• Korean Journal of Radiology
• /
• 제24권2호
• /
• pp.133-144
• /
• 2023

Objective: Cyclin-dependent kinase inhibitor (CDKN)2A/B homozygous deletion is a key molecular marker of isocitrate dehydrogenase (IDH)-mutant astrocytomas in the 2021 World Health Organization. We aimed to investigate whether qualitative and quantitative MRI parameters can predict CDKN2A/B homozygous deletion status in IDH-mutant astrocytomas. Materials and Methods: Preoperative MRI data of 88 patients (mean age ± standard deviation, 42.0 ± 11.9 years; 40 females and 48 males) with IDH-mutant astrocytomas (76 without and 12 with CDKN2A/B homozygous deletion) from two institutions were included. A qualitative imaging assessment was performed. Mean apparent diffusion coefficient (ADC), 5th percentile of ADC, mean normalized cerebral blood volume (nCBV), and 95th percentile of nCBV were assessed via automatic tumor segmentation. Logistic regression was performed to determine the factors associated with CDKN2A/B homozygous deletion in all 88 patients and a subgroup of 47 patients with histological grades 3 and 4. The discrimination performance of the logistic regression models was evaluated using the area under the receiver operating characteristic curve (AUC). Results: In multivariable analysis of all patients, infiltrative pattern (odds ratio [OR] = 4.25, p = 0.034), maximal diameter (OR = 1.07, p = 0.013), and 95th percentile of nCBV (OR = 1.34, p = 0.049) were independent predictors of CDKN2A/B homozygous deletion. The AUC, accuracy, sensitivity, and specificity of the corresponding model were 0.83 (95% confidence interval [CI], 0.72-0.91), 90.4%, 83.3%, and 75.0%, respectively. On multivariable analysis of the subgroup with histological grades 3 and 4, infiltrative pattern (OR = 10.39, p = 0.012) and 95th percentile of nCBV (OR = 1.24, p = 0.047) were independent predictors of CDKN2A/B homozygous deletion, with an AUC accuracy, sensitivity, and specificity of the corresponding model of 0.76 (95% CI, 0.60-0.88), 87.8%, 80.0%, and 58.1%, respectively. Conclusion: The presence of an infiltrative pattern, larger maximal diameter, and higher 95th percentile of the nCBV may be useful MRI biomarkers for CDKN2A/B homozygous deletion in IDH-mutant astrocytomas.

• Korean Journal of Radiology
• /
• 제23권10호
• /
• pp.949-958
• /
• 2022

Objective: To investigate the feasibility of using a deep learning-based analysis of auscultation data to predict significant stenosis of arteriovenous fistulas (AVF) in patients undergoing hemodialysis requiring percutaneous transluminal angioplasty (PTA). Materials and Methods: Forty patients (24 male and 16 female; median age, 62.5 years) with dysfunctional native AVF were prospectively recruited. Digital sounds from the AVF shunt were recorded using a wireless electronic stethoscope before (pre-PTA) and after PTA (post-PTA), and the audio files were subsequently converted to mel spectrograms, which were used to construct various deep convolutional neural network (DCNN) models (DenseNet201, EfficientNetB5, and ResNet50). The performance of these models for diagnosing ≥ 50% AVF stenosis was assessed and compared. The ground truth for the presence of ≥ 50% AVF stenosis was obtained using digital subtraction angiography. Gradient-weighted class activation mapping (Grad-CAM) was used to produce visual explanations for DCNN model decisions. Results: Eighty audio files were obtained from the 40 recruited patients and pooled for the study. Mel spectrograms of "pre-PTA" shunt sounds showed patterns corresponding to abnormal high-pitched bruits with systolic accentuation observed in patients with stenotic AVF. The ResNet50 and EfficientNetB5 models yielded an area under the receiver operating characteristic curve of 0.99 and 0.98, respectively, at optimized epochs for predicting ≥ 50% AVF stenosis. However, Grad-CAM heatmaps revealed that only ResNet50 highlighted areas relevant to AVF stenosis in the mel spectrogram. Conclusion: Mel spectrogram-based DCNN models, particularly ResNet50, successfully predicted the presence of significant AVF stenosis requiring PTA in this feasibility study and may potentially be used in AVF surveillance.

