• The Journal of Korean Society for Radiation Therapy
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• v.28 no.1
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• pp.7-16
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• 2016

Purpose : This study aimed to compare and evaluate between the efficiency of two respective devices, 3D-bolus and step-bolus when the devices were used for the treatment of patients whose chest walls were required to undergo the electron beam therapy after the surgical procedure of modified radical mastectomy, MRM. Materials and Methods : The treatment plan of reverse hockey stick method, using the photon beam and electron beam, had been set for six breast cancer patients and these 6 breast cancer patients were selected to be the subjects for this study. The prescribed dose of electron beam for anterior chest wall was set to be 180 cGy per treatment and both the 3D-bolus, produced using 3D printer(CubeX, 3D systems, USA) and the self-made conventional step-bolus were used respectively. The surface dose under 3D-bolus and step-bolus was measured at 5 measurement spots of iso-center, lateral, medial, superior and inferior point, using GAFCHROMIC EBT3 film (International specialty products, USA) and the measured value of dose at 5 spots was compared and analyzed. Also the respective treatment plan was devised, considering the adoption of 3D-bolus and stepbolus and the separate treatment results were compared to each other. Results : The average surface dose was 179.17 cGy when the device of 3D-bolus was adopted and 172.02 cGy when step-bolus was adopted. The average error rate against the prescribed dose of 180 cGy was -(minus) 0.47% when the device of 3D-bolus was adopted and it was -(minus) 4.43% when step-bolus was adopted. It was turned out that the maximum error rate at the point of iso-center was 2.69%, in case of 3D-bolus adoption and it was 5,54% in case of step-bolus adoption. The maximum discrepancy in terms of treatment accuracy was revealed to be about 6% when step-bolus was adopted and to be about 3% when 3D-bolus was adopted. The difference in average target dose on chest wall between 3D-bolus treatment plan and step-bolus treatment plan was shown to be insignificant as the difference was only 0.3%. However, to mention the average prescribed dose for the part of lung and heart, that of 3D-bolus was decreased by 11% for lung and by 8% for heart, compared to that of step-bolus. Conclusion : It was confirmed through this research that the dose uniformity could be improved better through the device of 3D-bolus than through the device of step-bolus, as the device of 3D-bolus, produced in consideration of the contact condition of skin surface of chest wall, could be attached to patients' skin more nicely and the thickness of chest wall can be guaranteed more accurately by the device of 3D-bolus. It is considered that 3D-bolus device can be highly appreciated clinically because 3D-bolus reduces the dose on the adjacent organs and make the normal tissues protected, while that gives no reduction of dose on chest wall.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1105-1113
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• 1997

Background : Prone position improves oxygenation in some patients with ARDS. According to some authors, prone position can also improve the deteriorated hemodynamics induced by PEEP. But these respiratory and hemodynamic effects of prone position has not yet been fully established. Methods : Twentythree consequtive patients with ARDS(M : F= 11 : 12, $62.1{\pm}20.8yrs$) were the subjects for this study. ABGA, static compliance of the respiratory system, mean arterial pressure and pulse rate were obtained in supine position and at 5min, 0.5h and 2h of prone position. Positive respiratory response was defined as 20mmHg or more increase in $PaO_2/FIO_2$ within 2h of prone position. Early of late respiratory responses were defined if the positive response was observed within of after 3 day of ARDS onset, respectively. Positive hemodynamic response was defined as 10mmHg or more increase in mean arterial pressure at 5min of prone position. Results : Fifteen patients (65%) showed positive respiratory response. In the respiratory responders, $PaO_2$ was $69.8{\pm}17.6mmHg$ in supine position, $83.2{\pm}22.6mmHg$ in prone position 0.5h, $96.8{\pm}22.7mmHg$ in prone position 2h(p<0.001), and $PaO_2/FIO_2$ was $108{\pm}41mmHg$, $137{\pm}57mmHg$, $158{\pm}50mmHg$, respectively(p=0.001). Age, sex, cause of ARDS, supine $PaO_2$ and $PaO_2/FIO_2$ were not different between the respiratory responders and the nonresponders. The respiratory responders, however, showed higher mean arterial pressure than the nonresponders($91.1{\pm}13.1mmHg$ vs. $76.0{\pm}18.7mmHg$, p=0.035), and tendency of higher survival rate(9/15 vs. 2/8, p=0.074). Static compliance of the respiratory system was decreased in prone position 0.5h($28.4{\pm}7.9ml/cm$ $H_2O$ vs. $23.8{\pm}7.6ml/cm$ $H_2O$, p=0.007). The overall rate of early response(n=23) and late response(n=11) were similar(14/23 vs. 7/11, p>0.05). But patient without early response showed late response only in 25%(1/4), while patient with early response showed late response in 85.7%(6/7)(p=0.072). Five patients(22%) showed positive hemodynamic response, two of them being respiratory nonresponders. There were no differences in the baseline mean arterial pressure or the level of PEEP applied in supine between the hemodynamic responders and the hemodynamic nonresponders. Conclusions : Prone position either improved oxygenation or increased arterial pressure in significant proportion of patients with ARDS. And the respiratory response to prone position was thought to be determined in the early stage of ARDS.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.871-888
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• 1997

