• Title/Summary/Keyword: Dose-response

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Novel nomogram-based integrated gonadotropin therapy individualization in in vitro fertilization/intracytoplasmic sperm injection: A modeling approach

  • Ebid, Abdel Hameed IM;Motaleb, Sara M Abdel;Mostafa, Mahmoud I;Soliman, Mahmoud MA
    • Clinical and Experimental Reproductive Medicine
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    • v.48 no.2
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    • pp.163-173
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    • 2021
  • Objective: This study aimed to characterize a validated model for predicting oocyte retrieval in controlled ovarian stimulation (COS) and to construct model-based nomograms for assistance in clinical decision-making regarding the gonadotropin protocol and dose. Methods: This observational, retrospective, cohort study included 636 women with primary unexplained infertility and a normal menstrual cycle who were attempting assisted reproductive therapy for the first time. The enrolled women were split into an index group (n=497) for model building and a validation group (n=139). The primary outcome was absolute oocyte count. The dose-response relationship was tested using modified Poisson, negative binomial, hybrid Poisson-Emax, and linear models. The validation group was similarly analyzed, and its results were compared to that of the index group. Results: The Poisson model with the log-link function demonstrated superior predictive performance and precision (Akaike information criterion, 2,704; λ=8.27; relative standard error (λ)=2.02%). The covariate analysis included women's age (p<0.001), antral follicle count (p<0.001), basal follicle-stimulating hormone level (p<0.001), gonadotropin dose (p=0.042), and protocol type (p=0.002 and p<0.001 for short and antagonist protocols, respectively). The estimates from 500 bootstrap samples were close to those of the original model. The validation group showed model assessment metrics comparable to the index model. Based on the fitted model, a static nomogram was built to improve visualization. In addition, a dynamic electronic tool was created for convenience of use. Conclusion: Based on our validated model, nomograms were constructed to help clinicians individualize the stimulation protocol and gonadotropin doses in COS cycles.

Experimental Allergic Contact Dermatitis in the Guinea Pig (기니픽에 있어서 실험적(實驗的) 앨러지성(性) 접촉성(接觸性) 피부염(皮膚炎))

  • Lee, Chai-yong;Lee, Chung-gil;Lee, Ju-mook
    • Korean Journal of Veterinary Research
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    • v.24 no.2
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    • pp.169-171
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    • 1984
  • An expeliment was carried out to measure the cellular immune response in guinea pigs by sensitizing the animals with 2, 4-dinitrochlorobenzene(DNCB). The guinea pigs could be sensitized with one application of DNCB. The sensitizing and challenge dose was standardized. The histological response was characteristic of a delayed hypersensitivity reaction.

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A Study on the Radiation Dose of $^{131}I$ in the Thyroid Gland during the Treatment of Hyperthyroidism (갑상선 기능항진증의 $^{131}I$ 치료시 갑상선 조사량에 관한 연구)

