• Progress in Medical Physics
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• v.9 no.4
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• pp.227-245
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• 1998

A most appropriate model of 3-D conformal radiotherapy has been induced by clinical evaluation and animal study, and therapeutic gains were evaluated by numerical equation of tumor control probability(TCP) and normal tissue complication probability (NTCP). The radiation dose to the tumor and the adjacent normal organs was accurately evaluated and compared using the dose volume histogram(DVH). The TCP and NTCP was derived from the distribution of given dosage and irradiated volume, and these numbers were used as the biological index for the assessment of the treatment effects. Ten patients with liver disease have been evaluated and 3 dogs were sacrificed for this study. Based on the 3-D images of the tumor and adjacent organs, the optimum radiation dose and the projection direction which could maximize the radiation effect while minimizing the effects to the adjacent organs could be decided. 3). The most effective collimation for the normal adjacent organs was made through the beams eye view with the use of multileaf collimator. When the dose was increased from 50Gy to 70Gy, the TCP for the conventional 2-port radiation and the 5-port multidimensional therapy was 0.982 and 0.995 respectively, while the NTCP was 0.725 and 0.142 respectively, suggesting that the 3-D conformal radiotherapy might be the appropriate therapy to apply sufficient radiation dose to the tumor while minimizing the damages to the normal areas of the liver. Positive correlation was observed between the NTCP and the actual complication of the normal liver in the animal study. The present study suggest that the use of 3-D conformal radiotherapy and the application of the mathematical models of TCP and NTCP may provide the improvements in the treatment of hepatoma with enhanced results.

• Progress in Medical Physics
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• v.16 no.4
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• pp.166-175
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• 2005

The purpose of this study is to develop the optimization method for adjusting the film isocenter shift and to suggest the quantitative acceptable criteria for film dosimetry after optimization In the dynamic conformal arc radiation therapy (DCAR). The DCAR planning was peformed In 7 patients with brain metastasis. Both absolute dosimetry with ion chamber and relative film dosimetry were peformed throughout the DCAR using BrainLab's micro-multileaf collimator. An optimization method for obtaining the global minimum was used to adjust for the error in the film isocenter shift, which is the largest pan of systemic errors. The mean of point dose difference between measured value using ion chamber and calculated value acquired from planning system was $0.51{\pm}0.43\%$ and maximum was $1.14\%$ with absolute dosimetry These results were within the AAPM criteria of below $5\%$. The translation values of film isocenter shift with optimization were within ${\pm}$1 mm in all patients. The mean of average dose difference before and after optimization was $1.70{\pm}0.35\%$ and $1.34{\pm}0.20\%$, respectively, and the mean ratios over $5\%$ dose difference was $4.54{\pm}3.94\%$ and $0.11{\pm}0.12\%$, respectively. After optimization, the dose differences decreased dramatically and a ratio over $5\%$ dose difference and average dose difference was less than $2\%$. This optimization method is effective in adjusting the error of the film isocenter shift, which Is the largest part of systemic errors, and the results of this research suggested the quantitative acceptable criteria could be accurate and useful in clinical application of dosimetric verification using film dosimetry as follows; film isocenter shift with optimization should be within ${\pm}$1 mm, and a ratio over $5\%$ dose difference and average dose difference were less than $2\%$.

• The Korean Journal of Nuclear Medicine
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• v.36 no.3
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• pp.195-202
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• 2002

Purpose: For clinical application of beta-emitter labeled antibody, high specific activity is imporiant. Carrier-free $^{188}Re$ from $^{188}W/^{188}Re$ generator is an ideal radionuclide for this purpose. However, low stability of $^{188}Re$ labeled antibody, especially in high specific activity, due to radiolytic decomposition by high energy (2.1 MeV) beta ray was problem. We studied the stability of $^{188}Re$ labeled antibody, and stabilizing effect of several stabilizers. Materials and Methods: Pre-reduced monoclonal antibody (CEA79.4) was labeled with $^{188}Re$ by incubating with generator-eluted $^{188}Re-perrhenate$ in the presence of stannous tartrate for 2 hr at room temperature. Radiochemical purity of each preparation was determined by chromatography. Human serum albumin was added to the labeled antibodies (2%). Stability of $^{188}Re-CEA79.4$ was investigated in the presence of ascorbic acid, ethanol, of Tween 80 as stabilizing agents. Results: Labeling efficiencies were $88{\pm}4%\;(n=12)$. Specific activities of $1.25{\sim}4.77MBq/{\mu}g$ were obtained. If stored after purging with $N_2$, all the preparations were stable for 10 hr. However, stability decreased in the presence of air. Perrhenate and $^{188}Re-tartrate$ was major impurity in declined preparation. colloid-formation was not a significant problem in all cases. Addition of ascorbic acid stabilized the labeled antibodies either under $N_2$ or under air by reducing the formation of perrhenate. Conclusion: High specific activity $^{188}Re$ labeled antibody is unstable, especially, in the presence of oxygen. Addition of ascorbic acid increased the stability.

