Decrease of 14–3-3 proteins by glutamate exposure in the cerebral cortex of newborn rats / 한국실험동물학회지

Glutamate is a representative excitatory neurotransmitter. However, excessive glutamate exposure causes neuronal cell damage by generating neuronal excitotoxicity. Excitotoxicity in neonates caused by glutamate treatment induces neurological deficits in adults. The 14–3-3 family proteins are conserved proteins that are expressed ubiquitously in a variety of tissues. These proteins contribute to cellular processes, including signal transduction, protein synthesis, and cell cycle control. We proposed that glutamate induces neuronal cell damage by regulating 14–3-3 protein expression in newborn animals. In this study, we investigated the histopathological changes and 14–3-3 proteins expressions as a result of glutamate exposure in the neonatal cerebral cortex. Rat pups at post-natal day 7 were intraperitoneally administrated with vehicle or glutamate (10 mg/kg). Animals were sacrificed 4 h after treatment, and brain tissues were fixed for histological study. Cerebral cortices were isolated and frozen for proteomic study. We observed serious histopathological damages including shrunken dendrites and atypical neurons in glutamate-treated cerebral cortices. In addition, we identified that 14–3-3 family proteins decreased in glutamate-exposed cerebral cortices using a proteomic approach. Moreover, Western blot analysis provided results that glutamate treatment in neonates decreased 14–3-3 family proteins expressions, including the β/α, ζ/δ, γ, ε, τ, and η isoforms. 14–3-3 proteins are involved in signal transduction, metabolism, and anti-apoptotic functions. Thus, our findings suggest that glutamate induces neonatal neuronal cell damage by modulating 14–3-3 protein expression.

Cognitive Function and Neuropsychological Comorbidities in Children with Newly Diagnosed Idiopathic Epilepsy

BACKGROUND: In this study, we aimed to identify cognitive function and neuropsychological comorbidities in children with newly diagnosed idiopathic epilepsy. METHODS: We retrospectively reviewed the records of 97 antiepileptic drug-naïve children (9.7 ± 2.9 years; 54 males and 43 females) with newly diagnosed idiopathic epilepsy, all of whom underwent a neuropsychological battery. The battery consisted of the Korean Wechsler Intelligence Scale, Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale, ADHD Diagnostic System, Children's Depression Inventory, and State-Trait Anxiety Inventory for Children. We investigated association between scores of the neuropsychological battery and epilepsy classification, lateralization of interictal epileptiform discharges (IEDs) on electroencephalography (EEG), and variables related to seizures. RESULTS: Thirteen patients (14.3%) had ADHD symptoms. Three patients (4.1%) had depressive symptoms, and 9 (12.3%) had anxiety symptoms. Patients with idiopathic generalized epilepsy (IGE) had significantly lower full-scale intelligence and performance intelligence quotient scores than patients with idiopathic localization-related epilepsy (ILRE) (89.0 ± 17.6 vs. 96.3 ± 14.8; P = 0.030 and 88.9 ± 16.3 vs. 97.0 ± 16.4; P = 0.016, respectively). Patients with ILRE having unilateral IEDs had significantly higher full-scale intelligence quotient scores than patients with ILRE having bilateral IEDs and patients with IGE (99.9 ± 12.2 vs. 93.7 ± 16.1 vs. 89.0 ± 17.6; P = 0.039, respectively). CONCLUSION: Our results suggest that idiopathic epilepsy may be accompanied by various neuropsychological comorbidities even at initial diagnosis. Patients with IGE and ILRE having bilateral IEDs on EEG appear more likely to be at high risk of decreased cognitive function.

