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Neuroprotection of Recombinant Human Erythropoietin Via Modulation of N-methyl-D-aspartate Receptors in Neonatal Rats with Hypoxic-ischemic Brain Injury (신생 백서의 저산소성 허혈성 뇌손상에서 NMDA receptor 조절을 통한 유전자 재조합 인 에리스로포이에틴의 신경보호)

  • Jang, Yoon-Jung;Seo, Eok-Su;Kim, Woo-Taek
    • Neonatal Medicine
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    • v.16 no.2
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    • pp.221-233
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    • 2009
  • Purpose: Erythropoietin (EPO) has neuroprotective effects in many animal models of brain injury, including hypoxic-ischemic (HI) encephalopathy, trauma, and excitotoxicity. Current studies have demonstrated the neuroprotective effects of EPO, but limited data are available for the neonatal periods. Here in we investigated whether recombinant human EPO (rHuEPO) can protect the developing rat brain from HI injury via modulation of NMDA receptors. Methods: In an in vitro model, embryonic cortical neuronal cell cultures from Sprague-Dawley (SD) rats at 19-days gestation were established. The cultured cells were divided into five groups: normoxia (N), hypoxia (H), and 1, 10, and 100 IU/mL rHuEPO-treated (H+E1, H+ E10, and H+E100) groups. To estimate cell viability and growth, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was done. In an in vivo model, left carotid artery ligation was performed on 7-day-old SD rat pups. The animals were divided into six groups; normoxia control (NC), normoxia Sham-operated (NS), hypoxia-ischemia only (H), hypoxia-ischemia+vehicle (HV), hypoxia-ischemia+rHuEPO before a HI injury (HE-B), and hypoxia-ischemia+rHuEPO after a HI injury (HE-A). The morphologic changes following brain injuries were noted using hematoxylin and eosin (H/E) staining. Real-time PCR using primers of subunits of NMDA receptors (NR1, NR2A, NR2B, NR2C and NR2D) mRNA were performed. Results: Cell viability in the H group was decreased to less than 60% of that in the N group. In the H+E1 and H+E10 groups, cell viability was increased to >80% of the N group, but cell viability in the H+E100 group did not recover. The percentage of the left hemisphere area compared the to the right hemisphere area were 98.9% in the NC group, 99.1% in the NS group, 57.1% in the H group, 57.0% in the HV group, 87.6% in the HE-B group, and 91.6% in the HE-A group. Real-time PCR analysis of the expressions of subunits of NMDA receptors mRNAs in the in vitro and in vivo neonatal HI brain injuries generally revealed that the expression in the H group was decreased compared to the N group and the expressions in the rHuEPO-treated groups was increased compared to the H group. Conclusion: rHuEPO has neuroprotective property in perinatal HI brain injury via modulation of N-methyl-D-aspartate receptors.

Obstetric and Neonatal Outcomes of the Teenage Pregnancy (청소년 임신에 따른 임산부와 신생아의 주산기 문제점)

  • Shin, Jeong-Hee;Bauer, Siegfried;Yoon, Young-Sun;Jeong, Hyun-Chul;Rhie, Young-Jun;Lee, Jang-Hoon;Woo, Chan-Wook;Choi, Byung-Min;Kim, Hai-Joong;Park, Sang-Hee;Song, Ji-Won
    • Neonatal Medicine
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    • v.17 no.1
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    • pp.94-101
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    • 2010
  • Purpose:In recent years, Korea has showed a steady increase in the frequency of teenage birth, while the overall birth rate has declined. As the teenage birth is known as a high risk pregnancy itself, we examined perinatal complications of teenage mothers and whose neonates in aspects of medical problem, and social status and support. Methods:We examined the perinatal characteristics of teenage mothers and whose babies, who were hospitalized at Korea University Ansan Hospital from January 2004 to July 2009 using medical records retrospectively. Twenty-seven teenage mothers and their 28 babies were enrolled in this study. Results:Teenage mothers were all unmarried and showed high rates of preterm labor, maternal anemia, and unexpected delivery. Among them, 11 (40.7%) were from families that were separated. Eleven mothers (40.7%) did not have any antenatal care. There were high rates of prematurity and low birth weight (60.7% and 64.3%, respectively). The complication included: respiratory distress syndrome, patent ductus arteriosus and necrotizing enterocolitis. Fourteen babies (51.9%) were not going to be brought up by their biological parents. Conclusion:Teenage pregnancy had high rates of preterm labor and associated complications, often caused by the lack of proper antenatal care. Babies from unmarried mothers were likely to be adopted and this could be a social burden. Therefore, to reduce unplanned teenage pregnancy and births, sex education and social supports should be provided to all teenagers.

