• Title/Summary/Keyword: Gross examination

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CRISPR/Cas9-mediated knockout of Rag-2 causes systemic lymphopenia with hypoplastic lymphoid organs in FVB mice

  • Kim, Joo-Il;Park, Jin-Sung;Kim, Hanna;Ryu, Soo-Kyung;Kwak, Jina;Kwon, Euna;Yun, Jun-Won;Nam, Ki-Taek;Lee, Han-Woong;Kang, Byeong-Cheol
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.166-175
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    • 2018
  • Recombination activating gene-2 (RAG-2) plays a crucial role in the development of lymphocytes by mediating recombination of T cell receptors and immunoglobulins, and loss of RAG-2 causes severe combined immunodeficiency (SCID) in humans. Rag-2 knockout mice created using homologous recombination in ES cells have served as a valuable immunodeficient platform, but concerns have persisted on the specificity of Rag-2-related phenotypes in these animals due to the limitations associated with the genome engineering method used. To precisely investigate the function of Rag-2, we recently established a new Rag-2 knockout FVB mouse line ($Rag-2^{-/-}$) manifesting lymphopenia by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease. In this study, we further characterized their phenotypes focusing on histopathological analysis of lymphoid organs. $Rag-2^{-/-}$ mice showed no abnormality in development compared to their WT littermates for 26 weeks. At necropsy, gross examination revealed significantly smaller spleens and thymuses in $Rag-2^{-/-}$ mice, while histopathological investigation revealed hypoplastic white pulps with intact red pulps in the spleen, severe atrophy of the thymic cortex and disappearance of follicles in lymph nodes. However, no perceivable change was observed in the bone marrow. Moreover, our analyses showed a specific reduction of lymphocytes with a complete loss of mature T cells and B cells in the lymphoid organs, while natural killer cells and splenic megakaryocytes were increased in $Rag-2^{-/-}$ mice. These findings indicate that our $Rag-2^{-/-}$ mice show systemic lymphopenia with the relevant histopathological changes in the lymphoid organs, suggesting them as an improved Rag-2-related immunodeficient model.

A Clinical Study for the Efficacy and Safety of Functional Cosmetics Containing peptide Scolopendrasin-I isolated from the Scolopendra subspinipes mutilans in Patients with Dry Skin due to Mild Atopic Dermatitis (아토피성 피부로 건조함을 가진 대상자에 대한 왕지네로부터 분리한 펩타이드 Scolopendrasin-I 함유 기능성 화장품의 기능성 및 안전성을 평가하기 위한 임상적 연구)

  • Park, Hye-Su;Kim, Tae-Jun;Park, Shin-Yong;Kim, Hee-Taek
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.32 no.3
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    • pp.23-36
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    • 2019
  • Objectives : The purpose of this study is to confirm the efficacy and safety of "Functional cosmetics containing peptide Scolopendrasin-I isolated from the Scolopendra subspinipes mutilans" on dry skin due to mild atopic dermatitis. Methods : A total of 24 patients who visited Semyung Oriental Medical Center from November 1st, 2018 to December 20th, 2018 were included in the study. In this study, the patients were treated with Functional cosmetics containing peptide Scolopendrasin-I isolated from the Scolopendra subspinipes mutilans. For 4 weeks of gross examination, instrumental assessment were made before and after the study to evaluate how well the products for treatment group in recovering the dry skin barriers by mild atopic dermatitis. Results : 1. In the primary endpoint, Skin Hydration showed a statistically significant increase in treatment group in baseline, 2 weeks and 4 weeks. 2. In the primary endpoint, Transepidermal Water Loss(TEWL) showed a statistically significant decrease in treatment group between Baseline and 4 weeks. 3. In the secondary endpoint, Skin pH showed a statistically significant decrease in treatment group between baseline and 4 weeks. 4. To evaluate the safety of the products for the human body, Adverse events, SCORAD Index Assessment were conducted; There were no severe adverse events during this study. And SCORAD Index showed a statistically significant decrease in treatment group in baseline, 2 weeks and 4 weeks. Therefore, it is suggested that products, if used for certain period, should be safe for the human body. Conclusions : According to the above experiments, it is suggested that "Functional cosmetics containing peptide Scolopendrasin-I isolated from the Scolopendra subspinipes mutilans" should be effective for dry skin due to mild atopic dermatitis.