  • Suh, Hwan-Jo;Koh, Chang-Soon;Lee, Mun-Ho
    • The Korean Journal of Nuclear Medicine
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    • v.9 no.1
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    • pp.59-71
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    • 1975
  • 53 patients with hyperthyroidism have been analyzed with special reference to therapeutic response to radioactive iodine ($^{131}I$) treatment. Mean effective half-life, 24 hour uptake rate and radiation dose of $^{131}I$ in hyperthyroid patients included in this study were respectively. 1. Mean effective half-life of $^{131}I\;was\;4.7{\pm}1.5$ days in the tracer dose and $5.0{\pm}1.5$ days in the therapeutic dose. 2. Mean 24 hour uptake rate of $^{131}I\;was\;72.7{\pm}11.1%$ in the tracer dose and $73.4{\pm}12.3%$ in the theapeutic dose. 3. Mean radiation dose of $^{131}I\;was\;5,319{\pm}2,648$ RAD as predicted and $5,692{\pm}2,843$ RAD as actual. A single dose of radioactive iodine treatment was satisfactory in 34 patients (radioiodine sensitive) and multiple doses of radioactive iodine treatments were required in 19 patients (radioiodine resistant). A radioiodine resistant group of patients with hyperthyroidism was distinctively characteristic in the following aspects. 1. Mean thyroid weight calculated in the resistant group ($63.9{\pm}14.0gm$) was significantly (p<0.01) greater than that of the sensitive group ($46.6{\pm}13.3gm$). 2. Mean 24 hour uptake rate of the tracer dose in the resistant group ($67.3{\pm}10.7%$) was significantly (p<0.01) lower than that of the sensitive group ($75.7{\pm}10.5%$). 3. Mean 24 hour uptake rate of the therapeutic dose in the resistant group ($68.5{\pm}13.7%$) was significantly (p<0.05) lower than that of the sensitive group ($76.1{\pm}10.9%$). 4. Mean predicted radiation dose, of $^{131}I$ in the resistant group ($3,684{\pm}1,745$ RAD) was significantly (p<0.01) lower than that of the sensitive group ($6,232{\pm}2,683$ RAD). 5. Mean actual radiation dose of $^{131}I$ in the resistant group ($4,100{\pm}1,691$ RAD) was significantly (p<0.01) lower than that of the sensitive group ($6,582{\pm}3,024$ RAD). 6. No significant difference was detected in terms of effective half-life of $^{131}I$ among the groups (p>0.05). 7. The average mean % difference of effective half-life, uptake rate and radiation dose measured following the tracer and therapeutic dose of $^{131}I$ were not statistically significant (p>0.05). Therefore effective half-life, uptake rate and radiation dose of the therapeutic dose of $^{131}I$ were readily predictable following the tracer dose of $^{131}I$. 8. It is concluded that the possibility of resistance to radioactive iodine treatment may be anticipated in patients with thyroid gland large in size and compromised $^{131}I$ uptake rate.

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Monitoring of Heparin and Protamine Therapy by Activated Clotting Time During Open-Heart Surgery (개심술시 Activated Clotting Time 을 이용한 Heparin 및 Protamine 양 조절에 관한 임상적 관찰)

  • Kim, Chun-Dong;Lee, Sung-Haing
    • Journal of Chest Surgery
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    • v.13 no.4
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    • pp.346-355
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    • 1980
  • It has been proposed that wide individual variation in response to heparin be not considered in the conventional set protocol for the control of heparin and protamine during extracorporeal circulation. In this paper, two protocol of heparin and protamine therapy were compared to assess the role of the Activated Clotting Time [ACT] in relation to heparin, protamine, and postoperative blood loss and transfusion. The study groups consisted of the 31 patients [adults 15 and children 16] anticoagulated with the conventional heparin protocol and the 31 patients [adults 15 and children 16] anticoagulated with ACT protocol during extracorporeal circulation. In the conventional heparin protocol, two mg of heparin per kg was administered initially with an additional 0.75 mg of heparin per kg every 30 minutes of extracorporeal circulation, and reversal was accomplished with protamine in a dose of 1.5 times the total milligram of heparin. In the ACT protocol, two mg of heparin per kg was administered initially with an additional dose of heparin enough to reach an ACT of 480 seconds [within safe zone 300 to 600 seconds] from the patient`s dose response curve every 1 hour of extracorporeal circulation, and reversal was done with protamine in a dose of 1.3 times the milligram of the residual heparin. The results were summarized as follows. After a dose of 2 mg per kg of heparin, the patient`s ACT varied from 240 to 600 seconds in adults and from 240 t~ 660 seconds in children. In the ACT group the total amount of heparin administered was markedly reduced when compared to the conventional group, and less protamine was required to neutralize heparin. The dose of heparin administered decreased from 7.07 [SE 0.42] mg/kg of the conventional group to 4.92 [SE 0.32] mg/k8 of the ACT group in adults and from 10.17 [SE 1.15] mg/kg to 5.23 [SE 0.24] mg/kg in children, which represent 30.4% and 48.6% decrease respectively. The dose of protamine administered for reversal decreased from 10.6 [SE 0.63] mg/kg of the conventional group to 3.35 [SE 0.35] mg/kg of the ACT group in adults and from 15.7 [SE 1.70] mg/kg to 3.26 [SE 0.27] mg/kg in children, which represent 68.4% and 79.2% respectively. The ratio of protamine to heparin administered in the conventional group was 1.50:1 in adults and 1.54:1 in children, but in the ACT group 0.68:1 in adults and 0.62:1 in children. Postoperative blood loss and transfusion revealed no statistically significant difference between the two groups. Although six patients in the conventional group and one in the ACT group needed re-exploration for continuous hemorrhage, no case of generalized oozing was encountered, and in each case a definite bleeding site was identified. Author would like emphasizing the value of the ACT protocol in controlling heparin and protamine administration during extracorporeal circulation.

