• Title/Summary/Keyword: Surrogate Marker

Search Result 38, Processing Time 0.028 seconds

Usefulness of End-tidal Carbon Dioxide as a Predictor of Emergency Intervention in Major Trauma Patients (중증 외상 환자에서의 응급중재술 시행 예측 인자로서의 호기말 이산화탄소 분압의 유용성)

  • Kim, Sung Ho;Kim, Seunghwan;Lee, Jae Gil;Chung, Sung Phil;Kim, Seung Ho
    • Journal of Trauma and Injury
    • /
    • v.27 no.4
    • /
    • pp.133-138
    • /
    • 2014
  • Purpose: If the survival of patients suffering from severe blunt trauma is to be improved, appropriate interventions should be taken immediately. The purpose of this study is to evaluate the clinical utility of end-tidal carbon dioxide ($ETCO_2$) as a surrogate marker for predicting both the need for intervention and the prognosis. Methods: This is a prospective observational study. Nasal cannula was applied to measure $ETCO_2$, and the following parameters, which are known to be related to the prognosis for a patient, were recorded: injury severity score (ISS), revised trauma score (RTS), arterial blood gas (ABG), lactate, and hemoglobin (Hb). To evaluate the outcome, we investigated the details of emergent interventions and expired patients. Results: A total of 93 patients were enrolled in this study. Emergent intervention was significantly associated with systolic blood pressure (sBP, p-value=0.001), $ETCO_2$ (p-value<0.001), serum lactate level (p-value<0.001), pH (p-value< 0.003), $HCO_3$ (p-value=0.004), base excess (p-value<0.002), ISS (p-value<0.001) and RTS (p-value=0.005). In the multivariate logistic regression, only $ETCO_2$ (odds ratio (OR): 0.897, 95% confidence interval (CI): 0.792-0.975, p-value= 0.048) and ISS (OR: 1.132, 95% CI: 1.053-1.233, p-value=0.002) were associated with emergent intervention whereas $ETCO_2$ (p-value=0.973) and ISS (p-value=0.511) were not statistically significant in predicting the survival of patients in the univariate analysis. An optimal ETCO cut-off of 29 mmHg on the ROC curve was determined, with the area under the ROC curve (AUC) being 0.824 (0.732-0.917)]. Conclusion: This study has revealed that $ETCO_2$, which can be rapid and easily measured through a nasal cannula, and the ISS may be prognostic indicators of emergent interventions in Emergency Departments.

Bioactivity-guided isolation of ginsenosides from Korean Red Ginseng with cytotoxic activity against human lung adenocarcinoma cells

  • Yu, Jae Sik;Roh, Hyun-Soo;Baek, Kwan-Hyuck;Lee, Seul;Kim, Sil;So, Hae Min;Moon, Eunjung;Pang, Changhyun;Jang, Tae Su;Kim, Ki Hyun
    • Journal of Ginseng Research
    • /
    • v.42 no.4
    • /
    • pp.562-570
    • /
    • 2018
  • Background: Lung cancer is the leading cause of cancer-related death worldwide. In this study, we used a bioactivity-guided isolation technique to identify constituents of Korean Red Ginseng (KRG) with antiproliferative activity against human lung adenocarcinoma cells. Methods: Bioactivity-guided fractionation and preparative/semipreparative HPLC purification were used with LC/MS analysis to separate the bioactive constituents. Cell viability and apoptosis in human lung cancer cell lines (A549, H1264, H1299, and Calu-6) after treatment with KRG extract fractions and constituents thereof were assessed using the water-soluble tetrazolium salt (WST-1) assay and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, respectively. Caspase activation was assessed by detecting its surrogate marker, cleaved poly adenosine diphosphate (ADP-ribose) polymerase, using an immunoblot assay. The expression and subcellular localization of apoptosis-inducing factor were assessed using immunoblotting and immunofluorescence, respectively. Results and conclusion: Bioactivity-guided fractionation of the KRG extract revealed that its ethyl acetate-soluble fraction exerts significant cytotoxic activity against all human lung cancer cell lines tested by inducing apoptosis. Chemical investigation of the ethyl acetatesoluble fraction led to the isolation of six ginsenosides, including ginsenoside Rb1 (1), ginsenoside Rb2 (2), ginsenoside Rc (3), ginsenoside Rd (4), ginsenoside Rg1 (5), and ginsenoside Rg3 (6). Among the isolated ginsenosides, ginsenoside Rg3 exhibited the most cytotoxic activity against all human lung cancer cell lines examined, with $IC_{50}$ values ranging from $161.1{\mu}M$ to $264.6{\mu}M$. The cytotoxicity of ginsenoside Rg3 was found to be mediated by induction of apoptosis in a caspase-independent manner. These findings provide experimental evidence for a novel biological activity of ginsenoside Rg3 against human lung cancer cells.

