사된 알라닌 선량계의 EPR 신호를 통해 선량반응곡선과 1차 회귀방정식을 제작하였다. 이를 통해 질량에 따른 신호 크기와 선량반응곡선을 비교하고 선량반응곡선 측정 불확도를 통해 신뢰도를 확인하였다. 그 결과, 질량이 커짐에 따른 EPR 신호의 크기는 64.5 mg 기준으로 약 1.3배 증가하며, 선량반응곡선의 민감도도 커지는 것을 알 수 있었다. 측정 불확도는 5.84 ~ 8.93 % (신뢰구간 약 95 %, k=2)로 평가되었다. 본 연구를 통해 선형가속기의 품질보증과 품질관리에 EPR/알라닌 선량평가 시스템이 적용 가능할 것으로 생각된다.

• 한국의학물리학회:학술대회논문집
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• 한국의학물리학회 2002년도 Proceedings
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• pp.174-176
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• 2002

A total of 134 patients with stage 1 of non-small cell lung cancer treated by carbon ion beam of HIMAC NIRS were investigated for control rate and delivered dose. The delivered dose of every patient was converted to biological effective dose (BED) of LQ model using fraction number, dose per fraction and alpha beta ratio which shows the maximum correlation between BED and tumor control. The BED of every patient was classified to establish a BED response curve for control. Assuming fraction numbers, dose response curves were introduced from BED response curve. The total doses to realize several control rates were obtained for the treatment of small fraction number.

• Biomolecules & Therapeutics
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• 제2권2호
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• pp.114-119
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• 1994

[$^3$H]Ouabain binding parameters ( $K_{D}$ and $B_{max}$) to control rat ventricular strips and Langendorff preparations which were not previously exposed to ouabain were compared with those to both preparations that had been first exposed to a complete ouabain dose range of dose-response curve (10$^{-8}$ to 10$^{4}$M). In rat ventricular strips and Langendorff perfused heart preparations, cumulative dose-response curves of ouabain revealed biphasic positive inotropic effects, a "low-dose" effect and a "high-dose" effect with E $d_{50}$ values of 0.5 $\mu$M and 35 $\mu$M ouabain, respectively. The "low-dose" effect in ventricular strip disappeared or was diminished significantly when the ouabain dose-response curve was repeated after the washout of the effects of the first dose-response curve, whereas there were no significant differences in the maximal "high-dose"effect in both exposures to oubain. However, both of the control and ouabain-preexposed Langendorff perfused hearts revealed the same low-dose effects. The $K_{D}$ value for [$^3$H] ouabain binding and the ouabain binding site concentration ( $B_{max}$) estimated by [$^3$H]ouabain displacement assay in control preparations were 230 nM and 2 pmol/mg protein, respectively. [$^3$H]Ouabain binding parameters were not changed by repeated exposure to high concentrations of ouabain. These results suggest that digitalis receptor desensitization in the rat ventricular strip may due to the change of post-receptor events induced by ouabain binding to a high affinity site ($\alpha$$_2$isoform).).).).).

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.301-301
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• 1994

〔$^3$H〕Ouabain binding parameters(K$\_$D/ and B$\_$max/,) in homogenates prepared fpom control rat ventricular strip and Langendorff preparations which were not previously exposed to ouabain were compared to those in homogenates from ventricular strip and Langendorff preparations that had been first exposed to a complete ouabain dose-response curve(10$\^$-7/M to 10$\^$-4/ M). In rat ventricular strips and Langendorff perfused rat heart preparations, cumulative dose-response cruves of ouabain revealed biphasic positive inotropic effects, a "low-dose" and a "high-dose" effect with ED$\_$50/ values of 0.5${\mu}$M and 35${\mu}$M ouabain, respectively- The "low-dose" effect in rat ventricular strips disappeared or was diminished significantly when the ouabain dose-response curve wag repeated after the washout of the effects of the first curve, whereas the maximal "high-dose" effect was identical in both exposures to oubain. However, there was no change in the "low-dose" effects in both sets of the Langendorff perfused hearts. The contractile activity of the pre-exposed strips did not indicate the presence of residual ouabain since their basal contractile force was decreased 10% compared to initial control. 〔$^3$H〕Ouabain binding parameters, K$\_$D/ and B$\_$max/, were not changed comparing homogenate of control ventricular strips with that of strips pre-exposed to ouabain. These results suggest that digitalis receptor desensitization in the rat ventricular strip may due to the change of post-receptor events induced by ouabain binding to a high affinity site(${\alpha}$$_2$ isoform).

