Search

Myung Il Bae, Jae-Kwang Shim, Jong Wook Song, Seo Hee Ko, Young Seo Choi, Young-Lan Kwak Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of KoreaCorrespondence: Young-Lan Kwak, Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea, Tel +82-2-2228-8513, Fax +82-2-2227-8063, Email YLKWAK@yuhs.acPurpose: The neutrophil-to-lymphocyte ratio (NLR) is an extensively analyzed prognostic inflammatory index in cardiac patients. The degree of change in NLR values before and after surgery (delta-NLR) can represent the inflammatory response induced by surgery and serve as a meaningful prognostic biomarker in surgical patients; however, this has not been well investigated. We aimed to investigate the predictive value of the perioperative NLR and delta-NLR for outcomes of off-pump coronary artery bypass (OPCAB) surgery by evaluating “days alive and out of hospital (DAOH)”, a novel patient-centered outcome.Patients and Methods: In this single-center retrospective study, perioperative data, including NLR data, from 1322 patients were analyzed. The primary endpoint was DOAH at 90 days postoperatively (DAOH 90), and the secondary endpoint was long-term mortality. Linear regression analysis and Cox regression analysis were performed to identify independent risk factors for the endpoints. In addition, Kaplan–Meier survival curves were plotted to assess long-term mortality.Results: The median NLR values significantly increased from 2.2 (1.6– 3.1) at baseline to 7.4 (5.4– 10.3) postoperatively, with median delta-NLR values of 5.0 (3.2– 7.6). Preoperative NLR and delta-NLR were independent risk factors for short DAOH 90 in the linear regression analysis. In Cox regression analysis, delta-NLR, but not preoperative NLR, was an independent risk factor for long-term mortality. When patients were divided into two groups according to delta-NLR, the high delta-NLR group had a shorter DAOH 90 than the low delta-NLR group. Kaplan–Meier curves showed higher long-term mortality in the high delta-NLR group than in the low delta-NLR group.Conclusion: In OPCAB patients, preoperative NLR and delta-NLR were significantly associated with DAOH 90, and delta-NLR was an independent risk factor for long-term mortality, indicating their role in risk assessment, which is essential for perioperative management.Keywords: neutrophil-to-lymphocyte ratio, off-pump coronary artery bypass, days alive and out of hospital

Jun Soo Park,1 Min Seop Kim,1 Min Yeong Joung,1 Hyun Jin Park,1 Myoung-Jin Ho,1 Jun Hyuk Choi,1 Jae Hee Seo,1 Woo Heon Song,1 Young Wook Choi,2 Sangkil Lee,3 Yong Seok Choi,1 Myung Joo Kang1 1College of Pharmacy, Dankook University, Cheonan, Republic of Korea; 2College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 3College of Pharmacy, Keimyung University, Daegu, Republic of KoreaCorrespondence: Myung Joo Kang, College of Pharmacy, Dankook University, Dongnam-gu, Cheonan, 31116, Republic of Korea, Tel +82 41 550 1446, Fax +82 41 550 7899, Email kangmj@dankook.ac.krBackground: Montelukast (MTK), a representative leukotriene receptor antagonist, is currently being investigated as a potential candidate for treating Alzheimer’s disease. For potent and effective dosing in elderly patients, a parenteral prolonged delivery system is favored, with improved medication adherence with reduced dosage frequency.Purpose: This study aimed to design a nanocrystalline suspension (NS)-based MTK prolonged delivery system and evaluate its pharmacokinetics profile and local tolerability following subcutaneous administration.Methods: To decelerate the dissolution rate, the amorphous MTK raw material was transformed into a crystalline state using a solvent-mediated transformation method and subsequently formulated into NS using a bead-milling technique. The MTK NSs were characterized by morphology, particle size, crystallinity, and in vitro dissolution profiles. The pharmacokinetic profile and local tolerability at the injection site following subcutaneous injection of MTK suspension were evaluated in rats.Results: Microscopic and physical characterization revealed that the amorphous MTK powder was lucratively transformed into a crystalline form in acidic media (pH 4). MTK crystalline suspensions with different diameters (200 nm, 500 nm, and 3 μm) were uniformly prepared using bead-milling technology, employing polysorbate 80 as suspending agent. Prepared crystalline suspensions exhibited analogous crystallinity (melting point, 150°C) and size-dependent in vitro dissolution profiles. MTK NSs with particle sizes of 200 nm and 500 nm provided a protracted pharmacokinetic profile for up to 4 weeks in rats, with a higher maximum drug concentration in plasma than the 3 μm-sized injectable suspensions. Histopathological examination revealed that MTK NS caused chronic granulomatous inflammation at the injection site, which resolved after 4 weeks.Conclusion: The MTK parenteral NS delivery system is expected to be a valuable tool for treating Alzheimer’s disease with extended dose intervals.Graphical Abstract: Keywords: montelukast, parenteral prolonged release delivery, crystallinity, nanocrystalline suspension, bead-milling, pharmacokinetics, local tolerability

