보조 면역억제제 사용에 따른 82마리의 뇌수막염 개에서의 예후와 생존 차이에 대한 후향적 연구

학위논문(석사) -- 서울대학교대학원 : 수의과대학 수의학과, 2022. 8. 윤화영.Leflunomide는 pyrimidine 생합성을 억제하여 면역 억제의 기능을 하는 약제로, 개에서 여러 자가 면역 질환에서 좋은 치료 효과를 가진다는 것이 확인되었다. 그러나 개의 원인 불명의 뇌수막염에서 보조 면역억제제로서의 leflunomide 사용은 현재까지 아직 보고가 매우 적다. 따라서 본 학위 논문에서는 원인 불명의 뇌수막염으로 진단된 82 마리의 개를 대상으로 보조 면역억제제에 따른 예후의 차이를 후향적으로 비교하고자 하였다. 환자의 치료에 사용된 면역억제제 별로 환자를 분류하였으며 각 치료 그룹의 생존 기간과 치료 반응을 비교하였다. 전체 환자의 평균 생존기간은 769일 (범위 14-2687일)이었다. 각각의 보조 면역억제제에 따른 평균 생존 기간은 leflunomide 1035일 (범위 126-2163일), mycophenolate mofetil 865일 (범위 39-2191일), cyclosporin 441일 (범위 11-2176 일), mycophenolate mofetil과 cytosine arabinoside를 함께 상용한 그룹에서는 132일 (범위 23-1227) 이었다. 부작용 발생률은 각 면역억제제 그룹간의 유의적인 차이가 확인되지 않았다. 그러나 lelfunomide를 사용한 16마리의 환자 중 3마리 (18.7%)에서 중등도 이상의 빈혈이 확인되었다. 치료 반응의 경우 mycophenolate mofetil 군이 전체 반응률 84%로 가장 높았으며 leflunomide 군이 82%로 두 번째로 높게 확인되었다. 원인불명의 뇌수막염 개에서의 생존 기간과 반응률이 어떤 보조면역억제제를 사용하냐에 따라 달라질 수 있다. 본 논문은 뇌수막염 개에서 leflunomide를 사용했을 때의 생존 기간을 구한 첫 보고이며, 개 뇌수막염에서 lelfunomide가 비교적 좋은 효과와 긴 생존 기간을 가진다는 것을 확인할 수 있었다. 그러나 장기 복용 시 중등도 이상의 빈혈이 확인될 수 있으므로 주기적인 모니터링이 필요할 것으로 고려된다.Meningoencephalomyelitis of unknown etiology (MUE) is a comprehensive term for non-infectious inflammatory brain diseases of the central nervous system (CNS) caused by abnormal autoimmune responses. This study aims to compare the differences in survival and clinical response of MUE according to the use of adjuvant immunosuppressant use. Medical records of 82 dogs diagnosed with MUE were reviewed retrospectively. The overall survival time was 769 days (range 14–2687 days). The median survival time for each adjunctive was: leflunomide 1035 days (range 126–2163 days), mycophenolate mofetil 865 days (range 39–2191 days), cytarabine 754 days (range 6–1898 days), cyclosporin 441 days (range 11–2176 days), and a combination of mycophenolate mofetil and cytosine arabinoside 132 days (range 23–1227 days). There was no significant difference in the incidence rate of adverse events according to the immunosuppressants, but moderate to severe anemia was confirmed in 3 patients (18.7%) in the leflunomide group. The survival time and response rate of MUE dogs differed depending on which adjunctive immunosuppressants were used. Leflunomide showed a long survival time and a relatively good response rate in dogs with MUE. However, a large-scale further study with standardized doses of immunosuppressants and supportive treatment and constant monitoring interval is required.1. Introduction 1 2. Material and Methods 3 2.1 Case selection 3 2.2 Treatment 3 2.3 Supportive treatment 4 2.4 Adverse events 5 2.5 Statistical analysis 5 3. Results 7 3.1 Signalments and clinical signs in affected dogs 7 3.2 MRI findings 8 3.3 CSF analysis 8 3.4 Analysis of survival time after adjunctive immunosuppressant treatment 9 3.5 Differences in treatment response by adjunctive immunosuppressants 10 3.6 Other factors affecting the survival time 11 3.7 Adverse events related to adjunctive immunosuppressant use 12 4. Discussion 15 5. Conclusion 19 6. References 27 국문초록 33 Table 1. Neurologic symptoms during the initial visit 20 Table 2. Survival time and treatment response according to the agents 21 Table 3. Adverse events according to the adjunctive immunosuppressants 22 Figure 1. Kaplan-Meier graph for comparing survival time of PDS alone and PDS with adjunctive immunosuppressants 23 Figure 2. Kaplan-Meier graph for comparing survival time according to which adjunctive immunosuppressants were used 24 Figure 3. Kaplan-Meier graph for 73 dogs in the complete response, partial response , and no response groups 25 Figure 4. Kaplan-Meier graph for 73 dogs in the seizure or non-seizure group 26석

