• Journal of the Korean Society of Radiology
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• v.15 no.5
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• pp.591-602
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• 2021

Acute ischemic stroke(AIS) should be diagnosed within a few hours of onset of cerebral infarction symptoms using diagnostic radiology. In this study, we evaluated the clinical usefulness of SVD and the Bayesian algorithm to measure the volume of cerebral infarction using computed tomography perfusion(CTP) imaging and magnetic resonance diffusion-weighted imaging(MR DWI). We retrospectively included 50 patients (male : female = 33 : 17) who visited the emergency department with symptoms of AIS from September 2017 to September 2020. The cerebral infarct volume measured by SVD and the Bayesian algorithm was analyzed using the Wilcoxon signed rank test and expressed as a median value and an interquartile range of 25 - 75 %. The core volume measured by SVD and the Bayesian algorithm using was CTP imaging was 18.07 (7.76 - 33.98) cc and 47.3 (23.76 - 79.11) cc, respectively, while the penumbra volume was 140.24 (117.8 - 176.89) cc and 105.05 (72.52 - 141.98) cc, respectively. The mismatch ratio was 7.56 % (4.36 - 15.26 %) and 2.08 % (1.68 - 2.77 %) for SVD and the Bayesian algorithm, respectively, and all the measured values had statistically significant differences (p < 0.05). Spearman's correlation analysis showed that the correlation coefficient of the cerebral infarct volume measured by the Bayesian algorithm using CTP imaging and MR DWI was higher than that of the cerebral infarct volume measured by SVD using CTP imaging and MR DWI (r = 0.915 vs. r = 0.763 ; p < 0.01). Furthermore, the results of the Bland Altman plot analysis demonstrated that the slope of the scatter plot of the cerebral infarct volume measured by the Bayesian algorithm using CTP imaging and MR DWI was more steady than that of the cerebral infarct volume measured by SVD using CTP imaging and MR DWI (y = -0.065 vs. y = -0.749), indicating that the Bayesian algorithm was more reliable than SVD. In conclusion, the Bayesian algorithm is more accurate than SVD in measuring cerebral infarct volume. Therefore, it can be useful in clinical utility.

• Korean Journal of Clinical Pharmacy
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• v.23 no.2
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• pp.151-157
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• 2013

Purpose: Warfarin is the most widely used anticoagulant drug for preventing cardiovascular diseases after ischemic stroke and thromboembolism related to atrial fibrillation, artificial heart valves, deep vein thrombosis, and pulmonary embolism. Warfarin is commonly used in combination with other drugs such as diuretics in order to treat the comorbidity. Although several warfarin-diuretics interactions have been reported, the results are conflicting. Therefore, the initial aim of this study was to identify the effects of diuretics on the warfarin response in patients with atrial fibrillation. Methods: One hundred forty six patients with atrial fibrillation who were on anticoagulation therapy with warfarin and maintained INR levels of 2-3 for three consecutive times were followed up, retrospectively. Stable warfarin doses and INR per stable warfarin dose were compared according to age, gender, comorbidity, and concurrent medication. The stable warfarin dose was defined as the maintenance dose of warfarin of the measured patient whose INR was within the target INR range more than 3 times consecutively. Results: The differences of stable warfarin doses in patients with ($3.22{\pm}1.21$ mg/day) and without ($3.58{\pm}1.14$ mg/day) diuretics were marginally significant (P=0.069). On the other hand, stable warfarin doses were $2.97{\pm}1.10$ mg/day in patients with thiazide (n=36) and $3.58{\pm}1.14$ mg/day in patients without diuretics (n=82), which was statistically significant (p=0.009). INR values per stable warfarin dose in patients with diuretics and thiazide were $0.84{\pm}0.31$ and $0.90{\pm}0.34$, respectively, which were statistically different from those without diuretics ($0.72{\pm}0.21$, P=0.010 and P=0.006, respectively). Age, gender, and concurrent use of thiazide diuretics were found to have significant influence on the warfarin response from multivariate analysis. Conclusion: Our study showed that the concurrent use of thiazide diuretics could increase the response of warfarin in patient with atrial fibrillation. Therefore, clinicians should be aware that warfarin dose needs to be adjusted when it is used with thiazide diuretics concomitantly.

