An Experimental Infarct Targeting the Internal Capsule: Histopathological and Ultrastructural Changes

BACKGROUND: Stroke involving the cerebral white matter (WM) has increased in prevalence, but most experimental studies have focused on ischemic injury of the gray matter. This study was performed to investigate the WM in a unique rat model of photothrombotic infarct targeting the posterior limb of internal capsule (PLIC), focusing on the identification of the most vulnerable structure in WM by ischemic injury, subsequent glial reaction to the injury, and the fundamental histopathologic feature causing different neurologic outcomes. METHODS: Light microscopy with immunohistochemical stains and electron microscopic examinations of the lesion were performed between 3 hours and 21 days post-ischemic injury. RESULTS: Initial pathological change develops in myelinated axon, concomitantly with reactive change of astrocytes. The first pathology to present is nodular loosening to separate the myelin sheath with axonal wrinkling. Subsequent pathologies include rupture of the myelin sheath with extrusion of axonal organelles, progressive necrosis, oligodendrocyte degeneration and death, and reactive gliosis. Increase of glial fibrillary acidic protein (GFAP) immunoreactivity is an early event in the ischemic lesion. WM pathologies result in motor dysfunction. Motor function recovery after the infarct was correlated to the extent of PLIC injury proper rather than the infarct volume. CONCLUSIONS: Pathologic changes indicate that the cerebral WM, independent of cortical neurons, is highly vulnerable to the effects of focal ischemia, among which myelin sheath is first damaged. Early increase of GFAP immunoreactivity indicates that astrocyte response initially begins with myelinated axonal injury, and supports the biologic role related to WM injury or plasticity. The reaction of astrocytes in the experimental model might be important for the study of pathogenesis and treatment of the WM stroke.

Reliability and Validity of the Korean Version of the Symptom Checklist-Post-Traumatic Stress Disorder Scale

The Symptom Checklist - Post-Traumatic Stress Disorder Scale (SCL-PTSD), also known as Crime-Related PTSD Scale has been validated in survivors of interpersonal trauma in the general population. However, the psychometric properties have not been investigated in a clinical setting for patients with PTSD from diverse traumatic events. This study investigates the reliability and validity of the Korean version of the SCL-PTSD among 104 psychiatric outpatients with PTSD, caused by interpersonal (n = 50) or non-interpersonal trauma (n = 54). Self-report data of the SCL-PTSD, Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), and Impact of Events Scale-Revised (IES-R) were gathered. The Korean version of the SCL-PTSD showed excellent internal consistency and moderate-to-good four-week temporal stability in both the interpersonal and non-interpersonal trauma groups. In comparison with other diagnostic groups, the scores of the SCL-PTSD were significantly higher compared to those of adjustment disorder, depression, other anxiety disorders, and schizophrenia, demonstrating its criteria-related validity. Convergent validity was confirmed because the scores of the SCL-PTSD were significantly correlated with BDI, SAI and TAI scores. Concurrent validity was demonstrated by significant correlation with the IES-R score. This study demonstrated the favorable psychometric prosperities of the Korean version of the SCL-PTSD, supporting its use in clinical research and practice.

Development of the Korean version of Postconcussional Syndrome Questionnaire / 정신신체의학

