Comparison of Melanoma Subtypes among Korean Patients by Morphologic Features and Ultraviolet Exposure

( Hong Sun Jang ),( Jee Hung Kim ),( Kyu Hyun Park ),( Jae Seok Lee ),( Jung Min Bae ),( Byung Ho Oh ),( Sun Young Rha ),( Mi Ryung Roh ),( Kee Yang Chung ) 대한피부과학회 2014 Annals of Dermatology Vol.26 No.4

Background: Genetic alterations have been identified in melanomas according to different levels of sun exposure. Whereas the conventional morphology-based classification provides a clue for tumor growth and prognosis, the new classification by genetic alterations offers a basis for targeted therapy. Objective: The purpose of this study is to demonstrate the biological behavior of melanoma subtypes and compare the two classifications in the Korean population. Methods: A retrospective chart review was performed on patients found to have malignant melanoma in Severance Hospital from 2005 to 2012. Age, sex, location of the tumor, histologic subtype, tumor depth, ulceration, lymph node invasion, visceral organ metastasis, and overall survival were evaluated. Results: Of the 206 cases, the most common type was acral melanoma (n=94, 45.6%), followed by nonchronic sun damage-induced melanoma (n=43, 20.9%), and mucosal melanoma (n=40, 19.4%). Twenty-one patients (10.2%) had the chronic sun-damaged type, whereas eight patients (3.9%) had tumors of unknown primary origin. Lentigo maligna melanoma was newly classified as the chronic sun-damaged type, and acral lentiginous melanoma as the acral type. More than half of the superficial spreading melanomas were newly grouped as nonchronic sun-damaged melanomas, whereas nodular melanoma was rather evenly distributed. Conclusion: The distribution of melanomas was largely similar in both the morphology-based and sun exposure-based classifications, and in both classifications, mucosal melanoma had the worst 5-year survival owing to its tumor thickness and advanced stage at the time of diagnosis. (Ann Dermatol 26(4) 485~490, 2014)

The level of urinary aflatoxin M1 in Korean adults

Yong-Dae Kim1, Hyojin Kwon, Sun-In Moon, Sang-Yong Eom, Jung-Duk Park, Byung-Sun Choi, Seok-Joon Sohn, Young-Seoub Hong, Ho Kim, Ho-Jang Kwon, Ji-Ae Lim, Hae-Jung Yoon, Gwang-Jin Kim, Heon Kim 충북대학교 동물의학연구소 2012 Journal of Biomedical and Translational Research Vol.13 No.3

Competitive ELISA methods were used to measure the level of aflatoxin M1 (AFM1) from urine in 1008 Korean adults. Subjects were selected by random sampling in all areas of Korea, except Cheju-do. The recovery rate of AFM1 using this method was 105% (73-124%). The geometric mean of urinary AFM1 in all subjects was 3.43 pg/mL (3.67 ng/g creatinine). The level of AFM1 in males was statistically higher, compared with female subjects. However, the levels of AFM1 did not differ according to age. Subjects in Chungbuk-do showed the highest urinary AFM1 concentration, whereas subjects in Kyeongnam-do showed the lowest concentration. Assuming an excretion rate of 5%, this AFM1 excretion corresponds to approximately 0.1 microgram/day in Korean adults.

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

외음부의 기저세포암

김보영 ( Bo Young Kim ),황선정 ( Sun Jung Hwang ),박병준 ( Byung Joon Park ),이은실 ( Eun Sil Lee ),한호섭 ( Ho Suap Han ),김용욱 ( Yong Wook Kim ),김태응 ( Tae Eung Kim ),노덕영 ( Duck Yeong Ro ),이안희 ( An Hi Lee ) 대한산부인과학회 2010 Obstetrics & Gynecology Science Vol.53 No.9

Basal cell carcinoma (BCC) is the most common human malignant neoplasm, accounting for 75% of all non-melanoma skin cancer. The incidence of BCC is strongly correlated with sun exposure as well as older age. Therefore, the vast majority of BCCs is observed in elderly patients on the sun-exposed skin of the head and neck with a frequency of more than 80%. BCC is very rare on sun-protected skin such as the perianal and genital regions and other etiologic factors must be considered in these cases. Although the pathogenesis of vulvar BCC is unclear, early diagnosis is very important. Because BCC in these areas sometimes seems innocuous, it is recommended that a biopsy of all suspect lesions be performed. We report a woman with BCC of the vulva treated with wide local resection and reviews the literatures on this subject.