A Clinical Study for the Efficacy and Safety of Functional Cosmetics Containing Humulus japonicus Extract in Patients with Dry Skin due to Mild Atopic Dermatitis (아토피성 피부로 건조함을 가진 대상자에 대한 환삼덩굴추출물 함유 기능성 화장품의 유효성 및 안전성을 평가하기 위한 임상적 연구)

  • Park, Hye-Su;Kim, Yong-Min;Kim, Hee-Tack
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.32 no.2
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    • pp.24-58
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    • 2019
  • Objectives : The purpose of this study is to confirm the Efficacy and Safety of "Functional cosmetics containing Humulus japonicus Extract" on dry skin due to mild atopic dermatitis. Methods : A total of 48 patients who visited Semyung Oriental Medical Center from March 20th, 2018 to July 5th, 2018 were included in the study. In this study, the patients were treated with Functional cosmetics containing Humulus japonicus Extract and positive control group. For 6 weeks of gross examination, instrumental assessment were made before and after the study to evaluate how well the products for treatment group with positive control products for control group in recovering the dry skin barriers by mild atopic dermatitis. Results : 1. In the primary endpoint, Skin Hydration showed a statistically significant increase and Transepidermal Water Loss(TEWL) showed a statistically significant decrease in treatment group between Baseline and 6 weeks. 2. In the secondary endpoint, Skin Hydration showed a statistically significant increase in treatment group between Baseline and 3 weeks, but TEWL showed no statistical significance. 3. In the secondary endpoint, Skin Hydration showed a statistically significant increase in treatment group between 3 weeks and 6 weeks, but TEWL showed no statistical significance. 4. In the secondary endpoint, Change of Skin Hydration and TEWL between treatment and control group showed a statistical significance in 6 weeks. 5. In the secondary endpoint, Change of Skin Hydration of 1cm below the medial aspect of the elbow between treatment and control group showed a statistical significance in 3 weeks. 6. In the secondary endpoint, Change of Skin Hydration between treatment and control group showed a statistical significance in 3 weeks and 6 weeks except Center between the medial aspect of the elbow and the wrist in 3 weeks, and Change of TEWL between treatment and control group showed a statistical significance in 6 weeks. 7. To evaluate the safety of the products for the human body, Adverse events, EASI Score, Itching Symptoms Assessment, vital sign check were conducted; There were no severe adverse events during this study. And both experimental group and control group showed no abnormal level. Therefore, it is suggested that products, if used for certain period, should be safe for the human body. Conclusions : According to the above experiments, it is suggested that "Functional cosmetics containing Humulus japonicus Extract" should be effective for dry skin due to mild atopic dermatitis.

Experimental renal artery embolization with iohexol-ethanol and barium-ethanol in dogs (개에서 iohexol-ethanol 및 barium-ethanol을 이용한 실험적 신동맥 색전술)

  • Hwang, Guk-jin;Chang, Dongwoo;Seo, Minho;Jung, Joohyun;Choi, Mincheol;Yoon, Junghee
    • Korean Journal of Veterinary Research
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    • v.41 no.3
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    • pp.429-436
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    • 2001
  • The present study was performed to investigate the effect of iohexol-ethanol mixture and barium-ethanol mixture on the induction of transcatheter renal artery embolization in healthy 18 dogs, which were divided into two groups of 9 dogs and the 9 dogs were divided into 3 subgroups of 3 dogs. The renal artery embolization was undertaken unilaterally with the dose of 1.5, 2.0, and 3.0 ml/kg iohexol-ehtanol mixture and with the dose of 0.2, 0.4, and 0.8 ml/kg barium-ethanol mixture. And serum chemistry on 0, 1,3, 7, and 14 days, intravenous pyelography on 7days, angiography on 14 days, and histopathology on 14 days were evaluated. Serum BUN and creatinine concentration of two groups with iohexol-ethanol mixture and barium-ethanol mixture administration were mildly increased a t 1 day after injection of embolic materials and then returned to baseline. No significant changes in BUN and creatinine levels occurred in any of dogs. In all dogs with the dose of 1.5 ml/kg iohexol-ethanol mixture, the renal arteries were not embolized. All dogs with the dose of 3.0 ml/kg died. In all dogs with the dose of 2.10 ml/kg, the treated arteries were completely occluded. In barium-ethanol mixture administered group, the renal artery in one dog with the dose of 0.2 ml/kg was not embolized. In all dogs with the dose of 0.8 ml/kg, the renal arteries were completely embolized, but loac overembolization occured in two dogs. All animals with the dose of 0.4 ml/kg had effective embolization and no evidence of radiopaque barium opacity in systemic arteries distal to the renal-artery was found. All embolized kidneys were shrunk and decreased in size in gross examination and were shown diffuse necrosis in histopathologic examination. In the present study, renal arteries were embolized with the dose of 2.0 ml/kg iohexol-ethanol mixture or 0.4 ml/kg barium-ethanol mixture. And it is considered that the dose had a satisfactory embolic effect.