OBJECTIVES: The purpose of this study was to evaluate reliability and validity of the Korean version of the Postconcussional Syndrome Questionnaire(KPCSQ) which was originally developed in 1992 by Lees-Haley. METHODS: Patients with traumatic brain injury were recruited from April 2009 to December 2011 from the Korean University Ansan Hospital. We selected patients that met the ICD-10 diagnostic criteria of postconcussional syndrome and organic mental disorder including organic mood disorder, organic emotionally labile disorder, organic anxiety disorder and organic personality disorder. The KPCSQ, Trait and State Anxiety Inventory(STAI-I, II), and Center for Epidemiologic Studies Depression Scale(CESD) were administered to all subjects. Factor analysis of the items were performed and test-retest correlation were evaluated. Internal consistency of the KPCSQ and its subscales was assessed with Cronbach's alpha. External validity of the KPCSQ were examined by correlation coefficient with the STAI-I, II, and CESD. RESULTS: The Cronbach's alpha coefficient of the total PCSQ was 0.956. The test-retest reliability coefficient was 0.845. The PCSQ showed significant correlation with STAI-I, II and CESD. The factor analysis of the PCSQ yielded 4 factors model. Factor 1 represented 'affective and cognitive symptoms', factor 2 represented 'somatic symptoms', factor 3 represented 'infrequent symptoms' and factor 4 represented 'exaggeration or inattentive response'. There was no significant difference between the PCS group and the organic mental disorder group in the score on each measure. The scores on KPCSQ and its subscales in the subjects that had scored 5 or more in 'exaggeration or inattentive response' are significantly higher than those in the subjects had scored 4 in 'exaggeration or inattentive response'. CONCLUSIONS: This study suggests that the Korean version of PCSQ is a valid and reliable tool for assessing psychiatric symptomatology of patients with traumatic brain injury. Further investigations with greater numbers of subjects are necessary to assess the clinical usefulness of the KPCSQ.

Combination Therapies of Amiodarone and Digoxin for Refractory Supraventricular Tachycardia Accompanied by Congenital Heart Diseases in a Preterm Infant with Hydrops Fetalis

Fetal tachycardia is at risk for developing low cardiac output, non-immune hydrops fetalis and ultimately fetal death. Spontaneous resolution of supraventricular tachycardia (SVT) is common during the first year of age, but some infants need long-term antiarrhythmic therapy. In almost neonatal tachyarrhythmia including SVT, adenosine is the drug of the first choice. Digoxin is used to treat the SVT which is not controlled with adenosine. Class Ic and III antiarrhythmic drugs are additionally recommended for the disease unresponsive to digoxin. Intravenous amiodarone is highly effective and safe in an infant with refractory or life threatening tachycardia. Some cases have been reported that amiodarone combined with digoxin therapy is effective for treating tachycardia. We herein report a case of a preterm infant-born at 32 weeks of gestational age-with hydrops fetalis and life-threatening refractory SVT accompanied by multiple congenital heart diseases. SVT was initially not responsive to adenosine therapy, however, it was then successfully controlled with combination therapies of amiodarone and digoxin.

Korean Addiction Treatment Guidelines (III) : Psychosocial Treatment of Alcohol Use Disorder / 신경정신의학

OBJECTIVES: The aim of this study is to develop guidelines for psychosocial treatment of alcohol use disorder. METHODS: According to the ADAPTE manual, the Korean alcohol use disorder treatment guidelines were developed by the guideline development committee. Recommendations from foreign guidelines were evaluated regarding the applicability and acceptability to domestic circumstances. In addition, a survey from experts was conducted, along with a review of Korean literature. By these means, recommendations of psychosocial treatment for alcohol use disorder were established. RESULTS: The main findings of the survey were as follows : 1) Although Group therapy was not recommended by foreign clinical guidelines, it was considered as a first-line treatment by Korean experts. 2) Among many psychosocial treatment programs, cognitive behavior therapy (CBT), coping skills training, 12-step facilitation, and Group therapy were commonly used programs in Korea. Finally, the following treatment methods were selected for recommendations : Group therapy, motivational enhancement treatment, CBT, behavioral self-management, alcoholic anonymous, 12-step facilitation, psychodynamic psychotherapy, psychoeducational intervention, continuous case management, and community residential rehabilitation program. CONCLUSION: Just as in treatment of chronic diseases such as hypertension, continuity is important for management of alcohol use disorder. Therefore, not only pharmacological treatment but also psychosocial treatment should be provided comprehensively after treatment of acute withdrawal symptoms.

