Background/Aims: Probe-based confocal laser endomicroscopy (pCLE) requires the administration of intravenous (IV) fluorescein. This study aimed to determine the optimal dose of IV fluorescein for both upper and lower gastrointestinal (GI) tract pCLE. Methods: Patients 20 to 79 years old with gastric high-grade dysplasia (HGD) or colorectal neoplasms (CRNs) were enrolled in the study. The dose de-escalation method was employed with five levels. The primary endpoint of the study was the determination of the optimal dose of IV fluorescein for pCLE of the GI tract. The reduced dose was determined based on off-line reviews by three endoscopists. An insufficient dose of fluorescein was defined as the dose of fluorescein with which the pCLE images were not deemed to be visible. If all three endoscopists determined that the tissue structure was visible, the doses were de-escalated. Results: A total of 12 patients with gastric HGD and 12 patients with CRNs were enrolled in the study. Doses were de-escalated to 0.5 mg/kg of fluorescein for both non-neoplastic duodenal and colorectal mucosa. All gastric HGD or CRNs were visible with pCLE with IV fluorescein at 0.5 mg/kg. Conclusions In the present study, pCLE with IV fluorescein 0.5 mg/kg was adequate to visualize the magnified structure of both the upper and lower GI tract.

Background/Aims: Probe-based confocal laser endomicroscopy (pCLE) requires the administration of intravenous (IV) fluorescein. This study aimed to determine the optimal dose of IV fluorescein for both upper and lower gastrointestinal (GI) tract pCLE. Methods: Patients 20 to 79 years old with gastric high-grade dysplasia (HGD) or colorectal neoplasms (CRNs) were enrolled in the study. The dose de-escalation method was employed with five levels. The primary endpoint of the study was the determination of the optimal dose of IV fluorescein for pCLE of the GI tract. The reduced dose was determined based on off-line reviews by three endoscopists. An insufficient dose of fluorescein was defined as the dose of fluorescein with which the pCLE images were not deemed to be visible. If all three endoscopists determined that the tissue structure was visible, the doses were de-escalated. Results: A total of 12 patients with gastric HGD and 12 patients with CRNs were enrolled in the study. Doses were de-escalated to 0.5 mg/kg of fluorescein for both non-neoplastic duodenal and colorectal mucosa. All gastric HGD or CRNs were visible with pCLE with IV fluorescein at 0.5 mg/kg. Conclusions In the present study, pCLE with IV fluorescein 0.5 mg/kg was adequate to visualize the magnified structure of both the upper and lower GI tract.

We describe a rare complication and treatment progression that occurred in a 64-year-old man with an aortic abdominal aneurysm (AAA) that had been treated by endovascular aneurysm repair (EVAR). He had undergone EVAR to treat an infra-renal type AAA 21 months previously and returned to the emergency department with back pain. Contrast-enhanced computed tomography (CT) revealed acute type B aortic dissection, so he was admitted and conservative medical management was started. Acute stomachache and limb pain appeared on hospital day 7, which prevented him from moving his lower limbs. The main body of the stent graft had collapsed, blocking blood flow, and contrast was not found in arteries from the collapsed stent graft portion to the knee level on emergency contrast CT images of the leg. His legs were revascularized by an extra-anatomical right axial-bilateral external iliac bypass. His symptoms disappeared and reperfusion injury was avoided. The collapsed stent graft had retained its original shape at 11 and 18 days after surgery. Furthermore, follow-up CT 4.5 years later showed that the stent graft retained its original form.

Afatinib is an oral tyrosine kinase inhibitor (TKI) approved for treating advanced non-small cell lung cancer. It is necessary to develop a simple quantification method for TKIs in order to facilitate therapeutic drug monitoring (TDM) in clinical settings. This study sought to develop a simple and sensitive com-petitive enzyme-linked immunosorbent assay (ELISA) to quantify afatinib in plasma for routine phar-macokinetic applications. An anti-afatinib antibody was obtained using (S)-N-4-(3-chloro-4-fluor-ophenyl)-7-(tetrahydrofuran-3-yloxy)-quinazoline-4,6-diamine (CTQD), which has the same sub-structure as afatinib, as a hapten. Enzyme labeling of afatinib with horseradish peroxidase was similarly performed using CTQD. A simple competitive ELISA for afatinib was developed based on the principle of direct competition between afatinib and the enzyme marker for the anti-afatinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Plasma afatinib concentrations below the limit of quantification of 30 pg/mL were reproducibly measurable. Also, the values of plasma afatinib levels measured from 20 patients were comparable with those measured by high-performance liquid chromatography, and there was a strong correlation between the values determined by both methods (Y = 0.976X – 0.207, r = 0.975). As indicated by its specificity and sensitivity, this newly developed ELISA for afatinib is an important tool for TDM and studies of the pharmacokinetics of afatinib.