Eun A Kim, Jun Soo Park, Min Seop Kim, Min Young Jeong, Hyun Jin Park, Jun Hyuk Choi, Jae Hee Seo, Yong Seok Choi, Myung Joo Kang College of Pharmacy, Dankook University, Cheonan, Chungnam, 330-714, KoreaCorrespondence: Myung Joo KangCollege of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, 330-714, KoreaTel +82 41 550 1446Fax +82 41 550 7899. Email kangmj@dankook.ac.krBackground: The titrated extract of Centella asiatica (CA) has received much attention as a cosmeceutical ingredient owing to its anti-wrinkle effect. However, due to the low solubility and high molecular weight of pharmacologically active constituents, including asiatic acid (AA), madecassic acid (MA), and asiaticoside (AS), it is challenging to fabricate high-payload topical preparations of CA with satisfactory skin absorption profiles.Purpose: This study aimed to design a high-payload topical preparation of CA using nanocrystallization technique and to evaluate its skin absorption profile and local tolerability.Methods: High-payload nanocrystal suspensions (NSs) were prepared using lab-scale bead-milling technology, by adjusting the type and amount of suspending agent, CA content, type of vehicle, and milling speed. CA-loaded NSs were characterized in terms of morphology, particle size, crystallinity, and in vitro dissolution pattern. Skin absorption of CA nanocrystals was evaluated using a vertical Franz diffusion cell mounted with porcine skin. In vivo skin irritation following topical application of high-payload NS was assessed in normal rats.Results: The optimized NS system, composed of 10% (w/v) CA, 0.5% polyvinylpyrrolidone (PVP) K30 as steric stabilizer, and 89.5% of distilled water, was characterized as follows: spherical or elliptical in shape, 200 nm in size, with low crystallinity. The in vitro dissolution of AA or MA from NSs was markedly faster compared to raw material, under sink condition. Penetration of AA, MA, and AS in the porcine skin was markedly elevated using the high-payload NS formula, providing 5-, 4-, and 4.5-fold higher accumulation in skin layer, compared to that of the marketed cream formula (CA 1%, Madeca cream). Moreover, topical application of high-payload NS was tolerable, showing neither erythema nor oedema in normal rats.Conclusion: The novel NS system is expected to be a virtuous approach for offering a better skin absorption of CA, without using an excess quantity of solubilizers.Keywords: Centella asiatica, asiatic acid, madecassic acid, asiaticoside, nanocrystal suspension, bead-milling, dissolution, skin absorption, skin irritation

Seon Ju Kim,1 Namo Kim,2,3 Eun Hwa Kim,4 Yun Ho Roh,4 Jeehyun Song,2 Kwang Hwan Park,5,* Yong Seon Choi2,3,* 1Department of Anesthesiology and Pain Medicine, National Health Insurance Service Ilsan Hospital, Goyang 10444, Korea; 2Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 03722, Korea; 3Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 03722, Korea; 4Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul 03722, Korea; 5Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul 03722, Korea*These authors contributed equally to this workCorrespondence: Yong Seon ChoiDepartment of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, KoreaTel +82 2 2228 2412Fax +82 2 2228 7897Email yschoi@yuhs.acKwang Hwan ParkDepartment of Orthopaedic Surgery, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, KoreaTel +82 2 2228 2185Fax +82 2 2228 7897Email khpark@yuhs.acPurpose: Lower extremity amputation (LEA) is associated with a high risk of postoperative mortality. The effect of type of anesthesia on postoperative mortality has been studied in various surgeries. However, data for guiding the selection of optimal anesthesia for LEA are limited. This study aimed to determine the effect of anesthesia type on perioperative outcomes in patients with diabetes and/or peripheral vascular disease undergoing LEA.Patients and methods: We reviewed the medical records of patients who underwent LEA at our center between September 2007 and August 2017, who were grouped according to use of general anesthesia (GA) or regional anesthesia (RA). Primary outcomes were 30-day and 90-day mortality. Secondary outcomes were postoperative morbidity, intraoperative events, postoperative intensive care unit admission, and postoperative length of stay. Propensity score-matched cohort design was used to control for potentially confounding factors, including patient demographics, comorbidities, medications, and type of surgery.Results: Five hundred and nineteen patients (75% male, mean age 65 years) were identified to have received GA (n=227) or RA (n=292) for above-knee amputation (1.5%), below-knee amputation (16%), or more minor amputation (82.5%). Before propensity score matching, there was an association of GA with coronary artery disease (44% [GA] vs 34.5% [RA], p=0.028), peripheral arterial disease (73.1% vs 60.2%, p=0.002), and preoperative treatment with aspirin and clopidogrel (68.7% vs 55.1%, p=0.001; 63% vs 41.8%, p

