• Toxicological Research
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• v.29 no.1
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• pp.53-60
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• 2013

Studies on milk transfer of drugs in non-human primates (NHPs) are among the crucial components in the assessment of peri- and postnatal toxicity because of the similarity between NHPs and humans. To evaluate the milk transfer of valproic acid (VPA) in NHPs, the toxicokinetics of VPA, an antiepileptic drug, were studied in pregnant cynomolgus monkeys. VPA was administered once daily to pregnant cynomolgus monkeys at doses of 0, 30, 90, and 270 mg/kg by oral gavage from Day 100 of gestation (GD 100) to Day 31 of lactation (LD 31). Concentrations of VPA and its metabolite, 4-ene-VPA, in the maternal plasma on GD 100, GD 140, and LD 30, and concentrations of VPA and 4-ene-VPA in the offspring plasma and milk on LDs 30 and 31, respectively, were quantified using liquid chromatography tandem mass spectrometry (LC/MS/MS). After administration of a single oral dose of VPA to pregnant monkeys on GD 100, the concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma of all treatment groups up to 24 hr after administration, which showed that VPA was absorbed and that the monkeys were systemically exposed to VPA and 4-ene-VPA. After administration of multiple doses of VPA to the monkeys, VPA was detected in the pup's plasma and in milk taken on LD 30 and LD 31, respectively, which showed that VPA was transferred via milk, and the pup was exposed to VPA. Further, the concentration of VPA in the milk increased with an increase in the dose. Extremely low concentrations of 4-ene VPA were detected in the milk and in the pup plasma. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at doses of 30, 90, and 270 mg/kg/day from GD 100 to LD 31. VPA was transferred via milk, and the VPA exposure to the pup increased with an increase in the dose of VPA. The metabolite, 4-ene VPA, was present in extremely low concentrations (< 0.5 ${\mu}g/ml$) in the milk and in the pup plasma. In this study, we established methods to confirm milk transfer in NHPs, such as mating and diagnosis of pregnancy by examining gestational sac with ultrasonography, collection of milk and pup plasma and determination of toxicokinetics, using cynomolgus monkeys.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.173-180
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• 1995

Purpose: Unresectable rectal cancer has a grave prognosis. regardless of the therapy used and median survival is less than 1 rear. Also, it is reported by many authors that $50-80\%$ of unresectable lesions were rendered resectable by radiation therapy and the median survival time for the completely resected patients were better than that of the unresected patients. So we analyzed retrospectively our data for the better treatment outcome in these patients. Materials and MEthods:From 1980 to 1992, 45 patients with initially unresectable tumors in the rectum were treated with radiation therapy with/without surgery in Department of Radiation Oncology, Yonsei Cancer Center 10 MV radiation and multiple field technique (box or AP/PA) were used. The total dose was 28-70 Gy and median dose was 48 Gy. We evaluated the lesion status at 45-50 Gy for operability. If the lesions appeared to be resectable, the Patients were operated on 4-6 weeks after radiation therapy. But if the lesions were still fixed, the radiation dose was increased to 60-65 Gy. Results: For all patients, the 2-year actuarial survival was $13.3\%$ and median survival was 9.5 months. Of 6 patients who had received less than 45 Gy, only $17\%$ of patients responded, but in the patients who had received more than 45 Gy, $60\%$ of response rate was achieved Six of the 24 patients$(25\%)$ underwent surgical resections following RT. For patients undergoing curative resection. the two-rear survival was $50\%,$ but that of the patients without resection was $9.5\%$ (p<0.01). Survival of patients with complete response following RT was $50\%$ at 2 years. Survival of patients with partial response, stable disease and progressive disease after RT was $13.4\%,\;15.4\%,\;0\%$ respectively (P<0.05). Conclision: Our data suffests that the efforts which can increase the response rate and aggressive surgical approach are needed to achieve the better local control and survival in unresectable rectal cancers.

• Tuberculosis and Respiratory Diseases
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• v.39 no.6
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• pp.536-541
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• 1992

Bronchiolitis obliterans organizing pneumonia (BOOP) is a type of diffuse interstitial lung disease that primarily affects the small conducting airways and characterized by the presence of granulation tissue plugs within the lumen of small airways often extending into alveolar ducts. It is associated with a number of different causes, including a variety of infections, fume exposures, drugs, collagen diseases and idiopathic. Recently we have experienced one patient with idiopathic BOOP. The patient was a 58 year old man presented with 2 months' history of dry cough and exertional dyspnea. The phyical examination showed inspiratory crackles at both lower lung field. Chest X-ray showed bilateral multiple patchy alveolar density. Pulmonary function studies showed a moderate degree of restrictive lung disease. Open lung biopsy carried out and revealed findings characteristic of BOOP. There was a dramatic response clinically and radiologically to high dose predinisolone therapy. Chest X-ray and pulmonary function test under-taken one year later showed marked improvement. New lesion on chest PA was developed during the period of tapering of prednisolone dose, but it was soon disappeared after increasing of prednisolone dose. One year later, he is well without steroid therapy.