위절제술 환자의 표준진료지침 개발 및 적용 효과

김은희,김철규,이순교,김순덕,이혜옥,권정순,이경미,이민미,심순미,유용만,신종식,강은희,이상일,김병식,오성태,육정환,박수길 한국의료QA학회 2003 한국의료질향상학회지 Vol.10 No.2

Background : Gastric cancer is the most common malignant tumor in Korea. surgical operation is one of the major treatment modalities for gastric cancer patients. Therefore, gastrectomy is one of the most common procedures in General Surgery. There were variation in length of hospital stay and medical treatment for gastrectomy between three surgeons at Asan Medical Center. Clinical pathways have received considerable attention as a tool for recucing the medical practice variation, increasing the efficiency of care process, and improving the quality of care. The aim of this study was to evaluate the effect of a clinical pathway for gastrectomy in gastric cancer patients. Methods : The clinical pathway for gastrectomy was developed and implemented by a multidisciplinary group in Asan Medical Center. A computerized clinical pathway program was developed and revised after a pilot test. A total of 145 patients underwent gastrectomy by three surgeons at Asan Medical Center. We compared the length of hospital stay, patient satisfaction, and unplanned readmission rate between the pre-pathway group(n=67) and the post-pathway group(n=78). We also investigated the degree of satisfaction among the physicians and nurses who were main end-users of the clinical pathway. Results : The clinical pathway was applied to all target patients. The average length of hospital stay was shortened from 12.7days to 10.6days(p<0.01). The degree of patient satisfaction with the care process changed from 90.3% to 89.2% after the implementation of the clinical pathway, but the difference was of satistically significant(p=0.761). Unplanned readmission rate was 2.9% in the pre-pathway group. More than 90% of physicians and nurses answered that the clinical pathway had been a useful tool in their medical practice. Conclusions : The findings of the study demonstrated that implementation of the clinical pathway for gastrectomy produced substantial reduction in the length of hospital stay while improving the quality of patient outcomes. The computerized clinical pathway program can be used as one of the powerful patient management tools for reducing the practice variations and increasing the efficiency of care process in Korea hospital settings.

신경섬유종증-제 2형의 진단과 치료 : 16례의 임상경험 Experience of 16 Cases

김정은,백선하,김종수,이상형,오창완,김동규,정희원,김현집,조병규,한대희,최길수 대한신경외과학회 1996 Journal of Korean neurosurgical society Vol.25 No.12

Neurofibromatosis type 2(NF-2) is a dominantly inherited disorder characterized by the occurrence of bilateral acoustic neurinomas and the frequent association of other central nervous system tumors. We present a retrospective review of 16 patients with NF-2 who were treated at our hospital from 1984 to 1995 in 13 cases, the diagnoses of Nf-2 were based on the criteria developed at the Consensus Development Conference of National Institute of Health in the United States, and in another 3 cases. the criterias of NF-2 were not fully satisfied, but the diagnoses of NF-2 were highly suspected. The average age of the patients was 27.6 years, ranging from 13 years to 56 years. The most common symptom was hearing difficulty : intervals between symptom onset and deafness ranged from 8 months to 6 years(mean : 2.9 years) One family of NF-2 was documented consisting of a sister a brother and their mother. Nine patients underwent operations on unilateral acoustic neurinomas : these were subtotally removed in eight patients and totally in one patient Among these patients five were deaf on the ipsilateral side at surgery. Among the other four patients with useful hearing before surgery, hearing was preserved to preoperative status in two patients. Four patients with diagnoses of meningioma, received operations to relieve mass effect with subtotal removal in two patients and total removal in the other two. Early diagnosis and treatment are the most important in the management planning of patients with NF-2 for reasons of early manifestation and rapid progression of the disease.