Yun-Sic Bang,1 Junbeom Park,1 Jihee Kim,1 Young-Soon Choi,2 Young Su Lim,2 Hyung Rae Cho,3 Young Uk Kim21Department of Anesthesiology and Pain Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea; 2Department of Anesthesiology and Pain Medicine, Catholic Kwandong University, College of Medicine, International ST. Mary’s Hospital, Incheon, Republic of Korea; 3Department of Anesthesiology and Pain Medine, Myongji Hospital, Hanyang University Medical Center, Seoul, Republic of KoreaPurpose: Knee tibiofemoral osteoarthritis (KOA) is a major health problem, affecting approximately 30% of elderly. Several studies have reported that the loss of patellar cartilage is associated with an increased risk of KOA. However, no study has reported the optimal cut off value of patellar cartilage cross-sectional area (PCA) in KOA. We hypothesize that PCA is a new sensitive morphologic parameter in the diagnosis of KOA. The purpose of this study was to determine whether PCA could be used as an important adjuvant morphological parameter in the diagnosis of KOA.Patients and methods: Data regarding PCA were collected from 88 subjects with KOA. A total of 77 subjects in the control group underwent knee MRI as part of nonsymptomatic medical examination. T2-weighted axial images were acquired from both groups. Using a picture archiving communications system, we analyzed the cross-sectional area of the patellar cartilage on MRI.Results: The average PCA was 98.66±22.18 mm2, in the control group, which was significantly (p

Seung Hyun Kim,1 Do-Hyeong Kim,2 Eungjin Kim,1 Hyun Jung Kim,3,* Yong Seon Choi2,* 1Department of Anesthesiology and Pain Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 2Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 3Department of Preventive Medicine, College of Medicine, Institute for Evidence-based Medicine, Korea University, Seoul, Korea *These authors contributed equally to this work Purpose: Perioperative dextrose-containing fluid administration has been used as a non-pharmacologic preventive measure against postoperative nausea and vomiting (PONV), a common and distressing complication of anesthesia. However, its efficacy remains unclear as previous studies reported inconsistent results. Our objective was to compare dextrose-containing fluid with non-dextrose-containing fluid in terms of PONV for 24 hours after surgery under general anesthesia. The effects of dextrose according to different types of surgery and the fluid volume were also examined.Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing dextrose-containing fluid with non-dextrose-containing fluids after general anesthesia in terms of PONV incidence and the need for rescue anti-emetic therapies for 24 hours after surgery. A literature search was performed, using Medline, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus, up to February 2018.Results: We included seven RCTs. Compared with the control group, perioperative dextrose administration did not reduce the risk for PONV, with a relative risk (RR) of 0.72 (95% CI: 0.50–1.03). However, perioperative dextrose reduced the requirement for anti-emetics, compared with the control group, with a RR of 0.60 (95% CI: 0.44–0.83). The quality of evidence in this meta-analysis was poor due to high risks of selection and performance biases and substantial statistical heterogeneity. After subgroup analysis, the risk for PONV was reduced in patients who had undergone laparoscopic cholecystectomy, but not other surgeries, and the effects of dextrose on the risk for PONV did not differ according to the fluid volume administered.Conclusion: Perioperative intravenous (i.v.) dextrose did not reduce the risk for PONV. However, it did reduce the need for anti-emetics after general anesthesia. Furthermore, the effects of dextrose varied according to the surgery type. Further studies are needed to determine the benefits of perioperative i.v. dextrose administration as a preventive measure against PONV. Keywords: general anesthesia, PONV, dextrose, laparoscopic cholecystectomy

Seung Hyun Kim,1 Minsu Park,2 Jinae Lee,2 Eungjin Kim,1 Yong Seon Choi3 1Department of Anesthesiology and Pain Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 2Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Korea; 3Department of Anesthesiology and Pain Medicine, Severance Hospital, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea Background: The use of capnography monitoring devices has been shown to lower the rates of hypoxemia via early detection of respiratory depression, and facilitate more accurate titration of sedatives during procedures. The aim of the current meta-analysis was to compare the incidence of hypoxemia associated with standard monitoring alone during gastrointestinal endoscopy to that associated with standard monitoring with the addition of capnography.Methods: The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials scientific databases were searched to identify relevant studies. We performed a meta-analysis of randomized controlled trials undertaken up to January 2018 that met our predefined inclusion criteria. The study outcome measures were incidence of hypoxemia, severe hypoxemia, apnea, the use of assisted ventilation, the use of supplemental oxygen, and change in vital signs.Results: We included nine trials assessing a total of 3,088 patients who underwent gastrointestinal procedural sedation. Meta-analysis of study outcome revealed that capnography significantly reduced the incidence of hypoxemia (odds ratio 0.61, 95% CI 0.49–0.77) and severe hypoxemia (odds ratio 0.53, 95% CI 0.35–0.81). However, there were no significant differences in other outcomes including incidence of apnea, assisted ventilation, supplemental oxygen, and changes in vital signs. Early procedure termination and patient satisfaction-related outcomes did not differ significantly in the capnography group and the standard monitoring group.Conclusion: This study indicates that capnography monitoring is an important addition with regard to the detection of hypoxemia during gastrointestinal procedural sedation, and should be considered in routine monitoring during gastrointestinal endoscopy. Keywords: endoscopy, additional monitoring, hypoxemia, apnea