A Case of Spontaneous Internal Carotid Artery Dissection Presenting as a Seizure without Focal Neurologic Signs / 대한소아신경학회지

Craniocervical artery dissection is an uncommon cause of acute ischemic stroke in children, although it is an important cause of stroke in young and middle-aged patients. Among craniocervical artery dissection, internal carotid artery (ICA) dissection usually presents with focal neurologic deficits, such as acute hemiparesis. However, if it presents with only non-localizing signs, such as headache and seizure, ICA dissection may be overlooked in a differential diagnosis. Here we describe an 8-year-old boy who had spontaneous internal carotid artery dissection presenting as a seizure without focal neurologic signs. The patient was admitted to the emergency department because of seizure. On arrival at the emergency department, focal neurologic signs, such as motor weakness, were not observed. The patient had no recent trauma history. Magnetic resonance imaging revealed diffusion-restriction in the left basal ganglia. Magnetic resonance angiography, computed tomography angiography, and cerebral angiography demonstrated occlusion of the left distal ICA with tapered stenosis (so-called “string sign”). The patient was treated with aspirin and oxcarbazepine to prevent thrombosis and further seizures. Three-month follow-up MRA revealed apparent improvement of the occlusion of the left distal internal carotid artery. The patient had no neurologic deficits or further seizures in the outpatient clinic 13 months after discharge. This case demonstrated that acute ischemic stroke resulting from ICA dissection can occur with seizures without focal neurologic signs. In addition, ICA dissection should be considered as a possible cause of acute ischemic stroke even in children with no history of trauma.

A Case of Spontaneous Internal Carotid Artery Dissection Presenting as a Seizure without Focal Neurologic Signs / 대한소아신경학회지

Craniocervical artery dissection is an uncommon cause of acute ischemic stroke in children, although it is an important cause of stroke in young and middle-aged patients. Among craniocervical artery dissection, internal carotid artery (ICA) dissection usually presents with focal neurologic deficits, such as acute hemiparesis. However, if it presents with only non-localizing signs, such as headache and seizure, ICA dissection may be overlooked in a differential diagnosis. Here we describe an 8-year-old boy who had spontaneous internal carotid artery dissection presenting as a seizure without focal neurologic signs. The patient was admitted to the emergency department because of seizure. On arrival at the emergency department, focal neurologic signs, such as motor weakness, were not observed. The patient had no recent trauma history. Magnetic resonance imaging revealed diffusion-restriction in the left basal ganglia. Magnetic resonance angiography, computed tomography angiography, and cerebral angiography demonstrated occlusion of the left distal ICA with tapered stenosis (so-called “string sign”). The patient was treated with aspirin and oxcarbazepine to prevent thrombosis and further seizures. Three-month follow-up MRA revealed apparent improvement of the occlusion of the left distal internal carotid artery. The patient had no neurologic deficits or further seizures in the outpatient clinic 13 months after discharge. This case demonstrated that acute ischemic stroke resulting from ICA dissection can occur with seizures without focal neurologic signs. In addition, ICA dissection should be considered as a possible cause of acute ischemic stroke even in children with no history of trauma.

Increased Expression of Thymosin β₄ Is Independently Correlated with Hypoxia Inducible Factor-1α (HIF-1α) and Worse Clinical Outcome in Human Colorectal Cancer

BACKGROUND: Thymosin β₄ is a multi-functional hormone-like polypeptide, being involved in cell migration, angiogenesis, and tumor metastasis. This study was undertaken to clarify the clinicopathologic implications of thymosin β₄ expression in human colorectal cancers (CRCs). METHODS: We investigated tissue sections from 143 patients with CRC by immunohistochemistry. In addition, we evaluated the expression patterns and the clinico-pathological significance of thymosin β₄ expression in association with hypoxia inducible factor-1α (HIF-1α) expression in the CRC series. RESULTS: High expression of thymosin β₄ was significantly correlated with lymphovascular invasion, invasion depth, regional lymph node metastasis, distant metastasis, and TNM stage. Patients with high expression of thymosin β₄ showed poor recurrence-free survival (p = .001) and poor overall survival (p = .005) on multivariate analysis. We also found that thymosin β4 and HIF-1α were overexpressed and that thymosin β₄ expression increased in parallel with HIF-1α expression in CRC. CONCLUSIONS: A high expression level of thymosin β₄ indicates poor clinical outcomes and may be a useful prognostic factor in CRC. Thymosin β₄ is functionally related with HIF-1α and may be a potentially valuable biomarker and possible therapeutic target for CRC.

