• Radiation Oncology Journal
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• v.19 no.1
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• pp.1-9
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• 2001

Purpose : To establish the role of stereotactic radiosurgery (SRS) for the treatment of patients with angiographically occult vascular malformation (AOVM). Materials and Methods : Eleven patients (12 lesions) with AOVM were treated with linear accelerator-based SRS between February 1995 and December 1999. A magnetic resonance imaging of each patients showed well-circumscribed vascular lesion with reticulated core of heterogeneous signal intensity and peripheral rim of low signal intensity. SRS were peformed with the median peripheral dose of 16 Gy (range 13~25). A single isocenter was used with median collimator size of 14 mm (range 8~20) diameter. Results : With a median follow-up period of 42 months (range 12~56), rebleeding occurred in 3 AOVMS at 5, 6 and 12 months after SRS but no further bleeding did. Two patients experienced radiation-induced necrosis associated with permanent neurologic deficit and one patient showed transient edema of increased 72 signal intensity. Conclusion : SRS may be effective for the prevention of rebleeding in AOVM located in surgically inaccessible region of the brain. Careful consideration should be needed in the decision of case selection and dose prescription because the incidence of radiation-induced complications is too high to be accepted.

• 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.4 no.2
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• pp.111-119
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• 2000

Purpose : Henoch-$Sch{\ddot{o}}nlein$ purpura(HSP) is a common pediatric discase presenting most frequently with skin, gastrointestinal, joint and renal manifestations. The prognosis of HSP is mainly determined by the involvement of the kidney, but prognostic markers have not been established. We evaluated the patients who have HSP nephritis with nephrotic syndrome. Method : Clinical manifestations and laboratory findings were observed and analyzed in 34 cases with HSP which were manifested by nephrotic syndrome hospitalized at Kyung Hee university Hospital during the period from Jan. 1990 to Dec. 1998. Results : 1) Male to female ratio was 1.3:1, and mean age at onset was 8.3 year. 2) Mean duration from symptom onset to renal biopsy was 10.5 weeks. 3) Proportion of patients presenting with acute nephritis was 32.4$\%$, gross hematuria 17.6$\%$, microscopic hematuria 50$\%$. 4) The findings of renal biopsy were 20 cases of grade II, 11 cases of grade III, 2 cases of grade I, 1 case of grade IV according to classification by ISKDC. 5) Patients with grade I were recovered with no residual defect, but patients with grade IV shows active renal disease(states C). Conclusion : Among the 디le patients with Henoch-$Sch{\ddot{o}}nlein$ purpura accompanying nephrotic syndrome, more aggressive treatment might be needed in patients showing crescents formation on renal biopsy. A prospective study will be needed to explore the progression of this disease.

• Journal of Chest Surgery
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• v.38 no.7 s.252
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• pp.468-475
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• 2005

Transmyocardial revascularization (TMR) in end stage ischemic heart disease results in variable clinical responses. We investigated the acute effect of early reperfusion and the angiogenesis after formation of the transmyocardial channel in a transplanted rat heart model with acute myocardial infarction. Material and Method: In the 30 transplanted hearts we induced acute myocardial infarction by ligating the proximal left coronary artery and inserted a porous 22G intravenous cannula into the left ventricle. After ten minutes of reperfusion, we removed the cannula. At every stage, we recorded the heart rate, QRS size, and left coronary arterial blood flow using the electrocardiogram and Doppler. One week later the rats were sacrificed and evaluated for the patency of intramyocardial channels and the angiogenesis. Result: The heart rates after ligation and after cannula insertion were $239.1\pm61.7,\;235.8\pm58.0bpm$ respectively, and they were statistically significantly slower than that of before ligation, $277.6\pm40.3bpm\;(p=0.017,\;p=0.007\;respectively)$. QRS sizes before ligation, after ligation, and after cannula insertion were $3.6\pm3.3mm,\;2.8\pm3.3 mm,\;and\;2.4\pm2.2mm,$respectively, and there was no significant difference in the three groups. Doppler findings after ligation showed that average peak and mean values of coronary perfusion were significantly decreased from $2.11\pm0.17kHz,\;1.25\pm0.22kHz\;to\;0.83\pm0.15kHz,\;0.38\pm0.11kHz$(p<0.05 respectively). After insertion of the porous cannula, the average peak and mean values of coronary perfusion were $0.61\pm0.05kHz\;and\;0.33\pm0.05 kHz$ respectively, but there was no statistically significant change compared to values after ligation. In all cases except one, pathologic findings showed no patent channels in the acute stage, however, one case showed the angiogenesis. Conclusion: We confirmed that TMR in a rat heart transplant model did not show blood flow through the channel in the acute stage. However, reperfusion effect in some cases had a potential for angiogenesis.