생체분해성 망막압정을 이용한 망막고정에 대한 실험적 연구

김용백,민병무,김창식,박근성,김승영,길숙종,조항진,이성복,노승무,송규상,강대영,조준식,양준묵,정경수,최선웅,이진호,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

Biodegradable retinal fixation devices obtain mechnical fixation of the retina with desirable chorioretinal scarring and with the potential for local, sustained release of antimetabolites and steroids to inhibit proliferative vitreoretinopathy. We manufactured a biodegradable retinal tack with barb that was designed in order to prevent intrusion from implantation of retinal tacks. This study was carried to evaluate the efficacy for retinal fixation and the capability for sustained release of drugs with a newly designed biodegradable retinal tack Biodegradable retinal tacks were made of polymers of glycolic acids and were designed with barbs in a shape to prevent the disinsertion. Biodegradale retinal tacks are divided into 3 parts, a conical portion that is inserted into the sclera, a cylinder portion that remains in the vitreous, and a neck portion between the pin and the cylinder. The tapered conical end was manufactured to allow easy insertion through the retina and choroid into the sclera. A cylinder portion was manufactured with a tapered angle that fixes firmly into the orifice of 19 gauge spinal needle. A neck portion, 0.4 mm in diameter, was designed to prevent disinsertion from following implantation of retinal tack. The applicator was a 19 gauge spinal needle and its orifice was prepared to 15°angle to accept the tapered cylinder portion of the retinal tack. The retinal tacks, secured in the needles, were passed through the formed vitreous and inserted into the retina, choroid, and sclera and were released by pushing the internal needle, usually within 2-3mm of the medullary ray of the posterior rabbit retina A retinal tack was placed in each of 8 pigmented rabbit eyes. Slit-lamp biomicroscopy, indirect ophthalmoscopy and fundus photography were performed periodically from 1 day to 8 weeks after surgery. Eight eyes were enucleated and studied by light microscopy at 8 weeks. Biomicroscopic evaluation of the animals revealed edemas adjacent to the retinal surfaces immediately after insertion of the biodegradable retinal tacks in all the animals. These edemas disappeared after 1 week. The first noticeable change in the size of retinal tacks was shown after 2weeks. The size of the retinal tacks gradually got smaller, decreasing to about one-half at 4 weeks and about one-third at 8 weeks. All retinal tacks remained in inserted places without any movement for an 8 week period. On light microscopy, epiretinal proliferations were seen to extend into the vitreous cavity. Cellular capsules that lined the inner aspect of the scleral defect caused by tack insertion were found. However the adjacent retina had a normal cytologic appearance and architecture in all specimens. We manufactured a biodegradable retinal tack that is designed to prevent intrusion from implantation of retinal tacks. All biodegradable retinal tacks reduce in size with time, but no retinal tacks extruded from the inserted place. The newly designed biodegradable retinal tack can be used for retinal fixation and may be used as a vehicle for the introduction of pharmacologic agents to prevent the cellular events that promote proliferative vitreoretinopathy.

Effects of Phenytoin and Diazepam on the Seizure Activity in the Cortical Dysplasia Animal Models

Kim, Si-Hyung,Choi, In-Sun,Cho, Jin-Hwa,Park, Eun-Ju,Jang, Il-Sung,Choi, Byung-Ju,Kim, Hyun-Jung,Kim, Young-Jin,Nam, Soon-Hyeun The Korean Academy of Oral Biology 2006 International Journal of Oral Biology Vol.31 No.2

Dysplasia-associated seizure disorders are markedly resistant to pharmacological intervention. Relatively little research has been conducted studying the effects of antiepileptic drugs(AEDs) on seizure activity in a rat model of dysplasia. We have used rats exposed to methylazoxymethanol acetate(MAM) in utero, an animal model featuring nodular heterotopia, to investigate the effects of AEDs in the dysplastic brain. Pilocarpine was used to induce acute seizure in MAM-exposed and age-matched vehicle-injucted control animals. Field potential recordings were used to monitor amplitude and numbers population spikes, and paired pulse inhibition in response to stimulation of commissural pathway. Two commonly used AEDs were tested: diazepam 5, 2.5mg/kg;phenytoin 40, 60mg/kg. Diazepam(DZP) and phenytoin(PHT) reduced the amplitude of population spike in control and MAM-exposed rats. However, the amplitude of population spike was nearly eliminated in control rats as compared to the MAM-exposed rats. Pharmaco-resistance was tested by measuring seizure latencies in awake rats after pilocarpine administration(320mg/kg, i.p.) with and without pretreatment with AEDs. Pre-treatment with PHT 60 mg prolonged seizure latency in control rats, but not in MAM-exposed animals. The main findings of this study are that acute seizures initiated in MAM-exposed rats are relatively resistant to standard AEDs assessed in vivo. These data suggest that animal model with cortical dysplasia can be used to screen the effects of potential AEDs.