• The korean journal of orthodontics
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• v.33 no.4 s.99
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• pp.279-291
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• 2003

Electric current is a highly probable way as a clinical tool for tooth movement. The purposes of this study were to determine the usefulness of exogenous electric currents in accelerating orthodontic tooth movement and to investigate the effects of electric-orthodontic treatment on the remodeling of the periodontal tissue histologically The study was performed with six male cats weighing around 3kg. The electric device wich is providing the direct electric current of $20{\mu}A$ was inserted to the removable appliance. The right and left maxillary canines were assigned as control and experimental sides respectively. The control canine was Provided with orthodontic force (75gm) oかy and the experimental side was given the same amount of force and electricity. The lingual buttons were bonded to the maxillary canines and both sides of canines were retracted with NiTi coil spring. The electric device was adjusted to provide 20uh direct current to the experimental canines S hours a day The amount of the canine movement was measured with electronic caliper every week. After 4 weeks of tooth movement, the animals were sacrificed and the histologic study was performed. The results of this study were as follows. 1. The application of a direct current to the experimental tooth significantly increased the final amount of orthodontic tooth movement. The amount of tooth movement after 28-day was 37% more in the experimental side. 2. The electrically stimulated tooth showed histologic evidence of significant increases in the amount of bones and matrix deposition in the area of tension. 3. In the compression side, the electric-orthodontic treatment stimulated bone resorption more extensively in the experimental canines. 4. After 28 days of electricity exposure and orthodontic force, the experimental side demonstrated significantly more osteoblasts, osteoclasts, capillaries and osteoid tissues, reflectinr an increase in the local tissue's cellular activity. 5. Intermittent electrical stimulation (five hours a day) had effects to enhance orthodontic tooth movement and tissue remodeling. These results suggested that the low-intensity exogenous electric current by the miniature electric device might accelerate orthodontic tooth movement and bone remodeling in vivo and have the possibility to reduce the orthodontic treatment duration.

• Progress in Medical Physics
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• v.12 no.1
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• pp.41-50
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• 2001

The quantification analysis of renal scintigraphy is strongly affected by the location, shape and size of region of interest(ROI). When ROIs are drawn manually, these ROIs are not reproducible due to the operators' subjective point of view, and may lead to inconsistent results even if the same data were analyzed. In this study, the effect of the ROI variation on the analysis of renal scintigraphy when the ROIs are drawn manually was investigated, and in order to obtain more consistent results, methods for automated ROI definition were developed and the results from the application of the developed methods were analyzed. Relative renal function, glomerular filtration rate and mean transit time were selected as clinical parameters for the analysis of the effect of ROI and the analysis tools were designed with the programming language of IDL5.2. To obtain renal scintigraphy, $^{99m}$Tc-DTPA was injected to the 11 adults of normal condition and to study the inter-operator variability, 9 researchers executed the analyses. The calculation of threshold using the gradient value of pixels and border tracing technique were used to define renal ROI and then the background ROI and aorta ROI were defined automatically considering anatomical information and pixel value. The automatic methods to define renal ROI were classified to 4 groups according to the exclusion of operator's subjectiveness. These automatic methods reduced the inter-operator variability remarkably in comparison with manual method and proved the effective tool to obtain reasonable and consistent results in analyzing the renal scintigraphy quantitatively.

