Yeong-Bae Lee

Bio-printing of collagen and VEGF-releasing fibrin gel scaffolds for neural stem cell culture

Time-released delivery of soluble growth factors (GFs) in engineered hydrogel tissue constructs promotes the migration and proliferation of embedded cells, which is an important factor for designing scaffolds that ultimately aim for neural tissue regeneration. We report a tissue engineering technique to print murine neural stem cells (C17.2), collagen hydrogel, and GF (vascular endothelial growth factor: VEGF)-releasing fibrin gel to construct an artificial neural tissue. We examined the morphological changes of the printed C17.2 cells embedded in the collagen and its migration toward the fibrin gel. The cells showed high viability (92.89+/-2.32%) after printing, which was equivalent to that of manually-plated cells. C17.2 cells printed within 1mm from the border of VEGF-releasing fibrin gel showed GF-induced changes in their morphology. The cells printed in this range also migrated toward the fibrin gel, with the total migration distance of 102.4+/-76.1microm over 3days. The cells in the control samples (fibrin without the VEGF or VEGF printed directly in collagen) neither proliferated nor migrated. The results demonstrated that bio-printing of VEGF-containing fibrin gel supported sustained release of the GF in the collagen scaffold. The presented method can be gainfully used in the development of three-dimensional (3D) artificial tissue assays and neural tissue regeneration applications.

Lenticulostriate arteries in chronic stroke patients visualised by 7 T magnetic resonance angiography.

Background Noninvasive magnetic resonance angiography using ultra-high-field magnetic resonance imaging has recently provided us with the potential to image cerebral microvascular structures such as the lenticulostriate arteries. However, most studies using ultra-high-field magnetic resonance angiography have been limited to the visualisation of microvessels in healthy subjects, and the direct comparison of patients with microvascular disease has not been reported. Aim The aim of this study was to investigate the lenticulostriate arteries of patients with lacunar strokes of the basal ganglia and surrounding areas using 7 T magnetic resonance angiography. Methods Ten stroke patients who had infarctions in the basal ganglia and adjacent areas detected using T2*-weighted images obtained from a conventional 1.5 T magnetic resonance imaging and 10 age-matched healthy subjects were recruited for this study. The large main vessels in the patient group were inspected to identify abnormalities such as stenosis. The characteristics of the lenticulostriate arteries visualised by 7 T magnetic resonance angiography, such as the number of branches and stems, curvature and tortuosity were analysed and compared between the patient and the control groups. Results All patients had infarctions in the basal ganglia and adjacent regions, which were clearly determined by T2*-weighted images. However, there was no evidence of large-vessel abnormalities in the patient group. Analysis of 7 T magnetic resonance angiography data revealed that the overall number of lenticulostriate arteries branches in the patient group was significantly less than the control group (P = 0.003). However, no statistical difference in the number of stems, curvature and tortuosity between the two groups was found (P = 0.396, 0.258 and 0.888, respectively). Conclusions This study demonstrates that noninvasive magnetic resonance angiography using 7 T magnetic resonance imaging can visualise abnormalities in the cerebral microvasculature of stroke patients, and that the number of lenticulostriate arteries supplying the region of the basal ganglia is less in these patients compared with age-matched controls.

Population pharmacokinetics of intravenous valproic acid in Korean patients

Objective:  To determine population‐based pharmacokinetic parameters for intravenous valproic acid, and the factors influencing these parameters, in Korean adults.

Prognosis of ocular myasthenia in Korea: a retrospective multicenter analysis of 202 patients