Nomogram of Transcutaneous Bilirubin Level after Birth Driven from a Single Center (단일기관에서 도출된 출생 후의 경피적 빌리루빈의 노모그램)

  • Han, Young-Ji;Kim, Eun-Ryoung;Lee, Myung-Sook;Lee, Won-Uk;Park, Su-Hwa;Lee, Jung-Ju
    • Neonatal Medicine
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    • v.17 no.1
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    • pp.102-108
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    • 2010
  • Purpose : The goal of this study was to measure bilirubin levels over 6 hours using a transcutaneous bilirubinometer. The change in the bilirubin levels were recorded in anomogram. The natural progress of jaundice in neonates was monitored using the nomogram and cases were identified that needed further follow-up observation and treatment. Methods : The subjects of this study were 986 healthy term or near-term infants at the age of 35 weeks or older who were born at Sung-Ae General Hospital during the period from October 1, 2007 to April 30, 2009 and whose parents were both Koreans. Transcutaneous bilirubin measurements were obtained using a transcutaneous bilirubinometer (Minolta, JM-103) from 6 hours of life to discharge at intervals of 6 hours. A nomogram was derived from the obtained data and compared to the delivery method, gestational age, and feeding method. Results : Percentile graphs were drawn according to time. Based on the graphs, phototherapy was necessary in more than 90 percent of the infants between 35 and 37.6 weeks of age and in 95 percent of the infants 38 weeks and older. The mean bilirubin level at 24, 48, 72 and 96 hours after birth were compared according to the delivery method, gestational age, and feeding method. The bilirubin level in 48 hours was significantly higher in neonates born via cesarean section delivery compared to the neonates born via vaginal delivery, however the levels were not statistically different at the other hours. Conclusion : The results of this study show the nomogram derived from hour-specific transcutaneous bilirubin levels. This information can be used to predict the risk for subsequent significant hyperbilirubinemia.

Genotoxicity of Therapeutic Dose of $^{131}I$ Analyzed by Micronuclei Test in the Mouse Bone Marrow (생쥐골수세포 미소핵검사에 의한 치료용량 방사성옥소($^{131}I$)의 유전독성 평가)

  • Bom, Hee-Seung;Kim, Ji-Yeul
    • The Korean Journal of Nuclear Medicine
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    • v.27 no.1
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    • pp.112-117
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    • 1993
  • Background Radioiodine ($^{131}I$), a major component of nuclear fallout and a valuable therapeutic agent for thyrotoxicosis and thyroid cancer, has been regarded as a mutagen or a carcinogen without any convincing evidence. To evaluate the genotoxicity of radioiodine ($^{131}I$) we performed a micronuclei test in mice bone marrow. Materials and methods : Mice (ICR strain, $25{\sim}30 g$) were divided to 4 groups: control, group 1 (0.17 mCi/kg, usual therapeutic dose for thyrotoxicosis), group 2 (1.67 mCi/kg, usual therapeutic dose for thyroid cancer), and group 3 (16.67 mCi/kg, usual accumulated dose causing bone marrow suppression). $^{131}I$ was administered intraperitoneally. Ten mice of each group were sacrificed at days 1 and 3. Bone marrow were smeared and stained with May-Grunwald Giemsa method. One thou-sand polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) were counted under the light microscope, and the number of micronucleated PCEs were recorded. Results : The frequency of micronuclei in PCE (and NCE in parenthesis) in the control group was $0.25{\pm}0.07$ ($0.23{\pm}0.07$)% in day 1 and $0.24{\pm}0.07$ ($0.21{\pm}0.07$)% in day 3. Those in group 1 was $0.27{\pm}0.1$ ($0.23{\pm}0.09$)% in day 1 and $0.28{\pm}0.07$ ($0.25{\pm}0.06$)% in day 3. Micronuclei was noted in $0.29{\pm}0.08$ ($0.26{\pm}0.09$)% in day 1 and $0.31{\pm}0.05$ ($0.29{\pm}0.06$)% in day 3 in group 2, and in $0.32{\pm}0.06$ ($0.25{\pm}0.09$)% in day 1 and $0.33{\pm}0.08$ ($0.3{\pm}0.06$)% in day 3 in group 3. There was no difference in the frequency of micronuclei between each groups (p> 0.05). Conclusion : Radioiodine ($^{131}I$) did not cause any genotoxicity in mice bone marrow even at the large dose (16.67 mCi/kg).