Do-Hyeong Kim, Namo Kim, Jae Hoon Lee, Minju Jo, Yong Seon Choi Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea Background: Children undergoing major orthopedic surgery of the lower extremities can experience severe postoperative pain; yet, the ideal postoperative pain management strategy is unknown. Thus, in this patient population, we investigated the effect of intraoperative epidural infusion of local anesthetic on acute postoperative pain and analgesic consumption. Patients and methods: Patients (N=50, 3–12 years) randomly received either ropivacaine 0.15% (preemptive group) or normal saline (control group) as an initial bolus of 0.2 mL/kg, followed by continuous infusion of 0.15 mL/kg/h throughout surgery. Following surgery, patient-controlled epidural analgesia with ropivacaine 0.1% was provided. The main study outcomes were the revised Face, Legs, Activity, Cry, and Consolability pain scores, epidural ropivacaine consumption, and additional analgesic requirements during the first 48 hours postoperatively. Results: Forty-seven patients completed the study, 23 in the preemptive group and 24 in the control group, respectively. The revised Face, Legs, Activity, Cry, and Consolability pain scores were significantly lower in the preemptive group only at 30 minutes after postanesthesia care unit arrival and 6 hours after surgery (median difference –1.0, 95% CI –2.0 to –1.0, P=0.001 and median difference –2.0, 95% CI –3.0 to –1.0, P=0.005, respectively). However, they were not significantly different between the groups at 12, 24, and 48 hours postoperatively. Epidural ropivacaine consumption and additional analgesic requirements throughout 48 hours postoperatively were not significantly different between the groups. Conclusion: Intraoperative epidural infusion of ropivacaine did not demonstrate preemptive analgesic efficacy within 48 hours postoperatively in children undergoing extensive lower limb orthopedic surgery. Keywords: epidural analgesia, postoperative analgesia, orthopedics, pediatrics

Do-Hyeong Kim,1 Seokyung Shin,1 Ji Young Kim,1 Seung Hyun Kim,2 Minju Jo,2 Yong Seon Choi1 1Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea Background: This study investigated the ability of pulse pressure variation (PPV) and pleth variability index (PVI) to predict fluid responsiveness of patients undergoing spinal surgery in the prone position.Patients and methods: A total of 53 patients undergoing posterior lumbar spinal fusion in the prone position on a Jackson table were studied. PPV, PVI, and hemodynamic and respiratory variables were measured both before and after the administration of 6 mL/kg colloid in both the supine and prone positions. Fluid responsiveness was defined as a 15% or greater increase in stroke volume index, as assessed by esophageal Doppler monitor after fluid loading.Results: In the supine position, 40 patients were responders. The areas under the receiver operating characteristic (ROC) curves for PPV and PVI were 0.783 [95% CI 0.648–0.884, P

Yong Seon Choi,1,* Hye-Min Sohn,2,* Sang-Hwan Do,2 Kyeong Tae Min,1 Jae Hee Woo,3 Hee Jung Baik3 1Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 3Department of Anesthesiology and Pain Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea *These authors contributed equally to this work Background: Postoperative nausea and vomiting (PONV) is a common complication after surgery, which increases physical and psychological discomfort and delays recovery. The aim of this study was to test the hypothesis that ramosetron is comparable to ondansetron for the treatment of established PONV after laparoscopic surgery using a prospective, randomized, double-blinded, noninferiority study.Methods: Patients who had at least two risk factors of PONV and underwent laparoscopic surgery under general anesthesia were assessed for eligibility. Patients who developed PONV within the first 2 h after anesthesia received ondansetron (4 mg) or ramosetron (0.3 mg) intravenously in a randomized double-blind manner. Patients were then observed for 24 h after drug administration. The incidence of nausea and vomiting, severity of nausea, rescue antiemetic necessity, and adverse effects at 0–2 or 2–24 h after drug administration was evaluated. The primary endpoint was the rate of patients exhibiting a complete response, defined as no emesis and no further rescue antiemetic medication for 24 h after drug administration.Results: Among the 583 patients, 210 (36.0%) developed PONV and were randomized to either the ondansetron (n=105) or ramosetron (n=105) group. Patient’s characteristics were similar between the groups. The complete response rate was 44.1% in the ondansetron group and 52.9% in the ramosetron group after 24 h of initial antiemetic administration. The incidence of adverse events was not different between the groups.Conclusion: We found evidence to support the noninferiority of ramosetron (0.3 mg) compared to ondansetron (4 mg) for the treatment of established PONV in moderate to high-risk patients undergoing laparoscopic surgery. Keywords: laparoscopic surgery, ondansetron, postoperative nausea and vomiting, ramosetron, non-inferiority, antiemetic