• 생명과학회지
• /
• 제27권1호
• /
• pp.32-37
• /
• 2017

Cyanidin-3-O-glucoside (C3G)는 오디와 붉은색의 과일에 풍부하게 함유되어 있으며, 항염증과 항산화 효과와 관련하여 보고되어있다. 그러나, C3G의 식후 혈당에 관한 연구 결과는 보고되지 않았다. ${\alpha}-glucosidase$ 억제제는 소장에서 탄수화물 소화의 속도를 방해함으로써 식후 고혈당을 조절한다. 본 연구에서는 C3G가 ${\alpha}$-글루코시다아제와 ${\alpha}$-아밀라아제에 미치는 억제효과 및 스트렙토조토신(STZ)이 유발하는 당뇨병 생쥐의 식후고혈당에 미치는 완화 효과를 조사하였다. ICR 마우스와 streptozothocin (STZ)으로 유도된 당뇨병 마우스에 수용성 전분(2 g/kg body weigh)으로 경구부하 후 C3G (10 mg/kg body weight) 또는 acarbose (10 mg/kg body weight)를 단독 또는 함께 투여하였다. 혈액 샘플은 꼬리에서 0, 30, 60, 120분 간격으로 채취하였다. ${\alpha}$-글루코시다아제와 ${\alpha}$-아밀라아제에 대한 C3G의 $IC_{50}$ 값은 각각 13.72와 $7.5\;{\mu}M$의 결과값을 나타내어, 양성대조군인 acarbose보다 더 효과적이었다. STZ으로 유발된 당뇨 쥐의 식후 혈당 수치는 대조군에 비해 C3G 투여시 유의적으로 더 낮았다. 게다가, C3G 투여는 당뇨병 흰쥐에서 포도당 반응에 대한 곡선하면적 감소와 관련이 있었다. 그러므로, C3G는 ${\alpha}$-글루코시다아제의 강력한 억제제이며 식이 탄수화물의 흡수를 지연시킬 수 있음을 나타낸다.

• Journal of Nutrition and Health
• /
• 제49권2호
• /
• pp.80-87
• /
• 2016

본 연구에서는 건강한 여대생 10명을 대상으로 하여 오리육에 농도를 달리한 울금을 첨가하여 섭취한 후 30분, 60분, 120분, 180분 후 혈액을 채취하여 울금 농도에 따른 혈중 지질농도의 변화를 살펴보았다. 연구결과는 다음과 같다. 1) 조사대상자는 병적 질환이 없고 신체조건이 한국인 기준에 해당되는 여대생 10명을 대상으로 하여 연구를 시행하였으며 대상자는 $159.6{\pm}2.6cm$, $51.3{\pm}3.5kg$이었으며, BMI는 $20.1{\pm}1.0$으로 정상 범위에 해당하였다. 공복시 혈당과 지질농도, GGT, GPT, GOT, CRP, 헤모글로빈 농도는 모두 정상 수준이었다. 2) 식후 혈중 포도당의 공복 시 혈당에 비해 증가된 ${\Delta}-AUC$값에서 유의적인 차이가 없었다. 3) 식후 혈중 총콜레스테롤은 울금 0.2%, 0.4% 첨가하였을 때 공복 시에 비한 ${\Delta}-AUC$값에서 대조군에 비해 유의적으로 낮았다. 4) 혈중 중성지방의 농도는 식후 90분 까지 0.4% 첨가군에서만 대조군에 비해 유의적으로 낮았다. 5) 식후 LDL의 공복 시에 비한 ${\Delta}-AUC$값은 울금 0.2%, 0.4% 첨가하였을 때 대조군에 비해 유의적으로 낮았다. 6) 식후 HDL의 공복 시에 비한 ${\Delta}-AUC$값은 울금 0.2%, 0.4% 첨가하였을 때 대조군에 비해 유의적으로 높았다. 본 연구는 혈중 지질상태가 정상인 여대생을 대상으로한 인체실험으로 0.2% 이상의 울금 첨가가 고지방식인 훈제오리육가공품의 섭취 시 혈중 지질농도에 영향을 미치고 있음을 밝힌 연구로 그 의미가 있다 할 것이다. 그러나 이의 기전을 보다 명확히 제시할 수 있는 다양한 조건에서의 추후 연구가 필요하다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권12호
• /
• pp.4933-4938
• /
• 2014