• The Korean Journal of Pain
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• v.20 no.2
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• pp.169-173
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• 2007

Background: Although the use of intravenous patient controlled analgesia (IVPCA) has been compared to the use of patient conrolled epidural analgesia (PCEA), there is no optimal administration route of alfentanil for the treatment of postoperative pain. This randomized double-blind study compared the efficacy of the use of IVPCA and PCEA for postoperative pain and the side effects after a total abdominal hysterectomy (TAH). Methods: Sixty patients undergoing a TAH were randomly assigned to receive either IVPCA (Group I) or PCEA (Group E) for the infusion of alfentanil for postoperative pain control. In both groups, a loading dose of $750{\mu}g$ alfentanil was administered. All patients received the same continuous infusion rate (0.3 mg/h), bolus dose (0.15 mg), and lockout time (15 min). The incidence of side effects, the VAS (visual analog scale) of pain, blood pressure, and heart rate were checked for 20 hours after the loading dose injection. Results: The VAS of pain was not significantly different between the two groups of patients. The onset of the analgesic effect was significantly more rapid in the Group I patients than in the Group E patients. There was no difference in side effects for either group. Conclusions: When considering multiple factors such as the onset of analgesia, technical difficulties or infection after the procedure, IVPCA using alfentanil is more useful than PCEA for postoperative pain control after a TAH.

• Korean Journal of Psychosomatic Medicine
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• v.24 no.2
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• pp.217-226
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• 2016

Objectives : To investigate changes in, and predictors of, metabolic syndrome(MetS) status over a 5-year period in chronic schizophrenic patients and to identify factors associated with the prevention of or recovery from MetS. Methods : In total, 107 patients, all of whom provided written informed consent, were followed from 2011 to 2016 at Naju National Hospital for this study. MetS was defined according to the revised National Cholesterol Education Program-Adult Treatment Panel III guidelines. Results : During follow-up period, 22(20.5%) patients were newly diagnosed to MetS, 14(13.1%) were disappeared, 77(66.4%) were not changed[MetS : 34(31.8%), No MetS 37(34.6%)]. Common significant factors in the two changed groups were triglyceride and waist circumference, not dose and type of antipsychotic medication. Multiple logistic regression analysis revealed that female gender(odds ratio[OR]=2.846, 95% confidence interval[CI] : 1.020-7.942), attending two or more outpatient visits per month(OR=3.155, 95% CI : 1.188-8.379) and taking antidepressant medication(OR=3.991, 95% CI : 1.048-15.205) were significantly associated with MetS after controlling for other confounding variables. Type and dose of antipsychotic medication were not significantly associated with MetS. Conclusions : Triglyceride and waist circumference were important manageable indicator of MetS. Adoption of a healthy lifestyle is more important than adjusting the dose or type of antipsychotic medication in the treatment of chronic schizophrenia patients with MetS.

• Korean Journal of Radiology
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• v.22 no.9
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• pp.1547-1554
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• 2021

Objective: We aimed to investigate whether repeated intravascular administration of iodinated contrast media (ICM) or gadolinium-based contrast agents (GBCAs) within a short interval was associated with an increased risk of post-contrast acute kidney injury (PC-AKI). Materials and Methods: This retrospective study included 300 patients (mean age ± standard deviation, 68.5 ± 8.1 years; 131 male and 169 female) who had undergone at least one ICM-enhanced perfusion brain CT scan, had their baseline and follow-up serum creatinine levels available, and had not undergone additional contrast-enhanced examinations 72 hours before and after a time window of interest were included. The study population was divided into three groups: single-dose group and groups of patients who had received multiple contrast administrations in the time window of interest with the minimum contrast repeat interval either within 4 hours (0-4-hour group) or between 4 to 48 hours (4-48-hour group). Multivariable logistic regression analysis was conducted to evaluate the association between AKI and repeated ICM administrations. A similar supplementary analysis was performed including both ICM and GBCA. Results: When ICM was only considered ignoring GBCA, among 300 patients, 207 patients received a single dose of ICM, 58 had repeated doses within 4 hours (0-4-hour group), and 35 patients had repeated doses between 4 to 48 hours (4-48-hour group). Most patients (> 95%) had a baseline estimated glomerular filtration rate (eGFR) of ≥ 30 mL/min/1.73 m². AKI occurred in 7.2%, 13.8%, and 8.6% of patients in the single-dose, 0-4-hour, and 4-48-hour groups, respectively. In the 0-4-hour and 4-48-hour groups, additional exposure to ICM was not associated with AKI after adjusting for comorbidities and nephrotoxic drugs (all p values > 0.05). Conclusion: Repeated intravascular administrations of ICM within a short interval did not increase the risk of AKI in our study patients suspected of acute stroke with a baseline eGFR of ≥ 30 mL/min/1.73 m².