Jae-Beom Lee,1 Yun-Seok Choi,2 Woo-Baek Chung,2 Ami Kwon,2 Chul-Soo Park,2 Man-Young Lee2 1Anyang Sam Hospital, 2Division of Cardiology, Department of Internal Medicine, Youido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea Purpose: High coronary calcium score (CCS) and post-procedural cardiac enzyme may be related with poor outcomes in patients with coronary stent implantation. Methods: A total of 1,072 patients (63.2% male, mean age: 61.7±10.3 years) who underwent coronary multi-detect computed tomography at index procedure and follow-up coronary angiography (CAG) after drug-eluting stent (DES) were divided into two groups: those with and without target lesion revascularization (TLR; >50% reduction in luminal stent diameter or angina symptoms on follow-up CAG). The CCSs for predicting stent revascularization were elucidated. Results: There were no significant differences between the two groups with regard to risk factors. The initial CCS was significantly higher in the TLR group (1,102.4±743.7 vs 345.8±51.05, P=0.04). After adjustment of significant factors for TLR, only CCS and post-procedural creatine kinase MB form (CK-MB) elevation were significant predictors of coronary artery TLR. Receiver operation curve revealed that >800 in CCS had 69% in sensitivity and 88% in specificity about predicting the TLR. Conclusion: High CCS with post-procedural CK-MB might be the useful predictors for TLR after DES implantation. Keywords: coronary restenosis, drug-eluting stents, calcium, creatine kinase

Dongseong Shin,1 Sook Joung Lee,2 Yu-Mi Ha,3 Young-Sim Choi,3 Jae-Won Kim,3 Se-Rin Park,3 Min Kyu Park3 1Clinical Trials Center, Gachon University Gil Medical Center, Incheon, 2Department of Rehabilitation Medicine, 3Department of Clinical Pharmacology and Therapeutics, Dong-A University College of Medicine and Hospital, Busan, South Korea Objective: Prostaglandin E2 (PGE2) synthesis is modulated by COX2. Changes in PGE2 could be used to quantify the COX2 inhibition after ibuprofen administration. This study investigated the pharmacokinetic and pharmacodynamic relationships for COX2 inhibition according to three formulations of ibuprofen in healthy male subjects.Materials and methods: A randomized, open-label, single-dose, three-treatment, six-sequence crossover study was performed in 36 healthy South Korean male volunteers. Enrolled subjects received the following three 200 mg ibuprofen formulations: ibuprofen arginine, solubilized ibuprofen capsule, and standard ibuprofen. Pharmacokinetic and pharmacodynamic blood samples were collected for 16 hours following treatment. For pharmacodynamic evaluations, lipopolysaccharide (LPS)-induced PGE2 inhibition at each time point compared to predose was measured. Noncompartmental analysis was used for pharmacokinetic assessment, and time-weighted average inhibition (WAI) of PGE2 was applied to the pharmacodynamic evaluation.Results: After a single oral dose of the ibuprofen formulations, the median times to maximum concentration were 0.42, 0.5, and 1.25 hours in ibuprofen arginine, solubilized ibuprofen capsule, and ibuprofen, respectively. The maximum observed plasma concentration was lower in ibuprofen, and the area under the plasma concentration–time curve was comparable among the three formulations. A significant difference was observed between fast-acting formulations and standard ibuprofen tablets for both maximum concentration and time taken to reach it. Individual formulations had an effect on PGE2 WAI during the 8 hours following treatment, resulting in significantly lower WAI in standard ibuprofen: ibuprofen arginine 18.4%, solubilized ibuprofen capsule 18.4%, and standard ibuprofen 11.6%.Conclusion: Rapid absorption and higher peak concentration were observed in ibuprofen arginine and the solubilized ibuprofen capsule. Additionally, fast-acting formulations had more predominant inhibitory activity on the COX2 enzyme. Keywords: ibuprofen, different formulation, COX2-inhibitory effects

Sung Rae Kim,1 Myoung Jin Ho,2 Sang Hyun Kim,1 Ha Ra Cho,2 Han Sol Kim,2 Yong Seok Choi,2 Young Wook Choi,1 Myung Joo Kang2 1Division of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University, Seoul, 2College of Pharmacy, Dankook University, Cheonan, Chungnam, South Korea Abstract: Piroxicam (PRX), a potent nonsteroidal anti-inflammatory drug, is prescribed to relieve postoperative and/or chronic joint pain. However, its oral administration often results in serious gastrointestinal adverse effects including duodenal ulceration. Thus, a novel cationic nanoparticle (NP) was explored to minimize the systemic exposure and increase the retention time of PRX in the joint after intra-articular (IA) injection, by forming micrometer-sized electrostatic clusters with endogenous hyaluronic acid (HA) in the synovial cavity. PRX-loaded NPs consisting of poly(lactic-co-glycolic acid), Eudragit RL, and polyvinyl alcohol were constructed with the following characteristics: particle size of 220 nm, zeta potential of 11.5 mV in phosphate-buffered saline, and loading amount of 4.0% (w/w) of PRX. In optical and hyperspectral observations, the cationic NPs formed more than 50 µm-sized aggregates with HA, which was larger than the intercellular gaps between synoviocytes. In an in vivo pharmacokinetic study in rats, area under the plasma concentration–time curve (AUC0–24 h) and maximum plasma concentration (Cmax) of PRX after IA injection of the cationic NPs were