Background: Although various tumor markers have been utilized in management of stomach cancer (SC), only a few reports have described relevance of examples such as CYFRA 21-1 and neuron-specific enolase (NSE). The purpose of this study was to evaluate the potential diagnostic performance of carcinoembryonic antigen (CEA), CA 19-9, CA72-4, CYFRA 21-1 and NSE in patients with SC. Materials and Methods: Ninety-six SC patients with pathologic confirmation between 2012 and 2013 were enrolled. Serum levels of five tumor markers were analyzed using a solid-phase immunoradiometric assay. Receiver operating characteristic (ROC) curves were plotted for the five tumor markers to investigate their diagnostic powers and adjusted cutoff values derived from analysis of ROC curves were evaluated to calculate the sensitivity of each for SC with recommended cutoff values. Results: Based on two different cutoff values (recommended and adjusted), CYFRA 21-1 (${\geq}2.0$ and 1.2 ng/ml) had a respective sensitivity of 50% and 78.1%, compared with 8.3% and 18.8% for CEA (${\geq}7.0$ and 3.9 ng/ml), 15.6% and 18.8% for CA 19-9 (${\geq}37$ and 26.7 ng/ml), 28.1% and 9.6% for CA 72-4 (${\geq}4.0$ and 13 ng/ml) and 7.3% and 7.3% for NSE (${\geq}14.7$ and 15.0 ng/ml) in the initial staging of primary SC. The area under the curve (AUC) for CYFRA 21-1, with a value of 0.978 (95% confidence interval, 0.964-0.991) was comparatively the highest. Univariate analysis revealed significant relationships between tumor marker level and lymph node involvement, metastasis and staging with CYFRA 21-1, CA 72-4 and NSE. Conclusions: CYFRA 21-1 was the most sensitive tumor marker and showed the most powerful diagnostic performance among the five SC tumor markers. NSE and CA 72-4 are significantly related to lymph node involvement, metastasis or stage. Further evaluations are warranted to clarify the clinical usefulness and prognostic prediction of these markers in SC.

• Journal of Pharmaceutical Investigation
• /
• 제39권2호
• /
• pp.141-147
• /
• 2009

The purpose of this study was to evaluate the bioequivalence of two nateglinide tablets, $PASTIC^{(R)}$ tablet (ILDONG Pharm. Co., Ltd., Seoul, Korea, reference drug) and $GLUNATE^{(R)}$ tablet (ILHWA. Co., Ltd., Seoul, Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Thirty-five healthy male volunteers, $23.1{\pm}2.3$ years in age and $69.2{\pm}8.8\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a tablet containing 90 mg of nateglinide was orally administrated, blood was taken at predetermined time intervals over a period of 8 hr and concentrations of nateglinide in plasma were monitored using LC-MS/MS. Pharmacokinetic parameters such as AUCt (the area under the plasma concentration-time curve from time 0 to 8 hr), $C_{max}$ (maximum plasma drug concentration) and $TC_{max}$ (time to reach $CC_{max}$) were calculated and analysis of variance (ANOVA) test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$ and $C_{max}$ and untransformed $T_{max}$. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $GLUNATE^{(R)}/PASTIC^{(R)}$ were ${\log}1.0782{\sim}{\log}1.1626$ and ${\log}0.9621{\sim}{\log}1.1679$, respectively. Since these values were within the acceptable bioequivalence intervals of ${\log}0.80{\sim}{\log}1.25$, recommended by KFDA, it was concluded that $GLUNATER^{(R)}$ tablet was bioequivalent to $PASTIC^{(R)}$ tablet, in terms of both rate and extent of absorption.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권10호
• /
• pp.4147-4152
• /
• 2014