• Progress in Medical Physics
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• v.12 no.1
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• pp.51-58
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• 2001

Synchrotron radiation (SR) has several advantages over convetional x-rays, including its phase, collimation, and high flux. A synchrotron radiation beamline 5C1 at Pohang Light Source (PLS) was recently built for imaging applications. We have shown that a SR imaging system is useful in imaging microscopic structures. SR with broad-band energy spectrum were adjusted to an object by Si wafers and their energy were approximately ranging from 6 keV to 30 keV. SR were passed through an object and finally transformed into visible lights by CdWO$_4$ scintillator screen. The visible lights which were reflected at an angle of 90 degrees by gold plated mirror were detected by a CCD camera and the image data were acquired using image acquisition system. A high-resolution phantom, capacitor, adult tooth, child tooth, cancerous breast tissue, and mouse lumbar vertebra were imaged with SR imaging system. The Objects were rotated within the field of view of the CCD detector, and their projection image data were obtained at 250 steps over 180 degrees rotation. Image reconstructions were carried out in a PC by using IDLTM(Research systems, Inc., US) program. The spatial resolution of the images acquired by the SR imaging system was measured with a high-resolution chart manufactured for several micrometer resolution. The specimens were also imaged with conventional x-ray radiography system to compare the image quality of radiography obtained with the SR imaging system. The results showed more structural details and high contrast images with SR imaging system than conventional x-ray radiography system. The SR imaging system may have a potential for imaging in biological researches, material applications, and clinical radiography.

• Clinical and Experimental Pediatrics
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• v.50 no.7
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• pp.686-693
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• 2007

Purpose : Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is a potent inhibitor of inosine-monophosphate dehydrogenase (IMPDH), a new immunosuppressive drug used. It was reported that MPA protected neurons after excitotoxic injury, induced apoptosis in microglial cells. However, the effects of MPA on hypoxic-ischemic (HI) brain injury has not been yet evaluated. Therefore, we examined whether MPA could be neuroprotective in perinatal HI brain injury using Rice-Vannucci model (in vivo) and in rat brain cortical cell culture induced by hypoxia (in vitro). Methods : Cortical cells were cultured using a 18-day-pregnant Sprague-Dawley (SD) rats and incubated in 1% $O_2$ incubator for hypoxia. MPA ($10{\mu}g/mL$) before or after a HI insult was treated. Seven-day-old SD rat pups were subjected to left carotid occlusion followed by 2 hours of hypoxic exposure (8% $O_2$). MPA (10 mg/kg) before or after a HI insult were administrated intraperitoneally. Apoptosis was measured using western blot and real-time PCR for Bcl-2, Bax, caspase-3. Results : H&E stain revealed increased brain volume in the MPA-treated group in vivo animal model of neonatal HI brain injury. Western blot and real-time PCR showed the expression of caspase-3 and Bax/Bcl-2 were decreased in the MPA-treated group In in vitro and in vivo model of perinatal HI brain injury, Conclusion : These results may suggest that the administration of MPA before HI insult could significantly protect against perinatal HI brain injury via anti-apoptotic mechanisms, which offers the possibility of MPA application for the treatment of neonatal HI encephalopathy.

• Radiation Oncology Journal
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• v.18 no.2
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• pp.150-156
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• 2000

Purpose : Stereotactic radiation therapy (SRT) can deliver highly focused radiation to a small and spherical target lesion with very high degree of mechanical accuracy. For non-spherical and large lesions, however, inclusion of the neighboring normal structures within the high dose radiation volume is inevitable in SRT This is to report the beam shaping using the partial closure of the independent jaw in SRT and the verification of dose calculation and the dose display using a home-made soft ware. Materials and Methods : Authors adopted the idea to partially close one or more independent collimator jaw(5) in addition to the circular collimator cones to shield the neighboring normal structures while keeping the target lesion within the radiation beam field at all angles along the arc trajectory. The output factors (OF's) and the tissue-maximum ratios (TMR's) were measured using the micro ion chamber in the water phantom dosimetry system, and were compared with the theoretical calculations. A film dosimetry procedure was peformed to obtain the depth dose profiles at 5 cm, and they were also compared with the theoretical calculations, where the radiation dose would depend on the actual area of irradiation. Authors incorporated this algorithm into the home-made SRT software for the isodose calculation and display, and was tried on an example case with single brain metastasis. The dose-volume histograms (DVH's) of the planning target volume (PTV) and the normal brain derived by the control plan were reciprocally compared with those derived by the plan using the same arc arrangement plus the independent collimator jaw closure. Results : When using 5.0 cm diameter collimator, the measurements of the OF's and the TMR's with one independent jaw set at 30 mm (unblocked), 15.5 mm, 8.6 mm, and 0 mm from th central beam axis showed good correlation to the theoretical calculation within 0.5% and 0.3% error range. The dose profiles at 5 cm depth obtained by the film dosimetry also showed very good correlation to the theoretical calculations. The isodose profiles obtained on the home-made software demonstrated a slightly more conformal dose distribution around the target lesion by using the independent jaw closure, where the DVH's of the PTV were almost equivalent on the two plans, while the DVH's for the normal brain showed that less volume of the normal brain receiving high radiation dose by using this modification than the control plan employing the circular collimator cone only. Conclusions : With the beam shaping modification using the independent jaw closure, authors have realized wider clinical application of SRT with more conformal dose planning. Authors believe that SRT, with beam shaping ideas and efforts, should no longer be limited to the small spherical lesions, but be more widely applied to rather irregularly shaped tumors in the intracranial and the head and neck regions.