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The Effect of Cultured Perichondrial Cell Sheet Covered Highly Active Engineered Cartilage: in vivo Comparative Assessment (배양연골막이 피복된 고효능 인공연골의 생체내 효과)

  • Park, Se-Il;Moon, Young-Mi;Jeong, Jae-Ho;Jang, Kwang-Ho;Ahn, Myun-Hwan
    • Journal of Veterinary Clinics
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    • v.28 no.5
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    • pp.486-496
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    • 2011
  • A special mesenchymal tissue layer called perichondrium has a chondrogenic capacity and is a candidate tissue for engineering of cartilage. To overcome limited potential for chondrocyte proliferation and re-absorption, we studied a method of cartilage tissue engineering comprising chondrocyte-hydrogel pluronic complex (CPC) and cultured perichondrial cell sheet (cPCs) which entirely cover CPC. For effective cartilage regeneration, cell-sheet engineering technique of high-density culture was used for fabrication of cPCs. Hydrogel pluronic as a biomimetic cell carrier used for stable and maintains the chondrocytes. The human cPCs was cultured as a single layer and entirely covered CPC. The tissue engineered constructs were implanted into the dorsal subcutaneous tissue pocket on nude mice (n = 6). CPC without cPCs were used as a controls (N = 6). Engineered cartilage specimens were harvested at 12 weeks after implantation and evaluated with gross morphology and histological examination. Biological analysis was also performed for glycosaminoglycan (GAG) and type II collagen. Indeed, we performed additional in vivo studies of cartilage regeneration using canine large fullthickness chondrial defect model. The dogs were allocated to the experimental groups as treated chondrocyte sheets with perichondrial cell sheet group (n = 4), and chondrocyte sheets only group (n = 4). The histological and biochemical studies performed 12 weeks later as same manners as nude mouse but additional immunofluorescence study. Grossly, the size of cartilage specimen of cPCs covered group was larger than that of the control. On histological examination, the specimen of cPCs covered group showed typical characteristics of cartilage tissue. The contents of GAG and type II collagen were higher in cPCs covered group than that of the control. These studies demonstrated the potential of such CPC/cPCs constructs to support chondrogenesis in vivo. In conclusion, the method of cartilage tissue engineering using cPCs supposed to be an effective method with higher cartilage tissue gain. We suggest a new method of cartilage tissue engineering using cultured perichondrial cell sheet as a promising strategy for cartilage tissue reconstruction.

Study about the clinical features and Pulmonary function Tst of Endobronchial Tuberculosis (기관지결핵의 임상상 및 폐기능검사에 관한 연구)