Korean Addiction Treatment Guidelines Series (I) : Development of Korean Guidelines for the Treatment of Alcohol Use Disorder / 신경정신의학

OBJECTIVES: The aim of this study is to develop Treatment Guidelines for Alcohol Use Disorder-the Korean Addiction Treatment Guidelines-using the Adaptation method. METHODS AND PROCEDURES: As the Adaptation method of Guidelines, the ADAPTE Manual, which is developed by ADAPTE collaboration is applied. In Part 1 : preparatory work prior to the beginning of Adaptation is performed. In Part 2 : the core phase of the Adaptation in which we searched the guidelines and performed a systematic review of the literature. The two guidelines (of the AU and the UK) are selected by gone through the methodological quality and currency evaluation for guidelines. And, in order to choose the proper recommendations, the contents were evaluated with regard to the applicability and acceptability of guidelines to the domestic. Finally, in Part 3 : the adapted guideline is reviewed externally, with review and plan update. Therefore, in this way, the Korean Guidelines for Treatment of Alcohol Use Disorder, comprised of 55 recommendations, was developed. CONCLUSION: In this study, Korean Guidelines for Treatment of Alcohol Use Disorder were developed by application of the Adaptation method of ADAPTE. These are the first evidence-based Korean Guidelines for Treatment of Alcohol Use Disorder, which were modified and accepted in accordance with Korean circumstances within the range not damaging the validity of the treatment worth, and it is expected to contribute to improvement in quality and efficiency enhancement of Korean treatment of Alcohol Use Disorder.

QTc Prolongation after Ventricular Septal Defect Repair in Infants

BACKGROUND AND OBJECTIVES: Prolonging of the corrected QT interval (QTc) has been reported after cardiac surgery in some studies. However, there have not been many studies on infant open cardiac surgery for ventricular septal defect (VSD) repair. This study was performed to define the changes in QTc and to find related post-surgery factors in this patient group. SUBJECTS AND METHODS: From 2008 to 2012, 154 infants underwent VSD repair at the Severance Cardiovascular Hospital. This study includes 105 of these cases. QTc was measured in these patients retrospectively. Demographic data and peri-procedural data, such as Aristotle score, cross-clamp time and bypass time, were analyzed. The exclusion criteria included multiple and small VSDs that underwent direct closure. RESULTS: Mean post-operative QTc was increased compared to the pre-operative measurements (from 413.6+/-2.3 to 444.9+/-2.5, p<0.001). In multiple linear regression, the comprehensive Aristotle score was associated with increasing QTc (p=0.047). The incidence of transient arrhythmia, such as atrial tachycardia, junctional ectopic tachycardia, premature atrial contraction, or premature ventricular contraction, was associated with QTc prolongation (p=0.005). Prolonged QTc was also associated with cross-clamp time (p=0.008) and low weight (p=0.042). Total length of stay at the intensive care unit and intubation time after surgery were not associated with QTc prolongation. CONCLUSION: Prolonged QTc could be seen after VSD repair in infants. This phenomenon was associated with peri-procedural factors such as the Aristotle score and cross-clamp time. Patients with QTc prolongation after cardiac surgery had an increased tendency towards arrhythmogenicity in the post-operative period.

DNA Methylation Profiles of MGMT, DAPK1, hMLH1, CDH1, SHP1, and HIC1 in B-Cell Lymphomas

BACKGROUND: This study was designed to examine the prevalence of aberrant promoter methylation in a selected panel of genes potentially involved in lymphoid tumors. METHODS: The promoter hypermethylation status of MGMT, DAPK1, hMLH1, CDH1, SHP1, and HIC1 was measured by methylation-specific PCR for 82 cases of B-cell lymphoma. Immunohistochemical staining using MGMT and SHP1 antibodies was conducted on 43 out of 82 cases. RESULTS: The number of MGMT aberrant methylations was lower in diffuse large B-cell lymphoma (DLBCL) than in other malignant lymphomas. The methylation of DAPK1 was frequently detected in follicular lymphoma (FL), marginal zone B-cell lymphoma (MZL) and DLBCL. With one exception, methylation of hMLH1 was not observed in B-cell lymphomas. The methylation frequency of CDH1, and HIC1 was similar in B-cell lymphomas. However, the methylation of SHP1 gene was more frequently observed in cases of FL, DLBCL, and MZL than in chronic lymphocytic lymphoma. MGMT and SHP1 promoter methylation were inversely correlated with the protein expression observed upon immunohistochemical staining. CONCLUSIONS: Aberrant promoter methylation of multiple genes occurs with variable frequency throughout the B-cell lymphomas, and methylation of hMLH1 is rarely observed in B-cell lymphomas.