A Case of Giant Colonic Muco-submucosal Elongated Polyps Associated with Intussusception

Colonic muco-submucosal elongated polyp (CMSEP), a newly categorized non-neoplastic colorectal polyp, is a pedunculated and elongated polyp composed of normal mucosal and submucosal layers without any proper muscle layer. We herein report a giant variant of CMSEP associated with intussusception in the rectosigmoid colon, with a review of the literature. A 48-year-old woman underwent a laparoscopic low anterior resection due to multiple large submucosal polypoid masses associated with intussusception. Grossly, the colonic masses were multiple pedunculated polyps with a long stalk and branches ranging in size from a few millimeters to 14.0 cm in length. Microscopically, there was no evidence of hyperplasia, atypia, or active inflammation in the mucosa. The submucosal layers were composed of edematous and fibrotic stroma with fat tissue, dilated vessels, and lymphoid follicles.

Late-onset trichloroethylene-induced hypersensitivity syndrome after intermittent exposure to low-dose trichloroethylene

Occupational exposure to trichloroethylene (TCE) can occasionally induce severe cutaneous disorders, including hypersensitivity syndrome and Stevens-Johnson syndrome. The clinical manifestation of TCE hypersensitivity syndrome is quite similar to that of drug-induced hypersensitivity syndrome and includes skin lesions, hepatitis, fever, and lymphadenopathy. Almost all cases of TCE hypersensitivity syndrome developed within 2–8 weeks after the first exposure to TCE in an occupational setting. This typical course and clinical feature of hypersensitivity syndrome together with occupational history of TCE contact may lead to prompt diagnosis and treatment of this potentially fatal disease. This report describes a 32-year-old man who has been intermittently engaged in cleaning work using TCE for about 3 years, and then developed TCE hypersensitivity syndrome. To the best of our knowledge, this is the first case of TCE hypersensitivity syndrome with a long duration of symptom onset due to intermittent exposure to TCE. Thus, physicians should take thorough occupational history when seeing a patient with hypersensitivity syndrome has neither history of drug intake nor regular exposure to TCE.

Difference of the Nuclear Green Light Intensity between Papillary Carcinoma Cells Showing Clear Nuclei and Non-neoplastic Follicular Epithelia in Papillary Thyroid Carcinoma

BACKGROUND: There is subjective disagreement regarding nuclear clearing in papillary thyroid carcinoma. In this study, using digital instruments, we were able to quantify many ambiguous pathologic features and use numeric data to express our findings. METHODS: We examined 30 papillary thyroid carcinomas. For each case, we selected representative cancer cells showing clear nuclei and surrounding non-neoplastic follicular epithelial cells and evaluated objective values of green light intensity (GLI) for quantitative analysis of nuclear clearing in papillary thyroid carcinoma. RESULTS: From 16,274 GLI values from 600 cancer cell nuclei and 13,752 GLI values from 596 non-neoplastic follicular epithelial nuclei, we found a high correlation of 94.9% between GLI and clear nuclei. GLI between the cancer group showing clear nuclei and non-neoplastic follicular epithelia was statistically significant. The overall average level of GLI in the cancer group was over two times higher than the non-neoplastic group despite a wide range of GLI. On a polygonal line graph, there was a fluctuating unique difference between both the cancer and non-neoplastic groups in each patient, which was comparable to the microscopic findings. CONCLUSIONS: Nuclear GLI could be a useful factor for discriminating between carcinoma cells showing clear nuclei and non-neoplastic follicular epithelia in papillary thyroid carcinoma.

Clinical Study of the Intranasal Hemangioma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Hemangioma of the nasal cavity is an uncommon benign vascular tumor. This study aimed to analyze the clinical manifestations, radiologic findings, treatment modalities, and outcomes of intranasal hemangiomas. SUBJECTS AND METHOD: Retrospective reviews of the medical record were performed on 13 patients, who were treated for intranasal hemangioma from 2005 to 2014. RESULTS: Of the 13 patients identified, there were seven males and six females ranging from 11 to 80 years of age (mean age of 48.1+/-21.5). Epistaxis was the most common presenting symptom. Most common site of origin was the inferior turbinate. CT scans showed variable enhancement of the nasal mass without bony erosion. Preoperative diagnosis accuracy rate was 76.9%. The tumor was histopathologically classified as follows: capillary hemangioma (n=6, 46.1%), cavernous hemangioma (n=3, 23.1%), venous hemangioma (n=2, 15.4%), and mixed hemangioma (n=2, 15.4%). Endoscopic excisional surgery (n=11, 94.6%) and local excision (n=2, 15.4%) were performed for complete removal of the hemangioma. Preoperative selective embolization was performed on one patient. No evidence of recurrence after the surgery was observed. CONCLUSION: Intranasal hemangioma was usually found to occur in the inferior turbinate and the most common symptom was epistaxis. Capillary hemangioma was the most common type. Complete excision was recommended to prevent recurrence.