• Journal of Ginseng Research
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• v.39 no.3
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• pp.189-198
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• 2015

Background: Antiallergic effect of 20(S)-protopanaxatriol (PPT), an intestinal metabolite of ginseng saponins, was investigated in guinea pig lung mast cells and mouse bone marrow-derived mast cells activated by a specific antigen/antibody reaction. Methods: Increasing concentrations of PPT were pretreated 5 min prior to antigen stimulation, and various inflammatory mediator releases and their relevant cellular signaling events were measured in those cells. Results: PPT dose-dependently reduced the release of histamine and leukotrienes in both types of mast cells. Especially, in activated bone marrow-derived mast cells, PPT inhibited the expression of Syk protein, cytokine mRNA, cyclooxygenase-1/2, and phospholipase $A_2$ ($PLA_2$), as well as the activities of various protein kinase C isoforms, mitogen-activated protein kinases, $PLA_2$, and transcription factors (nuclear factor-${\kappa}B$ and activator protein-1). Conclusion: PPT reduces the release of inflammatory mediators via inhibiting multiple cellular signaling pathways comprising the $Ca^{2+}$ influx, protein kinase C, and $PLA_2$, which are propagated by Syk activation upon allergic stimulation of mast cells.

• Korean Journal of Clinical Pharmacy
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• v.22 no.1
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• pp.73-80
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• 2012

This study was to determine the inappropriate drug use in pediatric outpatients who received 2 or more prescriptions on the same day. Retrospective drug utilization reviews (DURs) were implemented to samples obtained from national health insurance claims data during December 2008 to February 2009, using 5 DUR criteria (duplication, drug-drug interaction, drug-disease interaction, drug-age contraindication, incorrect dosage) established in the Drug Information Framework (DIF)-$Korea^{TM}$, DUR program. Among 38,451 claims analyzed in the study, 74.7% had more than one conflicts in the 5 DUR modules. Among 16,472 patients analyzed, 49.6% had conflicts with duplication criteria composing of ingredient duplication (23.3%) and therapeutic class duplication (39.6%). Incorrect dosages were found in 73.6% of patients and under-dosage conflicts accounted for 59.9%, which was higher than over-dosage conflicts (38.3%). In this study, inappropriate drug prescriptions such as under-dose, pediatric contraindication and therapeutic duplication were prevalent in pediatric outpatient settings, suggesting much more awareness to the society, to prevent drug related problems in a vulnerable pediatric group.

• The Journal of Korean Institute of Electromagnetic Engineering and Science
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• v.15 no.7
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• pp.669-676
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• 2004

In this paper, a new algorithm is proposed for resolving multiple broadband incoherent sources incident on a uniform linear array. The proposed method dose not require any initial estimates for finding the transformation matrix, while the Coherent Signal-Subspace Method(CSM) proposed by Wang and Kaveh requires preliminary estimates of multigroup source location. An effective procedure is derived for finding the enhanced spectral density matrix at the center frequency using signal enhancement approach and then constructing a common signal subspace by selecting a unitary transformation matrix which is obtained via rotation of signal subspace method. The proposed approach is found to provide superior performance relative to that obtained with the CSM method in terms of sample bias of direction-of-arrival estimates.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.259-263
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• 1999

Nefazodone, a newer antidepressant is a phenylpiperazine derivative that inhibits the reuptake of both norepinephrine and serotonin, and antagonizes $5-HT_{2A}$ and ${\alpha}_1$ adrenergic receptors. Compared with SSRIs, nefazodone caused the fewer activating symptoms, adverse gastrointestinal effects(nausea, diarrhea, anorexia) and adverse effects of sexual function, but is associated with the more dizziness, dry mouth, constipation, visual disturbances and confusion. We report on 4 cases of visual disturbances and hallucinations in patients taking nefazodone. It is not certain what mechanisms mediated these side effects, but three mechanisms are possible. 1) Nefazodone, as a 5-HT2 antagonist, might induce visual disturbances. 2) mCPP, metabolite of nefazodone might contribute to the hallucination through action on 5-HT receptor. 3) Dopaminergic enhancing activity of nefazodone might cause hallucination. These case report raises the possibility that dose-related perceptual disturbances may exist with nefazodone. The fact emphasizes the need to pay close attention to all possible drug interactions, particularly in patients treated with multiple psychoactive agents, older patients, and patients with decreased hepatic function.