• Journal of Korean Neurosurgical Society
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• v.63 no.1
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• pp.69-79
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• 2020

Objective : To analyze trends in the incidence and treatment of diseases associated with ischemic stroke, namely, cerebral infarction (CI), cerebral arterial stenosis (CASTN), and moyamoya disease (MMD), based on Korean National Health Insurance Service (NHIS) data from 2008 to 2016. Methods : Data was extracted from the national health-claim database provided by the NHIS for 2008-2016 using International Classification of Diseases codes. The crude and age-standardized incidences of each disease (CI, CASTN without a history of CI, and MMD) were calculated; additional analyses were conducted according to age and sex. Trends in the number of patients undergoing treatment according to treatment method were analyzed for each disease using the Korean Classification of Diseases procedure codes. Results : In 2016, the total number of adults with newly diagnosed CI was 83939, reflecting a 9.4% decrease from that in 2008. The age-standardized incidence of CI in adults was 153.2 per 100000 person-years in 2016, reflecting a 37.2% decrease from that in 2008, while that of CASTN was 167.3 per 100000 person-years in 2016, reflecting a 73.3% increase from that in 2008. Among treated cases, the number of patients who underwent intra-arterial (IA) treatment, including IA fibrinolysis and mechanical thrombectomy, showed the most prominent increase, increasing at an annual rate of 25.8%. For CASTN, the number of cases treated with carotid artery stenting or balloon angioplasty (CAS) showed the most prominent increase, increasing at a rate of 69.8% over the 9-year period. For MMD, the total number of patients with newly diagnosed MMD and that with adult MMD demonstrated significantly increasing trends, while the number of pediatric patients with newly diagnosed MMD declined by 18.0% over the 9-year period. The age-standardized incidences of pediatric and adult MMD in 2016 were 2.4 and 3.4 per 100000 person-years, respectively. Conclusion : Although the incidence of CI showed a declining trend over a 9-year period, the number and proportion of patients treated for CI increased. Meanwhile, the incidence of CASTN and the number of patients treated for CASTN have demonstrated increasing trends since 2008. On the other hand, the number of patients diagnosed with pediatric MMD decreased, despite no significant change in the incidence. In contrast, the number of patients and the incidence of adult MMD increased. These trends reflect changes in the population structure, gains in the accessibility of imaging examinations, and the development of endovascular techniques.

• The Journal of Korea Assosiation for Disability and Oral Health
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• v.13 no.2
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• pp.108-113
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• 2017

Moyamoya disease is a disorder in which certain arteries in the brain are constricted. Blood flow can be blocked by the constriction and blood clots. The patients frequently experience transient ischemic attacks (TIA), cerebral hemorrhage, or may not experience any symptoms at all. It is reported that they have a higher risk of recurrent stroke and a distinct underlying pathophysiology. A 3-year-8-month old boy with moyamoya disease experienced cerebral infarctions five times, and he underwent a cerebrovascular anastomosis surgery four years ago. He showed swallow disturbance, general delayed development, hemiplegia, and strabismus. Also he had hypocalcified teeth with or without multiple caries lesions in all dentitions. Dental treatment under general anesthesia using sevoflurane was performed due to his lack of cooperation. Moyamoya disease is associated with various medical conditions requiring a thoughtful deliberation and a careful examination before and during dental treatment. Pain and anxiety control during dental treatment is important because hyperventilation induced by crying has been seen to trigger TIA. Both isoflurane and sevoflurane are commonly used in patients with MMD, but dynamic autoregulation is better preserved during sevoflurane than isoflurane anesthesia. So sevoflurance general anesthesia may be recommendable to manage dental patients having multiple caries with moyamoya disease.