Background : It is now thought that the earliest manifestation of idiopathic pulmonary fibrosis is alveolitis, that is, an accumulation of inflammatory and immune effector cells within alveolar walls and spaces. Inflammatory cells including alveolar macrophages and resident normal pulmonary tissue cells participate through the release of many variable mediators such as inflammatory growth factors and cytokines, which contribute to tissue damage and finally cause chronic pulmonary inflammation and fibrosis. This study was performed to investigate the source and distribution pattern of transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), platelet derived growth factor(PDGF), basic fibroblast growth factor(bFGF), interleukin 1(IL-1), interleukin 6(IL-6), tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and the role of these mediators on bleomycin(BLM)-induced pulmonary injury and fibrosis in rats. Method : Wistar rats were divided into three groups(control group, BLM treated group, BLM and vitamine E treated group). Animals were sacrificed periodically at 1, 2, 3, 4, 5, 7, 14, 21, 28 days after saline or BLM administration. The effects were compared to the results of bronchoalveolar lavage fluid analysis, light microscopic findings, immunohistochemical stains for six different mediators(TGF-${\beta}_1$, PDGF, bFGF, IL-1, IL-6 and TNF-$\alpha$) and mRNA in situ hybridization for TGF-${\beta}_1$. Results : IL-1 and IL-6 are maximally expressed at postbleomycin 1~7th day which are mainly produced by neutrophils and bronchiolar epithelium. It is thought that they induce recruitment of inflammatory cells at the injury site. The expression of IL-1 and IL-6 at the bronchiolar epithelium within 7th day is an indirect evidence of contribution of bronchiolar epithelial cells to promote and maintain the inflammatory and immune responses adjacent to the airways. TNF-$\alpha$ is mainly produced by neutrophils and bronchiolar epithelial cells during 1~5th day, alveolar macrophages during 7~28th day. At the earlier period, TNF-$\alpha$ causes recruitment of inflammatory cells at the injury site and later stimulates pulmonary fibrosis. The main secreting cells of TGF-${\beta}_1$ are alveolar macrophages and bronchiolar epithelium and the target is pulmonary fibroblasts and extracellular matrix. TGF-${\beta}_1$ and PDGF stimulate proliferation of pulmonary fibroblasts and TGF-${\beta}_1$ and bFGF incite the fibroblasts to produce extracellular matrix. The vitamine E and BLM treated group shows few positive cells(p<0.05). Conclusion : After endothelial and epithelial injury, the neutrophils and bronchiolar epithelium secrete IL-1, IL-6, TNF-$\alpha$ which induce infiltration of many neutrophils. It is thought that variable enzymes and $O_2$ radicals released by these neutrophils cause destruction of normal lung architecture and progression of pulmonary fibrosis. At the 7~28th day, TGF-${\beta}_1$, PDGF, bFGF, TNF-$\alpha$ secreted by alveolar macrophages sting pulmonary fibroblasts into proliferating with increased production of extracellular matrix and finally, they make progression of pulmonary fibrosis. TNF-$\alpha$ compares quite important with TGF-${\beta}_1$ to cause pulmonary fibrosis. Vitamine E seems to decrease the extent of BLM induced pulmonary fibrosis.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1114-1124
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• 1997

