• Title/Summary/Keyword: Dose-response

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Quantitative Microbial Risk Assessment on Legionella Infection in Children Playing in Interactive Fountains (바닥분수에서 물놀이를 하는 아동들의 Legionella균 감염 위해도 분석)

  • Lee, In-Sup;Zo, Young-Gun
    • Korean Journal of Microbiology
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    • v.49 no.4
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    • pp.360-368
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    • 2013
  • Recently interactive water fountains are gaining popularity in making public facilities in South Korea. The total number of interactive fountains is rapidly growing at the rate of >50% annually. In this study, we performed quantitative microbial risk assessment to estimate infection risks in children by Legionella spp. while playing in interactive fountains. The exposure dose for a given concentration of Legionella in water was calculated using water-aerosol partition rate of Legionella, exposure duration, inhalation rate, and deposit rate of aerosols in the lungs following inhalation. The dose was converted to infection risk by using the dose-response function developed for L. pneumophila. High weight and/or old children, i.e., 12-year children, running around in fountains were the highest risk group by showing >0.05 infection probability for fountain waters containing ${\geq}10^4$ CFU/L Legionella. The result supported the current guideline by Korea Centers for Disease Control and Prevention, which permits use of water with < $10^3$ CFU/L Legionella cells for all purposes. However, the results still warrant further evaluation of the guideline to accommodate risks for children because the dose-response relationship in the model was developed for healthy adults. Further risk assessment studies need to be conducted by employing dose-response model for children who generally carries weaker immune system than adults.

Effects of Diuretics on Warfarin Responses in Patients with Atrial Fibrillation (심방세동 환자에서 Warfarin 반응성에 이뇨제가 미치는 영향)

  • Park, Hee Joo;La, Hyen-Oh;Gwak, Hye Sun
    • Korean Journal of Clinical Pharmacy
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    • v.23 no.2
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    • pp.151-157
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    • 2013
  • Purpose: Warfarin is the most widely used anticoagulant drug for preventing cardiovascular diseases after ischemic stroke and thromboembolism related to atrial fibrillation, artificial heart valves, deep vein thrombosis, and pulmonary embolism. Warfarin is commonly used in combination with other drugs such as diuretics in order to treat the comorbidity. Although several warfarin-diuretics interactions have been reported, the results are conflicting. Therefore, the initial aim of this study was to identify the effects of diuretics on the warfarin response in patients with atrial fibrillation. Methods: One hundred forty six patients with atrial fibrillation who were on anticoagulation therapy with warfarin and maintained INR levels of 2-3 for three consecutive times were followed up, retrospectively. Stable warfarin doses and INR per stable warfarin dose were compared according to age, gender, comorbidity, and concurrent medication. The stable warfarin dose was defined as the maintenance dose of warfarin of the measured patient whose INR was within the target INR range more than 3 times consecutively. Results: The differences of stable warfarin doses in patients with ($3.22{\pm}1.21$ mg/day) and without ($3.58{\pm}1.14$ mg/day) diuretics were marginally significant (P=0.069). On the other hand, stable warfarin doses were $2.97{\pm}1.10$ mg/day in patients with thiazide (n=36) and $3.58{\pm}1.14$ mg/day in patients without diuretics (n=82), which was statistically significant (p=0.009). INR values per stable warfarin dose in patients with diuretics and thiazide were $0.84{\pm}0.31$ and $0.90{\pm}0.34$, respectively, which were statistically different from those without diuretics ($0.72{\pm}0.21$, P=0.010 and P=0.006, respectively). Age, gender, and concurrent use of thiazide diuretics were found to have significant influence on the warfarin response from multivariate analysis. Conclusion: Our study showed that the concurrent use of thiazide diuretics could increase the response of warfarin in patient with atrial fibrillation. Therefore, clinicians should be aware that warfarin dose needs to be adjusted when it is used with thiazide diuretics concomitantly.