Comparing survival functions with interval-censored data in the presence of an intermediate clinical event

의과대학/석사The primary endpoint is considered a time metric such as the time taken to reach a well-defined endpoint in the presence of an intermediate clinical event (IE). A subject may experience an IE including an intervention during the period of follow-up. When an IE occurs, it may change the survival distribution. When deriving the statistics of Nam and Zelen (2001), the data was divided into two parts according to an IE; one part was right-censored data that does not reach the time of experiencing an IE and the other part was left-truncated and right-censored data, which is having an IE and truncation at that time. Considering the primary endpoint was interval-censored, we extended the approach of Finkelstein (1986) as accommodating left-truncated data. After that, for convenience, we applied multiple imputation techniques to left truncated and interval-censored data. Firstly, we proposed a uniform method to impute data of uniform weight in a characterized set. The second method applies the non-parametric maximum likelihood estimator (NPMLE) from the original data as weight. We applied two forms of variance, which are formed by adding and subtracting within- and between variance for all proposed models. Both variances worked efficiently, but the first one was slightly over- while the second one was marginally underestimated. Through simulation, the stratified log-rank test is unsatisfactory when the proportion of an IE is different between two groups. When the survival distribution is changed after experiencing an IE in addition to the difference proportion of an IE for two groups, the log-rank test is not appropriate. The proposed methods satisfied a nominal level of 0.05 and had superior power to compare the proposed methods with the log-rank and stratified log-rank tests for all scenarios.ope

Furosemide induced medullary nephrocalcinosis mimicking Bartter syndrome

Clinical presentation of Bartter syndrome is similar to surrepitious vomiting or use of diuretics. Therefore, precise differential diagnosis of Bartter syndrome is crucial. We report a case of medullary nephrocalcinosis (MNC) induced by furosemide mimicking Bartter syndrome. A 55-year-old female patient visited our hospital with renal dysfunction on basis of hypokalemia and metabolic alkalosis. She had no history of hypertension or drug use except allopurinol and atorvastatin. She did not complain of nausea or vomiting on presentation and the serum magnesium level was normal. We performed ultrasonography, that showed MNC. For these reasons, we suspected Bartter syndrome and corrected the electrolyte imbalance. During outpatient follow up, we found that the patient had been taking 400 mg of furosemide daily for 30 years. We could diagnose furosemide induced MNC, and recommended to her to reduce the amount of furosemide.ope

Subclinical vascular inflammation in subjects with normal weight obesity and its association with body fat: an 18F-FDG-PET/CT study.

BACKGROUND: Although body mass index (BMI) is the most widely accepted parameter for defining obesity, recent studies have indicated a unique set of patients who exhibit normal BMI and excess body fat (BF), which is termed as normal weight obesity (NWO). Increased BF is an established risk factor for atherosclerosis. However, it is unclear whether NWO subjects already have a higher degree of vascular inflammation compared to normal weight lean (NWL) subjects; moreover, the association of BF with vascular inflammation in normal weight subjects is largely unknown. METHODS: NWO and NWL subjects (n = 82 in each group) without any history of significant vascular disease were identified from a 3-year database of consecutively recruited patients undergoing 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT) at a self-referred Healthcare Promotion Program. The degree of subclinical vascular inflammation was evaluated using the mean and maximum target-to-background ratios (TBRmean and TBRmax) of the carotid artery, which were measured by 18 F-FDG-PET/CT (a noninvasive tool for assessing vascular inflammation). RESULTS: We found that metabolically dysregulation was greater in NWO subjects than in NWL subjects, with a significantly higher blood pressure, higher fasting glucose level, and worse lipid profile. Moreover, NWO subjects exhibited higher TBR than NWL subjects (TBRmean: 1.33 ± 0.16 versus 1.45 ± 0.19, p < 0.001; TBRmax: 1.52 ± 0.23 versus 1.67 ± 0.25, p < 0.001). TBR was significantly associated with total BF (TBRmean: r = 0.267, p = 0.001; TBRmax: r = 0.289, p < 0.001), age (TBRmean: r = 0.170, p = 0.029; TBRmax: r = 0.165, p = 0.035), BMI (TBRmean: r = 0.184, p = 0.018; TBRmax: r = 0.206, p = 0.008), and fasting glucose level (TBRmean: r = 0.157, p = 0.044; TBRmax: r = 0.182, p = 0.020). In multiple linear regression analysis, BF was an independent determinant of TBRmean and TBRmax, after adjusting for age, BMI, and fasting glucose level (TBRmean: regression coefficient = 0.020, p = 0.008; TBRmax: regression coefficient = 0.028, p = 0.005). Compared to NWL, NWO was also independently associated with elevated TBRmax values, after adjusting for confounding factors (odds ratio = 2.887, 95% confidence interval 1.206-6.914, p = 0.017). CONCLUSIONS: NWO is associated with a higher degree of subclinical vascular inflammation, of which BF is a major contributing factor. These results warrant investigations for subclinical atherosclerosis in NWO patients.ope