  • Chung, Hee-Soon;Lee, Jae-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.2
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    • pp.147-158
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    • 1996
  • Background : Endobronchial tuberculosis(ET) is known to affect frequently young female and serious complication like bronchial stenosis would occur if early diagnosis and treatment for ET is not performed immediately. But ET shows normal chest roentgenogram in about 10% of patients, and is often confused with bronchial asthma because ET presents clinical features like cough, dyspnea, wheezing in history and physical examination. The pulmonary function test(PFT) feature of ET is not well known, but when we consider the fact that ET is pathophysiologically different from bronchial asthma, if there is any feature of PFT in ET, and we know it, PFT will be very helpful for diagnosis and follow up of ET. Methods : We performed both PFT and bronchoscopy in 68 ET patients who visited Boramae hospital, and were confirmed as ET by bronchoscopic biopsy and were followed prospectively from November 1991 to March 1995. After history taking and physical examination, we performed chest roentgenogram, complete blood count, sputum AFB stain and culture, and also performed PFT before anti-tuberculosis chemotherapy. PFT was classified as restrictive, if only PVC was reduced below 80%, and obstructive, if only FEV1 was reduced below 75%. In the case of both FVC and FEV1 were reduced, PFT was classified as restrictive if FEY1/FVC was greater than 75%, and mixed if FEV1/FVC was reduced below 75%. We repeated the PFT and bronchoscopy for 68 ET patients who were proven by biopsy in the first month and sixth month after starting anti-tuberculosis chemotherapy, and studied the feature and change of PFT of the ET and the relation between PFT and the bronchoscopic finding, and obtained following results. Results: 1) Number of male patients was 12, and that of female patient was 56, and mean age was $35.4{\pm}17yr$.(17-74yr). Clinical symptom was in the order of cough(86.8%), dyspnea(63.2%), fever(17.6%) and hemoptysis (10.3%), and the wheezing and stridor were audible among the 40 patients(58.4%) in the physical examination. 2) Hemoglobin level was below 12g/dl among 25 patients (36.8%), and WBC level was above $10,000/mm^3$ among 9 patients(13.2%) and ESR was above 20 among 46 patients (67.6%) and AFB stain and culture were positive among 50 patients(73.5%). 3) The dominant roentgenographic finding of ET was fibronodular feature in 35 patients(51.5%), pneumonic feature in 14 patients (20.6%), collapse in 11 patients(16.2%), mass-like lesion in 3 patients(4.4%), cavitary lesion in 2 patients(2.9%), and normal in 3 patients(4.4%). 4) PFT feature at the time of diagnosis of ET was normal in 16 patients(23.5%), restrictive pattern in 32 patients (47%), obstructive in 4 patients(5.8%), and mixed in 14 patients(23.5%). So restrictive pattern was the dominate feature of ET. 5) The PFT feature was little correlated with the gross finding of bronchoscopy, but the change of PFT during treatment of ET showed relatively good correlation with the change of bronchoscopic finding. 6) FVC(2.30L vs. 2.61L) and FEV1(1.74L vs. 2.06L) increased significantly (p < 0.01), but FEV1/FVC(82% vs. 83%) and PEF(3.45L/sec vs. 3.95L/sec) did not change significantly after 1 month of treatment (p > 0.01), and there was no significant change among all parameters during first and sixth month of treatment(p > 0.01). Conclusion : PFT may be useful in the diagnosis and treatment follow up of ET but further study would be needed to confirm it.

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Usefulness Evaluation of Open Mouth View when PET/CT scan In Tongue Cancer Patients (Tongue Cancer 환자에서 PET/CT 검사 시 Open Mouth 촬영법의 유용성 평가)