OBJECTIVES The aims of this study were to obtain data on the frequency with which Korean patients with autoimmune myasthenia gravis (MG) present solely with ocular disturbances and progress to develop generalized disease and to identify the prognostic factors associated with secondary generalization. METHODS We conducted a retrospective multicenter survey in which a total of 376 adult patients who were newly diagnosed with MG from 2000 through 2005 were reviewed for analysis. Patients with ocular MG at the time of symptom presentation (n=202, 53.7%) were divided into two subgroups according to their prognosis: the patients whose disease remained ocular throughout the follow-ups were placed in the OMG-R group, and the patients who progressed to develop generalized disease were placed in the OMG-G group. Clinical characteristics and laboratory findings were compared between the two subgroups. RESULTS Secondary generalization developed in 47 (23.3%) of the 202 study subjects, mostly within the first 6 months after symptom presentation, while the disease remained ocular throughout the follow-up duration (median 11.8 months) in the remaining 155 patients (76.7%). AChR antibody, abnormal repetitive nerve stimulation tests (RNST) and thymoma were more frequently observed in the patients in the OMG-G group than in those in the OMG-R group (p<0.01 in all). In seropositive cases, the titers of AChR antibody were also significantly higher in the OMG-G group than in the OMG-R group (median, 3.8 nM vs. 6.4 nM; p<0.05). Cox proportional hazards regression analyses showed that early oral prednisolone treatment significantly reduced the risk of secondary generalization (HR, 0.24; 95% CI, 0.11-0.56), whereas abnormal AChR antibody (HR, 5.34; 95% CI, 1.60-17.8) and thymoma (HR, 2.32; 95% CI, 1.21-4.45) were predictive of the development of secondary generalization. CONCLUSIONS Our findings suggest that several factors, including the AChR antibody, thymoma, early corticosteroid treatment, and possibly latent neuromuscular abnormality revealed by RNST, may have an impact on the risk of developing generalized disease in Korean patients presenting with ocular myasthenia.

Sleep problems associated with behavioral and psychological symptoms as well as cognitive functions in Alzheimer's disease.

Background and Purpose It has been shown that sleep problems in Alzheimers disease (AD) are associated with cognitive impairment and behavioral problems. In fact, most of studies have founded that daytime sleepiness is significantly correlated with cognitive decline in AD. However, a few studies have also shown that nighttime sleep problems are associated with cognitive function and behavioral symptoms in AD. Accordingly, the aim of this study was to evaluate the effects of nighttime sleep on cognition and behavioral and psychological symptoms of dementia (BPSD) in AD. Methods The study population comprised 117 subjects: 63 AD patients and 54 age- and sex-matched non-demented elderly subjects. Detailed cognitive functions and behavioral symptoms were measured using the Seoul Neuropsychological Screening Battery (SNSB) and the Korean version of the Neuropsychiatric Inventory (NPI-K). Sleep characteristics were evaluated using the Korean version of the Pittsburgh Sleep Quality Index (PSQI-K). The correlations between PSQI-K and SNSB scores and between PSQI-K and NPI-K scores were analyzed. Results In AD patients, sleep latency was found to be negatively correlated with praxis (p=0.041), Rey-Osterrieth Complex Figure Test (RCFT) immediate recall (p=0.041), and RCFT recognition (p=0.008) after controlling for age and education, while sleep duration and sleep efficiency were positively correlated with praxis (p=0.034 and p=0.025, respectively). Although no significant correlation was found between PSQI-K and NPI-K scores, sleep disturbance and total PSQI-K scores were found to be significantly associated with apathy/indifference in AD. Conclusions Sleep problems such as prolonged sleep duration, sleep latency, and poor sleep efficiency in AD patients were correlated with cognitive dysfunction, and especially frontal executive and visuospatial functions, and BPSD. These findings suggest that treatment of nighttime sleep problems might improve cognition and behavioral symptoms in AD patients.

Tau positron emission tomography using [18F]THK5351 and cerebral glucose hypometabolism in Alzheimer's disease

This study aims to evaluate the clinical validity of [18F]THK5351 positron emission tomography (PET) for the assessment of disease progression and symptoms in Alzheimers disease (AD). Fifty-one patients with AD dementia, 30 patients with amnestic mild cognitive impairment (aMCI), and 43 controls with normal cognition (NC) were included. All subjects underwent [18F]THK5351 PET, 3.0-T magnetic resonance imaging, and detailed neuropsychological tests. Regions of interest and voxel-based statistical analyses were performed. In patients with AD dementia, [18F]THK5351 retention was greater in most association cortices as well as the limbic area compared to NC or aMCI participants. Patients with aMCI also showed higher THK5351 retention in those areas compared to NC. [18F]THK5351 retention significantly correlated with neuropsychological test results. Negative correlations between [18F]THK5351 and [18F] fluorodeoxyglucose were observed in AD dementia and aMCI groups. Mirror images of [18F]THK5351 retention and glucose hypometabolism in [18F] fluorodeoxyglucose were noticeable in the focal variants of AD. [18F]THK5351 PET reflects disease severity and symptoms in AD. Our results suggest [18F]THK5351 is reflective of tau-related AD pathology.

Evolution of abnormal eye movements in Wernicke's encephalopathy: correlation with serial MRI findings.