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Clinical Utility of Bone Scan in the Diagnosis of Temporomandibular Disorders (측두하악장애의 진단에서 Bone Scan의 유용성)

  • Kim, In-Joo;Kang, Yang-Ho;Son, Seok-Man;Lee, Kyoung-Seog;Lee, Jae-Bok;Kim, Yong-Ki;Seo, Bong-Jik;Park, June-Sang;Ko, Myung-Yun;Son, Seong-Pyo
    • The Korean Journal of Nuclear Medicine
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    • v.29 no.4
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    • pp.511-517
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    • 1995
  • Bone scan is a very sensitive diagnostic imaging test for detecting bone and joint disorders. So it might be useful in the diagnosis of temporomandibular disorders of the joint origin. Thus, the effectiveness of bone scan for detecting temporomandibular joint(TMJ) diseases and differentiating the TMJ disc displacement from the TMJ arthritis was evaluated. Bone scan was done in 21 patients with TMJ disc displacement(13 unilaterally affected, 8 bilaterally affected), 25 patients with TMJ arthritis(23 unilateral, 3 bilateral), and 39 volunteers with no signs, symtoms, or history of TMJ disease. TMJ simple uptake rate(SUR) and difference of both TMJ SUR were calculated from the 100,000 count lateral image of head and neck region in 99mTc MDP bone scan. Transcranial and panorama X-ray examination was also done in all patients. TMJ SUR(%) were $1.673{\pm}0.606$ in TMJs affected with arthritis, $1350{\pm}0.351$ in TMJs affected with disc displacement, and $1.084{\pm}0.172$ in TMJs of controls. Significant differences were demonstrated among them(p<0.01) Difference of bith TMJ SUR was highest in patients with unilateral TMJ arthritis($0.608{\pm}$0.533, p<001), and there is no significant difference between that of controls and that of unilateral TMJ dist displacement patients($0.062{\pm}0.063$ vs $0.122{\pm}0.100$). TMJ SUR of Joint with bone change on X-ray finding was not significantly different from that of joint with normal X-ray finding. Those in patients with unilateral TMJ disc displacement(696% and 87% vs 23.1% and 23%). The proportions of patients with increased TMJ SUR and difference of both TMJ SUR(>mean+2SD of controls) in unilateral TMJ arthritis patients were significantly higher than those in patients with unilateral TMJ disc displacement(69.6% and 87% vs 23.1% and 23%). Conclusively, bone scan nay help to detect TMJ disease and differentiate TMJ disc displacement from TMJ arthritis.

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Assessment of Quantitative Analysis Methods for Lung F-18-Fluorodeoxyglucose PET (폐 종양 FDG PET 영상의 다양한 추적자 역학 분석 방법 개발과 유용성 고찰)

  • Kim, Joon-Young;Choi, Yong;Choi, Joon-Young;Lee, Kyung-Han;Kim, Sang-Eun;Choe, Yearn-Seong;Kim, Yong-Jin;Kim, Byung-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.4
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    • pp.332-343
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    • 1998
  • Purpose: The purpose of this study was to assess the diagnostic accuracy of various quantitation methods using F-18-fluorodeoxyglucose (FDG) in patients with malignant or benign lung lesion. Materials and Methods: 22 patients (13 malignant including 5 bronchoalverolar cell cancer; 9 benign lesions including 1 hamartoma and 8 active inflammation) were studied after overnight fasting. We performed dynamic PET imaging for 56 min after injection of 370 MBq (10 mCi) of FDG. Standardized uptake values normalized to patient's body weight and plasma glucose concentration (SUVglu) were calculated. The uptake rate constant of FDG and glucose metabolic rate were quantified using Patlak graphical analysis (Kpat and MRpat), three compartment-five parameter model (K5p, MR5p), and six parameter model taking into account heterogeneity of tumor tissue (K6p, MR6p). Areas under receiver operating characteristic curves (ROC) were calculated for each method. Results: There was no significant difference of rate constant or glucose metabolic rate measured by various quantitation methods between malignant and benign lesions. The area under ROC curve were 0.73 for SUVglu, 0.66 for Kpat, 0.77 for MRpat, 0.71 for K5p, 0.73 for MR5p, 0.70 for K6p, and 0.78 for MR6p. No significant difference of area under the ROC curve between these methods was observed except the area between Kpat vs. MRpat (p<0.05). Conclusion: Quantitative methods did not improve diagnostic accuracy in comparison with nonkinetic methods. However, the clinical utility of these methods needs to be evaluated further in patients with low pretest likelihood of active inflammation or bronchoalveolar cell carcinoma.