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Assessment of Effective Doses in the Radiation Field of Contaminated Ground Surface by Monte Carlo Simulation (몬테칼로 시뮬레이션에 의한 지표면 오염 방사선장에서의 유효선량 평가)

  • Chang, Jai-Kwon;Lee, Jai-Ki;Chang, Si-Young
    • Journal of Radiation Protection and Research
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    • v.24 no.4
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    • pp.205-213
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    • 1999
  • Effective dose conversion coefficients from unit activity radionuclides contaminated on the ground surface were calculated by using MCNP4A rode and male/female anthropomorphic phantoms. The simulation calculations were made for 19 energy points in the range of 40 keV to 10 MeV. The effective doses E resulting from unit source intensity for different energy were compared to the effective dose equivalent $H_E$ of previous studies. Our E values are lower by 30% at low energy than the $H_E$ values given in the Federal Guidance Report of USEPA. The effective dose response functions derived by polynomial fitting of the energy-effective dose relationship are as follows: $f({\varepsilon})[fSv\;m^2]=\;0.0634\;+\;0.727{\varepsilon}-0.0520{\varepsilon}^2+0.00247{\varepsilon}^3,\;where\;{\varepsilon}$ is the gamma energy in MeV. Using the response function and the radionuclide decay data given in ICRP 38, the effective dose conversion coefficients for unit activity contamination on the ground surface were calculated with addition of the skin dose contribution of beta particles determined by use of the DOSEFACTOR code. The conversion coefficients for 90 important radionuclides were evaluated and tabulated. Comparison with the existing data showed that a significant underestimates could be resulted when the old conversion coefficients were used, especially for the nuclides emitting low energy photons or high energy beta particles.

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Gamma-ray Induced DNA Repair Synthesis in Relation to Chromosome Exchanges in Mammalian Cells in Vitro (哺乳動物細胞에 있어 감마線에 의한 DNA 回復合成과 染色體交換과의 聯關性)

  • Park, Sang-Dai
    • The Korean Journal of Zoology
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    • v.18 no.1
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    • pp.41-49
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    • 1975
  • Dose response and time dependence of DNA repair synthesis were investigated to determine the possible relationship between DNA repair synthesis and chromosome exchanges in $\\gamma$-ray irradiated BHK-21 and KB cell lines. DNA repair synthesis induced by $\\gamma$-ray was dose dependent up to 5kR, then leveling off occurred until 50 kR was reached. Time dependence of DNA repair synthesis was continued for up to 1$\\sim$2 hours after irradiation although the initial dose responses were cell line specific. Chromosome exchanges induced by $\\gamma$-ray showed different radiosensitivities in these cell lines and did not show a correlation with the DNA repair synthesis.