Analysis of HPV-other Samples by Performing HPV DNA Sequencing

BACKGROUND: HPV-other samples are designated as being positive on HPV-PCR, but negative when using specific HPV hybridization probes. We wanted to determine the types on the HPV-other samples by performing sequencing, and to know the pathologic status of the uterine cervix according to the HPV type detected on sequencing. METHODS: For HPV genotying, we used the commercially available HPV DNA Chip test, which contains 15 types of high-risk HPV and 9 types of low-risk HPV. The HPV DNA sequencing was performed for the HPV-other samples of 209 patients who subsequently underwent cervical biopsy. RESULTS: For 204 of the 209 samples, the HPV types detected by sequencing were absent types at used HPV DNA chip. For the remaining 5 samples, sequencing was impossible due to mixed peaks. HPV-81 (19.6%), HPV-61 (18.6%), HPV-62 (16.7%) and HPV-84 (13.9%) were frequently detected. For the HPV-81, -62, -71, and -72 samples, most of the samples displayed normal or LSIL. However, HPV-84 and -61 were more associated with HSIL or worse, as compared to the other types. Conclusion: HPV-81, -61, -62 and -84 were frequently found on sequencing analysis of the HPV-other samples. The pathologic status was diverse, according to the HPV type detected on sequencing.

Cytologic Diagnosis of Malignant Pleural Effusion in Multiple Myeloma: Two Case Reports

Malignant pleural effusion in multiple myeloma (MM) is extremely rare and is associated with poor prognosis. We experienced two cases of MM IgA type with malignant pleural effusion. The diagnoses were based on characteristic cytology and CD138 immunocytochemistry. The patients received several cycles of combination chemotherapy, since symptoms were more aggressive with an uncontrolled pleural effusion. We review the clinical features of these cases and literature concerning myelomatous pleural effusion.

Effect of sildenafil citrate on interleukin-1beta-induced nitric oxide synthesis and iNOS expression in SW982 cells

The purpose of this study was to identify the effect of sildenafil citrate on IL-1 beta induced nitric oxide (NO) synthesis and iNOS expression in human synovial sarcoma SW982 cells. IL-1 beta stimulated the cells to generate NO in both dose- and time-dependent manners. The IL-1 beta -induced NO synthesis was inhibited by guanylate cyclase (GC) inhibitor, LY83583. When the cells were treated with 8-bromo-cGMP, a hydrolyzable analog of cGMP, NO synthesis was increased upto 5-fold without IL-1 beta treatment suggesting that cGMP is an essential component for increasing the NO synthesis. Synoviocytes and chondrocytes contain strong cGMP phosphodiesterase (PDE) activity, which has biochemical features of PDE5. When SW982 cells were pretreated with sildenafil citrate (Viagra), a PDE5 specific inhibitor, sildenafil citrate significantly inhibited IL-1 beta -induced NO synthesis and iNOS expressions. From this result, we noticed that PDE5 activity is required for IL-1 beta -induced NO synthesis and iNOS expressions in human synovial sarcoma cells, and sildenafil citrate may be able to suppress an inflammatory reaction of synovium through inhibition of NO synthesis and iNOS expression by cytokines.