Granulocytic Sarcoma: Results of Radiotherapy (Granulocytic Sarcoma : 방사선 치료 성적)

  • Song Mi Hee;Chung Eun Ji;Seong Jin Sil;Suh Chang Ok
    • Radiation Oncology Journal
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    • v.10 no.2
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    • pp.261-266
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    • 1992
  • We analyzed retrospectively the patients of granulocytic sarcoma treated with radiotherapy at the Department of Radiation Oncology, Yonsei University College of Medicine from Mar 1987 to Mar.1992 in an attempt to review our experience with irradiation of granulocytic sarcoma and to evaluate the treatment results for the radiation dose response. Fourteen lesions of granulocytic sarcoma in 9 patients were developed in variable clinical settings such as AML, CML and without leukemia. The involved lesions were bone, lymph node, soft tissue and skin in descending order of occurrence. All of the lesions in 9 patients were treated with external beam radiotherapy (Co-60 or electron beam). Both age distribution and clinical settings did not show any correlation with the response to treatment. The response to treatment seemed to be better for lesions in the bone than in other involved lesions. The majority received local irradiation of a total dose of more than 2000 cGy. Radiation dose of more than 2000 cGy showed excellent local control of $100\%$, (11/11), while local control decreased to $33\%$(1/3) with total dose less than 2000 cGy. In conclusion, local radiotherapy seems to be very effective for palliative or curative aim of granulocytic sarcoma, and a radiation dose more than 2000 cGy is highly recommended.

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p53 Nuclear Accumulation as a Possible Biomarker for Biological Radio-dosimetry in Oral Mucosal Epithelial Cells

  • Kim, Youn-Young;Kim, Jong-il;Kim, Jin;Yook, Jong-In;Kim, The-Hwan;Son, Young-Sook
    • BMB Reports
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    • v.34 no.2
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    • pp.123-129
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    • 2001
  • Cellular response to ionizing radiation is affected by cell types, radiation doses, and post-irradiation time. Based on the trypan blue dye exclusion assay in normal oral mucosal cells (OM cells), a 48 h post-irradiation was sufffcient and an adequate time point for the evaluation of radiation sensitivity Its $LD_{50}$ was approximately 1.83 Gy To investigate possible biomarkers useful for the biological radiodosimetry of normal epithelial cells (p53, c-fos, cyclin D1, cdc-2, pRb) EGF receptor phosphorylation and Erk activation were evaluated at different radiation doses and different post-irradiation times. From 0.5 Gy, p53 was accumulated in the nucleus of basal cells of the OM raft culture at 4 h post-irradiation and sustained up to 24 h post-irradiation, which suggests that radiation-induced apoptosis or damage repair was not yet completed. The number of p53 positive cells and biosynthesis of p53 were correlated with radiation doses. Both cyclin D1 and c-fos were only transiently induced within 1 h post-irradiation. Cyclin D1 was induced at all radiation doses. However, cfos induction was highest at 0.1 Gy, approximately 7.3 fold more induction than the control, whose induction was reduced in a reverse correlation with radiation dose. The phosphorylation pattern of cdc-2 and pRb were unaffected by radiation. In contrast to A431 tails overexpressing the EGF receptor approximately 8.5 fold higher than normal epithelial, the OM cells reduced the basal level of the EGF receptor phosphorylation in a radiation dose dependent fashion. In conclusion, among radiation-induced biomolecules, the p53 nuclear accumulation may be considered for the future development of a useful marker far biological radiodosimetry in normal epithelial tissue since it was sustained for a longer period and showed a dose response relationship. Specific c-fos induction at a low dose may also be an important finding in this study It needs to be studied further for the elucidation of its possible connection with the low dose radio-adaptive response.

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Selective Radiotherapy after Distant Metastasis of Nasopharyngeal Carcinoma Treated with Dose-Dense Cisplatin plus Fluorouracil