Normal-weight obesity is associated with increased risk of subclinical atherosclerosis

BACKGROUND: Subjects with normal body mass index (BMI) but elevated amounts of body fat (normal-weight obesity; NWO) show cardiometabolic dysregulation compared to subjects with normal BMI and normal amounts of body fat (normal-weight lean; NWL). In this study, we aimed to evaluate whether NWO individuals have higher rates of subclinical atherosclerosis compared to NWL subjects. METHODS: From a large-scale health checkup system, we identified 2078 normal weight (18.5 ≤ BMI 1 mm(2) within and/or adjacent to the vessel lumen and classified according to the presence/proportion of intraplaque calcification. RESULTS: NWO subjects (n = 283) demonstrated metabolic dysregulation compared to NWL individuals (n = 1795). After adjusting for age, sex, and smoking, NWO individuals showed higher PWV values than NWL individuals (1474.0 ± 275.4 vs. 1380.7 ± 234.3 cm/s, p = 0.006 by ANCOVA). Compared with NWL subjects, NWO subjects had a higher prevalence of soft plaques even after age, sex, and smoking adjustment (21.6% vs. 14.5%, p = 0.039 by ANCOVA). The PWV value and the log{(number of segments with plaque) + 1} showed a positive correlation with numerous parameters such as age, systolic blood pressure, visceral fat, fasting glucose level, serum triglyceride level, and C-reactive protein (CRP) in contrast to the negative correlation with high-density lipoprotein-cholesterol level. The visceral fat was an independent determinant of log{(number of segments with plaque) + 1} (ß = 0.027, SE = 0.011, p = 0.016) even after adjustment for other significant factors. Most importantly, NWO was an independent risk factor for the presence of soft plaques (odds ratio 1.460, 95 % confidence interval 1.027-2.074, p = 0.035) even after further adjustment for multiple factors associated with atherosclerosis (blood pressure, blood glucose, lipid level, CRP, medication, smoking status, physical activity). CONCLUSIONS: NWO individuals carry a higher incidence of subclinical atherosclerosis compared with NWL individuals, regardless of other clinical risk factors for atherosclerosis.ope

다양한 스트레스에 대한 열충격단백질 유전자 hsp70 프로모터의 조절부위 규명

학위논문(석사)--서울대학교 대학원 :의학과 생화학전공,2004.Maste

Ion-induced secondary electron emission coefficients of MgO-based mixed oxides

Thesis(master`s)--서울대학교 대학원 :화학생물공학부,2006.Maste

인공 대구치에서 두 가지 근관 충전법을 이용하여 칼슘 실리케이트 계통 실러 및 가타퍼챠콘 충전 시 충전의 질 평가

The purpose of this study was to assess the root filling quality of calcium silicate-based sealer and gutta percha cones by measuring, via micro-computed tomography (micro-CT), the percentage of voids when a single cone or continuous wave filling technique was used for filling artificial molar root canals. Additionally, sealer penetration, as measured by confocal laser scanning microscopy (CLSM), into the isthmus area in human extracted mandibular molars was compared between the two different filling techniques. Twenty artificial molar-shaped teeth were instrumented using rotary files. Three specimens were overlapped by micro-CT to confirm that the prepared canal space was consistent. Teeth were randomly divided into two groups; one group was obturated using the single cone (SC) technique, and the other group was obturated using the continuous wave (CW) technique. Additionally, six human mandibular molars were divided into two groups and prepared similarly. Obturated teeth were scanned by micro-CT, and the percentage of void volume between the filling materials and the root canal walls was calculated in both the apical and coronal areas. Human molars underwent CLSM. The percentage of voids between the filling materials and the root canal walls (%Vout) was not significantly different between the two obturation techniques (p > 0.05), except that, in the coronal area of the distal canal, the CW group showed a significantly higher void volume (p 0.05). In confocal microscopic images of human extracted molars, most of the isthmus area was obturated both in SC and CW groups, but in the SC group, the sealer penetrated the isthmus, while in the CW groups, gutta percha filled the isthmus.open석