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N-Methyl-1-(naphthalen-2-yl)propan-2-amine (methamnetamine, PAL-1046) is an amphetamine-based new psychoactive substance (NPS). Methamnetamine has been reported to cause excessive release of serotonin, and it is classified as an empathogen or entactogen. It is not regulated as a controlled substance in most countries, and there are no studies on its metabolism. In this study, in vitro phase I metabolism of methamnetamine in human liver microsomes (HLM) and flavin-containing monooxygenase (FMO) was investigated by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS). Eight metabolites of methamnetamine were identified and were structurally characterized achieved by a combination of accurate mass analysis and tandem mass spectrometry. The identified metabolic processes include N-demethylation, N-hydroxylation, aromatic hydroxylation, and a combination of these processes. N-Hydroxylated metabolites were confirmed based on expressed FMOs. The major metabolite was formed from methamnetamine via hydroxylation of the naphthalene ring after the in vitro phase I process. These results could help detect methamnetamine ingestion by NPS abusers.

In this study, we investigated the amino acid variations and mRNA expression of PhoPQ and PmrAB two-component regulatory systems in colistin-resistant Enterobacter cloacae isolates from Korea. We determined the nucleotide sequences of phoP, phoQ, pmrA, and pmrB in 51 colistin-resistant, 5 colistin-susceptible, and 8 skip-well isolates and consequently, the corresponding amino acid sequences as well. PhoPQ and PmrAB sequences showed large variations among the isolates (14, 67, 20, and 68 sites, respectively). Although there was some discrepancy between the genes, the colistin-resistant E. cloacae isolates were grouped into four clades and the susceptible isolates were grouped into two clades. We did not find any distinct amino acid substitutions associated with colistin resistance. Furthermore, mRNA expression of phoQ and pmrB was not significantly higher in the colistin-resistant isolates. Our data suggests that the colistin resistance mechanisms might be different in E. cloacae when compared to other gram-negative bacteria.

Purpose: It has been reported that cancer stem cells (CSCs) can be isolated from primitive neuroectodermal tumor (PNET) specimens. Moreover, mesenchymal stem-like cells (MSLCs) have been isolated from Korean glioma specimens. Here, we tested whether tumor spheres and MSLCs can be simultaneously isolated from a single PNET specimen, a question that has not been addressed., Methods: We isolated single-cell suspensions from PNET specimens, then cultured these cells using methods for MSLCs or CSCs. Cultured cells were analyzed for surface markers of CSCs using immunocytochemistry and for surface markers of bone marrow-derived mesenchymal stem cells (BM-MSCs) using fluorescence-activated cell sorting (FACS). Tumor spheres were exposed to neural differentiation conditions, and MSLCs were exposed to mesenchymal differentiation conditions. Possible locations of MSLCs within PNET specimens were determined by immunofluorescence analysis of tumor sections., Results: Cells similar to tumor spheres and MSLCs were independently isolated from one of two PNET specimens. Spheroid cells, termed PNET spheres, were positive for CD133 and nestin, and negative for musashi and podoplanin. PNET spheres were capable of differentiation into immature neural cells and astrocytes, but not oligodendrocytes or mature neural cells. FACS analysis revealed that adherent cells isolated from the same PNET specimen, termed PNET-MSLCs, had surface markers similar to BM-MSCs. These cells were capable of mesenchymal differentiation. Immunofluorescence labeling indicated that some CD105(+) cells might be closely related to endothelial cells and pericytes., Conclusion: We showed that both tumor spheres and MSLCs can be isolated from the same PNET specimen. PNET-MSLCs occupied a niche in the vicinity of the vasculature and could be a source of stroma for PNETs.