Background : Endothelin(ET) is a very potent vasoconstrictive peptide produced by endothelial cells of pulmonary artery. The endothelin level was increased in plasma of primary pulmonary hypertension and acute pulmonary thromboembolism and it was suggested that the endothelin might do a critical role in the cardiopulmonary dysfunction in these two conditions. But the exact mechanism of increase of ET has not been known. In these two conditions, platelet activation and thrombosis are the main pathophysiologic findings. So there is a possibility that the platelet might stimulate endothelin secretion from endothelial cells. Therefore, we performed this study to evaluate the role of platelet and its mediators on endothelin production in bovine pulmonary artery endothelial(BPAE) cells. Method : Bovine pulmonary artery endothelial cells, ATCC certified cell line 209, were cultured and treated with human platelets($10^6{\sim}10^8/ml$), thrombin (0.1~10u/ml), TGF-${\beta}1$(1~100uM), serotonin(1~100uM), and endotoxin(1ug/ml) in a final volume of 500ul for 18 hours. Levels of ir(immunoreactive)-ET in each conditioned medium were measured by a radioimmunoassay specific for ET. Result : The increase of ir-ET levels was platelet number and time dependent over 18 hours. When washed human platelets were added($10^8/ml$), the ir-ET levels were significantly higher than that of control(p<0.05) at 8 and 18 hours after culture. Subthreshold concentration of platelets($10^7/ml$) coincubated with endotoxin(1ug/ml) or subthreshold dose of thrombin(0.1u/ml) stimulated ir-ET secretion from BPAE cells significantly(p<0.05) compared with control. Thrombin(1ug/ml, 10ug/ml) and TGF-${\beta}1$(100pM, 1000pM) significantly increased ir-ET secretion from BP AE cells(p<0.05) compared with control, but serotoin(1~100uM) and endotoxin(1ug/ml) did not stimulate the ir-ET secretion. Conclusions : Platelets stimulate endothelin secretion from bovine pulmonary artery endothelial cells. The mechanism of increase of endothelin secretion seems to be a stimulation by platelet itself or by mediators, such as TGF-${\beta}1$, secreted from activated platelets. And, in this study, the priming effect of platelets on endothelin secretion from BPAE cells could be another possibility.

• Tuberculosis and Respiratory Diseases
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• v.57 no.5
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• pp.449-460
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• 2004

Background : PS-341 is a novel, highly selective and potent proteasome inhibitor, which showed cytotoxicity against some tumor cells. Its anti-tumor activity has been suggested to be associated with modulation of the expression of apoptosis-associated proteins, such as p53, $p21^{WAF/CIP1}$, $p27^{KIP1}$, NF-${\kappa}B$, Bax and Bcl-2. c-Jun N-terminal kinase (JNK) and glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) are important modulators of apoptosis. However, their role in PS-341-induced apoptosis is unclear. This study was undertaken to elucidate the role of JNK and GSK-$3{\beta}$ in the PS-341-induced apoptosis in lung cancer cells. Method : NCI-H157 and A549 cells were used in the experiments. The cell viability was assayed using the MTT assay and apoptosis was evaluated by proteolysis of PARP. The JNK activity was measured by an in vitro immuno complex kinase assay and by phosphorylation of endogenous c-Jun. The protein expression was evaluated by Western blot analysis. Dominant negative JNK1 (DN-JNK1) and GSK-$3{\beta}$ were overexpressed using plasmid and adenovirus vectors, respectively. Result : PS-341 reduced the cell viability via apoptosis, activated JNK and increased the c-Jun expression. Blocking of the JNK activation by overexpression of DN-JNK1, or pretreatment with SP600125, suppressed the apoptosis induced by PS-341. The activation of caspase 3 was mediated by JNK activation. Blocking of the caspase 3 activation suppressed PS-341-induced apoptosis. PS-341 activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, but its blockade enhanced the PS-341-induced cell death via apoptosis. GSK-$3{\beta}$ was inactivated by PS-341 via the PI3K/Akt pathway. Overexpression of constitutively active GSK-$3{\beta}$ enhanced PS-341-induced apoptosis; in contrast, this was suppressed by dominant negative GSK-$3{\beta}$ (DN-GSK-$3{\beta}$). Inactivation of GSK-$3{\beta}$ by pretreatment with lithium chloride or the overexpression of DN-GSK-$3{\beta}$ suppressed both the JNK activation and c-Jun up-regulation induced by PS-341. Conclusion : The JNK/caspase pathway is involved in PS-341-induced apoptosis, which is negatively regulated by the PI3K/Akt-mediated inactivation of GSK-$3{\beta}$ in lung cancer cells.