• Journal of Chest Surgery
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• v.11 no.4
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• pp.404-415
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• 1978

The present study was carried out to develop the better measures for safety of open heart surgery under extracorporeal circulation (ECC) with Heart-Lung-Machine by preventing changes in the concentrations of serum electrolytes during and after ECC. For this purpose, the cocentrations of serum electrolytes were measured before, during, and after ECC in 21 patients with congenital and acquired heart diseases who received open heart surger, - under ECC using Heart-Lung-Machine. Also considered was the development of safety measured by which changes in serum electrolyte concentrations were prevented during and after open heart surgery under ECC. The mean values for serum sodium levels were observed to be ; $13.14{\pm}0.47$mEq./L. for the samples obtained before ECC. $139.59{\pm}0.68$mEq./L. for the samples obtained 10 minutes after ECC and $138.0{\pm}0.68$mEq./L. for the samples obt"ined 24 hours after ECC. These results indicate that serum sodium concentrations were \\'ithin normal range during and until 24 hours after ECC. 2) The concentrations of serum chloride were found to be $105.38{\pm}0.70$105.38$\pm$0. 70 mEq./L. for the samples collected before ECC, $105.07{\pm}1.01$mEq./L. for the Simples collected 24 minutes aiter ECC and $101.95{\pm}1.09$mEq./L. for the samples collectect 24 hours afte ECC. As was tile case with serum sodium levels, no significant changes were observed in serum chloride levels during and 24 hours after ECC. 3)With proper provisions of potassium chloride solution during ECC, the concentrations of serum potassium were found to be $4.22{\pm}0.06$mEq./L. for the samples removed before EeC, $4.06{\pm}0.14$mEq./L. for the samples removed 10 minutes after ECC and $4.39{\pm}0.07$ mEq./L. for the samples removed 24 hours after ECC. 4)The concentrations of serum calcium were also maintained within normal during and after ECC; $9.15{\pm}0.14$mg/dl for the serum collected before ECC, $8.36{\pm}0.21$mg/dI for the serum collected 10 minutes after ECC and $8.47{\pm}0.14$mg/dl 21 hours after ECC. The maintenance of serum calcium level within normal throughout ECC was achieved by parenteral administrations of calcium gluconate as frequent as required. 5) As were the cases with serum potassium and calcium, the concentrations of plasma bicarbonate was regulated within normal range during and after ECC, only when sodium bicarbonate solution was admini"tered parenterally as it was required; $23.7{\pm}0.50$mEq./L. for the serum collected before ECC. $22.33{\pm}1.09$mEq.lL. for the serum collected 10 minutes after ECC and $25.3{\pm}0.96$mEq./L. for the serum collected 24 hours after ECC. The above results indicate tha t during and after ECC serum sodium and chloride levels remined unchanged without any provision of normal saline, while serum potassium, calcium, and bicarbonate concentrations were kept within normal limits only when these ealectrolytes were administered through parenteral routes. With these results it can be concluded that serum potassium, calcium, and bicarbonate levels should be determined as often as possible during and after ECC and that in order to maintain serum electrolyte levels within normal these electrolytes in the forms of potassium chloride, calcium gluconate, and sodium bicarbonate shou'd be given parenterally as they were found to be required.

• Journal of Chest Surgery
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• v.36 no.1
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• pp.15-20
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• 2003

Myasthenia gravis is a rare autoimmune disease involving acetylcholine receptor and its autoantibody on neuromuscular junction. The methods of treatment are medical treatment and surgical thymectomy. In this paper we analyzed the result of thymectomy and the factors affecting the postoperative symptom improvement. Material and method : This study obtained medical records of 37 patients who received the thymectomy for myasthenia gravis from March 1986 to December 1998. Result Out of 37 cases, 21 cases(57%) showed improvement, of which 8 cases (50%) in the group of thymoma(n=16), and 13 cases (62%) in the group of thymic hyperplasia(n=21) showed the improvement of symptoms. Postoperative complications were respiratory insufficiency due to aggravation of symptoms after operation, including tracheal intubation for ventilator support in 9 cases, pneumonia in 3 cases, pneumothorax in 2 cases and left vocal cord palsy in 1 case. There was one postoperative mortality. The relation between postoperative improvement and sex(P=0.3222), age(P=0.7642), thymic pathologic variants,(P=0.4335) and classification of thymoma(P=0.20) showed no statistically significant correlation. However, the lower grade of preoperative symptoms can predict the lower grade of postoperative symptoms significantly(P=0.0032). Follow up study to 36 postoperative survivors was performed in October 2002 based on the out-patient records and call with patients. Out of 36 cases, 33 cases(91.7%) could be investigated and 3 cases could not. Mean follow up period was 83.2 months. Out of 33 cases, 25 cases(75.8%) showed symptomatic improvement, of which 8 cases(53.3%) in the group of thymoma(n=15) and 17 cases(94.4%) in the group of thymic hyperplasia(n=18) showed the improvement of$\boxUl$ symptoms. Conclusion : In myasthenia gravis, thymectomy showed the good improvement, and more important factor affecting the improvement of symptoms was the grdae of preoperative symptoms. Also midterm and long term follow up results showed good symptomatic improvement.