• The Korean Society of Law and Medicine
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• v.21 no.1
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• pp.223-259
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• 2020

With COVID-19 spreading rapidly around the world, research and development issues on treatments and vaccines for the virus are of high interest. Among them, Remdesivir was the first to show noticeable therapeutic effects and began clinical trials, with each country authorizing the use of the drug through emergency approval. However, Gilead Co., Ltd., the developer of Remdesivir, received a lot of criticism from civic groups for submitting the application for the marketing authorization as an orphan drug. This is because when a new drug got a marketing authorization as an orphan drug could be granted an exclusive status for seven year. The long-term exclusive status of an orphan drug comes from the policy purpose of motivating pharmaceutical companies to develop treatment opportunities for patients suffering from rare diseases, which was not appropriate to apply to infectious disease treatments. This paper provides a review of the problems and improvement directions of the domestic system through comparative legal consideration against the United States, Europe and Japan for the statutes which give exclusive status to medicines. The domestic system has a fundamental problem that it does not have explicit provisions in the statute in the manner of granting exclusive status, and that it uses the review system to give it exclusive status indirectly. In addition, in the case of orphan drugs, the "Rare Diseases Management Act" and the "Regulations on Examination of Items Permission and Reporting of Drugs" provide overlapping review periods, and despite the relatively long monopoly period, there seems to be no check clause to recover exclusive status in the event of a change in circumstances. Given that biopharmaceuticals are difficult to obtain patents, the lack of such provisions is a pity of domestic legislation, although granting exclusive rights may be a great motivation to induce drug development. In the United States, given that the first biosimilar also has a one-year monopoly period, it can be interpreted that domestic legislation is quite strictly limited to granting exclusive status to biopharmaceuticals. The need for improvement of the domestic system will be recognized in that it could undermine local pharmaceutical companies' willingness to develop biopharmaceuticals in the future, and in that it is also necessary to harmonize international regulations. Taking advantage of the emergence of COVID-19 as an opportunity, we look again at the problems of the domestic system that grants exclusive rights to medicines and hope that an overall revision of the relevant legislation will be made to establish a unified legal basis.

• Childhood Kidney Diseases
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• v.1 no.2
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• pp.101-108
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• 1997

Purpose : The clinical characteristics of renovascular hypertension (RVHT) in children were analyzed. Methods : Medical records of 16 children diagnosed as RVHT on the basis of angiography during Jan. '86 to Jun. 94 in our hospital were reviewed retrospectively. Results : The mean age at the onset was 8.5 yrs and the sex ratio(M:F) was 7:9. The causes of RVHT were Takayasu arteritis in 6, Moyamoya disease in 5, and fibromuscular dysplasia in 3 patients. Abdominal bruit was noted in 6 patients (38%). Peripheral renin activity was raised in all tested patients. Bilateral renal arterial involvemnent was found in 9 patients (56%). Captopril renal scans showed good correlation with angiographic findings. Five patients were treated with antihypertensives only, and blood pressure was controlled completely in 2 and incompletely in 3. Percutaneous transluminal angioplasty was performed in 10 patients with 50% of success rate. However, hypertension was recurred due to restenosis or accompaning aortic stenosis in 3 patients. Surgical treatment was performed in 4 patients, and the blood pressure was controlled partially in 1 and poorly in the remaining 3. Conclusions : Takayasu arteritis, Moyamoya disease and fibromuscular dysplasia are the major causes of childhood RVHT in our country. The diagnosis of RVHT in children should be based on a set of tests individually selected for case by case. For the low curability of the current treatment modalities available, RVHT in children should not be regarded as 'curable' so far. We expect, however, that the outcome will be improved by more extensive application of the newly developed surgical technique.