Dae Ro Lee,1 Myoung Jin Ho,1 Hyuck Jun Jung,1 Ha Ra Cho,1 Jun Seo Park,1 Suk-Hyun Yoon,2 Yong Seok Choi,1 Young Wook Choi,3 Chung-Hun Oh,2,4,5 Myung Joo Kang1 1College of Pharmacy, 2Department of Medical Laser, Graduate School, Dankook University, Dongnam-gu, Choenan, Chungnam, 3College of Pharmacy, Chung-Ang University, Dongjak-gu, Seoul, 4Department of Oral Physiology, College of Dentistry, Dankook University, 5Abel Medi-Tech Inc., Dongnam-gu, Cheonan, Chungnam, Korea Abstract: A new Soluplus (polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer)-based supersaturable self-emulsifying drug delivery system (S-SEDDS) was formulated to enhance oral absorption of tacrolimus (FK506) with minimal use of oil, surfactant, and cosurfactant. A high payload supersaturable system (S-SEDDS) was prepared by incorporating Soluplus, as a precipitation inhibitor, to SEDDS consisting of Capmul MCM, Cremophor EL, and Transcutol (FK506:vehicle:Soluplus =1:15:1). In vitro dissolution profile and in vitro pharmacokinetic aspect of S-SEDDS in rats were comparatively evaluated with those of conventional SEDDS formulas containing four times greater content of vehicle components (FK506:vehicle =1:60). Both formulations formed spherical drug-loaded microemulsion 80% of accumulated dissolution rate for 24 hours, analogous to that from conventional SEDDS. Moreover, pharmacokinetic parameters of the maximum blood concentration and area under the curve from S-SEDDS formula in rats were not statistically different (P>0.05) than those of conventional SEDDS. The results suggest that the Soluplus-based supersaturable system can be an alternative to achieve a comparable in vitro dissolution profile and in vivo oral absorption with conventional SEDDS, with minimal use of vehicle ingredients. Keywords: tacrolimus, supersaturation, precipitation inhibitor, Soluplus, microemulsion, oral bioavailability

GeeHee Kim,1 Ho-Joong Youn,2 Yun-Seok Choi,2 Hae Ok Jung,2 Wook Sung Chung,2 Chul-Min Kim1 1Department of Internal Medicine, St Vincent’s Hospital, The Catholic University of Korea, Suwon, 2Division of Cardiology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Objective: Routine measurement of the carotid intima–media thickness is not recommended in recent clinical practice guidelines for risk assessment of the first atherosclerotic cardiovascular disease (ASCVD) event (the definition of which includes acute coronary syndromes, a history of myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease presumed to be of atherosclerotic origin). The aim of the present study was to elucidate the role of carotid artery evaluation for primary prevention of ASCVD in asymptomatic high-risk patients visiting a teaching hospital.Methods: Eight hundred seventy-three patients (487 male [55.8%], mean age 59.4±11.5 years) who were statin-naive and without ASCVD, which was proven by coronary angiography or coronary CT angiography, were enrolled in this study. The patients underwent carotid scanning in the Medical Department of St Mary’s Hospital from September 2003 to March 2009. ASCVD outcomes were evaluated for median follow-up of 1,402 days.Results: A total of 119 participants experienced ASCVD events. In multivariate Cox regression analysis, age (hazard ratio [HR] =1.026, 95% confidence interval [CI] =1.002–1.050, P=0.033), history of smoking (HR =1.751, 95% CI =1.089–2.815, P=0.021), statin therapy (HR =0.388, 95% CI =0.205–0.734, P=0.004), and carotid plaques (HR =1.556, 95% CI =1.009–2.400, P=0.045) were associated with ASCVD events. In middle-aged group (45≤ age