• Journal of Korean Neurosurgical Society
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• v.54 no.6
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• pp.467-476
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• 2013

Objective : This study aimed to evaluate the hypotheses that administration routes [intra-arterial (IA) vs. intravenous (IV)] affect the early stage migration of transplanted human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in acute brain infarction. Methods : Male Sprague-Dawley rats (n=40) were subjected to photothrombotic infarction. Three days after photothrombotic infarction, rats were randomly allocated to one of four experimental groups [IA group : n=12, IV group : n=12, superparamagnetic iron oxide (SPIO) group : n=8, control group : n=8]. All groups were subdivided into 1, 6, 24, and 48 hours groups according to time point of sacrifice. Magnetic resonance imaging (MRI) consisting of T2 weighted image (T2WI), $T2^*$ weighted image ($T2^*WI$), susceptibility weighted image (SWI), and diffusion weighted image of rat brain were obtained prior to and at 1, 6, 24, and 48 hours post-implantation. After final MRI, rats were sacrificed and grafted cells were analyzed in brain and lung specimen using Prussian blue and immunohistochemical staining. Results : Grafted cells appeared as dark signal intensity regions at the peri-lesional zone. In IA group, dark signals in peri-lesional zone were more prominent compared with IV group. SWI showed largest dark signal followed by $T2^*WI$ and T2WI in both IA and IV groups. On Prussian blue staining, IA administration showed substantially increased migration and a large number of transplanted hBM-MSCs in the target brain than IV administration. The Prussian blue-positive cells were not detected in SPIO and control groups. Conclusion : In a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration. MRI and histological analyses revealed the time course of cell migration, and the numbers and distribution of hBM-MSCs delivered into the brain.

• Journal of Korean Neurosurgical Society
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• v.61 no.1
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• pp.42-50
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• 2018

Objective : Massive intracerebral hemorrhage (ICH) and major infarction (MI) are devastating cerebral vascular diseases. Decompression craniectomy (DC) is a common treatment approach for these diseases and acceptable clinical results have been reported. Author experienced the postoperative intracranaial pressure (ICP) trend is somewhat different between the ICH and MI patients. In this study, we compare the ICP trend following DC and evaluate the clinical significance. Methods : One hundred forty-three patients who underwent DC following massive ICH (81 cases) or MI (62 cases) were analyzed retrospectively. The mean age was $56.3{\pm}14.3$ (median=57, male : female=89 : 54). DC was applied using consistent criteria in both diseases patients; Glasgow coma scale (GCS) score less than 8 and a midline shift more than 6 mm on brain computed tomography. In all patients, ventricular puncture was done before the DC and ICP trends were monitored during and after the surgery. Outcome comparisons included the ictus to operation time (OP-time), postoperative ICP trend, favorable outcomes and mortality. Results : Initial GCS (p=0.364) and initial ventricular ICP (p=0.783) were similar among the ICH and MI patients. The postoperative ICP of ICH patients were drop rapidly and maintained within physiological range if greater than 80% of the hematoma was removed. While in MI patients, the postoperative ICP were not drop rapidly and maintained above the physiologic range (MI=18.8 vs. ICH=13.6 mmHg, p=0.000). The OP-times were faster in ICH patients (ICH=7.3 vs. MI=40.9 hours, p=0.000) and the mortality rate was higher in MI patients (MI=37.1% vs. ICH=17.3%, p=0.007). Conclusion : The results of this study suggest that if greater than 80% of the hematoma was removed in ICH patients, the postoperative ICP rarely over the physiologic range. But in MI patients, the postoperative ICP was above the physiologic range for several days after the DC. Authors propose that DC is no need for the massive ICH patient if a significant portion of their hematoma is removed. But DC might be essential to improve the MI patients' outcome and timely treatment decision.

• Journal of Nutrition and Health
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• v.45 no.4
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• pp.347-361
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• 2012

Limited studies are available concerning the effect of heavy metal exposure on cardiovascular diseases. As environmental pollution increases, food contamination, including heavy metal contamination of fish, also increases. However, researches based on the intake of heavy metals, cardiovascular disease, and fish intakes are inconclusive. We assessed an association of heavy metal exposure with cardiovascular disease and fish intake in a nationally representative group of general Korean adults. We used data from the combined 2008-2010 Korean National Health and Nutrition Examination Survey (KNHANES), and analyzed the data of 5,139 Koreans who participated in KNHANES. All participants were older than 20 years, and were diagnosed with stroke, ischemic heart disease, or hypertension. The mean blood cadmium, lead concentration, and mercury concentration of subjects were $1.07{\pm}0.01{\mu}g/L$, $2.49{\pm}0.02{\mu}g/dL$, and $5.19{\pm}0.08{\mu}g/L$, respectively. We used the survey logistic regression model to account for the complex sample design of the cardiovascular disease risk in order to estimate the odds ratios (OR). After adjusting for age, education, income, alcohol, smoking, and BMI, the increase of serum cadmium in blood was associated with the increase in the prevalence of hypertension. Further, the increase in blood cadmium concentration was associated with the increase of both systolic blood pressure (SBP) and diastolic blood pressure (DBP). Although higher fish intakes were significantly associated with higher blood mercury concentration (p for trend < 0.0001), fish intakes did not affect either blood cadmium or lead concentration. Comparing the highest fish intake group with the lowest intake group, the OR of hypertension was 0.31 (95% CI: 0.19-0.59) in the crude model for total fish. However, these associations were no longer significant after the adjustment for potential confounding factors. In conclusion, cadmium in blood was associated with an increased risk of hypertension in the general Korean adult population. However, we found no evidence of a clear relationship between cardiovascular disease and frequency of fish consumption.

