Assessment of blood-brain barrier integrity by dynamic contrast enhanced MRI in transient middle cerebral artery occlusion model after localized brain cooling

Dept. of Medicine/박사Introduction: Localized brain cooling before reperfusion reportedly helps to reduce the inflammatory response and recover the function of brain neurons in stroke therapy. Little is known about the effects of localized brain cooling on permeability changes associated with alterations to the blood-brain barrier (BBB).Purpose: The purpose of this study was to evaluate the effects of localized brain cooling on BBB permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast enhanced- (DCE-) MRI.Materials and method: Thirty rats were divided into three groups (10 rats each): control group, localized cold-saline (20°C) infusion group, and localized warm-saline (37°C) infusion group. The left middle cerebral artery (MCA) was occluded for 1 h in anesthetized rats, followed by 3 h of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 min after MCA occlusion. DCE-MRI investigations were performed after 3 h and 24 h of reperfusion. Four pharmacokinetic parameters of the Tofts model (wash-in rate [Ktrans], wash-out rate [Kep], leakage-space volume [Ve], and plasma-space volume [Vp]) were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1–9 after tMCAO. Myeloperoxidase (MPO) immunohistochemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain.Result: There was a statistically significant decrease in Ktrans and Kep at the infarction site in the cold-saline group compared with the control group (P < 0.05) and a decrease in Kep that approached significance in the cold-saline group compared with the warm-saline group (Kep: cortex, P = 0.0892 basal ganglia, P = 0.0925). The percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (P < 0.05). However, behavioral testing did not reveal a statistically significant difference among the three groups.Conclusion: Localized brain cooling can inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model.ope

Relationships between thickening of reticular basement membrane and the clinical features in children with asthma

Dept. of Medicine/석사[한글]목적: 천식은 기도 염증과 과민성, 기도 폐쇄를 특징으로 하는 만성 염증성 질환이다. 천식이 부분적으로는 가역적인 기도 폐쇄를 일으키지만, 궁극적으로 비가역적인 폐쇄를 일으키는 기도 개형을 발생 시키게 된다. 기도 개형이 일어난 기도는 여러 구조적 변화를 동반하게 되는데 상피세포 층의 탈락, 기저막의 비후, 기도 평활근의 증식, 신생 혈관의 증가 등의 소견을 보인다. 본 연구에서는 소아 천식환자의 기저막의 두께를 측정하여 기도 기저막 비후가 소아 천식에 미치는 영향을 알아보고자 하였다.방법: 기관지 내시경을 통해 조직검사를 시행한 18명의 천식 환아와 24명의 대조군을 대상으로 하였다. 기도 기저막의 두께를 측정하였고, 기저막의 두께와 연령, 성별, 천식 발병기간, 천식의 중등도, FEV1, FEV1/FVC, FEF25-75%, 메타콜린 PC20및 호산구 수, 혈청 총 IgE, 집먼지 진드기 (Dermatophagoides pteronyssinus) 에 대한 특이 IgE와의 상관관계를 분석하였다.결과: 천식 환아에서의 기저막의 두께는 8.3±1.4 ㎛로 6.8±1.3 ㎛인 대조군에 비해 기도 기저막이 의미있게 비후되어 있었다 (p=0.0008). 다중 회귀 분석을 시행해 보았을 때 성별, FEV1/FVC, 혈청 총 IgE, 집먼지 진드기에 대한 특이 IgE가 기도 기저막 비후를 예견할 수 있는 인자로 나타났다. 기도 기저막 비후와 연령, 천식 발병기간, FEV1, FEF25-75%, 메타콜린 PC20및 호산구 수, 천식의 중등도 간에는 유의한 상관관계를 보이지 않았다.결론: 소아 천식 환아들은 대조군에 비해 의의있게 기도 기저막의 비후가 관찰되었으며, 성별, FEV1/FVC, 혈청 총 IgE, 집먼지 진드기에 대한 특이 IgE와 관련을 보였다. [영문]RATIONALE: Asthma is chronic inflammatory disease characterized by airway inflammation, bronchial hyperresponsiveness, airway obstruction. Although asthma induces partially reversible airway obstruction, in some patients, airflow obstruction can become irreversible. Such obstruction might be a consequence of airway remodeling. Remodeling comprises a number of structural changes, including epithelial detatchment, reticular basement membrane thickening, smooth muscle hypertrophy, and new vessel formation. This study investigated whether reticular basement membrane thickening is already present in children with asthma.METHODS: 18 children with asthma and 24 control subjects underwent flexible bronchoscopy with endobronchial biopsy. We used light microscopy to measure reticular basement thickness in plastic-embedded biopsy sections. We examined the relationship between reticular basement membrane thickening and age, sex, duration of asthma, asthma severity, FEV1, FEV1/FVC, FEF25-75%, methacholine PC20, eosinophil count, or presence of atopy.RESULTS: Reticular basement membrane thickness was greater in subjects with asthma (8.3 ± 1.4 ㎛) than in control subjects (6.8 ± 1.3 ㎛, p=0.0008). Multiple regression analysis revealed that sex, FEV1/FVC, total IgE, or atopy (IgE for Dermatophagoides pteronyssinus > 0.34 kUA/L) were the significant predictive factors for reticular basement membrane thickness. There was no significant difference between reticular basement membrane thickness and age, duration of asthma, FEV1, FEF25-75%, methacholine PC20, eosinophil count, or asthma severity.CONCLUSIONS: Reticular basement membrane thickening is already present in children with asthma. In addition, we find association between reticular basement membrane thickness and sex, FEV1/FVC, total IgE, or presence of specific IgE to Dermatophagoides pteronyssinus.ope