Background: A low level of high-density lipoprotein cholesterol (HDL-C) is strongly associated with cardiovascular events. However, the significance of HDL-C after statin therapy on the outcome of patients who have undergone percutaneous coronary intervention (PCI) with drug eluting stents (DES) is unclear.Objectives: To investigate the significance of HDL-C after statin therapy on cardiovascular events in patients with coronary artery disease after DES implantation.Methods: Patients who underwent PCI with DES from January 2004 to December 2009 were prospectively enrolled. The follow-up lipid panel of 2693 patients (median lab follow-up duration 225 days) who had continued using statins after PCI and who attained low-density lipoprotein cholesterol (LDL-C) <100 mg/dl was analysed. Major adverse cardiac events (MACE), including all-cause death, non-fatal myocardial infarction, and target vessel revascularisation according to follow-up HDL-C level (40 mg/dl for men or 50 mg/dl for women) were compared with the use of propensity scores matching.Results: Median follow-up duration was 832 days. 1585 (58.9%) patients had low follow-up HDL-C and 1108 had high follow-up HDL-C. The low follow-up HDL-C group had significantly higher rates of MACE. Low follow-up HDL-C was a significant independent predictor of MACE (adjusted HR 1.404, 95% CI 1.111 to 1.774, p=0.004). In further analysis with propensity scores matching, overall findings were consistent.Conclusions: Raising HDL-C levels may be a subsequent goal after achieving target LDL-C levels in patients with DES implantation. [ABSTRACT FROM AUTHOR]

Stress-induced cardiomyopathy is an acute cardiac syndrome mimicking ST-segment elevation myocardial infarction and is characterised by transient left ventricular dysfunction in the absence of obstructive coronary artery disease. Caesarean delivery is associated with intense emotional and physical stress, which may precipitate stress-induced cardiomyopathy mimicking acute myocardial infarction. We report a case of a woman who was supported with extracorporeal membrane oxygenation for acute heart failure and severe pulmonary oedema, which may have resulted from stress-induced cardiomyopathy in the early postpartum period following caesarean delivery. [ABSTRACT FROM AUTHOR]

Goals Of Work: Family caregivers play an important role in caring for cancer patients, but the impact of caregivers' unmet needs on the quality of end-of-life (EOL) care they deliver and on their workplace performance are less understood.Patients and Methods: We identified 1,662 family caregivers of cancer patients who had died at any of 17 hospitals in Korea during 2004. The caregivers answered a telephone questionnaire about needs that were not met when they delivered terminal cancer care and how those unmet their needs affected their workplace performance; they also answered the Quality Care Questionnaire-End of Life (QCQ-EOL).Results: Compared with caregivers who did not have unmet needs, caregivers who had unmet needs for symptom management, financial support, or community support showed poorer QCQ-EOL scores (P < 0.01). Caregivers who had unmet needs for financial support (adjusted odds ratio (aOR) = 7.55; 95% confidential interval (CI) 3.80-15.00), psychosocial support (aOR = 6.24; 95% CI 2.95-13.05), symptom management (aOR = 3.21; 95% CI 2.26-4.54), community support (aOR = 3.82; 95% CI 2.38-6.11), or religious support (aOR = 4.55; 95% CI 1.84-11.26) were more likely to experience work limitations. Caregivers of patients receiving conventional hospital care were more likely to have unmet needs for symptom management (aOR = 1.21; 95% CI 1.00-1.47), psychosocial support (aOR = 1.99; 95% CI 1.37-2.88), and religious support (aOR = 1.73; 95% CI 1.08-2.78) than those of patients receiving palliative hospice care.Conclusions: Caregivers' unmet needs negatively affected both the quality of EOL care they delivered and their workplace performance. More investment in caregiver support and public policies that meet caregiver needs are needed, and hospice use should be encouraged. [ABSTRACT FROM AUTHOR]

Goals Of Work: The goal of this study was to develop a new, objective prognostic score (OPS) for terminally ill cancer patients based on an integrated model that includes novel objective prognostic factors.Materials and Methods: A multicenter study of 209 terminally ill cancer patients from six training hospitals in Korea were prospectively followed until death. The Cox proportional hazard model was used to adjust for the influence of clinical and laboratory variables on survival time. The OPS was calculated from the sum of partial scores obtained from seven significant predictors determined by the final model. The partial score was based on the hazard ratio of each predictor. The accuracy of the OPS was evaluated.Main Results: The overall median survival was 26 days. On the multivariate analysis, reduced oral intake, resting dyspnea, low performance status, leukocytosis, elevated bilirubin, elevated creatinine, and elevated lactate dehydrogenase (LDH) were identified as poor prognostic factors. The range of OPS was from 0.0 to 7.0. For the above cutoff point of 3.0, the 3-week prediction sensitivity was 74.7%, the specificity was 76.5%, and the overall accuracy was 75.5%.Conclusions: We developed the new OPS, without clinician's survival estimates but including a new prognostic factor (LDH). This new instrument demonstrated accurate prediction of the 3-week survival. The OPS had acceptable accuracy in this study population (training set). Further validation is required on an independent population (testing set). [ABSTRACT FROM AUTHOR]