Primary Extrauterine Endometrial Stromal Sarcoma in the Sigmoid Colon

An endometrial stromal sarcoma (ESS) is an uncommon uterine neoplasm, and its primary occurrence in the intestine as an extrauterine ESS (EESS) is exceedingly rare. We hereby report a primary EESS arising in the sigmoid colon with a review of the literature. A 52-year-old woman presented with bloody stool and underwent a colon fiberscopy, which revealed a fungating mass obstructing the lumen at the distal sigmoid. A laparoscopic low anterior resection was performed, and an umbilicated polypoid mass was identified; on section, it had infiltrated the mesocolic fat and measured 3.8 cm x 2.5 cm. The tumor showed geographic sheets or nests composed of relatively monotonous stromal cells, expansion or infiltration to the proper muscle and mesocolic fat, and extensive lymphovascular invasion and metastasis to regional lymph nodes and the pelvic peritoneum. The tumor cells were strongly and diffusely immunoreactive for CD10, but negative for c-kit, CD34, and Dog1. Two months later, a hysterectomy with a bilateral salpingo-oophorectomy was performed, and no evidence of an ESS was found in the uterus.

Strongyloides Hyperinfection in an Elderly Patient Treated for Stomach Cancer

Strongyloides stercoralis is an intestinal nematode with a complex life cycle, including a free living cycle, a parasitic cycle, and an auto-infection cycle. S. stercolaris infection may occur in both immunocompetent and immunocompromised individuals. It is usually asymptomatic and undetectable for decades in a healthy host. In immunocompromised patient, however, it may cause life threatening hyperinfection involving multiple organs. In Korea, several cases of Strongyloides hyperinfection have been reported since 1959. However, reports with gastric involvement and peritoneal invasion are rare. This is a report of gastric strongyloidiasis hyperinfection identified at ascites in an elderly patient who had subtotal gastrectomy due to stomach cancer.

Effect of Dialysate Sodium Concentration on Sodium Gradient and Hemodialysis Parameters

This retrospective study was performed to determine the ranges of the sodium gradient (SG) between the dialysate sodium concentration (DNa) and serum sodium concentration (SNa) in hemodialysis (HD) patients and to examine the relationships between HD parameters over a 1 year period. Fifty-five clinically stable HD patients, who had been on HD >2 years were enrolled. Monthly HD [ultrafiltration (UF) amount, systolic blood pressure (SBP), frequency of intradialytic hypotension (IDH)] and laboratory data were collected and 12-month means were subjected to analysis. The SG was calculated by subtracting SNa from prescribed DNa. Mean SG values were 1.5+/-3.3 (range -5.6~9.1). SG was positively related to DNa and the frequency of IDH. A higher SG was associated with larger UF amounts and SBP reduction during HD. The percentages of patients with a SG > or =3mEq/L increased as DNa increased. On the other hand, SG was not found to be associated with SNa or pre-HD SBP. DNa appears to cause a significant increase in SG, and this seems to be related to HD parameters, such as, UF amount and IDH.