  • Kim, Jae Hwan;Yun, Jong Jun;Jung, Ji Wook;Kim, Jung Wook;Hwang, Ju Won;Ji, Hye In
    • The Korean Journal of Nuclear Medicine Technology
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    • v.20 no.2
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    • pp.14-20
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    • 2016
  • Purpose Tongue cancer is 1.8% of all cancer tumors occur in the tongue, it is known that the high incidence enough to account for 75% of oral cancer conducted a PET / CT examination for early diagnosis, metastasis, staging, etc. and. Tongue when PET / CT scan of a cancer patient and a Torso taken to close mouth lesions if the condition was caused due to the overlapping or corresponding artifacts are not clearly observed. The purpose of this study is to evaluate the changes that occur during PET / CT scan with open mouth and its usefulness under. Materials and Methods From June 2015 to March 2016 complained of herein by May 21 had received a diagnosis of tongue cancer underwent PET / CT scan patients were treated with a target (16 males, 5 female). The first was taken to close mouth Torso state, it was taken to add 1 bed open mouth condition. Tumor (T), measuring the Normal Tongue (NT), Lymph Node (LN) standard intake coefficient by setting a region of interest in the (standardized uptake value, SUV) SUVmean, the average value was measured SUVmax, drawn to each region of interest 3 times and Background (Carotid artery) was out of the SUV. In Chapter 3 of the slice to the tumor clearly visible by setting the region of interest to measure the change Tumor size was calculated average value. Gross Image resolution assessment were analyzed statistically through were divided into 1-5 points by the Radiation 7 people in 2, more than five years worked in specialized nuclear medicine compare to proceed with the blind test nonparametric test (wilcoxon signed rank test). (SPSS ver.18) Results $SUV_{mean}$ T's were in close mouth $5.01{\pm}2.70$ with open mouth $5.48{\pm}2.88$ (P<0.05), $SUV_{max}$ were respectively $8.78{\pm}5.55$ and $9.70{\pm}5.99$ (P<0.05). $SUV_{mean}$ in the NT were respectively $0.43{\pm}0.30$ and $0.34{\pm}0.24$ (P=0.20), $SUV_{max}$ was $0.56{\pm}0.34$ and $0.45{\pm}0.25$ (P=0.204). LN $SUV_{mean}$ were respectively $1.62{\pm}1.43$ and $1.69{\pm}1.49$ (P=0.161), $SUV_{mean}$ was $2.09{\pm}1.88$ and $1.99{\pm}1.74$ (P=0.131). Tumor size change is close mouth $4.96{\pm}4.66cm^2$ $5.33{\pm}4.64cm^2$ with 7.45% increase was (P<0.05), gross image resolution evaluation is $2.87{\pm}0.73$, $3.77{\pm}0.68$ with open mouth examinations 30.5% increase was (P<0.05). Conclusion Tumor SUV on the changes that had an increase in open mouth during inspection, the normal tongue and lymph node, but there was no significant difference in the change slightly. It is also one open mouth PET / CT scan will provide improved image to all patients with tongue cancer, but it could be confirmed that similar overall through the blind test, or tumor size changes and showing a high resolution image. It can be the perfect alternative method for problems that occur when the close mouth Open mouth PET / CT scan, but is believed to be through the open mouth to observe the boundary of overlapping or tumor of the oral cavity other structures a little more clearly. Tongue cancer patients how to recommend that the shooting further open mouth PET / CT.

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The relationship between the time from arrival at a hospital to delivery and the occurrence of cerebral palsy in premature infants of less than 34 weeks of gestational age (재태주령 34주 이전에 출생한 미숙아에서 병원도착시점에서 분만까지 소요된 시간과 뇌성마비 발생과의 관련성)

  • Hwang, Jae Woong;Heo, A Lum;Koo, Soo Hyun;Lee, Hae Jung;Lee, Jun Wha;Lee, Joo Seok;Cho, Kyung Lae
    • Clinical and Experimental Pediatrics
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    • v.52 no.11
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    • pp.1228-1233
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    • 2009
  • Purpose : This study aimed to evaluate whether a shorter time from the arrival at a hospital to delivery is related to the occurrence of cerebral palsy in premature infants of less than 34 weeks of gestational age. Methods : We studied 142 newborns of less than 34 weeks of gestational age. The time from the arrival at the hospital to delivery was measured. The correlation between the time required for delivery and the occurrence of cerebral palsy was elucidated by diagnosing cerebral palsy in neonates using the Korean Infant Development Screening Test and neurological examination. Results : Preliminary result suggested that a shorter time from hospital arrival to delivery was related to a lower development score for gross motor activity and to a higher frequency of cerebral palsy occurrence. Moreover, it was responsible for a tendency of obtaining lower Apgar scores at 1 and 5 minutes. The shorter delivery time was associated with a higher probability of respiratory distress syndrome (RDS) occurrence when the length of delivery time was less than 6 hours and there was a higher probability of a shorter gestation period. However, the multifactor analysis revealed that there was little impact of delivery time on the occurrence of cerebral palsy. Conclusions : The length of hospital arrival time to delivery did not significantly influence the occurrence of cerebral palsy in premature infants of less than 34 weeks of gestational age.