An Immunohistochemical Study of Angiogenesis in Tumor Emboli

BACKGROUND: Angiogenesis, which is essential for tumor growth, is known to occur in the extravascular stroma. However, vascular structures were noted in intravascular tumor emboli in surgical specimens. This prompted our investigation of the frequency and morphology of angiogenesis in tumor emboli. METHODS: Hematoxylin-eosin stained specimens were reviewed for tumor emboli, in 21 cases of stomach adenocarcinoma and 22 cases of colon adenocarcinoma. The cases were examined with immunohistochemistry using antibodies against epithelial antigen (cytokeratin), endothelial antigens (CD31, CD34), lymphatic endothelial antigen (D2-40), and proliferation-associated antigen (MIB1). RESULTS: Endothelial cells were observed in 16 tumor emboli among four (19.1%) of the 21 cases of stomach adenocarcinoma and in 32 tumor emboli among four (18.2%) of the 22 cases of colon adenocarcinoma. The endothelial cells in the tumor emboli showed papillary ingrowth from the vessel wall, formation of vascular lumens, scattered distribution, or surface coating of the emboli. Some of the endothelial cells in the tumor emboli were D2-40-positive, and some were MIB1- positive. CONCLUSIONS: These findings demonstrated that angiogenesis occurs in intravascular tumor emboli as well as in the extravascular stroma. Angiogenesis in the tumor emboli may reflect an active process and may facilitate tumor growth.

Expression of VEGF, MMP-9 and Neovascularization in Relationship to the Clinical Behavior of Giant Cell Tumors of Bone

BACKGROUND: Giant cell tumors (GCT(s)) of bone are benign but can be locally aggressive neoplasms. Their clinical behavior has been difficult to predict on the basis of histology alone. This study investigated the neovascularization and expression of vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase-9 (MMP-9) in GCT(s) of bone; in addition we evaluated their relationship to clinical behavior. METHODS: We evaluated the microvessel number and density in 33 samples of giant cell tumor using CD34 immunohistochemistry. In addition, we examined the immunohistochemical expression of VEGF and MMP-9. RESULTS: The microvessel number alone, not the microvessel density, had statistical association with the clinical stage of GCT(s) (p=0.045). The proportion of cases with strong expression of VEGF increased with advancing clinical stage, however, these results were not statistically significant (p=0.257). The percentage of the cases with strong expression of MMP-9 also increased with advancing clinical stage and this was statistically significant (p=0.022). CONCLUSIONS: These results suggest that intratumor microvessel count and the expression of MMP-9 correlate with GCT stage. Evaluation of their expression may therefore provide prognostic information on the aggressive behavior of GCT(s) of bone.

Heat Production and Thermal Necrosis by Cortical Drilling / 대한정형외과연구학회지

PURPOSE: The present study was performed to determine the optimum conditions(RPM, load, sharpness of drill) for drilling human cortical bone with standard drill, and to evaluate the histological changes occuring in bone after drilling. MATERIALS AND METHODS: in experiment I, we measured temperature elevations and the durations of temperature elevation in cadaveric femoral cortices at specific distances from the drill hole wall while drilling. The effects of drilling force, speed and new versus worn drill on the termperature were determined. In experiment II, we also measured temperature elevations in the same manner in porcine femoral cortices and evaluated the histological changes occuring in bone after drilling. RESULTS: In experiment I, the most significant temperature elevation(68.4degrees C ) was found when worn drill was used. The lower drilling force and faster speed resulted in 55.1degrees C and 45.8degrees C temperature elevation, respectively. However, drill diameter was not a significant factor for temperature elevation. In experiment II, greater heat production was measured with worn drill, at lower drilling forces, at faster drill speed. The acute histologic reactions in bone were hyperemia, degeneration of osteocytes, change in bone stainability, tears, and fragmentation of the bone edges around the drill holes. The observed histological changes were proportional to the amount of trauma produced, that is, the greater the degree of thermal irritation, the greater the degree of histologic activity. CONCLUSION: In cortical drilling, greater heat production was measured with worn drill, at lower drilling forces, at faster drill speed and the greater the degree of thermal irritation, the greater the degree of histologic activity. A further study of the reaction of bone to drilling at longer intervals of time at different conditions may possibly show whether aseptic thermal necrosis could be prevented.