Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.

Carbon monoxide (CO) can cause a variety of electrocardiogram (ECG) changes. The Brugada ECG patterns are very rare in CO poisoning cases. We detected a patient with a CO-induced type 1 Brugada ECG pattern with chest pain. The panel genetic test and echocardiogram revealed normal findings. The Brugada phenocopy gradually improved over 3 days. We reviewed the literature and suggested possible mechanisms.

OBJECTIVE: Persistent infection of HPV increases the chance of carcinoma in situ of cervix through stages of cervical intraepithelial neoplasia (CIN) 1, 2, and 3, and finally progresses into cervical cancer. We aimed to explore the safety and efficacy of BLS-M07 which is orally administered agent expressing human papillomavirus (HPV) 16 E7 antigen on the surface of Lactobacillus casei in patients with CIN 3. METHODS: Patients with CIN 3 were recruited in our clinical trial. Reid Colposcopic Index (RCI) grading and serum HPV16 E7 specific antibody production were used to evaluate efficacy of BLS-M07. In phase 1, BLS-M07 was administered orally, 5 times a week, on weeks 1, 2, 4, and 8 with dosages of 500 mg, 1,000 mg, and 1,500 mg. In phase 2a, patients were treated with 1,000 mg. The primary endpoints were the safety and the pathologic regression on colposcopic biopsy. RESULTS: Nineteen patients were enrolled in the CIN 3 cohort. In phase 1, no patients experienced dose limiting toxicity. No grade 3 or 4 treatment-related adverse events or deaths were observed. At 16 weeks after treatment, RCI grading was improved and serum HPV16 E7 specific antibody production increased (p<0.05). Six of 8 (75%) patients with CIN 3 were cured in phase 2a. CONCLUSIONS: Oral immunization with BLS-M07 increases production of serum HPV16 E7 specific antibody which induces protective humoral immunity. The safety of this oral vaccine was proved and could be a competitive non-surgical therapeutic agent of CIN 3. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02195089
Antibody Formation ; Biopsy ; Carcinoma in Situ ; Cervical Intraepithelial Neoplasia ; Cervix Uteri ; Cohort Studies ; Female ; Humans ; Immunity, Humoral ; Immunization ; Lactobacillus casei ; Papillomavirus E7 Proteins ; Papillomavirus Vaccines ; Uterine Cervical Neoplasms

The aim of this study was to investigate morphological development of filiform papillae (FP) in Korean native goats by using scanning electron microscopy. Tongues were removed from goat fetuses (days 60, 90, and 120), neonates, and juveniles (days 30, 60, 90, 120, 150, and 180 after birth). During the prenatal period, primordia of FP appeared at fetal day 60 and were observed to be developed at day 90. At fetal day 120, the FP were observed like flower leaves of a double flower bud. In neonates, FP were shaped like an obliquely sectioned cylinder with secondary papillae irregularly arranged in a saw blade-like manner. In 60-day-old juvenile goats, the FP were densely distributed at the inner base of 1/3–1/2 degrees. In 90-, 120-, and 150-day-old goats, FP were compacted at the inner base of 1/2–2/3, 3/4, and 4/5 degrees, respectively. In 180-day-old goats, FP were found to be completely compacted on the inner surface with complete morphogenesis. Microridges, microplicae, and micropits were well-developed on the epithelial surface of lingual papillae from embryonic day 120 to juvenile day 180. These results indicate that FP of goats have different shapes and sizes during development both before and after birth.
Fetus ; Flowers ; Goats ; Humans ; Infant, Newborn ; Microscopy, Electron, Scanning ; Morphogenesis ; Parturition ; Tongue

BACKGROUND AND OBJECTIVES: Although many studies have assessed factors related to adherence of PAP therapy, there were no studies about factors related to doctors or device managers. The purpose of this study was to investigate the relationship between PAP therapy adherence and doctor or device manager. SUBJECTS AND METHODS: Between February 2013 and June 2015, 163 patients newly diagnosed with moderate to severe OSA in one of five hospitals were enrolled in this study. All patients received 4 weeks of PAP treatment with intervention consisting of mechanical support and motivation by doctor and device manager. Data from the PAP device were obtained following a minimum of an initial 30 days, with adherence defined as >4 h/night on 70% of nights. RESULTS: After 30 days, total adherence rate to PAP therapy was 35.6% (n=58). The adherence rate of device manager ① was 26.3% (31/118), and that of device manager ② was 60% (27/45), and there was statistically significant difference between the two device managers. Furthermore, there were statistically significant differences in the adherence to PAP therapy ranging from 85.6% to 0.0% according to doctor. CONCLUSION: Our study demonstrates that the device manager and doctor may be important factors for good adherence to PAP therapy in patients with OSA.
Continuous Positive Airway Pressure ; Humans ; Motivation ; Patient Compliance ; Sleep Apnea, Obstructive*