Purpose: It was presented that mesenchymal stem cells (MSCs) can be isolated from western glioma specimens. However, whether MSCs exist in glioma specimens of different ethnicities is unknown. To verify the existence of MSCs in an independent cohort, we undertook studies to isolate MSCs from a group of Korean patients. We hypothesized that cells resembling MSCs that were deemed mesenchymal stemlike cells (MSLCs) exist in an independent cohort of Korean gliomas., Methods: We cultured fresh glioma specimens using the protocols used for culturing MSCs. The cultured cells were analyzed with fluorescence-activated cell sorting (FACS) for surface markers associated with MSCs. Cultured cells were exposed to mesenchymal differentiation conditions. To presume possible locations of MSLCs in the glioma, sections of glioma were analyzed by immunofluorescent labeling for CD105, CD31, and NG2., Results: From nine of 31 glioma specimens, we isolated cells resembling MSCs, which were deemed Korean glioma stroma MSLCs (KGS-MSLCs). KGS-MSLCs were spindle shaped and adherent to plastic. KGS-MSLCs had similar surface markers to MSCs (CD105(+), CD90(+), CD73(+), and CD45(-)). KGS-MSLCs were capable of mesenchymal differentiation and might be located around endothelial cells, pericytes, and in a disorganized perivascular area inside glioma stroma., Conclusions: We found that cells resembling MSCs indeed exist in an independent cohort of glioma patients, as presented in western populations. We could presume that the possible location of KGS-MSLCs was in perivascular area or in glioma stroma that was a disorganized vascular niche. It might be possible that KGS-MSLCs could be one of constituent of stroma of glioma microenvironment.

Recent studies have indicated the usefulness of endoscopic endonasal transsphenoidal approach (EETSA). A few studies have reported on the postoperative nasal symptoms of patients who have undergone EETSA. Therefore, we adopted a rhinologic perspective to compare preoperative and postoperative nasal symptoms after performing a binostril, four-hand EETSA. Patients who were scheduled to undergo binostril, four-hand EETSA underwent preoperative nasal evaluation using the Nasal Obstruction Symptom Evaluation (NOSE), Sino-Nasal Outcome Test-20 (SNOT-20), and a visual analogue scale (VAS) to assess several nasal symptoms. Repeat testing was performed 6 months postoperatively. Paired Student's t tests were used to compare preoperative and postoperative scores. A total of 142 patients who underwent a binostril, four-hand EETSA were included in this study. We found no statistically significant differences between preoperative and postoperative NOSE, total SNOT-20 scores, or scores on the VAS for nasal obstruction, sneezing, rhinorrhea, snoring, or facial pain. However, VAS of olfactory change increased significantly after EETSA (p < 0.05). The binostril, four-hand EETSA would be a useful method because it permits operative manipulability and a wide visual field for skull base lesions. However, rhinologists must consider postoperative nasal symptoms and perform a proper preoperative examination, especially with regard to the olfactory function, and inform patients scheduled for EETSA of potential postoperative changes.

Purpose: The existence of cancer stem cells (CSCs) in glioblastoma has been proposed. However, the unknown knowledge that is yet to be revealed is the presence of glioma CSCs (gCSCs) in correlation to each WHO grades of glioma. We approached this study with a hypothesis that specimens from high-grade gliomas would have higher isolation rate of gCSCs in comparison to those of lower-grade gliomas., Methods: The glioma specimens were obtained from patients and underwent gliomasphere assay. The gliomaspheres were chosen to be analyzed with immunocytochemisty for surface markers. Then the selected gliomaspheres were exposed to neural differentiation conditions. Lastly, we made mouse orthotopic glioma models to examine the capacity of gliomagenesis., Results: The gliomaspheres were formed in WHO grade IV (13 of 21) and III (two of nine) gliomas. Among them, WHO grade IV (11 of 13) and III (two of two) gliomaspheres showed similar surface markers to gCSCs and were capable of neural differentiation. Lastly, among the chosen cells, 10 of 11 WHO grade IV and two of two WHO grade III gliomaspheres were capable of gliomagenesis. Thus, overall, the rates of existence of gCSCs were more prominent in high-grade gliomas: 47.6% (10 of 21) in WHO grade IV gliomas and 22.2% (two of nine) in WHO grade III gliomas, whereas WHO grade II and I gliomas showed virtually no gCSCs., Conclusions: This trend of stage-by-stage increase of gCSCs in gliomas showed statistical significance by chi-square test linear-by-linear association. We prove that the rates of existence of gCSCs increase proportionally as the WHO grades of gliomas rise.