직업적 노출에 의한 스티븐스-존슨 증후군에서 트리클로로에틸렌의 노출수준 : 3예의 사례와 문헌고찰을 중심으로

이선웅,김은아,김대성,고동희,강성규,김병규,김민기 大韓産業醫學會 2008 대한직업환경의학회지 Vol.20 No.2

배경: TCE는 심각한 전산적 피부염과 관련 있는 것으로 몇몇 사례들을 통해서 보고되어 왔으나,기존의 사례 보고들에서 노출평가가 수행된 사례는 드물었고 추정되는 노출량 역시 매우 다양하였다. 본 연구에서는 TCE 노출에 의한 것으로 판단되는 스티븐스-존슨 증후군 3예를 확인하고 각 사례들에 대한 작업재연을 통해 노출수준을 추정하였으며,이를 통해 TCE의 직업적 노출수준과 스티븐스-존슨 증후군을 포함하는 전신적 박탈성 피부염 발생의 관계를 이해하고자 하였다. 증례: 사례 1은 24세 필리핀인 여자로 TCE를 이용한 탈지작업을 시작한 35일 후 발진을 포함한 피부증상이 발생하였고 증상이 진행되면서 간기능 이상이 발견되었다. 환자는 스티븐스 존슨 증후군과 독성간염으로 진단되었고 증상발생 39일 간부전으로 사망하였다. 증상발생 전 약물 복용력은 없었고 바이러스 감염 등의 비직업적 원인은 찾을 수 없었으며,작업재연을 통한 TCE의 개인 노출수준 은 TWA 21.9 ppm과 32.3 ppm이었다. 사례 2는 47세 한국인 남자로 TCE를 이용한 탈지 작업을 시작한 20일 후 발진을 포함한 피부증상이 발생하였고 증상이 진행되면서 간기능 이상이 발견되었다. 환자는 중독성 표피괴사증 또는 스티븐스 -존슨 증후군, 전격성간염 및 동반된 패혈증으로 진단되었고 증상발생 42일 간부전 및 패혈증으로 사망하였다. 증상발생 전 약물복용력은 없었고 바이러스 감염 등의 비직업적 원인은 찾을 수 없었으며,작업재연을 통한 TCE의 개인 노출수준은 TWA 30.1 ppm이었으며 세척조 주위의 지역시료는 TWA 116.5 ppm∼229. 7 ppm 이었다. 사례 3은 22세 베트남인 여자로 TCE를 이용한 탐지작업을 시작한 30일 후 발전을 포함한 피부증상이 발생하였고 증상이 진행되면서 간기능 이상이 발견되었다. 환자는 스티븐스-존슨 증후군 및 동반된 독성간염으로 진단되었고 증상발생 37일 증세 호전되어 퇴원하였다. 증상발생전 약물복용력은 없었고 바이러스 감염 등의 비직업적 원인은 찾을 수 없었으며,작업재연을 통한 TCE의 개인 노출수준은 TWA 107.2 ppm이었다. 고찰: TCE에 노출된 일부의 사람들에서 노출 후 2주에서 5주 사이에 심각한 급성 간염이 동반되는 스티븐스­존슨 증후군이 발생할 수 있음을 확인 하였고,이번의 연구결과와 기존의 연구를 종합 할 때 TCE에 대한 감수성이 있는 사람의 상당수는 노출기준 이상의 고 노출에 노 출 후 스티븐스- 존슨 증후군이 발생함을 확인할 수 있었다. 따라서. TCE에 대한 고 노출을 막기 위해 TCE 세척작업에 대한 작업환경 확인과 개선이 우선적으로 필요하며,동시에 노출 후 증상발생기간의 일관성과 노출기준 이하의 저 노출에서의 감작 가능성을 배제할 수 없음을 고려하여,작업시작 후 1개월경의 특수건강검진 역시 고려되어야 할 것으로 판단된다. Back ground: Trichloroethylene (TCE) has been reported to be related to severe generalized exfoliative dermatitis frequently accompanied by toxic hepatitis. The measurements of environmental exposure were limited in the previous case reports and the reported exposure values were also diverse. We reviewed three cases of Stevens-Johnson syndrome associated with TCE. The work environment was measured by the Korea Occupational Safety and Health Agency (KOSHA) after the cases occurred. From the study results, we intended to clarify the relationship between TCE exposure level and Stevens-Johnson syndrome. Case report: Case 1. A 24-year-o1d Filipino female worker developed a skin rash 35 days after starting to use TCE for degreasing. The skin rash developed into a bullous eruption and the liver function findings were abnormal. She was diagnosed with Stevens-Johnson syndrome and toxic hepatitis. She died of hepatic failure 39 days after the onset of the first symptom. She had no previous history of taking medicine or viral infection. The work environment measured 22.0 to 32.3 ppm (Personal exposure level) with TWA. Case 2. A 47-year-o1d Korean male worker developed a skin rash, 20 days after starting to use TCE for degreasing. The skin rash developed into a