Standard therapy for advanced head and neck cancer consists of a combination of surgery and radiation. However, survival of this patient population has not improved during the past 20 years. Many different multimodality treatment schedules have been proposed, and chemotherapy is often used with the intent of organ preservation. The present study was intended to establish the efficacy of concomitant chemoradiation with a single agent carboplatin in advanced head and neck cancers.The objectives were to investigate the feasibility of concomitant administration of carboplatin, monitor acute toxicity during radiotherapy, and determine subacute side effects, such as wound healing following surgery after chemoradiotherapy. A prospective study was conducted wherein a total of 40 patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx were enrolled. All patients were treated with external beam radiotherapy and weekly carboplatin area under curve (AUC of 5). Radiotherapy was given in single daily fractions of 1.8-2 grays (Gy) to a total dose of 66-72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Neck dissection was recommended for all patients with neck disease showing less than a complete response after chemoradiation. A total of 40 patients were enrolled of whom 32 were males and 8 were females. Highest incidence of cancer was seen in the 5th-6th decades of life with a median age of 47.7 years. Oropharyngeal tumours constituted a maximum of 21 patients followed by hypopharynx in 10, larynx in 7 and oral cavity in 2. 80% of the patients had a neck node on presentation of which 40% had N2-N3 nodal status. TNM staging revealed that 58% of patients were in stage III and 43% in stage IV. Evaluation of acute toxicity revealed that 50% had grade II mucositis, 25% grade III mucositis, 2.5% grade IV mucositis. 50% of patients had grade I skin reactions, 65% of patients had grade I thrombocytopenia, and 24% of patients had grade I anaemia. After completion of treatment 65% of patients had complete response at the primary and regional sites, and 35% of patients had a partial response of whom 23% underwent neck dissection and 5% of them underwent salvage surgery at the primary site. At the end of one year there were six deaths and four recurrences and 70% were free of disease. Concurrent chemoradiation with carboplatin provided good locoregional control for locally advanced head and neck cancers. This regimen, although toxic, is tolerable with appropriate supportive intervention. Primary site conservation is possible in many patients. Chemoradiotherapy appears to have an emerging role in the primary management of head and neck cancers.

• 한국임상수의학회지
• /
• 제27권3호
• /
• pp.284-288
• /
• 2010

이 연구의 목적은 개에서 실험적으로 복수를 유발한 후, 컴퓨터 촬영술과 필름 촬영술을 실시하여 복수의 정량적인 비교를 한 것이다. 건강한 4 마리의 비글견과 1 마리의 말티즈 견을 사용하였으며, 각 개체마다 무균적으로 복강 내로 멸균 생리 식염수를 6 ml, 8 ml, 12 ml, 15 ml, 그리고 18 ml 을 주입하였으며, 우외측상과 복배상으로 컴퓨터 촬영과 필름 촬영을 실시하였다. 총 5명의 평가자에게 복수량에 따른 컴퓨터 촬영 사진과 필름 촬영 사진을 보였주었으며, 각 사진마다 복수량에 따라 5 가지의 점수를 순차적으로 평가하도록 하였다 (0 =복수 없음, 5 =중등도의 복수가 있음). 5명의 평가자가 평가한 데이터를 이용하여 ROC 분석 방법을 이용하여, 두 진단 모델간의 민감도와 특이도를 평가하였다. 이 연구를 통해, 복수의 양을 평가하는데 있어 두 진단 모델간의 유의적인 차이는 보이지 않았다. 그러나 RCO 분석 방법을 통해, 컴퓨터 촬영술이 필름 촬영술에 비해 민감도가 상대적으로 높았으며, 각 평가자 간에도 복수의 양을 평가하는데 있어, 상대적으로 컴퓨터 촬영술이 우위인 것을 알 수 있었다.