• The Korean Journal of Nuclear Medicine
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• v.39 no.6
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• pp.413-420
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• 2005

Purpose: Neuroreceptor PET studies require 60-120 minutes to complete and head motion of the subject during the PET scan increases the uncertainty in measured activity. In this study, we investigated the effects of the data-driven head mutton correction on the evaluation of endogenous dopamine release (DAR) in the striatum during the motor task which might have caused significant head motion artifact. Materials and Methods: $[^{11}C]raclopride$ PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a monetary reward for 40 min. Dynamic frames acquired during the equilibrium condition (pre-task: 30-50 min, task: 70-90 min, post-task: 110-120 min) were realigned to the first frame in pre-task condition. Intra-condition registrations between the frames were performed, and average image for each condition was created and registered to the pre-task image (inter-condition registration). Pre-task PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the others. Volumes of interest (VOI) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DAR was calculated as the percent change of BP during and after the task. SPM analyses on the BP parametric images were also performed to explore the regional difference in the effects of head motion on BP and DAR estimation. Results: Changes in position and orientation of the striatum during the PET scans were observed before the head motion correction. BP values at pre-task condition were not changed significantly after the intra-condition registration. However, the BP values during and after the task and DAR were significantly changed after the correction. SPM analysis also showed that the extent and significance of the BP differences were significantly changed by the head motion correction and such changes were prominent in periphery of the striatum. Conclusion: The results suggest that misalignment of MRI-based VOI and the striatum in PET images and incorrect DAR estimation due to the head motion during the PET activation study were significant, but could be remedied by the data-driven head motion correction.

• Tuberculosis and Respiratory Diseases
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• v.51 no.3
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• pp.248-259
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• 2001

Background : In diagnosis or monitor of the airway obstruction in bronchial asthma, the measurement of $FEV_1$ in the standard method because of its reproducibility and accuracy. But the measurement of peak expiratory flow(PEF) by peak flow meter is much simpler and easier than that of $FEV_1$ especially in children. Yet there have been still no data of the predicted normal values of PEF measured by peak flow meter in Korean children. This study was conducted to provide equations to predict the normal value of PEF and correlation between PEF and $FEV_1$ in healthy children. Method : PEF was measured by MiniWright peak flow meter, and the forced expiratory volume and the maximum expiratory flow volume curves were measured by Microspiro HI 501(Chest Co.) in 346 healthy children(age:5-16 years, 194 boys and 152 girls) without any respiratory symptoms during 2 weeks before the study. The regression equations for various ventilatory parameters according to age and/or height, and the regression equations of $FEV_1$ by PEF were derived. Results : 1. The regression equation for PEF(L/min) was: $12.6{\times}$age(year)+$3.4{\times}$height(cm)-263($R^2=0.85$) in boys, and $6{\times}$age(year)+$3.9{\times}$height(cm)-293($R^2=0.82$) in girls. 2. The value of FEFmax(L/sec) derived from the maximum expiratory flow volume curves was multiplied by 60 to compare with PEF(L/min), and PEF was faster by 125 L/min in boys and 118 L/min in girls, respectively. 3. The regression equation for $FEV_1$(ml) by PEF(L/min) was:$7{\times}$PEF-550($R^2=0.82$) in boys, and $5.8{\times}$PEF-146 ($R^2=0.81$) in girls, respectively. Conclusion : This study provides regression equations predicting the normal values of PEF by age and/or height in children. And the equations for $FEV_1$, a gold standard of ventilatory function, was predicted by PEF. So, in taking care of children with airway obstruction, PEF measured by the peak flow meter can provide useful information.

• Clinical and Experimental Pediatrics
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• v.49 no.12
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• pp.1329-1339
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• 2006

Purpose : Failure of hematopoietic stem cell transplantation(HSCT) may be encountered in practice because of either relapse of the malignancy or dysfunction of the graft. Second HSCT may be the only option for some patients whose initial HSCT failed. Methods : From May, 1991 to December, 2004, 115 HSCTs were performed at the Pediatric Blood & Marrow Transplantation Center, Chonnam National University. This study was a retrospective analysis of the medical records of 15 patients who received the second HSCT after initial graft. Results : Among eight patients with nonmalignant diseases, two patients underwent the second HSCT because of primary graft failure and five because of late graft rejection. The remaining Fanconi anemia patient was re-transplanted due to development of AML. Two patients died and one experienced primary graft failure, but is still alive. The Kaplan-Meier 5-year overall survival rate was 75 percent and the disease free survival rate was 62.5 percent in nonmalignant diseases. All malignant patients underwent second transplants because of relapses. Four died of relapse and one of treatment-related complications. The Kaplan-Meier 2-year overall and event free survival rate was 28.6 percent each in malignant diseases. Conclusion : Second HSCT for graft dysfunction of nonmalignant disease seems to be feasible and should be considered as a standard practice. The relapse of malignant diseases remains a big obstacle even after the second HSCT, although a small portion of patients might be salvaged. Further investigation of novel therapeutic strategies, as well an the understanding of the biology should be explored.