Expression of HuR and Cyclooxygenase-2 in Nodular Fasciitis and Low-Grade Sarcoma: An Immunohistochemical Study

BACKGROUND: Nodular fasciitis is the most common reactive mesenchymal lesion to be misidentified as a type of sarcoma. HuR is an mRNA-binding protein that can stabilize cyclooxygenase-2 (COX-2) mRNA leading to COX-2 overexpression. The aim of this study is a comparison of the expressions of COX-2 and HuR and the relationships between their expressions and the clinicopathological parameters in nodular fasciitis and low-grade sarcoma. METHODS: We measured the expression of HuR and COX-2 in 21 cases of nodular fasciitis and 37 cases of low-grade sarcoma using immunohistochemistry. RESULTS: The frequency of cytoplasmic immunoreactivity for HuR was 5 of 21 cases of nodular fasciitis (23.8%) and 23 of 37 cases of low-grade sarcoma (62.1%) (p=.013). COX-2 expression was moderate or strong in nodular fasciitis (12/21, 57.1%) and in low-grade sarcoma (29/37, 78.4%) (p=.034). In addition, a significant difference existed between these two entities in terms of the relationship between moderate or strong COX-2 expression and HuR cytoplasmic immunoreactivity (p=.009). Moderate or strong COX-2 immunoreactivity correlated with nuclear (p=.016) or cytoplasmic HuR (p=.024) expression in low-grade sarcoma but not in nodular fasciitis. CONCLUSIONS: This study suggests that HuR and COX-2 expression may be useful to differentiate nodular fasciitis from low-grade sarcoma.

Clinical Characteristics of Korean Rheumatoid Arthritis Patients with Indications for TNF-alpha Blocker

OBJECTIVE: The aim of this study was to examine clinical characteristics of Korean rheumatoid arthritis (RA) patients with clinically indications for TNF-alpha blocker, and to compare their clinical parameters with the Korean National Health Insurance reimbursement criteria. METHODS: Data were obtained from a registry of RA patients who visited rheumatology clinics of Hallym University affiliated hospitals. Among patients who were previously prescribed DMARDs for more than three months, rheumatologists selected patients clinically indicated for TNF-alpha blocker. The clinical characteristics at the time TNF-alpha blocker use was deemed indicated were examined. Radiographic damage was quantified by Modified Sharp van der Heijde score in hand and foot simple AP radiograph. RESULTS: From August 2010 to January 2013, five rheumatologists in four hospitals selected 109 patients clinically indicated for TNF-alpha blocker. When TNF-alpha blocker was considered, mean DAS28 was 5.2 (range 2.1~8.05), mean swollen joint count was 6 (range 0~22), mean tender joint count was 10.6 (range 0~28), mean ESR was 43.2 mm/hr (range 1~140) and mean CRP was 2.5 mg/dL (range 0.1~18.3). The mean total modified Sharp van der Heijde score was 32.72 (range 0~240). Eighty one percent of subjects did not have enough active joints to satisfy the Korean National Health Insurance reimbursement standard. CONCLUSION: Our results show that patients with clinically indications for TNF-alpha blocker had a broad range of disease activity and clinical parameters, and the majority did not meet the Korean National Health Insurance reimbursement criteria.

Spectral entropy for assessing the depth of propofol sedation / 대한마취과학회지

BACKGROUND: For patients in the intensive care unit (ICU) or under monitored anesthetic care (MAC), the precise monitoring of sedation depth facilitates the optimization of dosage and prevents adverse complications from underor over-sedation. For this purpose, conventional subjective sedation scales, such as the Observer's Assessment of Alertness/Sedation (OAA/S) or the Ramsay scale, have been widely utilized. Current procedures frequently disturb the patient's comfort and compromise the already well-established sedation. Therefore, reliable objective sedation scales that do not cause disturbances would be beneficial. We aimed to determine whether spectral entropy can be used as a sedation monitor as well as determine its ability to discriminate all levels of propofol-induced sedation during gradual increments of propofol dosage. METHODS: In 25 healthy volunteers undergoing general anesthesia, the values of response entropy (RE) and state entropy (SE) corresponding to each OAA/S (5 to 1) were determined. The scores were then analyzed during each 0.5 mcg/ml- incremental increase of a propofol dose. RESULTS: We observed a reduction of both RE and SE values that correlated with the OAA/S (correlation coefficient of 0.819 in RE-OAA/S and 0.753 in SE-OAA/S). The RE and SE values corresponding to awake (OAA/S score 5), light sedation (OAA/S 3-4) and deep sedation (OAA/S 1-2) displayed differences (P < 0.05). CONCLUSIONS: The results indicate that spectral entropy can be utilized as a reliable objective monitor to determine the depth of propofol-induced sedation.