Goals Of Work: The goal of this study was to investigate the utilization of and attitudes toward life-sustaining treatments (LSTs) at the end of life.Materials and Methods: We identified 4,042 families of cancer patients who had died at any of 17 hospitals in Korea during 2004. Among those, we analyzed the interviews provided by 1,592 (39.4%) primary caregivers. Only women who provided information in baseline and follow-up point could be included for internal comparison.Main Results: Most caregivers did not discuss with their patient the option of utilizing the intensive care unit (ICU; 92.7%) or cardiopulmonary resuscitation (CPR; 93.7%) to prolong an ending life. Logistic regressions indicated that the ICU was more likely to be utilized when patients experienced an unexpected medical problem before dying, discussed the ICU with the family caregiver, or were low-educated. CPR was more likely to be used if the patient died within 6 months of diagnosis or the family caregiver was <65 years old. Family caregivers more likely to use the ICU if placed in the same situation again were those whose patients had a higher monthly income or died within 6 months of diagnosis, low-educated, or had utilized the ICU.Conclusions: Our findings underscore the importance of discussing LST with terminally ill patients based on adequate information. [ABSTRACT FROM AUTHOR]

OH, S., et al.: Differential Diagnosis of Slow/Slow Atrioventricular Nodal Reentrant Tachycardia from Atrioventricular Reentrant Tachycardia Using Concealed Posteroseptal Accessory Pathway by 12-Lead Electrocardiography. Slow pathways are used as both antegrade and retrograde conduction pathway in slow/slow atrioventricular nodal reentrant tachycardia (SS-AVNRT), and patients with SS-AVNRT have tachycardia ECGs mimicking atrioventricular reentrant tachycardia using concealed posteroseptal accessory pathway (PS-AVRT). Therefore, SS-AVNRT can be misdiagnosed as PS-AVRT, and the differential diagnosis is clinically important. Standard 12-lead ECGs during tachycardia were analyzed in patients with SS-AVNRT (n = 10) and PS-AVRT (n = 10). All these patients were diagnosed by electrophysiological study and underwent successful catheter ablation. Differences of the RP' intervals (dRP') between V1 and the inferior leads were evaluated. SS-AVNRT had significantly longer RP' intervals measured in V1 (167 ± 25.2 vs 137 ± 26.8 ms, SS-AVNRT vs PS-AVRT, respectively, P = 0.02), longer dRP' between V1 and II (dRP'[V1-II], 37 ± 14 vs 17 ± 6.7 ms, P = 0.0007), longer dRP'[V1-III] (39 ± 14 vs 17 ± 9.9 ms, P = 0.0011), and longer dRP'[V1-aVF] (39 ± 13 vs 20 ± 9.5 ms, P = 0.0008). The following criteria were suggested for differential diagnosis of SS-AVNRT from PS-AVRT: dRP'[V1-II] >25 ms (sensitivity and specificity: 80% and 100%, respectively), dRP'[V1-III] >23 ms (90% and 90%), dRP'[V1-aVF] >30 ms (90% and 90%). Differences of the RP' intervals between V1 and the inferior leads in the tachycardia ECGs were useful for differential diagnosis of SS-AVNRT from PS-AVRT. (PACE 2003; 26:2296-2300) [ABSTRACT FROM AUTHOR]

Opioid antagonists have well-established indications in the reversal of life-threatening opioid toxicity, but also hold considerable promise for other applications in palliative care practice, particularly management of opioid-related constipation. We briefly review current understanding of opioid receptors, focusing on their complex role in gastrointestinal physiology. We summarize the pharmacology, conventional indications, and clinical usage of three major groups of opioid antagonists, including a promising new peripherally acting agent, methylnaltrexone, which is not commercially available. We suggest an approach to administering opioid antagonists for reduction of life-threatening opioid toxicity in patients with pain. The literature on opioid-induced constipation and its treatment with opioid-antagonists is reviewed in detail. Finally, other potential uses of opioid antagonists in palliative care are described, especially strategies for reducing such opioid side effects as nausea and pruritus and for improving analgesia or reducing tolerance by concomitantly administrating both an opioid agonist and low dosages of an antagonist. [ABSTRACT FROM AUTHOR]

Studies the system of nonlinear partial differential equations modelling the electrodiffusion of ions inside living cells. Imposition of jump conditions for species concentrations and electropotential across membranes; Establishment of mathematical bounds; Steady-state solutions for more than one membranes; Evidence for a global stability result.

Hemangiomas are known to be common benign tumors. However, hemangiomas of female genital organs are very rare. Furthermore, a retroperitoneal hemangioma arising from ovarian vessels has never been reported. Here we report a case of a 29-year-old woman with a retroperitoneal cavernous hemangioma arising from the ovarian vessels of infundibulopelvic ligament, which was treated with laparoscopic resection. The operating time was 30 minutes, and resection was carried out with minimal blood loss. The postoperative period was uneventful, and the patient was discharged on postoperative day 3. Laparoscopic resection of this type of hemangioma is feasible. [ABSTRACT FROM AUTHOR]