Factors Affecting Basilar Artery Pulsatility Index on Transcranial Doppler (뇌혈류 초음파 검사에서 기저동맥 박동지수에 영향을 미치는 인자)

  • Jeong, Ho Tae;Kim, Dae Sik;Kang, Kun Woo;Nam, Yun Teak;Oh, Ji Eun;Cho, Eun Kyung
    • Korean Journal of Clinical Laboratory Science
    • /
    • v.50 no.4
    • /
    • pp.477-483
    • /
    • 2018
  • Transcranial doppler is a non-invasive method that measures the blood flow velocity and the direction of cerebral blood vessels through the doppler principle. The pulsatility index is an index for measuring the transcranial doppler that reflects the distal vascular resistance and is used as an index for the presence and diffusion of cerebral small vessel diseases. The purpose of this study was to evaluate the risk factors affecting the basilar artery pulsatility index in ischemic stroke patients. From January 2014 to May 2015, 422 patients were selected by measuring the transcranial doppler pulsatility index, considering their basilar artery pulsatility index. Univariate analysis was performed using the basilar artery pulsatility index as a dependent variable. Multiple regression analysis was performed considering the factors affecting the pulsatility index as variables. Univariate analysis revealed age, presence of hypertension, presence of diabetes mellitus, presence of hyperlipidemia, and hematocrit (P<0.1) as factors. Multiple regression analysis showed statistically significant results with age (P<0.001), presence of diabetes (P=0.004), and presence of hyperlipidemia (P=0.041). The risk factors affecting the basilar artery pulsatility index of transcranial doppler were age, diabetes, and hyperlipidemia. Further research will be needed to increase the cerebral pulsatility index as a surrogate marker of the elderly, diabetes, and hyperlipidemia.

Blood Biomarkers for Alzheimer's Dementia Diagnosis (알츠하이머성 치매에서 혈액 진단을 위한 바이오마커)

  • Chang-Eun, Park
    • Korean Journal of Clinical Laboratory Science
    • /
    • v.54 no.4
    • /
    • pp.249-255
    • /
    • 2022
  • Alzheimer's disease (AD) represents a major public health concern and has been identified as a research priority. Clinical research evidence supports that the core cerebrospinal fluid (CSF) biomarkers for AD, including amyloid-β (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau), reflect key elements of AD pathophysiology. Nevertheless, advances in the clinical identification of new indicators will be critical not only for the discovery of sensitive, specific, and reliable biomarkers of preclinical AD pathology, but also for the development of tests that facilitate the early detection and differential diagnosis of dementia and disease progression monitoring. The early detection of AD in its presymptomatic stages would represent a great opportunity for earlier therapeutic intervention. The chance of successful treatment would be increased since interventions would be performed before extensive synaptic damage and neuronal loss would have occurred. In this study, the importance of developing an early diagnostic method using cognitive decline biomarkers that can discriminate between normal, mild cognitive impairment (MCI), and AD preclinical stages has been emphasized.

Clinical trial to evaluate the efficacy and safety of Tongxinluo in high risk group of cardiovascular diseases (심혈관질환 고위험군에 대한 통심락(通心絡)의 유효성 및 안전성 평가를 위한 임상시험)

