Evaluation of food effects on the pharmacokinetics of Pelargonium sidoides and Coptis with each bioactive compound berberine and epicatechin after a single oral dose of an expectorant and antitussive agent UI026 in healthy subjects

UI026 is an expectorant and antitussive agent which is a new combination of Pelargonium sidoides extract andCoptis extract. The bioactive compounds of Pelargonium sidoides and Coptis extracts were identified as epicatechin and berberine, respectively. This study evaluated the effect of food on the pharmacokinetics (PKs) and safety of UI026. A randomized, openlabel, single-dose, 2-treatment, parallel study in 12 healthy male subjects was performed. Subjects received a single oral dose of UI026 (27 mL of syrup) under a fed or fasted condition according to their randomly assigned treatment. Blood samples for the PK analysis were obtained up to 24 hours post-dose for berberine and 12 hours post-dose for epicatechin. The PK parameters were calculated by non-compartmental analysis. In the fed condition, the mean maximum plasma concentration (C max ) and mean area under the plasma concentrationtime curve from time zero to the last observed time point (AUC last ) for berberine were approximately 33% and 67% lower, respectively, compared with the fasted condition, both showing statistically significant difference. For epicatechin, the mean C max and mean AUC last were about 29% and 45% lower, respectively, compared to the fasting condition, neither of which showed a statistically significant difference. There were no drug-related adverse events. This finding suggests that food affects the systemic exposure and bioavailability of berberine and epicatechin.

Comparative pharmacokinetics between two tablets of tramadol 37.5 mg/acetaminophen 325 mg and one tablet of tramadol 75 mg/acetaminophen 650 mg for extended-release fixed-dose combination

An extended-release (ER) fixed-dose combination (FDC) of tramadol 37.5 mg/acetaminophen 325 mg was developed due to the demand for varying dosages. This study aimed to evaluate the pharmacokinetics (PKs) for two tablets of the new developed tramadol 37.5 mg/acetaminophen 325 mg ER FDC (DW-0920, Wontran Semi ER®) as test formulation compared to one tablet of the tramadol 75 mg/acetaminophen 650 mg ER FDC (DW-0919, Wontran ER®) as reference formulation. A randomized, open-label, 2-way crossover study was conducted in 30 healthy subjects. Subjects were orally administered one of 2 formulations followed by an alternate formulation with a 7-day washout period. Blood samples were collected up to 36 hours post-dose. Plasma concentrations of tramadol and acetaminophen were determined using a validated high-performance liquid chromatography with tandem mass spectrometric method. The geometric mean ratios (GMRs) and their 90% confidence intervals (90% CIs) of test formulation to reference formulation were calculated for the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve from zero to the last measurable time point (AUClast). The PK profiles of 2 formulations were comparable. The GMRs (90% CI) of Cmax and AUClast for tramadol were 1.086 (1.047–1.127) and 1.008 (0.975–1.042), respectively. The corresponding values for acetaminophen were 0.956 (0.897–1.019) and 0.986 (0.961–1.011), respectively. All the values were within the bioequivalence range of 0.80–1.25. Two tablets of DW-0920 were comparable to one tablet of DW-0919. The DW-0920 may be used for optimal pharmacotherapy for pain control with a lower dose.

Quantitative assessment of nipple perfusion with laser-assisted indocyanine green imaging in nipple-sparing mastectomy with breast reconstruction