Purpose: Currently, the interaction between the niche and glioma cancer stem cells (gCSCs) is gaining attention. However, there are few studies concerned with the effects of repeated exposure to a new microenvironment on gCSCs characteristics. In this study, serial in vivo subtransplantation was performed to create a new microenvironment. We evaluated and compared the biological characteristics of gCSCs after serial in vivo subtransplantation., Methods: We cultured gCSCs from human glioma specimens according to cultured gliomasphere methods. The isolated gCSCs were termed zero-generation gCSCs (G0-gCSCs). By subsequent serial subtransplantation, we obtained first-generation gCSCs (G1-gCSCs) and second-generation gCSCs (G2-gCSCs). We evaluated and compared the biological characteristics of G0-gCSCs, G1-gCSCs, and G2-gCSCs. The in vitro characteristics included the morphology, surface marker profiles, and neural differentiation capacity and the in vivo characteristics was the survival of mice xenografts. Additionally, brain sections were analyzed using PCNA, TUNEL, and CD31 staining., Results: We observed no significant differences in the in vitro characteristics of G0-gCSCs, G1-gCSCs, and G2-gCSCs. However, the survival time of mice glioma xenografts was significantly decreased upon serial subtransplantation. In addition, immunohistochemical analyses showed that the number of TUNEL(+) cells was significantly decreased while the number of CD31(+) cells was significantly increased with serial in vivo subtransplantation., Conclusions: There were significant in vivo biological changes in gCSCs upon serial in vivo subtransplantation, which were shorter xenograft survival, increased angiogenesis, and decreased apoptosis. This study suggests that the repeated exposure to new microenvironments may affect the biological changes in gCSCs in vivo.

Purpose: High-grade gliomas are closely related to the mesenchymal phenotype which might be explained by unorthodox differentiation of glioma cancer stem cells (gCSCs). We reasoned that other non-neural stem cells, especially mesenchymal stem cells (MSCs), might play a role in expressing mesenchymal phenotype of high-grade gliomas. Thus we hypothesized that cells resembling MSCs exist in glioma specimens., Methods: We created a mouse (m) orthotopic glioma model using human gCSCs. Single-cell suspensions were isolated from glioma specimens and cultured according to the methods for mMSCs or gliomaspheres. These cells were analyzed by fluorescence-activated cell sorting (FACS) for surface markers associated with mMSCs or gCSCs. Glioma stroma (GS)-MSCs were exposed to mesenchymal differentiation conditions. To decide the location of GS-MSCs, sections of orthotopic glioma models were analyzed by immunofluorescent labeling., Results: GS-MSCs were isolated which were morphologically similar to mMSCs. FACS analysis showed that the GS-MSCs had similar surface markers to mMSCs (stem cell antigen-1 [Sca-1](+), CD9(+), CD45(-), CD11b(-), CD31(-), and nerve/glial antigen 2 [NG2](-)). GS-MSCs were capable of mesenchymal differentiation. Immunofluorescent labeling indicated that GS-MSCs are located around blood vessels, are distinct from endothelial cells, and have features that partially overlap with vascular pericytes., Conclusions: Our results indicate that cells similar to mMSCs exist in glioma specimens. The GS-MSCs might be located around vessels, which suggests that GS-MSCs may provide the mesenchymal elements of the vascular niche. GS-MSCs may represent non-neural stem cells that act as an important source of mesenchymal elements, particularly during the growth of gliomas.

We report a rare case of patient with dermatomyositis (DM) who developed spontaneous pneumomediastinum (PnM) and subcutaneous emphysema. She was successfully treated with oral prednisolone and cyclosporine A (CsA). We reviewed the cases of PnM in patients with DM treated with CsA. A review of four previously reported cases revealed that treatment with systemic glucocorticoid and CsA was effective for the DM and PnM. We indicate that initial and early treatment of the patients with DM and PnM with CsA enabled rapid tapering of the dose of glucocorticoid and improved the disease.