  • Liang, Yong;Bu, Jun-Guo;Cheng, Jin-ling;Gao, Wei-Wei;Xu, Yao-Can;Feng, Jian;Chen, Bo-Yu;Liang, Wei-Chao;Chen, Ke-Quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.6011-6017
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    • 2015
  • Purpose: To investigate the efficacy and safety of selective radiotherapy after distant metastasis of nasopharyngeal carcinoma (NPC) treated with dose-dense cisplatin plus fluorouracil. Materials and Methods: Eligible patients were randomly assigned to a study group treated with dose-dense cisplatin plus fluorouracil following selective radiotherapy and a control group receiving traditional cisplatin plus fluorouracil following selective radiotherapy according to a 1:1 distribution using a digital random table method. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate, relapse or progression rate in the radiation field and treatment toxicity. Results: Of 52 patients in the study group, 20 cases underwent radiotherapy., while in the control group of 51 patients, 16 underwent radiotherapy. The median PFS, median OS, survival rates in 1, 2 and 3 years in study and control group were 20.9 vs 12.7months, 28.3 vs 18.8months, 85.2%vs 65.9%, 62.2% vs 18.3%, and 36.6%vs 5.2% (p values of 0.00, 0.00, 0.04, 0.00 and 0.00, respectively). Subgroup analysis showed that the median OS and survival rates of 1, 2, 3 years for patients undergoing radiotherapy in the study group better than that in control group( 43.2vs24.1 months, 94.1% vs 86.7%, 82.4% vs 43.3%, 64.7% vs 17.3%, (p=0.00, 0.57, 0.04 and 0.01, respectively). The complete response rate, objective response rate after chemotherapy and three months after radiotherapy, relapse or progression rate in radiation field in study group and in control group were 19.2% vs 3.9%, 86.5% vs 56.9%, 85% vs 50%, 95% vs 81.3% and 41.3% vs 66.7% (p =0.03, 0.00, 0.03,0.30, 0.01 respectively). The grade 3-4 acute adverse reactions in the study group were significantly higher than in the control group (53.8% vs 9.8%, p=0.00). Conclusions: The survival of patients benefits from selective radiotherapy after distant metastasis of NPC treated with dose-dense cisplatin plus fluorouracil.

LiF TLD in TLD Holder for In Vivo Dosimetry (생체 내 선량측정을 위한, TLD홀더에 넣은 LiF TLD)

  • Kim Sookil;Loh John J.K.;Min Byungnim
    • Radiation Oncology Journal
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    • v.19 no.3
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    • pp.293-299
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    • 2001
  • Prupose : LiF TLD has a problem to be used in vivo dosimetry because of the toxic property of LiF. The aim of this study is to develop new dosimeter with LiF TLD to be used in vivo dosimetry. Materials and methods : We designed and manufactured the teflon box(here after TLD holder) to put TLD in. The external size of TLD holder is $4\times4\times1\;mm^3$ To estimate the effect of TLD holder on TLD response for radiation, the linearity of TLD response to nominal dose were measured for TLD in TLD holder. Measurement were peformed in the 10 MV x-ray beam with LiF TLD using a solid water phantom at SSD of 100 cm. Percent Depth Dose (PDD) and Tissue-Maximum Ratio (TMR) with varying phantom thickness on TLD were measured to find the effect of TLD holder on the dose coefficient used for dose calculation in radiation therapy. Results : The linearity of response of TLD in TLD holder to the nominal dose was improved than TLD only used as dosimeter And in various measurement conditions, it makes a marginnal difference between TLD in TLD holder and TLD only in their responses. Conclusion : It was proven that the TLD in TLD holder as a new dosimetry could be used in vivo dosimetry.

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Evidence-based approach for herbal medicine-safety classification : Human equivalent dose-based the margin of safety (한약의 안전성 등급화를 위한 evidence-based approach : Human equivalent dose-based the margin of safety)

  • Park, Yeong-Chul;Lee, Sundong
    • Journal of Society of Preventive Korean Medicine
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    • v.17 no.3
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    • pp.19-30
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    • 2013
  • This study was aimed to develop a new formula for herbal medicine-safety classification in terms of evidence-based medicine. Recently, human equivalent dose(HED)-based therapeutic index was developed for herbal medicine-safety classification by transforming $LD_{50}$ to HED. However, the use of the $ED_{50}$ and $LD_{50}$ to derive the therapeutic index may be misleading as to safety, depending on the slope of the dose-response curves for therapeutic and lethal effects. To overcome this deficiency, HED-based MOS(Margin of Safety)was developed and suggested in this study. The HED-based MOS developed by using $LD_1$, changing to ALD(approximate lethal dose), and $ED_{99}$. The HED-based MOS seems to be more useful and safer than HED-based therapeutic index since its values for several herbal medicines are basically two times less than the values from HED-based therapeutic index. Thus, HED-based MOS can be a good example of Evidence-based approach for herbal medicine-safety classification.