The aim of this study was to investigate morphological development of filiform papillae (FP) in Korean native goats by using scanning electron microscopy. Tongues were removed from goat fetuses (days 60, 90, and 120), neonates, and juveniles (days 30, 60, 90, 120, 150, and 180 after birth). During the prenatal period, primordia of FP appeared at fetal day 60 and were observed to be developed at day 90. At fetal day 120, the FP were observed like flower leaves of a double flower bud. In neonates, FP were shaped like an obliquely sectioned cylinder with secondary papillae irregularly arranged in a saw blade-like manner. In 60-day-old juvenile goats, the FP were densely distributed at the inner base of 1/3–1/2 degrees. In 90-, 120-, and 150-day-old goats, FP were compacted at the inner base of 1/2–2/3, 3/4, and 4/5 degrees, respectively. In 180-day-old goats, FP were found to be completely compacted on the inner surface with complete morphogenesis. Microridges, microplicae, and micropits were well-developed on the epithelial surface of lingual papillae from embryonic day 120 to juvenile day 180. These results indicate that FP of goats have different shapes and sizes during development both before and after birth.

In addition to classical synaptic transmission, information is transmitted between cells via the activation of extrasynaptic receptors that generate persistent tonic current in the brain. While growing evidence supports the presence of tonic NMDA current (INMDA) generated by extrasynaptic NMDA receptors (eNMDARs), the functional significance of tonic I(NMDA) in various brain regions remains poorly understood. Here, we demonstrate that activation of eNMDARs that generate I(NMDA) facilitates the α-amino-3-hydroxy-5-methylisoxazole-4-proprionate receptor (AMPAR)-mediated steady-state current in supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs). In low-Mg2+ artificial cerebrospinal fluid (aCSF), glutamate induced an inward shift in I(holding) (I(GLU)) at a holding potential (V(holding)) of -70 mV which was partly blocked by an AMPAR antagonist, NBQX. NBQX-sensitive I(GLU) was observed even in normal aCSF at V(holding) of -40 mV or -20 mV. I(GLU) was completely abolished by pretreatment with an NMDAR blocker, AP5, under all tested conditions. AMPA induced a reproducible inward shift in I(holding) (I(AMPA)) in SON MNCs. Pretreatment with AP5 attenuated I(AMPA) amplitudes to ~60% of the control levels in low-Mg2+ aCSF, but not in normal aCSF at V(holding) of -70 mV. I(AMPA) attenuation by AP5 was also prominent in normal aCSF at depolarized holding potentials. Memantine, an eNMDAR blocker, mimicked the AP5-induced I(AMPA) attenuation in SON MNCs. Finally, chronic dehydration did not affect I(AMPA) attenuation by AP5 in the neurons. These results suggest that tonic I(NMDA), mediated by eNMDAR, facilitates AMPAR function, changing the postsynaptic response to its agonists in normal and osmotically challenged SON MNCs.
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid* ; Brain ; Cerebrospinal Fluid ; Dehydration ; Glutamic Acid ; Memantine ; N-Methylaspartate* ; Neurons ; Receptors, AMPA ; Receptors, N-Methyl-D-Aspartate* ; Supraoptic Nucleus ; Synaptic Transmission

Lymphangioma is an uncommon malformation of the lymphatic system that involves a benign proliferation of the lymphatics, with no established treatment method. Multiple colonic lymphangioma, or colonic lymphangiomatosis, is an extremely rare condition. We report a case of colonic lymphangiomatosis that was detected during a colonoscopic examination conducted as part of a general health check-up. The lesion completely resolved after excisional biopsy.
Biopsy* ; Colon* ; Lymphangioma ; Lymphatic System

No abstract available.
Bicuspid* ; Echocardiography*

Cytokeratin (CK) comprises the intermediate filament cytoskeleton of epithelial cells. Patterns of CK expression can be regarded as a specific marker for epithelial differentiation status. The aim of this study was to identify CK expression on tongues of Korean native goats ranging from 60-day-old fetuses to newborns during prenatal development using immunohistochemistry. The tongues of fetuses were removed from 2- to 4-year-old female Korean native goats by caesarean section performed under general anesthesia. Immunohistochemistry was performed to assess CK expression patterns on developing goat tongues using serial paraffin-embedded sections. Light zones signifying CK immunoreactivity in dorsal lingual epithelia were weakly positive in 60-day-old fetuses. In 90-day-old fetuses, deep areas in dorsal lingual epithelia were strongly positive for CK expression and superficial areas were moderately positive. In 120-day-old fetuses, light zones of lingual epithelia in the vallate papilla were strongly positive for CK expression, whereas ducts of von Ebner's glands were moderately positive. In neonates, taste buds were positive for CK expression, whereas non-taste epithelial cells and von Ebner's glands were negative. These findings indicate that goat tongues have different patterns of CK expression during development and provide a morphological basis for studies on the biological mechanism of epithelial differentiation.
Anesthesia, General ; Cesarean Section ; Child, Preschool ; Cytoskeleton ; Epithelial Cells ; Epithelium ; Female ; Fetus ; Goats* ; Humans ; Immunohistochemistry ; Infant, Newborn ; Intermediate Filaments ; Keratins* ; Pregnancy ; Taste Buds ; Tongue* ; von Ebner Glands