bullous eruption and the liver function findings were abnormal. He was diagnosed with Stevens-Johnson syndrome, toxic hepatitis and sepsis. He died of hepatic failure and sepsis 42 days after the onset ofthe first symptom. He had no previous history of taking medicine or viral infection. The work environment measured 30.1 ppm (Personal exposure level) and 116.5∼229.7 ppm (area exposure level close to the degreasing rnachine) with TWA. Case 3. A 22-year-old Vietnamese female worker developed a skin rash 30 days after starting to use TCE for degreasing. The skin rash developed into a bullous eruption and the liver function findings were abnormal. She was diagnosed with Stevens-Johnson syndrome and toxic hepatitis. Her symptoms improved and she was discharged 37 days after the onset of the first symptom. She had no previous history of taking medicine or viral infection. The work environment measured 107.2 ppm (Personal exposure level) with TWA. Discussion: These three case reports and the previously reported cases indicated that the majority of people susceptible to TCE develops Stevens-Johnson syndrome after high-level TCE exposure (above the TWA occupational exposure limit of 50 ppm). Therefore, work environmental survey and improvements to the TCE degreasing process are essential to prevent high exposure. Furthermore, considering the consistency of the latency period in symptoms and the possibility of sensitization in low-level exposure, we recommend that the first specific health examination also should be conducted 1 month after workers have commenced working.

랫드에서 인체 재조합 적혈구 조혈인자, rHuEPO의 13주 정맥투여 아만성독성에 관한 연구

김형식,곽승준,천선아,박현선,한하수,임소영,안미영,김원배,김병문,안병옥,홍성렬,이병무 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1

A recombinant human erythropoietin (rHuEPO) was administered intravenously at dosage levels of 0, 100, 500, and 2500 IU/㎏/day for a period of 13 weeks. There were no observed clinical signs and deaths related to treatment in all groups tested. Decreases in body weight gain and food consumption were observed only in males of 2,500 IU/㎏ group after 2 weeks. In hematological parameters, erythrocyte content, hematocrit values and hemoglobin concentration were dose-dependently increased in rHuEPO treated groups. The ratio between kidney weight and whole body weight was significantly increased in females of 500 and 2,500 IU/㎏ groups. The spleen weight was also increased in both sexes of 500 and 2,500 IU/㎏ groups. However, the absolute weight change of other organs was not observed. In histopathological examinations, the renal tubular basophilia was observed only in males and females of 2,500 IU/㎏ groups. From these results, it is concluded that the no-observed adverse effect level(NOAEL) of rHuEPO is 100 IU/㎏ in rats in the present study.