  • Park, Seong Uk;Jung, Woo Sang;Moon, Sang Kwan;Go, Chang Nam;Cho, Ki Ho;Kim, Young Suk;Bae, Hyung Sup
    • The Journal of the Society of Stroke on Korean Medicine
    • /
    • v.6 no.1
    • /
    • pp.25-32
    • /
    • 2005
  • Background and purpose: Arterial stiffness is an important, independent determinant of cardiovascular risk. Pulse wave velocity (PWV) has been used as a valuable index of arterial stiffness and as a surrogate marker for atherosclerosis. The Framingham risk score was developed using categorized risk factors to predict the 10 year absolute risk of developing coronary heart disease (CHD). This algorithm is established using recommended guidelines for blood pressure, total cholesterol, and high density lipoprotein cholesterol in addition to age, smoking history and history of diabetes. Tongxinluo(TXL) has been shown to have anti hyperlipidemic activity and anti atherogenic effects. To determine its efficacy and safety, we examined whether TXL improves PWV, ABI, Framingham score, blood pressure, and lipid profile in high risk group of cardiovascular diseases. Subjects and methods: 49 subjects with the high risk of cardiovascular diseases were recruited. Subjects were administered TXL with the dose of 1110mg three times a day for 8 weeks. baPWV, ABI, Framingham risk score, Blood pressure and serum lipid profile were assessed at baseline and after 4 and 8weeks. Results: Total cholesterol, LDL cholesterol, triglyceride, total lipid and phospolipid significantly decreased after 4 weeks of medication. Total cholesterol, total lipid and phospolipid significantly decreased after 8 weeks of medication. There were no significant changes in Framingham risk scores, ABI, PWV and blood pressure. On safety assessment, there were no adverse effects, hepatic or renal toxicity. Conclusion: We suggest that TXL is a safe and useful herbal medicine for hyperlipidemia and as for anti-atherognic effects, further research would be necessary.

  • PDF

Clinical Usefulness of the Line Probe Assay for Rapid Detection of Rifampicin-resistant Tuberculosis (Line probe assay를 이용한 신속한 rifampicin내성결핵 진단법의 임상적 유용성)

  • Hong, Sang-Bum;Lim, Chae-Man;Lee, Sang-Do;Koh, Youn-Suck;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong;Shim, Tae-Sun
    • Tuberculosis and Respiratory Diseases
    • /
    • v.50 no.3
    • /
    • pp.334-342
    • /
    • 2001
  • Background : RpoB gene mutations have been found in about 96-98% of rifampicin (RMP)-resistant Mycobacterium tuberculosis. Recent reports confirm that the in laboratory settings a rpoB gene mutation can be used as a surrogate marker for multi-drug resistant tuberculosis. However, its usefulness in clinical applications has not been evaluated. This study was performed to confirm whether mutation analysis of the rpoB gene of M. tuberculosis is useful in clinical settings. Methods : The medical records of 33 patients in whom rpoB gene analysis was conducted using an INNOLiPA Rif. TB assay (LiPA) from June, 1998, to July, 2000, at the Asan Medical Center were retrospectively reviewed in 33 patients. The clinical characteristics in addition to the drug susceptibility and LiPA results were analyzed. The drug susceptibility test was considered as a gold standard method for M. tuberculosis susceptibility and these results were compared with those of the rpoB gene study and sequencing analysis. Sequencing analysis of the rpoB gene was done in cases where there was a discrepancy between the results of the drug susceptibility an d rpoB gene study. Results : The mean age and sex ratio was $42{\pm}18$, and 24:9 (M:F), respectively. There were 19 RMP susceptible (58%) and 14 RMP-resistant cases (42%) according to the rpoB gene study. The mean time from the request to reporting the results of the rpoB gene study was $5.2{\pm}2.6$ days. The mean gap from reporting the rpoB gene study to reporting the susceptibility was $56{\pm}35$ days. Twenty-eight cases (85%) showed identical results compared with the drug susceptibility results, whereas five cases (15%) showed contradictory results. When compared with the sequencing analysis, of the five cases that showed contradictory results, two had LiP A analysis errors and the remaining three were identical to the sequencing results. The rpoB gene study was of assistance in choosing the appropriate drugs in 28 cases (85%). Conclusions : An rpoB gene study using an LiP A assay was useful in rapidly diagnosing RMP-resistant tuberculosis, which enabled a proper choice of the appropriate drugs in clinical practices. However, an LiPA assay always should be performed in conjunction with microscopy, culture, and susceptibility tests.