Inflammatory bowel disease in Korea: epidemiological, genomic, clinical, and therapeutic characteristics

Inflammatory bowel disease (IBD) describes chronic inflammatory disease of the intestines and has a variable course; Crohn's disease and ulcerative colitis comprise the two main forms of the condition. Although IBD occurs worldwide, its epidemiologic and clinical characteristics vary depending upon the geographic location and the ethnicity of the population. Identifying the characteristic features of IBD in populations living in different geographical locations and with different ethnicities may provide significant clues about its etiology and pathophysiology, which in turn may be helpful in the development of more appropriate treatment strategies for IBD for these different populations. Therefore, it is important for each country and region to evaluate critically the epidemiology, genomics, and clinical characteristics of IBD among its own population. We have performed a critical review of the recent data in Korea, and describe herein the current epidemiologic and genotypic status, as well as the clinical manifestations and therapeutic responses of IBD that are unique to Korean patientsope

Increased Serum Thymus and Activation-regulated Chemokine (TARC) Levels in Children with Atopic Dermatitis

Purpose: Thymus and activation-regulated chemokine(TARC) is responsible for the trafficking of Th2 lymphocytes into sites of allergic inflammation. We tested whether TARC is a useful marker for childhood atopic dermatitis(AD) and we evaluated age-related differences in the level of TARC. Methods: Serum TARC level, serum total IgE level, total eosinophil count and specific IgE level were measured in 401 children. They were characterized as having IgE-mediated atopic dermatitis(n=157), non-IgE mediated atopic dermatitis(n=107), or as healthy control subjects(n=137). Results: TARC levels in AD significantly were higher than those in healthy control subjects.(152.9+/-11.6 vs 56.7+/-5.2 pg/mL, P<0.05) Serum TARC levels significantly correlated with disease severity(SCORAD index) both in children with IgE mediated AD(r=0.670, P<0.05) and children with non-IgE mediated AD.(r=0.605, P<0.05) Serum TARC levels in control subjects decreased in accordance with age.(r=-0.201, P<0.05) Conclusion: Serum TARC might be a useful marker for disease severity both in children with IgE mediated AD and children with non-IgE mediated AD. Serum TARC levels in control subjects decreased in accordance with ages.ope

Effect of Obesity on Atopy and Bronchial Hyperresponsiveness in Children

Purpose : The prevalence of asthma and allergic diseases is on the increase and that of obesity is on the continuous increase all over the world. There are recent studies on the association between asthma and obesity, which are still controversial. This study aimed at identifying the effect of obesity on atopy and bronchial hyperresponsiveness in children. Methods : This study was conducted with 443 subjects ranging from six to 15 years of age, and consisted of 283 boys and 160 girls. They went through pulmonary function tests and methacholine challenge tests with their eosinophil counts within blood, total serum IgE levels, serum eosinophil cationic protein(ECP) levels, heights, and weights measured. After determining body mass index(BMI), BMI percentiles were determined by using a BMI percentile curve based on gender and age. After the classification on the basis of the 85th, 90th, and 95th BMI percentiles, a comparison was made in frequencies of atopy, total serum IgE, eosiniphil counts within blood, and serum ECPs as well as in frequencies of bronchial hyperresponsiveness for the total group, the boys, and the girls, respectively. Results : Among the groups classified by BMI percentiles, there was no significant differences in total serum IgE, eosinophil counts within blood, and serum ECPs. There also was no significant differences in bronchial hyperresponsiveness or pulmonary functions among them. Effect of atopy and pulmonary function test variables on BMI did not show any statistical significance in boys, girls or the total group. Conclusion : There was domestically no association between obesity and atopy and bronchial hyperresponsiveness among children.ope

A Good Outcome for a Case of Chronic Pneumonitis of Infancy

Chronic pneumonitis of infancy (CPI) is a very rare interstitial lung disease. Its pathological features differ from other types of interstitial pneumonia that occur in adults and children. The mortality rate of CPI is high, even with treatment. We report a case of a 3 month old girl diagnosed with CPI after an open lung biopsy who improved after proper treatment.ope

Polymorphisms of the CTLA-4 promoter(-318) and exon 1(＋49) genes with atopic dermatitis in Korean children