BACKGROUND: It remains unknown whether perfusion mapping using the SPY system can predict mastectomy skin flap necrosis in each type of breast surgery. We analyzed intraoperative indocyanine green (ICG) angiography images of breast cancer patients who underwent nipple-sparing mastectomy (NSM) with implant-based breast reconstruction, and evaluated the perfusion of the nipple-areolar complex (NAC) with the SPY Elite system to predict NAC necrosis with a single quantitative value. METHODS: We analyzed nipple perfusion in 30 patients from October 2016 to November 2018. After NSM, ICG injection and SPY angiography were performed to characterize NAC perfusion before immediate reconstruction. The nipple perfusion rate was measured by analyzing fluorescence at the central point of the nipple, and the presence of NAC necrosis was evaluated at 5 days and 1 month postoperatively. RESULTS: Three of the 30 patients developed NAC necrosis that secondarily healed within 1 month, and five developed NAC necrosis and underwent surgical debridement within 1 month. Seven of eight patients with a perfusion rate < 13% developed NAC necrosis, and all four patients with a perfusion rate < 10% needed partial surgical debridement or total NAC excision. CONCLUSIONS: The nipple perfusion rate could be useful for predicting NAC necrosis before immediate reconstruction. For patients at a high risk for NAC necrosis, tissue expander insertion rather than a direct-to-implant procedure may be considered, and close follow-up with thorough wound management should be done to reduce complications.

Real-Time Computed Tomography Volume Visualization with Ambient Occlusion of Hand-Drawn Transfer Function Using Local Vicinity Statistic / 대한의료정보학회지

OBJECTIVES: In this paper, we present an efficient method to visualize computed tomography (CT) datasets using ambient occlusion, which is a global illumination technique that adds depth cues to the output image. We can change the transfer function (TF) for volume rendering and generate output images in real time. METHODS: In preprocessing, the mean and standard deviation of each local vicinity are calculated. During rendering, the ambient light intensity is calculated. The calculation is accelerated on the assumption that the CT value of the local vicinity of each point follows the normal distribution. We approximate complex TF forms with a smaller number of connected line segments to achieve additional acceleration. Ambient occlusion is combined with the existing local illumination technique to produce images with depth in real time. RESULTS: We tested the proposed method on various CT datasets using hand-drawn TFs. The proposed method enabled real-time rendering that was approximately 40 times faster than the previous method. As a result of comparing the output image quality with that of the conventional method, the average signal-to-noise ratio was approximately 40 dB, and the image quality did not significantly deteriorate. CONCLUSIONS: When rendering CT images with various TFs, the proposed method generated depth-sensing images in real time.

Sinonasal intestinal-type adenocarcinoma in the frontal sinus

Sinonasal intestinal-type adenocarcinoma is a rare neoplasm which can be diagnosed by pathologic report. Nasal obstruction, epistaxis, and rhinorrhea are common symptoms, but presenting with a benign-looking palpable mass is also possible. This is a report of our experience in diagnosing and treating a sinonasal intestinal-type low grade adenocarcinoma. A 63-year-old man initially presented with a rapidly growing palpable mass in the glabella region for 4 months. A malignancy of sinus origin was suspected on imaging studies. We performed further preoperative evaluations for cancer staging, and curative surgery was planned. Radical resection and immediate reconstruction with free anterolateral thigh flap were performed. The pathology findings confirmed a diagnosis of sinonasal intestinal-type adenocarcinoma.

Association between Promoter Polymorphisms of TFF1, TFF2, and TFF3 and the Risk of Gastric and Diffuse Gastric Cancers in a Korean Population

Gastric cancer is one of the most common cancers in the world. The aims of this study were to evaluate the association between polymorphisms in TFF gene family, TFF1, TFF2, and TFF3 and the risk of gastric cancer (GC) and GC subgroups in a Korean population via a case-control study. The eight polymorphisms in TFF gene family were identified by sequencing and genotyped with 377 GC patients and 396 controls by using TaqMan genotyping assay. The rs184432 TT genotype of TFF1 was significantly associated with a reduced risk of GC (odds ratio, [OR) = 0.45; 95% confidence interval, [CI] = 0.25-0.82; P = 0.009), more protective against diffuse-type GC (OR = 0.20; 95% CI = 0.05-0.89; P = 0.035) than GC (OR = 0.34; 95% CI = 0.14-0.82; P = 0.017) in subjects aged < 60 yr, and correlated with lymph node metastasis negative GC and diffuse-type GC (OR = 0.44; 95% CI = 0.23-0.86; P = 0.016 and OR = 0.20; 95% CI = 0.05-0.87; P = 0.031, respectively). In addition, a decreased risk of lymph node metastasis negative GC and diffuse-type GC was observed for rs225359 TT genotype of TFF1 (OR = 0.46, 95% CI = 0.24-0.88; P = 0.020 and OR = 0.21, 95% CI = 0.05-0.88; P = 0.033, respectively). These findings suggest that the rs184432 and rs225359 polymorphisms in TFF1 have protective effects for GC and contribute to the development of GC in Korean individuals.