BACKGROUND: The canonical Wnt/β-catenin signaling pathway is a fundamental regulatory system involved in various biological events. ICG-001 selectively blocks the interaction of β-catenin with its transcriptional co-activator cyclic AMP response element-binding protein (CBP). Recent studies have provided convincing evidence of the inhibitory effects of ICG-001 on Wnt-driven disease models, such as organ fibrosis, cancer, acute lymphoblastic leukemia, and asthma. However, the effects of ICG-001 in atopic dermatitis (AD) have not been investigated. OBJECTIVE: To investigate whether β-catenin/CBP-dependent signaling was contributed in the pathogenesis of AD and ICG-001 could be a therapeutic agent for AD. METHODS: We examined the effects of ICG-001 in an AD-like murine model generated by repeated topical application of the hapten, oxazolone (Ox). ICG-001 or vehicle alone was injected intraperitoneally every day during the development of AD-like dermatitis arising from once-daily Ox treatment. RESULTS: Ox-induced AD-like dermatitis characterized by increases in transepidermal water loss, epidermal thickness, dermal thickness accompanied by increased myofibroblast and mast cell counts, and serum levels of thymic stromal lymphopoietin and thymus and activation-regulated chemokine, and decreases in stratum corneum hydration, were virtually normalized by the treatment with ICG-001. Elevated serum levels of periostin tended to be downregulated, without statistical significance. CONCLUSION: These results suggest that β-catenin/CBP-dependent signaling might be involved in the pathogenesis of AD and could be a therapeutic target.
Animals ; Asthma ; Chemokine CCL17 ; Cyclic AMP Response Element-Binding Protein ; Cyclic AMP ; Dermatitis ; Dermatitis, Atopic ; Fibrosis ; Mast Cells ; Mice ; Myofibroblasts ; Oxazolone ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Water

BACKGROUND/AIMS: We applied a back light system (BLS) with a magnifying glass to improve the ability to assess the adequacy of specimen sampling using endosonography. We conducted this study to evaluate the efficacy of the BLS in sampling of specimens by endoscopic ultrasound-guided fine needle aspiration of solid pancreatic masses. METHODS: This was a prospective, randomized, crossover, single-center clinical trial. An endosonographer evaluated adequacy on gross visual inspection and identified whitish specimen sampling sites with and without the BLS according to a randomization sequence in the first and second passes with a 25-G needle. On cytological evaluation, the presence of well-defined pancreatic ductal epithelium was evaluated by a cytopathologist who was blinded to any clinical information. RESULTS: A total of 80 consecutive patients were eligible during the study period. Adequacy was observed for 52 specimens (65%) with the BLS and 54 (68%) without the BLS (p=0.88). In assessment of specimen adequacy on gross examination, only fair agreement was observed both with and without BLS (kappa score 0.40 and 0.29, respectively). CONCLUSIONS: The BLS did not influence the ability to identify specimen sampling sites or reliable assessment of specimen site adequacy using gross visual inspection.
Biopsy, Fine-Needle ; Cross-Over Studies ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Endosonography ; Epithelium ; Glass ; Humans ; Needles ; Pancreatic Ducts ; Pancreatic Neoplasms ; Prospective Studies ; Random Allocation

We report two cases effectively treated with Kampo medicines for comorbid sleep disorder in developmental disorder. Case 1 was a 15-year-old woman diagnosed Asperger's syndrome, and her main complaints were difficulty in rising, difficulty in falling asleep and fatigability. We thought that the symptoms might be caused by in and ketsu deficiency, which lost control of kanki hyperactivity and evoked tension/excitement state easily. The difficulty in rising was improved with yokukansan and kambakutaisoto and she was able to go to school every day. Case 2 was a 17-year-old man diagnosed the attention-deficit/hyperactivity disorder. His symptoms were difficulty in rising, feeling of weariness, fatigability, and frequent tension/excitement state. The previous use of shokenchuto had improved the symptoms slightly. After shigyakusan was added to cure kanki dysregulation, he succeeded in going to school every day. In the oriental medicine, ketsu has important roles in mental stability and sleep, whereas qi and ketsu tend to be insufficient in childhood. Our results suggest that replacement of in and ketsu would be useful in treating comorbidities in developmental disorder.