Ocular Neuromyotonia in a Patient with Orbital Metastasis

No abstract available.

A case of back pain caused by Salmonella spondylitis: A case report / 대한마취과학회지

Salmonella spondylitis is a rare illness, and it generally occurs in patients who have already had sickle cell anemia, and it is even rarer in patients who are without sickle cell anemia. A 61-year-old male patient was hospitalized for the evaluation of his renal function and then treatment was started for his back pain. His back pain had developed about 2 months previously without any specific trauma. Only a bulging disc was detected on the initial lumbar MRI. Regarding his fever, it was diagnosed as possible atypical pneumonia, scrub typhus, etc., and multiple antibiotic therapy was administered. At the time of transfer, the leucocytes and hs-CRP were normal and the ESR was elevated. A diagnostic epidural block was performed for his back pain, but his symptoms were not improved. Lumbar MRI was performed again and it showed findings of infective spondylitis. Salmonella D was identified on the abscess culture and so he was diagnosed as suffering from Salmonella spondylitis. After antibiotic treatment, his back pain was improved and the patient was able to walk.

Concurrent Chemoradiation in a Patient with Unresectable Cholangiocarcinoma

Cholangiocarcinoma is a catastrophic tumor with a high mortality rate, for which surgery is the most reliable treatment. However, these tumors progress insidiously and are difficult to diagnose early. Most patients lack the opportunity to receive surgery due to the advanced disease stage at the time of the diagnosis, at which point only few alternative treatments are available. There is a need for more effective therapy to improve the survival or quality of life of these patients. The present case was a 73-year-old male who presented with jaundice and fatigue underwent CT imaging, in which a 3.5x4.0-cm low-attenuation mass was found in hepatic segment 4. Cholangiocarcinoma was diagnosed by cytological examination of the bile juice. A combination of CyberKnife radiosurgery and S-1 oral chemotherapy was performed. The patient was alive at a 8-month follow-up, and serial CT scans revealed a markedly regressed tumor. Therefore, we suggest that concurrent chemoradiation with the CyberKnife and S-1 is a treatment option for advanced cholangiocarcinoma.

The Neurological Safety of Epidural Pamidronate in Rats

BACKGROUND: Pamidronate is a potent inhibitor of osteoclast-mediated bone resorption. Recently, the drug has been known to relieve bone pain. We hypothesized that direct epidural administration of pamidronate could have various advantages over oral administration with respect to dosage, side effects, and efficacy. Therefore, we evaluated the neuronal safety of epidurally-administered pamidronate. METHODS: Twenty-seven rats weighing 250-350 g were equally divided into 3 groups. Each group received an epidural administration with either 0.3 ml (3.75 mg) of pamidronate (group P), 0.3 ml of 40% alcohol (group A), or 0.3 ml of normal saline (group N). A Pinch-toe test, motor function evaluation, and histopathologic examination of the spinal cord to detect conditions such as chromatolysis, meningeal inflammation, and neuritis, were performed on the 2nd, 7th, and 21st day following administration of each drug. RESULTS: All rats in group A showed an abnormal response to the pinch-toe test and decreased motor function during the entire evaluation period. Abnormal histopathologic findings, including neuritis and meningeal inflammation were observed only in group A rats. Rats in group P, with the exception of 1, and group N showed no significant sensory/motor dysfunction over a 3-week observation period. No histopathologic changes were observed in groups P and N. CONCLUSIONS: Direct epidural injection of pamidronate (about 12.5 mg/kg) showed no neurotoxic evidence in terms of sensory/motor function evaluation and histopathologic examination.

Diffusion Tensor Imaging Findings in Two Cases of Internal Capsular Genu Infarction

Internal capsular genu infarcts infrequently cause cognitive impairment and behavioral changes, and little is known about the underlying mechanism. Using diffusion-tensor imaging (DTI) and the fractional anisotropy (FA) index in the region of interest (ROI) and ipsilesional frontal cortex, we evaluated two patients with internal capsular genu infarction who presented with frontal dysfunction and cognitive impairment. The reported findings help to elucidate the mechanism underlying cognitive deterioration in internal capsular genu infarction.