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Bone Marrow Scintigraphy with Antigranulocyte Antibody in Multiple Myeloma: Comparison with Simple Radiography and Bone Scintigraphy (항과립구 항체 골수스캔을 이용한 다발성 골수종 병변의 평가: 단순골X-선점사 및 골스캔과의 비교)

  • Kim, Dong-Hwan;Lee, Jae-Tae;Baek, Jin-Ho;Jung, Jin-Tae;Hyun, Dong-Woo;Chun, Kyung-Ah;Lee, Young-Hak;Sohn, Sang-Kyun;Song, Hong-Seok;Lee, Kyu-Bo
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.4
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    • pp.354-364
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    • 1998
  • Purpose: Simple X-ray study and bone scan have limitations for early diagnosis of bone or bone marrow lesions in multiple myeloma. The purpose of this study was to evaluate the diagnostic usefulness of bone marrow immunoscintigraphy using anti-granulocyte monoclonal antibody for the evaluation of bone involvement in multiple myeloma. Materials and Methods: In 22 patients (Male: 15, Female: 7) with multiple myeloma, we performed whole-body immunoscintigraphy using $^{99m}Tc$-labelled antigranulocyte antibody (BW 250/183, Scintimum $Granulozyt^{(R)}$ CIS, France) and compared the findings with those of simple bone radiography and $^{99m}Tc$-MDP bone scan. Abnormal findings in bone marrow scintigraphy were, considered to be present in case of expansion of peripheral bone marrow or focal photon defect in axial bones. Results: Marrow expansion was noted in 15 of 22 patients (68%). Focal photon defects were found in 18 patients (82%). While one (33%) of 3 patients with Stage II disease showed focal defects in bone marrow scan, abnormal focal defects were observed in 17 of 19 (90%) patients with Stage III. Among 124 focal abnormal sites which were observed in bone marrow scan, bone scan or simple bone radiography, bone marrow scan detected 92 sites (74%), whereas 82 sites (66%) were observed in simple bone radiography(58 sites, 47%) or bone scan(40 sites, 32%). Fifty-one (41%) out of 124 bone lesions were detected by bone marrow scan only, and located mostly in thoracolumbar spine. Conclusion: Bone marrow scan using $^{99m}Tc$-labelled antigranulocyte antibody seems to be a more sensitive procedure for the detection of pathologic bone lesions than simple bone X-ray or bone scan in patients with multiple myeloma.

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Artifactual Perfusion Defects due to the Parameters of Reconstruction Filter in Tc-99m-MIBI Myocardial SPECT Images (Tc-99m-MIBI 심근 SPECT 영상에서 재구성 필터에 의한 인위적 관류결손에 관한 연구)

  • Kwark, Cheol-Eun;Lee, Kyung-Han;Lee, Dong-Soo;Park, Yong-Woo;Chung, June-Key;Lee, Myung-Chul;Seo, Joung-Don;Koh, Chang-Soon
    • The Korean Journal of Nuclear Medicine
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    • v.29 no.1
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    • pp.41-47
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    • 1995
  • Tc-99m-MIBI(Sestamibi) myocardial SPECT along with T1-201 tomographic imaging has demonstrated wide application and high image qualify sufficient for the diagnosis of myocardial perfusion defect, which consequently reflects regional myocardial blood flow, The qualitative values of myocardial SPECT with Tc-99m-MIBI as well as the quantitative cases depend in some degree on the reconstruction techniques of multiple projections. Filtered backprojection(FBP) is the common standard for reconstruction rather than the complicated and time-consuming arithmetic methods. In FBP it Is known that the distribution of radioactivity in reconstructed transverse slices varies with the selected filter parameters such as cutoff frequencies and order(Butterworth case). The cutoff frequencies basically remove and decrease the true radioactive distribution and alter the pixel counts, which lead to underestimation of true counts in specific myocardial regions. In this study, we have investigated the effect of cutoff frequencies of reconstruction filter on the artifactually induced perfusion defects, which are often demonstrated near inferior and/or inferoseptal cardiac walls due to the intense hepatic uptake of Tc-99m-MIBI. A computerized method for identifying the relative degree of artifactual perfusion defect and for comparing those degrees along with the relative amount of hepatic uptake to myocardium was developed and patient images were studied to observe the quantitative degree of underestimation of myocardial perfusion, and to propose some reasonable thresh-old of cutoff frequency in the diagnosis of perfusion defect quantitatively. We concluded that from the quantitative viewpoint cutoff frequencies may be used as high as possible with the sacrifice of homogeneity of image quality, and those frequencies lower than the common 0.3 Nyquist frequency would reveal severe degradation of radio-active distribution near inferior and/or Inferoseptal myocardium when applying Butterworth or low pass filter.