Massive gastrointestinal bleeding is a very rare manifestation of gastrointestinal Behçet's disease, mainly from the gastrointestinal mucosal lesions. We report herein the case of a 50-year-old man with intestinal Behçet's disease who suffered massive hemorrhage from ruptured arterial aneurysm. Colonoscopy demonstrated large amount of fresh blood in the entire colon, but we were not able to localize bleeding focus anywhere in the colon. Angiography was performed and it revealed that a small aneurysm on the right ileocolic artery with apparent extravasation of contrast material. A guiding catheter was inserted to a right ileocolic artery and superselective arterial embolization using microcoils was successful. Following this procedure, the gastrointestinal bleeding gradually subsided and completely stopped within a few days. He is now treating with prednisolone and sulfasalazine without recurrent bleeding until now.

Antiphospholipid syndrome (APS) is an autoimmune disease, and its most critical pathologic process is thrombosis, which may explain most of the clinical features. Acute management of thrombosis involves immediate anticoagulation. Acute proximal venous thrombosis can be managed with thrombolytic therapy to reduce the long-term complications of the postthrombotic syndrome (pain, swelling, skin discoloration, or ulceration) and perform recanalization of occluded vessels. However, thrombolytic therapies are associated with high risks of bleeding. To our knowledge, this is the first report of epidural hematoma mimicking transverse myelitis after catheter-directed thrombolysis in a patient with primary APS. A 42-year-old male was admitted with sudden onset pain and swelling on left lower extremity. Venography demonstrated multiple thrombi on superficial femoral vein, common femoral vein, common iliac vein, and external iliac vein. Laboratory tests indicated the presence of IgM anticardiolipin antibody. He was diagnosed with primary APS with multiple venous thrombi. He was treated with urokinase (200,000/h) as thrombolytic therapy. After 1 day, he complained both leg weakness and urinary dysfunction. T1- and T2-weighted magnetic resonance images of spine showed about 8 cm-sized mass, suggesting hematoma on the posterior epidural space at thoracolumbar area. Despite the successful evacuation of hematoma, neurologic symptoms persisted and he is now receiving aspirin, warfarin, and physical therapy.

Accurate assessment and replacement of blood loss and fluid-electrolyte deficit during craniosynostosis repair is difficult owing to patient size and the diversity of surgical technique. Forty-three patients undergoing primary craniosynostosis repair over a 10-year period were studied retrospectively to determine blood loss and fluid deficit and to assess blood transfusion practices during both intraoperative and postoperative periods. Blood loss was calculated on the basis of estimated red cell mass (ERCM) and fluid-electrolyte imbalance was investigated with blood samplings. Blood transfusion was considered appropriate if the postoperative or posttransfusion ERCM was within 12% of the preoperative value. Estimated fluid requirement (EFR) was used in 4 ml kg(-1) h(-1) except for neonates. Intraoperatively, 80% of all patients were appropriately managed with respect to blood transfusion and EFR. Postoperatively only 20% of the patients receiving transfusions were transfused appropriately. In 23.3% of these patients (10/43) unexpected respiratory distress developed immediately after their recovery from the anesthesia. With the measurement of estimated blood volume and allowable blood loss, appropriate transfusion could be achieved for the successful treatment of the primary craniosynostosis.

The results are reported of a retrospective review of the presentation and outcome of 43 pineal region tumors treated from 1982 to 1996, including 20 identified tumors: 5 germinomas, 8 teratomas, 2 embryonal carcinomas, 1 endodermal sinus tumor, 2 pineocytomas and 2 pineoblastomas. Of the 43 tumors reviewed, 36 were located in the pineal region, 5 in the suprasellar, and 2 in both the pineal and suprasellar regions. Twenty patients underwent surgical resection: total in 6 and partial in 10, while only a biopsy was taken in 4 cases. Fifteen patients were managed on the basis of serum CSF tumor markers and radiation response. Twenty-three patients with germinomas received radiotherapy (RT) and had a 5-year survival rate of 87%. Fifteen patients with non-germinomatous germ cell tumors received RT and chemotherapy following direct surgery, and 5 died (mortality rate of 33.3%). The overall survival rate of the 43 patients with pineal tumors was 79.1% (34/43) and the death rate was 20.9% (9/43). It is now recognized that the wide variety of tumor types found in the pineal region necessitates different modes of treatment, and improved microsurgical and stereotactic surgical techniques have made mortality and morbidity rates acceptably low. Because the radiation response and CSF cytology are not enough to determine optimum treatment, a tissue diagnosis should be obtained in all patients.