• Biomolecules & Therapeutics
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• v.15 no.1
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• pp.16-26
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• 2007

Tissue plasminogen activator (tPA) is a serine protease catalyzing the proteolytic conversion of plasminogen into plasmin, which is involved in thrombolysis. During last two decades, the role of tPA in brain physiology and pathology has been extensively investigated. tPA is expressed in brain regions such as cortex, hippocampus, amygdala and cerebellum, and major neural cell types such as neuron, astrocyte, microglia and endothelial cells express tPA in basal status. After strong neural stimulation such as seizure, tPA behaves as an immediate early gene increasing the expression level within an hour. Neural activity and/or postsynaptic stimulation increased the release of tPA from axonal terminal and presumably from dendritic compartment. Neuronal tPA regulates plastic changes in neuronal function and structure mediating key neurologic processes such as visual cortex plasticity, seizure spreading, cerebellar motor learning, long term potentiation and addictive or withdrawal behavior after morphine discontinuance. In addition to these physiological roles, tPA mediates excitotoxicity leading to the neurodegeneration in several pathological conditions including ischemic stroke. Increasing amount of evidence also suggest the role of tPA in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis even though beneficial effects was also reported in case of Alzheimer's disease based on the observation of tPA-induced degradation of $A{\beta}$ aggregates. Target proteins of tPA action include extracellular matrix protein laminin, proteoglycans and NMDA receptor. In addition, several receptors (or binding partners) for tPA has been reported such as low-density lipoprotein receptor-related protein (LRP) and annexin II, even though intracellular signaling mechanism underlying tPA action is not clear yet. Interestingly, the action of tPA comprises both proteolytic and non-proteolytic mechanism. In case of microglial activation, tPA showed non-proteolytic cytokine-like function. The search for exact target proteins and receptor molecules for tPA along with the identification of the mechanism regulating tPA expression and release in the nervous system will enable us to better understand several key neurological processes like teaming and memory as well as to obtain therapeutic tools against neurodegenerative diseases.

• Korean Journal of Clinical Pharmacy
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• v.26 no.3
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• pp.201-206
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• 2016

Objective: Direct current cardioversion for atrial fibrillation could be associated with the risk of thromboembolic events. Anticoagulation therapy with warfarin (INR 2.0-3.0) is recommended 3 weeks before and 4 weeks after cardioversion to reduce the risk of thromboembolism. This study evaluated warfarin therapy in pharmacist-managed anticoagulant services (ACS). Methods: This retrospective study was performed in 106 patients with atrial fibrillation from 2012 to 2013. The primary efficacy endpoint was the composite of stroke, transient ischemic attack, myocardial infarction, and cardiovascular death. The primary safety measure was major bleeding. To evaluate the peri-procedural effects of warfarin treatment, we studied whether target INR was maintained, as well as the maintenance period of the therapeutic range. Quality of treatment was measured by time in therapeutic range (TTR) by using the Rosendaal method. Results: There were no thromboembolic events, but TEE examination at time of cardioversion showed a left atrial thrombus in three patients (2.8%). Bleeding complications after cardioversion occurred in 2 patients (1.9%). The average INR value at the time of cardioversion was $2.59{\pm}0.8$, and was within the therapeutic range in 83 patients (78%). Analysis of the patients in whom the value was within the therapeutic range twice consecutively showed that the ratio of TTR was 80% and the therapeutic range was maintained in 67 patients (63%) for an average of 4.90 weeks prior to cardioversion. Similarly, 76 patients (72%) had a stable INR within the therapeutic range for an average of 5.70 weeks and a mean TTR of 83%. Conclusion: Pharmacists significantly contributed to appropriate warfarin treatment with close monitoring during cardioversion. Likewise, active pharmacist monitoring and systemic management should be considered to reduce thromboembolism and bleeding complications in the peri-cardioversion period.