• The Korean Journal of Nuclear Medicine
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• v.33 no.1
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• pp.65-75
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• 1999

Purpose: The aim of this study is to demonstrate the feasibility of 2-[fluorine-18] fluoro-2-deoxy-D-glucose (F-18-FDG) whole body scan (FDG W/B Scan) using dual-head gamma camera equipped with ultra high energy collimator in patients with various cancers, and compare the results with those of coincidence imaging. Materials and Methods: Phantom studies of planar imaging with ultra high energy and coincidence tomography (FDG CoDe PET) were performed. Fourteen patients with known or suspected malignancy were examined. F-18-FDG whole body scan was performed using dual-head gamma camera with high energy (511 keV) collimators and regional FDG CoDe PET immediately followed it Radiological, clinical follow up and histologic results were correlated with F-18-FDG findings. Results: Planar phantom study showed 13.1 mm spatial resolution at 10 cm with a sensitivity of 2638 cpm/MBq/ml. In coincidence PET, spatial resolution was 7.49 mm and sensitivity was 5351 cpm/MBq/ml. Eight out of 14 patients showed hypermetabolic sites in primary or metastatic tumors in FDG CoDe PET. The lesions showing no hypermetabolic uptake of FDG in both methods were all less than 1 cm except one lesion of 2 cm sized metastatic lymph node. The metastatic lymph nodes of positive FDG uptake were more than 1.5 cm in size or conglomerated lesions of lymph nodes less than 1cm in size. FDG W/B scan showed similar results but had additional false positive and false negative cases. FDG W/B scan could not visualize liver metastasis in one case that showed multiple metastatic sites in FDG CoDe PET. Conclusion: FDG W/B scan with specially designed collimators depicted some cancers and their metastatic sites, although it had a limitation in image quality compared to that of FDG CoDe PET. This study suggests that F-18-FDG positron imaging using dual-head gamma camera is feasible in oncology and helpful if it should be more available by regional distribution of FDG.

• Radiation Oncology Journal
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• v.21 no.2
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• pp.107-111
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• 2003

Purpose: To establish the role of stereoactic radiosurgery using a linear accelerator for the treatment of patients with cavernous angloma. Materials and Methods: Between February 1995 and May 1997, 11 patients with cavernous angioma were treated with stereotactic radiosurgery using a linear accelerator. Diagnoses were based on the magnetic resonance imaging in 8 patients, and the histological in 3. The vascular lesions were located on the brainstem (5 cases), cerebellum (2 cases) thalamus (1 case) and cerebrum (3 cases). The clinical presentation at onset included previous intracerebral hemorrhages (9 cases) and seizures (2 cases). All patients were treated with a a linac-based radiosurgery. The median dose of radiation delivered was 16 Gy ranging from 14 to 24 Gy, which was typically proscribed to the 80$\%$ isodose surface (range 50 $\~$ 80$\%$), corresponding to the periphery of the lesion with a single isocenter. Ten patients were followed-up. Results: The median follow-up was 49 months ranging from 8 to 73 months, during which time two patients developed an intracerebral hemorrhage, 1 at 8 months, with the other at 64 months post radiosurgery. One patient developed neurological deficit after radiosurgery, and two developed an edema on the T2 weighted images of the MRI surrounding the radiosurgical target. Conclusion: The use of stereotactic radiosurgery in the treatment of a cavernous angioma may be effective in the prevention of rebleedlng, and can be safely delivered. However, a longer follow-up period will be required.

• Journal of Chest Surgery
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• v.29 no.6
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• pp.639-645
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• 1996

A 14-year-old male patient with previous surgical repair of tetralogy of Fallot was admitted with hemodynamically significant ventricular tachycardia (VT). On preoperative electrophysiologic study (EPS), the morphology of documented VT was RBBB of vertical axis with 320 msec cycle length. The endocardial mapping during VT delineated the origin of VT at right ventricular outflow tract (RVOT), where the patch was attached. The clinical VT had a clockwise reentry circuit around the patch with the earliest activation at the same site seen during the preoperative EPS. The previously placed right ventricular outflow patch and fibrous tissue were removed. During a postoperative EPS, it was no longer possible to induce the VT. Ventricular tachycardia following repair of tetralogy of Fallot seen in this patient was caused by a macro-reentry around the right ventricular outflow patch. We were able to ablate the VT with the aid of a detailed mapping of its epicardial activation sequence.