Purpose: The gene-encoding cytotoxic T lymphocyte-associated antigen-4(CTLA-4) is one of the candidate genes for conferring susceptibility to atopic dermatitis(AD). The aim of the study was to investigate the association between Korean children with AD and the polymorphisms of CTLA-4 gene promoter(-318) and exon 1(+49). Methods: The CTLA-4 promoter(-318 T/C) and exon 1(+49 A/G) polymorphisms were genotyped via restriction fragment length polymorphism methods in 145 children with atopic eczema, 69 children with non-atopic eczema, and 96 healthy controls. Results: There was no significant difference in genotype and allele frequencies of the CTLA-4 promoter -318 T/C and exon 1 +49 A/G polymorphisms when the atopic eczema, non-atopic eczema, and control groups were compared. Additionally the CTLA-4 promoter -318 T/C and exon 1 +49 A/G polymorphisms were not shown to be associated with severity, IgE level, or eosinophil counts. Conclusion: Our data show that the polymorphisms within the CTLA-4 promoter(-318 T/C) and exon 1(+49 A/G) genes are not associated with susceptibility to AD in Korean children.ope

Two Cases of Urticaria Developed by Antianemics which Contain Cow's Milk Protein(casein) or Egg White Protein(ovalbumin)

Hemo-Q and AlbumaxV solution are widely used antianemics. Hemo-Q8 contains cow´s milk protein(casein) and Albumaxe contains egg white protein(ovalbumin). Cow´s milk protein and egg protein can cause common allergic diseases in infants and young children. We reported two cases of young children with milk and egg allergy who presented skin symptoms after ingestion or cutaneous contact with Hemo-Q8 or Albumaxe solution. When Hemo--Q or Albumax@ solution was taken or rubbed on, erythematous papules and wheals were developed in 10-20 minutes, but other antianemics which don´t contain milk or egg protein contents didn´t show skin manifestations.ope

Diagnostic yield of double-dose gadobutrol in the detection of brain metastasis: intraindividual comparison with double-dose gadopentetate dimeglumine

BACKGROUND AND PURPOSE: Accurate assessment of the number and lesion characteristics of brain metastasis is very important in GKS. The purpose of this study was to compare the diagnostic efficacy of DD gadobutrol in the detection of brain metastases compared with a DD 0.5-mol/L gadolinium contrast, gadopentetate dimeglumine. MATERIALS AND METHODS: Records of 27 patients (male to female ratio, 15:12; mean age, 57.1 years) diagnosed with brain metastasis and having undergone GKS were retrospectively analyzed. All patients underwent the first 3D-T1-GRE MR imaging with a DD of gadopentetate dimeglumine. The second MR imaging with a DD of gadobutrol was performed during GKS by using the same parameters used for the first scan. Two neuroradiologists counted the number of enhancing lesions on 2 consecutive MR imaging examinations and reached consensus. Lesion-brain CNR was measured from 45 lesions, and paired t test analysis was performed between DD gadopentetate dimeglumine and gadobutrol MR imaging. RESULTS: On DD gadopentetate dimeglumine-enhanced images, a total of 130 lesions were detected visually. With DD gadobutrol, 25 additional lesions were detected on GKS MR imaging. There was no missing lesion on DD gadobutrol MR imaging. The mean lesion-brain CNR was higher on DD gadobutrol MR imaging than on DD gadopentetate dimeglumine imaging (2.17 +/- 0.19 versus 1.90 +/- 0.26; P = .00011, paired t test, 2-tailed). Only 2 cases showed lower CNR on DD gadobutrol images: 1 with hemorrhagic metastasis from renal cell carcinoma and the other with steroid treatment after the first MR imaging. CONCLUSIONS: DD 1.0-mol/L gadobutrol provides higher lesion conspicuity and enhances lesion detection in brain metastasis compared with DD 0.5-mol/L gadolinium contrast agentsope

Changes in integrity of normal-appearing white matter in patients with moyamoya disease: a diffusion tensor imaging study

BACKGROUND AND PURPOSE: DTI is widely used for the evaluation of white matter integrity in various neurologic diseases. The purpose of this study was to investigate changes in white matter integrity by using DTI in NAWM of patients with MMD and to evaluate the correlation between diffusion and perfusion characteristics through an interhemispheric comparison. MATERIALS AND METHODS: We retrospectively reviewed 20 primary MMD patients with asymmetric disease stage and 20 age-matched healthy controls. FA(CS) and ADC(CS) values of bilateral centrum semiovale were measured by using region of interest analysis. Mean FA(CS) and ADC(CS) were compared between patient and control groups by unpaired t test. Interhemispheric differences in FA(CS) and ADC(CS) were assessed and compared between the H-TTP(delayed) and the H-TTP(shorter) by using paired t test. AIs also were assessed to verify interhemispheric differences. RESULTS: The patient group showed a significantly lower mean FA(CS) and a higher mean ADC(CS) value than the control group. In the patient group, the H-TTP(delayed) had a significantly lower FA(CS) and higher ADC(CS) value than the H-TTP(shorter). Both AI(FA) and AI(ADC) were significantly higher in the patient compared with the control group. CONCLUSIONS: DTI can describe subtle changes in white matter integrity in NAWM of patients with primary MMD that are not detected by conventional MR imaging. In addition, diffusion characteristics are well correlated with perfusion characteristics. We believe that DTI is a useful ancillary tool to evaluate patients with MMD.ope