• Journal of Pharmaceutical Investigation
• /
• 제30권1호
• /
• pp.55-59
• /
• 2000

Bioequivalence of two cisapride tablets, test drug ($Cisple^{\circledR}$ tablet: Hanmi Pharm Co., Ltd.) and reference drug ($Prepulsid^{\circledR}$ tablet: Janssen Pharm. Co., Ltd.), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty two healthy male volunteers were divided randomly into two groups and administered the drug orally at the dose of 10 mg as cisapride in a $2{\times}2$ crossover study. There was a week washout period between administrations. Blood samples were taken at predetermined time intervals for 36 hr and the plasma concentration of cisapride was determined by a HPLC method. $AUC_{0-36hr}$ (area under the plasma concentration-time curve from time zero to 36 hr), $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were estimated from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed no difference in $AUC_{0-36hr},\;C_{max}\;and\;T_{max}$ between two products. The apparent differences of these parameters between two products were less than 20% (i.e., 5.38, 6.17 and 0.00% for $AUC_{0-36hr},\;C_{max}\;and\;T_{max},$ respectively). The powers $(1-\beta)$ for $AUC_{0-36hr},\;C_{max}\;and\;T_{max}$ were over 0.9. Minimal detectable differences $(\Delta)$ at ${\alpha}=0.05,\;1-{\beta}=0.8$ were less than 20% (i.e. 17.67, 14.84 and 19.72% for $AUC_{0-36hr},\;C_{max}\;and\;T_{max},$ respectively). The 90% confidence intervals $(\delta)$ for these parameters were also within ${\pm}20%$ $(i.e.\;-4.97\;{\le}{\delta}{\le}\;15.73,\;-2.53{\le}{\delta}{\le}\;14.86\;and\;-11.55{\le}{\delta}{\le}\;11.55$ for $AUC_{0-36hr},\;C_{max}\;and\;T_{max},$ respectively). These results satisfied the criteria of KFDA guidelines for bioequivalence, indicating the two tablets of cisapride were bioequivalent.

• 한국식품영양과학회지
• /
• 제44권11호
• /
• pp.1607-1611
• /
• 2015

본 연구는 당뇨유발모델 쥐에서 아프리칸 망고(Irvingia gabonesis, IGOB $131^{TM}$) 추출물의 혈당 조절 효과를 알아보기 위해 SD계 수컷 흰쥐에 IGOB $131^{TM}$ 1%, IGOB $131^{TM}$ 2%(IGOB $131^{TM}$ 353 mg/kg body weight, IGOB $131^{TM}$ 706 mg/kg body weight)와 pinitol을 5주간 매일 강제 경구 투여하였다. 그리고 streptozotocin을 복강 주사하여 당뇨를 유발시킨 후 경구 당부하 검사(OGTT)를 실시하였다. 정상군에 비해 당뇨 유발군(DM, pinitol, IGOB $131^{TM}$ 1%, IGOB $131^{TM}$ 2%)의 체중 증가는 유의적으로 감소하였고, 당뇨 유발군 간의 유의적인 차이는 나타나지 않았다. 경구 당부하 검사 결과에서 DM군이 정상군에 비해 유의적으로 높았고, pinitol군, IGOB $131^{TM}$ 1%, IGOB $131^{TM}$ 2%군은 DM에 비해 각각 39.70%, 33.00%, 29.67% 유의적으로 감소하였다. 혈청 glucose 농도는 정상군에 비해 당뇨 유발군에서 유의적으로 높게 나타났고, pinitol, IGOB $131^{TM}$ 1%, IGOB $131^{TM}$ 2%군은 DM에 비해 유의적으로 감소하였다. 또한 혈청 insulin 농도는 정상군에 비해 당뇨 유발군에서 유의적으로 낮게 나타났고, pinitol, IGOB $131^{TM}$ 1%, IGOB $131^{TM}$ 2%군은 DM에 비해 유의적으로 증가한 것으로 나타났다. 따라서 아프리칸 망고 추출물이 STZ 유도 당뇨쥐의 혈청 insulin 함량을 개선시켜 혈청 glucose를 감소하는 효과가 있는 것으로 사료된다.