Effect of Submucosal Formalin Injection on Bladder Wall in Rats (백서에서 Formalin의 방광점막하주사가 방광벽에 미치는 영향)

  • Lee, Dong-Heon;Park, Tong-Choon
    • Journal of Yeungnam Medical Science
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    • v.4 no.2
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    • pp.113-120
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    • 1987
  • The effect of intravesical formalin instillation as a therapeutic modality for intractable bladder hemorrhage is well known. And despite clear evidence of therapeutic efficacy of intravesical cytotoxic drugs and/or BCG immunotherapy, there have been substantial recurrences during followup after transurethral resection for superficial bladder tumor. If formalin injected at the bed of superficial bladder tumor is able to coagulate and necrotize the tumor, it will be greatly helpful to the patients With recurrent bladder tumor developed during followup. Since this technique is applicable on outpatient basis, an economical as well as a psychological burden of the patients can be reduced considerably. The purpose of this study is to evaluate the effect of submucosal formalin injection on rat bladder wall, 36 healthy adult male Sprague-Dawley rats (weighing 350gm in average) were divided into 3 groups: In Group I (control group), 0.01ml of normal saline was injected submucosally at the left posterolateral wall of the bladder opened under intraperitoneal Nembutal anesthesia ; In Group II and III, 0.01 ml of 10% and 4% formalin, respectively, were administered at the same site as in the Group I, two rats in each group were sacrificed at day 1, 2, and 3, and week 1, 2 and 4 after injection, respectively. Gross and microscopic examination of the cystectomized specimen were done in each group. In the Group II, bladder stones were formed at week I, and in both the Group I and III, stones were seen at week 2 post injection. There was no significant difference III histologic findings of the bladder between the group II and III. Mucosal ulcer and/or prominent mucosal disruption was observed at 24 hours after injection in both Group II and III. Epithelial regeneration began at day 2, and was marked at day 3, and epithelial lining was almost normalized one week after injection. Subepithelial edema, telangiectasia and inflammatory reaction were prominent at 24 hours post formalin injection. Subepithelial edema persisted in moderate degree for 1 week. Telangiectasia and inflammatory reaction were noted for 4 weeks. Mild degree of these findings also appeared In the control group. Fibroblastic proliferation appeared at day 2 and persisted in moderate degree for 4 weeks. There has been no mortality or bladder perforation. These results suggest that clinical application of this technique is feasible for the selected cases of recurrent, solitary superficial bladder tumor. However, optimal dosage of formalin in relation to the size of the lesion remains to be investigated.

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A Study of the Changes of Breast Uptake in Menstrual Cycle on 18F-FDG PET/CT (월경 주기에 따른 18F-FDG PET/CT에서 유방 섭취 변화에 관한 고찰)

  • Tak, Yeojin;Park, Min Soo;Lee, Juyoung;Park, Hoon-Hee
    • Journal of radiological science and technology
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    • v.38 no.1
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    • pp.31-38
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    • 2015
  • $^{18}F-FDG$ PET/CT has been known a useful modality to diagnose high-glucose-using cells such as cancer cells by glucose metabolism of FDG. Mainly, FDG takes on cancer and inflammatory cells; however, there have been FDG uptakes on normal tissues by individual physiological characteristics, occasionally. Especially, in fertile females, unusual FDG uptake of breast changes as the menstrual cycle, and disturb diagnosis. Therefore, the study aimed to evaluate the change of breast FDG uptake in menstrual cycle on $^{18}F-FDG$ PET/CT. 160 females ($34{\pm}3.5$ years old) who do not undergo a gynecologic anamnesis and have regular menstrual cycle over the previous 6 months were examined. They were divided 4 groups (each 40 patients) as flow phase, proliferative phase, ovulatory phase and secretory phase using Pregnancy Calculator 0.14. and history taking. Discovery Ste (GE Healthcare, Milwaukee, Mi, USA) was used a s PET/CT. We analyzed SUVs on accumulated region on breast, and 3 nuclear medicine specialists did the Blind test. SUVs on the Breast were flow phase ($1.64{\pm}0.25$), proliferative phase ($0.93{\pm}0.28$), ovulatory phase ($1.66{\pm}0.26$) and secretory phase ($1.77{\pm}0.28$). It showed high uptake value in secretory, flow phase and ovulatory phase (p<0.05). In gross analysis, the accumulation of breast was divided into 3 grades as comparing with lung and liver. The breast's uptake was equal to lung (Grade I); between lung and liver (Grade II); equal to or greater than liver (Grade III). The results showed high uptake value in secretory, flow phase and ovulatory phase (p<0.05). In fertile females, FDG uptake of breast changed as menstrual cycle, and it available to diagnose breast disease. Therefore, we consider reducing false-negative finding of breast disease, by doing examination on appropriate period through history taking about individual menstrual cycle.