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Effects of Fish Oil Supplementation to Korean Lactasting Women -II. The Effects on Lipid Content and Fatty Acid Composition of Breast Milk- (한국인 수유부에 어유의 보충 급여 효과에 관한 연구 - II. 모유의 지질 농도 및 지방산 조성에 미친 영향-)

  • 임현숙
    • Journal of Nutrition and Health
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    • v.29 no.2
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    • pp.188-191
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    • 1996
  • This study was undertaken to determine the effects of fish oil supplementation with low dose on the lipid content and fatty acid composition of breast milk. Among 18 lactating women who were exclusively breast-fed their babies, 6 were in control group and 12 were in fish lil groups. The subjects in fish oil groups were supplemented with 1.96g/d or 3.92g/d of fish oil for 2 weeks from 10 to 12 weeks of postpartum. All subjects consumed their usual diet at home. Breast milk samples were collected at the final day of experiment. By fish oil supplementation, the concentrations of triglyceride, cholesterol, free fatty acid and phospholipid as well as total lipid in breast milk tended to increase, but not significant. There was no dose-dependent response. The fatty acid composition of breast milk was not changed by fish oil supplementation. These results suggest that low dose of fish oil supplementation may increase of lipid content, but does not affect on the fatty acid composition of breast milk.

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DNA Repair Enhancement by Radioprotective Ginseng Protein Fraction (항 방사선 인삼단백분획의 DNA수복능력 증진효과)

  • Kim, Choon-Mi;Choi, Mi-Kyung
    • YAKHAK HOEJI
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    • v.36 no.5
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    • pp.449-454
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    • 1992
  • The effect of radioprotective ginseng protein fraction on DNA repair capacity was determined by measuring the amount of $^{3}H-thymidine$ incorporated into DNA in the process of repair synthesis for UV damaged DNA. CHO-Kl cells were prepared whose semiconservative replication was inhibited by trimethylpsoralen plus near-UV(PUVA) treatment. When the cells were exposed to UV light alone, the DNA repair capacity was increased at first and then decreased as UV dose increased. However, when the ginseng fraction was treated to the cells, the DNA repair capacity was kept increasing regardless of UV dose increment. When the concentration of protein contained in the added fraction was increased gradually, the repair capacity was also increased almost linearly showing dose-response relationship of the effect. These results suggest that the enhancement of DNA repair capacity of the cell can be one of the mechanisms of radioprotection by the ginseng fraction.

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Radiosensitivity and Dobe-Survival Characteristics of Crypt Cells of Mouse Jejunum (마우스공장 소낭선세포의 방사선 감수성에 관한 실험적 연구)

  • Huh, Seung-Jae;Park, Charn-Il
    • Radiation Oncology Journal
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    • v.3 no.1
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    • pp.9-12
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    • 1985
  • To determine the radiosensitivity and dose-survival characteristics of jejunal crypt cells, experimental study was done using total 40 mice. Single irradiation of 1,000 rad to 1,600rad was delivered to whole bodies of mice, using a cesium 137 animal irradiator. The number of regenerating crypts per jejunal circumference was counted, by using a jejunal crypt cell assay technique, and dose response curve was measured. The average number of jejunal crypt Per circumference in control group was $140\pm10$. Mean lethal dose$(D_0)$ of moose jejunal crypt cell was 135rad.

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A Bayesian joint model for continuous and zero-inflated count data in developmental toxicity studies

  • Hwang, Beom Seuk
    • Communications for Statistical Applications and Methods
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    • v.29 no.2
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    • pp.239-250
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    • 2022
  • In many applications, we frequently encounter correlated multiple outcomes measured on the same subject. Joint modeling of such multiple outcomes can improve efficiency of inference compared to independent modeling. For instance, in developmental toxicity studies, fetal weight and number of malformed pups are measured on the pregnant dams exposed to different levels of a toxic substance, in which the association between such outcomes should be taken into account in the model. The number of malformations may possibly have many zeros, which should be analyzed via zero-inflated count models. Motivated by applications in developmental toxicity studies, we propose a Bayesian joint modeling framework for continuous and count outcomes with excess zeros. In our model, zero-inflated Poisson (ZIP) regression model would be used to describe count data, and a subject-specific random effects would account for the correlation across the two outcomes. We implement a Bayesian approach using MCMC procedure with data augmentation method and adaptive rejection sampling. We apply our proposed model to dose-response analysis in a developmental toxicity study to estimate the benchmark dose in a risk assessment.