Dose Dependence of the Severity of Radiation-Induced Thymic Lymphoma in Mice

  • GU, Yeunhwa;Oshima, Masami;Hasegawa, Takeo
    • Environmental Mutagens and Carcinogens
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    • v.22 no.4
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    • pp.266-273
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    • 2002
  • The dose dependence of the severity of radiation-induced thymic lymphoma in C57BL/6J mice was studied. Mice were exposed to fractionated irradiation at the total doses of 4.0, 6.0 and 8.0 Gy (four irradiations at 8-day intervals) starting from 33 days after birth. Pathological and histological changes of each mouse were observed after periodical sacrifice at day 75, 100, 125, 150, 175, 200, 250, 300 after the first irradiation. The severity of cancers were classified into 4 stages by clinical signs with respect to the enlargement of the thymus, spleen, liver, the progression of the cancer in the thymus, and the metastasis to the spleen, liver, lung and the lymphatic nodes. Among the 490 mice observed, 146 mice had thymic lymphoma. A clear dose-effect relationship was observed as well as the dose-response relationship. Also, periodical observation showed that thymic lymphoma was first induced in mice sacrificed at day 100 (130days old), and metastasize in the order of spleen, lung, liver and then the lymphatic nodes. The results suggest that radiation may be involved not only as a tumor initiator but also as a tumor promoter, and a tumor progression-enhancing agent.

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Basic Concepts of Western Medicine Toxicology and $LD_{50}$ in Herbal Drugs (서양의학 독성학의 기본적 개념 및 한약의 $LD_{50}$)

  • Park Yeon-Chul;Lee Sun-Dong;Park Kyoung-Sik
    • Journal of Society of Preventive Korean Medicine
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    • v.3 no.2
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    • pp.91-100
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    • 1999
  • Today, toxicology is used for many purpose, in many fields. Classification of special toxic effect is related next 4 important principles. 1. The chemical substance must move to target organ or tissue that can induce Biological effect. For this movement, we have to understand the physical-chemical characteristic of substance, and the rout of absorption, metabolism, diffusion and excretion of toxic substance. 2. Every biological effect that induced by chemical substance is not harmful. For example, some specific chemical substance is not harmful in liver enzyme system. 3. The strength of biological effect induced by chemical substance is deep related with dose. Nearly all substance is not effective below the specific dose, and it may toxic to death over the specific dose. It is the 'Dose - response relationship' But carcinogen may toxic whether it is law dose or not. 4. The information that was obtained by experimental animal test, could have to adapt in human biology. Because biological effect of chemical substance could be different in every biological species. In past, drugs was obtained by animal or plants. But in the future, it could be obtained by biochemistry, and genome project. Therefore, in Oriental medicine, research and approach is needed at this time, and have to develop new method of experience in toxic method.

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A Experimental Study on the Citri Reticulatae Viride Pericarpium( I ) (청피(靑皮)의 실험적(實驗的) 연구(硏究) ( I ))

  • Kang Sung-Yong;Lee Won-Suk;Jeong Hyun-Woo;Han Jong-Hyun
    • Herbal Formula Science
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    • v.8 no.1
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    • pp.329-342
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    • 2000
  • Citri Reticulatae Viride Pericarpium(CRVP) is being used to regulate the flow of Q(氣) However, the mechanism of it's pharmacological actions is not well understood. The purpose of this research was to investigate effects of CRVP contractil response of isolated on abdominal and femoral artery in rabbits and renal artery in pigs. 1. Abdominal artery was relaxed by CRVP in a dose-dependent manner. 2. Femoral artery was relaxed by CRVP in a dose-dependent manner 3. Pretreatment with methylene blue and indomethacin did not inhibited CRVP induced relax in abdominal artery and femoral artery. 4. Renal artery was relaxed by $H_{2}O$ fraction in a dose-dependent manner, 5. Pretreatment with regitine inhibited $H_{2}O$ fraction(CRVP) induced relax in renal artery in a dose-dependent manner. 6. Renal artery was not relaxed by hexane fraction(CRVP) in a dose-dependent manner. 7. Pretreatment with regitine$(10^{-7}M)$ was relaxed by methylene chloride(MC)(CRVP) and $H_{2}O$ fraction in a $0.5{\mu}g/m{\ell}$.

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