A 33-year-old woman with Wernickes encephalopathy (WE) due to poor oral intake after allogeneic stem cell transplantation for acute myeloid leukemia showed a sequential development of bilateral gaze-evoked nystagmus (GEN), rightward gaze palsy, and upbeat nystagmus. Initial MRIs obtained when she had GEN only showed a lesion involving the medullary tegmentum, and follow-up MRIs revealed additional lesions in the pontine and midbrain tegmentum along with development of rightward gaze palsy, and finally bilateral medial thalamus lesions in association with upbeat nystagmus. The evolution of abnormal ocular motor findings and serial MRI changes in our patient with WE provide imaging evidence on relative vulnerability of the neural structures, and on the progression of lesions and ocular motor findings in thiamine deficiency.

Eikenella Corrodens Cervical Spinal Epidural Abscess Induced by a Fish Bone

Cervical spinal epidural abscess, caused by fish bone injury and a secondary infection by Eikenella Corrodens which is part of the normal flora, has not been reported. A 72-yr-old man came to the hospital with pain in his posterior neck and both shoulders for 2 months. He also was experiencing weakness on his right side for 3 days. A fish bone had been stuck in his throat for about 2 months. Neurological examination revealed right hemiparesis, hypesthesia on the left extremities and neck stiffness. Laboratory findings showed an elevated ESR/CRP and leukocytosis, and magnetic resonance imaging revealed a retropharyngeal abscess and cervical myelitis. The patient was treated with emergency surgical decompression and antibiotics. A fish bone was removed from the C3-C4 intervertebral disc space. In the culture of chocolate blood agar and 5% sheep blood agar plate, E. corrodens was detected as a causative organism.

[18F]-THK5351 PET Imaging in Patients With Semantic Variant Primary Progressive Aphasia.

Background: Semantic variant primary progressive aphasia (svPPA) has been associated with a variety of proteinopathies, mainly transactive response DNA-binding protein, but also with tau and &bgr;-amyloid. Recently selective tau tracers for positron emission tomography (PET) have been developed to determine the presence of cerebral tau deposits in vivo. Here, we investigated the topographical distribution of THK5351 in svPPA patients. Materials and Methods: Five svPPA patients, 14 Alzheimer’s disease patients, and 15 age-matched normal controls underwent [18F]-THK5351 PET scans, magnetic resonance imaging, and detailed neuropsychological tests. [18F]-fluorodeoxyglucose PET was obtained in 3 svPPA patients, whereas the remaining 2 underwent amyloid PET using [18F]-flutemetamol. Tau distribution among the 3 groups was compared using regions of interest–based and voxel-based statistical analyses. Results: In svPPA patients, [18F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared with the normal controls group (left>right), and in the left inferior and temporal polar region compared with Alzheimer’s disease patients. [18F]-THK5351 retention inversely correlated with glucose metabolism, whereas regional THK retention correlated with clinical severity. [18F]-flutemetamol scans were negative for &bgr;-amyloid. Conclusions: These findings show that [18F]-THK5351 retention may be detected in cortical regions correlating with svPPA pathology.

Relation Between Left Atrial Enlargement and Stroke Subtypes in Acute Ischemic Stroke Patients

Objective Increased atrial size is frequently seen in ischemic stroke patients in clinical practice. There is controversy about whether left atrial enlargement (LAE) should be regarded as a risk factor for cerebral infarction. We investigated the association between indexed left atrial volume (LAVI) and conventional stroke risk factors as well as stroke subtypes in acute ischemic stroke patients. Methods One hundred eighty two acute cerebral infarction patients were included in this study. Brain magnetic resonance imaging and transthoracic echocardiography were done for all patients within 30 days of diagnosis of acute cerebral infarction. Echocardiographic LAE was identified when LAVI was more than 27 mL/m2. Stroke subtypes were classified by the Trial of Org 10171 in acute stroke treatment classification. Results There were significant differences between subjects with normal and increased LAVI in prevalence of stroke risk factors including atrial fibrillation (p = 0.001), hypertension (p = 0.000), valvular heart disease (p = 0.011) and previous stroke (p = 0.031). An increased LAVI was associated with cardioembolic subtype with an adjusted odds ratio was 6.749 (p = 0.002) compared with small vessel disease. Conclusion Increased LAVI was more prevalent in those who had cardiovascular risk factors, such as atrial fibrillation, hypertension, valvular heart disease and history of previous stroke. LAE influenced most patients in all subtypes of ischemic stroke but was most prevalent in the cardioembolic stroke subtype. Increased LAVI might be a risk factor of cerebral infarction, especially in patients with cardioembolic stroke subtype.