• Proceedings of the Korean Journal of Food and Nutrition Conference
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• 2003.07a
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• pp.82-82
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• 2003

오디는 옛부터 보혈자음(補血滋陰), 생진윤조(生津閏操), 현훈이명(眩最耳鳴), 심계실면(心悸失眠), 수발조백(鬚髮早白) 등을 치료하는 효능을 가진다고 알려져 있다. 상심자(桑 子)라 하여 뽕나무 열매로서 한방에서 상심(桑 ), 상실(桑實), 오심(烏 ), 흑심(黑 ) 등으로 지칭되며, 뽕나무과(Moraceae)에 속하는 뽕나무(Morus alba L)의 성숙한 과실로 취화과(聚花果)에 속하며 작은 수과(瘦果)가 많이 모여 이루어진 장원형으로 길이 1 내지 2 cm, 지름 0.5 내지 0.8 cm이며 황갈색, 갈홍색 또는 암자색을 띠고 짧은 줄기가 있다. 작은 수과(瘦果)는 난원형으로 조금 납작한 편이며, 길이는 약 2 mm, 너비는 약 1 mm 이고 육질의 화편(花片) 4개가 둘러싸고 있다. 그러나 아직까지는 오디에 대하여 자연과학적인 연구방법을 이용하여 구체적으로 연구된 바가 많지 않다. 또한 이의 생리활성 성분에 대해서도 그 작용과 연관지어 보고된 바가 많지 않다. 뇌졸중 가운데 뇌조직으로 가는 혈액 공급의 감소 혹은 차단으로 발생되는 허혈성 뇌졸중(ischemic stroke)은 전체 뇌졸중 환자의 약 80%정도를 차지하고 있으나 아직까지 뇌신경세포 손상기전의 복잡성 등으로 뇌졸중으로 발생하는 뇌신경세포의 손상을 보호해 줄 수 있는 물질이 개발되어 있지 못한 실정이다. 한편, 천연물로부터 뇌허혈 보호작용을 가지는 물질의 도출은 주로 한방에서 처방을 중심으로 이루어지고 있으며, 따라서 처방으로부터 신경보호작용을 가지는 물질의 도출은 그 처방에 함유되어 있는 각종 생약이 갖는 다양한 활성으로 인해 어려운 점이 있으며, 비록 효과가 있다고 하더라도 과학적인 입증자료가 매우 미비한 실정이다. 이에 본 연구에서는 위에 언급된 자료를 토대로 오디추출물이 뇌허혈에 효과가 있을 것이라는 가정하에 in vitro system을 이용하여 오디추출물의 신경보호작용기전을 검색하고자 DPPH radical 의 생성억제효과, PC12 cell line을 이용한 산화적 스트레스에 의한 오디추출물의 방어효과, LSP에 의하여 활성화된 BV-2 cell에 미치는 영향 등을 검색하였다. 오디의 DPPH 소거활성은 단일화랍물인 bacicalein과 유사한 효과를 나타냈으며 PC12 cell line을 이용한 산화적 스트레스에 의한 오디의 방어 효과는 LDH activity를 행한 결과 농도 의존적으로 LDH 유리 량을 감소시켰다. 뇌손상시에 오디추출물의 염증방어 효과를 관찰하기 위하여 microglial cell line인 BV2 세포주를 선택하여 배양한 후 LPS로 자극을 준 후 일차적인 염증지표인 NO양을 측정한 결과 BV2 cell에 LPS 100 ng/ml을 처리하는 경우 nitrite량이 유의적으로 증가하였는데 이때 오디추출물을 1, 5, 10 ug/ml의 용량으로 처리하는 경우 역시 저농도에서 NO생성량을 감소시켰다. 정리해보면 뽕나무과 식물인 오디는 신경보호효과가 있는 것으로 사료되는데 이러한 효과는 아마도 오디의 항산화효과에 기인한 것으로 추정된다.