  • PDF

Semi-Quantitative Analysis for Determining the Optimal Threshold Value on CT to Measure the Solid Portion of Pulmonary Subsolid Nodules (폐의 아고형결절에서 침습적 병소를 검출하기 위한 반-정량 분석을 통한 최적의 CT 임계 값 결정)

  • Sunyong Lee;Da Hyun Lee;Jae Ho Lee;Sungsoo Lee;Kyunghwa Han;Chul Hwan Park;Tae Hoon Kim
    • Journal of the Korean Society of Radiology
    • /
    • v.82 no.3
    • /
    • pp.670-681
    • /
    • 2021
  • Purpose This study aimed to investigate the optimal threshold value in Hounsfield units (HU) on CT to detect the solid components of pulmonary subsolid nodules using pathologic invasive foci as reference. Materials and Methods Thin-section non-enhanced chest CT scans of 25 patients with pathologically confirmed minimally invasive adenocarcinoma were retrospectively reviewed. On CT images, the solid portion was defined as the area with higher attenuation than various HU thresholds ranging from -600 to -100 HU in 50-HU intervals. The solid portion was measured as the largest diameter on axial images and as the maximum diameter on multiplanar reconstruction images. A linear mixed model was used to evaluate bias in each threshold by using the pathological size of invasive foci as reference. Results At a threshold of -400 HU, the biases were lowest between the largest/maximum diameter of the solid portion of subsolid nodule and the size of invasive foci of the pathological specimen, with 0.388 and -0.0176, respectively. They showed insignificant difference (p = 0.2682, p = 0.963, respectively) at a threshold of -400 HU. Conclusion For quantitative analysis, -400 HU may be the optimal threshold to define the solid portion of subsolid nodules as a surrogate marker of invasive foci.

Measuring Intracellular Mycobacterial Killing Using a Human Whole Blood Assay (인체 전혈 모델을 이용한 세포내 결핵균 살균력에 관한 연구)

  • Cheon, Seon-Hee;Song, Ho-Yeon;Lee, Eun-Hee;Oh, Hee-Jung;Kang, In-Sook;Cho, Ji-Yoon;Hong, Young-Sun
    • Tuberculosis and Respiratory Diseases
    • /
    • v.53 no.5
    • /
    • pp.497-509
    • /
    • 2002
  • Background : The mechanisms through which cellular activation results in intracellular mycobacterial killing is only partially understood. However, in vitro studies of human immunity to Mycobacterium tuberculosis have been largely modeled on the work reported by Crowle, which is complicated by several factors. The whole blood culture is simple and allows the simultaneous analysis of the relationship between bacterial killing and the effect of effector cells and humoral factors. In this study, we attempted to determine the extent to which M. tuberculosis is killed in a human whole blood culture and to explore the role of the host and microbial factor in this process. Methods : The PPD positive subject were compared to the umbilical cord blood and patients with tuberculosis, diabetes and lung cancer. The culture is performed using heparinized whole blood diluted with a culture medium and infected with a low number of M. avium or M. tuberculosis $H_{37}Ra$ for 4 days by rotating the culture in a $37^{\circ}C$, 5% $CO_2$ incubator. In some experiments, methlprednisolone- or pentoxifyline were used to inhibit the immune response. To assess the role of the T-cell subsets, CD4+, CD8+ T-cells or both were removed from the blood using magnetic beads. The ${\Delta}$ log killing ratio was defined using a CFU assay as the difference in the log number of viable organisms in the completed culture compared to the inoculum. Results : 1. A trend was noted toward the improved killing of mycobacteria in PPD+ subjects comparing to the umbilical cord blood but there was no specific difference in the patients with tuberculosis, diabetes and lung cancer. 2. Methylprednisolone and pentoxifyline adversely affected the killing in the PPD+ subjects umbilical cord blood and patients with tuberculosis. 3. The deletion of CD4+ or CD8+ T-lymphocytes adversely affected the killing of M. avium and M. tuberculosis $H_{37}Ra$ by PPD+ subjects. Deletion of both cell types had an additive effect, particularly in M. tuberculosis $H_{37}Ra$. 4. A significantly improved mycobacterial killing was noted after chemotherapy in patients with tuberculosis and the ${\Delta}$ logKR continuously decreased in a 3 and 4 days of whole blood culture. Conclusion : The in vitro bactericidal assay by human whole blood culture model was settled using a CFU assay. However, the host immunity to M. tuberculosis was not apparent in the human whole blood culture bactericidal assay, and patients with tuberculosis showed markedly improved bacterial killing after anti-tuberculous chemotherapy compared to before. The simplicity of a whole blood culture facilitates its inclusion in a clinical trial and it may have a potential role as a surrogate marker in a TB vaccine trial.