• Toxicological Research
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• 제6권2호
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• pp.205-213
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• 1990

The regulation of neurotoxicants has usually been based upon setting reference doses by dividing a no observed adverse effect level (NOAEL) by uncertainty factors that theoretically account for interspecies and intraspecies extraploation of experimental results in animals to humans. Recently, we have proposed a four-step alternative procedure which provides quantitative estimates of risk as a function of dose. The first step is to establish a mathematical relationship between a biological effect or biomarker and the dose of chemical administered. The second step is to determine the distribution (variability) of individual measurements of biological effects or their biomarkers about the dose response curve. The third step is to define an adverse or abnormal level of a biological effect or biomarker in an untreated population. The fourth and final step is to combine the information from the first three steps to estimate the risk (proportion of individuals exceeding on adverse or abnormal level of a biological effect or biomarker) as a function of dose. The primary purpose of this report is to enhance the certainty of the first step of this procedure by improving our understanding of the relationship between a biomarker and dose of administered chemical. Several factors which need to be considered include: 1) the pharmacokinetics of the parent chemical, 2) the target tissue concentrations of the parent chemical or its bioactivated proximate toxicant, 3) the uptake kinetics of the parent chemical or metabolite into the target cell(s) and/or membrane interactions, and 4) the interaction of the chemical or metabolite with presumed receptor site(s). Because these theoretical factors each contain a saturable step due to definitive amounts of required enzyme, reuptake or receptor site(s), a nonlinear, saturable dose-response curve would be predicted. In order to exemplify this process, effects of the neurotoxicant, methlenedioxymethamphetamine (MDMA), were reviewed and analyzed. Our results and those of others indicate that: 1) peak concentrations of MDMA and metabolites are ochieved in rat brain by 30 min and are negligible by 24 hr, 2) a metabolite of MDMA is probably responsible for its neurotoxic effects, and 3) pretreatment with monoamine uptake blockers prevents MDMA neurotoxicity. When data generated from rats administerde MDMA were plotted as bilolgical effect (decreases in hippocampal serotonin concentrations) versus dose, a saturation curve best described the observed relationship. These results support the hypothesis that at least one saturable step is involved in MDMA neurotoxicity. We conclude that the mathematical relationship between biological effect and dose of MDMA, the first step of our quantitative neurotoxicity risk assessment procedure, should reflect this biological model information generated from the whole of the dose-response curve.

• 대한암한의학회지
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• 제20권1호
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• pp.11-21
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• 2015

Objectives : The cancer incidence and cancer burden is increasing. In addition, the use of botanical agents in cancer care is increasing. This article aims to review a research strategy for botanical agents. Methods : The clinical studies of anticancer botanical agents and the papers about clinical research methodology of botanical agents were reviewed. Results : In phase I study, safety confirmation, optimal dose determination and drug interaction study are important. Most botanical agents have low toxicity and some have non-monotone dose response. Therefore, dose-response curve must be evaluated separately from the dose-toxicity curve to determine optimal dose. Although anticancer botanical agents can't shrink tumor size rapidly, they do extend survival. So, in phase II study, response should be evaluated by the survival. Conclusions : Clinical research of botanical agents in cancer is different from traditional methods and strategies. Considering the characteristics of botanical agents and experimental mechanism is necessary in conducting botanical based clinical trials.

• Journal of the Korean Data and Information Science Society
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• 제25권5호
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• pp.987-998
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• 2014

본 연구에서는 우리나라 환경부에서 최근에 구축한 아동 동집단 경시적 자료인 아동 건강과 환경 연구 (CHEER) 자료에 기초하여 주의력 결핍 과잉행동 장애 (ADHD)와 혈중 납 농도의 상관을 선형혼합모형을 사용하여 규명하고, CHEER 자료의 경시적 특성으로 나타나는 ADHD 점수의 "평균으로의 회귀" 현상을 보고하고자 한다. 또한 ADHD를 종점으로 한 혈중 납 농도의 용량-반응 곡선을 도출하며, 이렇게 도출된 용량-반응 곡선에 기초하여 몇 가지 상황 하에서 독성기준치인 벤치마크 용량 하한 (BMDL)을 유도한다.

• 한국의학물리학회지:의학물리
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• 제33권4호
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• pp.158-163
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• 2022

Purpose: We subjected scanning electron microscopic (SEM) images of the active layer of EBT3 film to texture analysis to determine the dose-response curve. Methods: Uncoated Gafchromic EBT3 films were prepared for direct surface SEM scanning. Absorbed doses of 0-20 Gy were delivered to the film's surface using a 6 MV TrueBeam STx photon beam. The film's surface was scanned using a SEM under 100× and 3,000× magnification. Four textural features (Homogeneity, Correlation, Contrast, and Energy) were calculated based on the gray level co-occurrence matrix (GLCM) using the SEM images corresponding to each dose. We used R-square to evaluate the linear relationship between delivered doses and textural features of the film's surface. Results: Correlation resulted in higher linearity and dose-response curve sensitivity than Homogeneity, Contrast, or Energy. The R-square value was 0.964 for correlation using 3,000× magnified SEM images with 9-pixel offsets. Dose verification was used to determine the difference between the prescribed and measured doses for 0, 5, 10, 15, and 20 Gy as 0.09, 1.96, -2.29, 0.17, and 0.08 Gy, respectively. Conclusions: Texture analysis can be used to accurately convert microscopic structural changes to the EBT3 film's surface into absorbed doses. Our proposed method is feasible and may improve the accuracy of film dosimetry used to protect patients from excess radiation exposure.