Bioequivalence of Two Erlotinib Formulations in Healthy Volunteers

BACKGROUND: Erlotinib is a tyrosine kinase inhibitor prescribed for the treatment of non-small cell lung cancer and pancreatic cancer. The aim of this study was to compare the safety and pharmacokinetics (PK) of a generic (test) formulation of erlotinib with those of a reference formulation in healthy volunteers. METHODS: A randomized, open-label, single-dose two-treatment, two-period, two-sequence, crossover study was conducted in Clinical Trials Center, Chungnam National University Hospital with 40 healthy men. Subjects orally received either one 150 mg tablet of the test or the corresponding dose of the reference, and crossover phases were separated by 14-day washout. Plasma samples were collected up to 72 hr post-dose. Plasma erlotinib concentrations were determined by liquid chromatography-tandem mass spectrometry. PK parameters were calculated by non-compartmental analysis. The safety was monitored throughout the study. RESULTS: A total of 21 cases of adverse events were reported. They are mild and relieved without an intervention. There was no serious adverse event. Median times to peak concentration of two formulations were 3.0. Means [SD] for peak concentration (Cmax) and area under the plasma concentration-time curve (AUC) of the test were 1,298 [346] microg/L and 25,318 [7,668] hrxmicrog/L. Those of the reference were 1,193 [378] microg/L and 24,853 [8,419] hrxmicrog/L. Geometric mean ratios (90% confidence intervals) for the test to the reference were 1.10 (1.02-1.18) for Cmax and 1.02 (0.97-1.09) for AUC. CONCLUSION: Two formulations were safe and well-tolerated. PK findings suggest that the test formulation is equivalent to the reference in terms of pharmacokinetics.

An Experience of Operating the Pediatric Emergency Room

OBJECTIVE: This hospital has operated the pediatric emergency room from 2011 as being appointed for 'the pediatric emergency room model construction project' by the government. Thus, the author attempted to evaluate the effect of emergency room crowding by comparing the length of stay before and after the introduction of the pediatric emergency room. METHODS: This study compared and analyzed the length of stay according to age, time distribution, injury/non-injury, in-patient/returning home to young patients under 15 years before the operating the pediatric emergency room between January and December 2010 and after the introduction between January and December 2011, respectively. The length of stay of adult patients in the same period was also examined. RESULTS: Despite the increase of pediatric emergency room and in-hospital patients by 63% and 94% after the operation of the pediatric emergency room respectively, the length of stay of the emergency room reduced from 1.8 to 1.4 hours. However, due to the shortage of sick-beds the length of stay of in-hospital patients increased from 3.4 to 4.3 hours. While the hospitalization admission procedure time reduced considerably from 1.8 to 0.9 hours, the time of injured patients had no changes. The number of adult patients and in-hospital patients increased 18%, 8%, respectively, and the length of stay in the emergency room reduced from 2.7 to 2.5 hours. CONCLUSION: Despite increasing the number of pediatric and in-hospital adult patients, the length of stay of the emergency room reduced owing to the operation of the pediatric emergency room which helped to reduce emergency room crowding. However, the ultimate resolution of congestion of the emergency room requires sufficient professional personnel and hospital's policy support to solve a sick-bed shortage problem.