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$^{99m}Tc-MAG_3$ Elimination Index on Normal Functioning Transplanted Kidney ($^{99m}Tc-MAG_3$ 제거지수를 이용한 이식신장의 기능평가)

  • Jeon, Woo-Jin;Kim, Ju-Heon;Park, Mi-Ok;Lee, Hee-Jung;Hyun, Jung-Ae;Zeon, Seok-Kil
    • The Korean Journal of Nuclear Medicine
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    • v.29 no.1
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    • pp.79-83
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    • 1995
  • Purpose : We analysed $^{99m}Tc-MAG_3$ renal scans to evaluate renal function of transplanted kidney and to detect various renal transplant complications, measuring the ratio of renal radioactivity at three minutes to that at 20 minutes(elimination index). Material and Methods : The fifty seven renal transplantation recipients were studied. There were 50 normal functioning transplanted kidneys as group I and 7 abnormal function-ing transplanted kidney, including 5 cases of acute renal rejection, 2 cases of acute tubular necrosis as group IIl. The protocol consisted of: (1) $^{99m}Tc-MAG_3$ 740MBq injection intravenously : (2) sequential imaging for 2min(60two-second images) followed by 30min(30 sixty-second images) : (3) drawing of region of interest(ROI) on renal imaging; (4) time-activity corves were generated from renal ROI after background subtraction, and time of maximum activity($T_{max}$) and half time of maximal peak radioactivity($T_{1/2}$) were produced in the renogram curve. (5) EI through Bischof-Delaloye method as determined on the renogram curve. Results : Normal group( I ) shows mean EI of 2.21(95.0% Confidence limit of 2.01-2.87), $T_{max}$ of 154 sec, $T_{1/2}$ of 1,139 sec. Abnormal group(II) shows mean EI of 0.74, $T_{max}$ of 1,466 sec, $T_{1/2}$ of 19,224 sec. The EI, $T_{max}$, $T_{1/2}$, BUN and serum creatinine values are significantly different between normal group(I) and abnormal group(II) (p<0.0001). Conclusion : By measuring EI with $^{99m}Tc-MAG_3$, renal function of transplanted kidney could be easily evaluated and various complications could be detected early.

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Avascular Necrosis of Bone after Renal Transplantation - Prevalence and Usefulness of Bone SPECT - (신장 이식후에 발생한 무혈관성 골괴사 -발생 빈도 및 골 SPECT의 유용성에 관하여 -)

  • Choi, Yun-Young;Yang, Seoung-Oh;Ryu, Jin-Sook;Moon, Dae-Hyuk;Lee, Hee-Kyung
    • The Korean Journal of Nuclear Medicine
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    • v.29 no.4
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    • pp.504-510
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    • 1995
  • Avascular necrosis(AVN) of bone can be resulted from various causes that distrub vascular supply to bone tissue, including steroid therapy after renal transplantation. In this study, we determine the prevalence of the avascular necrosis of bone after renal transplantation and compare the role of the bone scan, SPECT and MRI. In 301 patients with transplanted kidney, the prevalence of avascular necrosis was deter-mined clinically. Site of bone necrosis was evaluated by clinical symptom, bone scan, SPECT and MRI. Bone scan was done in all patients with AVN. Bone SPECT and MRI were done in six cases; and MRI was done in two cases. The prevalence of AVN was 3.3% (10/301), and the site of AVN was 16 femoral heads in 10 patients (bilateral: 60%) and bilateral calcaneal tuberosity in one patient. Bone scan showed typical AVN (cold area with surrounding hot uptake) in 13 lesions, only hot uptake in three lesions (including two calcaneal tuberosities), decreased uptake in one lesion, and normal in one lesion. Decreased uptake and normal lesion showed an equivacal cold area without surrounding hot uptake on SPECT. A symptomatic patient with positive bone SPECT showed normal finding on MRI. The prevalence of AVN of bone after renal transplantation was 3.3%, and whole body bone scan showed multiple bone involvement. Two symptomatic hip Joints without definite lesion on whole body bone scan or MRI showed cold defect on SPECT. Therefore, we conclude that bone SPECT should be perfomed in a symptomatic patient with negative bone scan or MRI in case with high risk of AVN after renal transplantation.

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