• Clinical and Experimental Pediatrics
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• v.51 no.6
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• pp.634-639
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• 2008

Purpose : There has been considerable disagreement regarding the most appropriate dosage of gonadotropin-releasing hormone agonist in cases of central precocious puberty. The aim of this study was to determine the appropriate dosage for suppression of the puberty in girls with central precocious or early puberty. Methods : Twenty-two girls with early puberty were randomly subjected to 3 types of dosages of leuprolide acetate for at least 6 months. The number of cases in groups 1, 2, and 3 were 7, 7, and 8, and dosages were 70, 90, and $110{\mu}g/kg/-month$, respectively. Height, weight, bone age, Tanner stage of breast development, and serum levels of LH, FSH, estradiol, and progesterone were measured before treatment and after 6 months of treatment. The number of cases of puberty suppression was compared using a modified puberty suppression score with a nonparametric chi-square test. Results : There were no significant differences of chronologic and bone ages among the groups. There was a significant decrease in height SDS gain after 6 months in group 3 (P<0.05) compared with groups 1 and 2. Serum levels of LH, FSH, estradiol and progesterone were all significantly decreased after treatment in all 3 groups (P<0.05). The number of cases of puberty suppression in each group were 4 (57%), 5 (71%), and 8 (100%). There was a significantly increased proportion of suppression of puberty in group 3 (P<0.05). Conclusion : It was necessary to use a higher dose of gonadotropin-releasing hormone agonist to suppress early puberty in girls; however further longitudinal study will be needed for their prognosis of final adult height.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.222-230
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• 2005

Purpose : ARC syndrome refers to an association of arthrogryposis, renal tubular dysfunction, and cholestasis. The VPS33B gene was recently identified as the causative gene. So far, 41 cases of ARC syndrome have been reported worldwide, and it has rarely been reported in Korea. This study was conducted to report the clinical findings of seven ARC syndrome cases in Korean children, focusing especially on renal tubular dysfunction. Methods : The hospital records of 7 cases diagnosed as ARC syndrome at Severance Hospital between Mar. 1995 and Aug. 2005 were reviewed and analyzed. Results : Of the 7 cases, 4 were boys and 3 were girls. Six patients(85$\%$) were born with normal birth weight at term, and one was born at preterm. All cases presented with cholestasis and severe jaundice. According to the type of arthrogryposis described by Brown et al, type 3 and 4 were found in 2 patients and type,6, 7, and the undistributed type in one patient respectively. Other associated clinical findings were as follows : failure to thrive in 6(85$\%$), lax skin in 5(71$\%$), and gray platelet syndrome in 4(57$\%$). Urine analysis revealed 6 cases(85$\%$) with proteinuria, 3(43$\%$) with hematuria, 5(71$\%$) with glycosuria, 2(29$\%$) with phosphaturia and 2(29$\%$) with calciuria. Serum electrolytes showed 4 cases(57$\%$) with hyponatremia, 3(43$\%$) with hypokalemia, and 1(14$\%$) with creatinine elevation. Renal tubular dysfunctions were diagnosed as renal tubular acidosis in 6 cases(85$\%$), nephrogenic diabetes insipidus in 2(29$\%$), and Fanconi syndrome in 2(29$\%$). During the follow-up period, 2(29$\%$) had no treatment, 5(85$\%$) had continuous supplementation to correct the electrolyte imbalance and acidosis, and 1(14$\%$) had dialysis. Only one patient had a family history of ARE syndrome in a sibling. Four cases(57$\%$) were diagnosed at the mean age of 8.2 months, and one case was lost during follow-up. Ages of the survived 2 cases were 13 and 25 months, respectively. Conclusion : The rare disease of ARC syndrome Is associated with severe renal dysfunction. However, this study revealed that the renal manifestation of ARC syndrome in Korean children is relatively mild and survival rate is higher than that of previous studies. Contrary to previous reports, this study showed that familial cases are rare and sporadic occurence is possible in Korea. Thus, the diagnosis of this syndrome requires a careful evaluation of the venal function in cases of congenital arthrogryposis, and a mandatory genetic counseling of affected family for prevention of familial occurance. (J Korean Soc Pediatr Nephrol 2005;9:222-230)