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1.  Second Complete Remission of Relapsed Stage IV Non-Small Cell Lung Cancer Following Retreatment 
Non-small cell lung cancer (NSCLC) is the leading cause of cancer related deaths. Most patients were presented with advanced disease at the time of diagnosis. In advanced NSCLC, it is almost impossible to anticipate complete remission by using only cytotoxic chemotherapy or molecularly targeted agents. In our case, two patients were diagnosed as advanced NSCLC and received chemotherapy. They achieved complete response (CR). After finishing treatment, disease recurred. They were retreated with the same regimens and achieved second CR. Until now, they have received each regimen, continuously, and the CR state has been maintained.
doi:10.4046/trd.2012.72.4.381
PMCID: PMC3510290  PMID: 23227080
Carcinoma, Non-Small-Cell Lung; Remission Induction; Retreatment; Maintenance Chemotherapy
2.  Silver nanoparticles modify VEGF signaling pathway and mucus hypersecretion in allergic airway inflammation 
The anti-inflammatory action of silver nanoparticles (NPs) has been reported in a murine model of asthma in a previous study. But more specific mechanisms of silver NPs in an attenuation of allergic airway inflammation have not yet been established. Vascular and mucous changes are believed to contribute largely in pathophysiology in asthma. Among various factors related to vascular changes, vascular endothelial growth factor (VEGF) plays a pivotal role in vascular changes in asthma. Mucin proteins MUC5AC and MUC5B have been implicated as markers of goblet cell metaplasia in lung pathologies. The aim of this study was to investigate the effects of silver NPs on VEGF signaling pathways and mucus hypersecretion. Ovalbumin (OVA)-inhaled female BALBc mice were used to evaluate the role of silver NPs and the related molecular mechanisms in allergic airway disease. In this study, with an OVA-induced murine model of allergic airway disease, it was found that the increased levels of hypoxia-inducible factor (HIF)-1α, VEGF, phosphatidylinositol-3 kinase (PI3K) and phosphorylated-Akt levels, and mucous glycoprotein expression (Muc5ac) in lung tissues were substantially decreased by the administration of silver NPs. In summary, silver NPs substantially suppressed mucus hypersecretion and PI3K/HIF-1α/VEGF signaling pathway in an allergic airway inflammation.
doi:10.2147/IJN.S27159
PMCID: PMC3310409  PMID: 22457593
allergic airway disease; hypoxia inducible factor-1α; vascular endothelial growth factor
3.  Effect of Exercise Intervention on Changes in Free Fatty Acid Levels and Metabolic Risk Factors in Stroke Patients 
[Purpose] The present study investigated the effects of regular exercise on the improvement of free fatty acid (FFA) levels and metabolic risk factors of stroke patients. [Methods] The subjects were 20 male patients aged 47−59 years who were diagnosed as having hemiplegia resulting from stroke. Exercise was conducted using a stationary bicycle, a rehabilitative exercise machine. The exercise program utilized the heart rate reserve (HRR) method to create an exercise intensity amounting to 50−70% of the target heart rate (THR). The program lasted for 30 minutes and was conducted 5 times per week for a total of 12 weeks. [Results] In stroke patients, 12 weeks of exercise training yielded a significant interaction effect with weight, body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR). There were also significant differences in triglycerides (TG) according to the time of measurement, and an interaction effect was observed for triglycerides (TC). High-density lipoprotein cholesterol (HDLC), an important marker of improvement in metabolic risk factors, showed a significant interaction effect with exercise training. In addition, free fatty acids (FFA) showed a significant difference based on the time of measurement and showed a significant negative correlation with HDLC (r = −0.77). [Conclusion] The results of the present study suggest that regular exercise by stroke patients reduces their risk of metabolic complications and stroke recurrence by reducing obesity indices, improving serum lipid and FFA levels, and increasing HDLC levels.
doi:10.1589/jpts.26.275
PMCID: PMC3944305  PMID: 24648648
Stroke patient; Metabolic risk factors; Free fatty acids (FFA)
4.  Treadmill exercise reduces spinal cord injury-induced apoptosis by activating the PI3K/Akt pathway in rats 
Apoptosis occurring secondary to spinal cord injury (SCI) causes further neural damage and functional loss. In this study, a rat model was used to investigate the effect of treadmill exercise on SCI-induced apoptosis and expression of neurotrophic factors. To produce SCI, a contusion injury (10 g × 25 mm) was applied subsequent to laminectomy at the T9–T10 level. Following SCI, treadmill exercise was performed for six weeks. Hindlimb motor function was evaluated with a grid-walking test. The expression of neurotrophic factors and the level of apoptosis at the site of SCI were determined by western blotting. SCI reduced hindlimb motor function and suppressed expression of neurotrophin (NT)-3 and insulin-like growth factor (IGF)-1. Expression of phosphatidylinositol 3-kinase (PI3K), the ratio of phosphorylated Akt to Akt (pAkt/Akt) and the ratio of B-cell lymphoma 2 (Bcl-2) to Bax (Bcl-2/Bax) were decreased, and cleaved caspase-3 expression was increased by SCI. Treadmill exercise enhanced hindlimb motor function and increased expression of nerve growth factor (NGF), NT-3 and IGF-1 in the SCI rats. Treadmill exercise increased PI3K expression, the pAkt/Akt and the Bcl-2/Bax ratios, and suppressed cleaved caspase-3 expression in the injured spinal cord. This study demonstrated that treadmill exercise promotes the recovery of motor function by suppressing apoptosis in the injured spinal cord. The beneficial effect of exercise may be attributed to the increase in expression of neurotrophic factors via activation of the PI3K/Akt pathway.
doi:10.3892/etm.2013.1451
PMCID: PMC3919853  PMID: 24520250
spinal cord injury; treadmill exercise; motor function; apoptosis; neurotrophic factors
5.  Combined Primary Tumor and Extracranial Metastasis Status as Constituent Factor of Prognostic Indices for Predicting the Overall Survival in Patients with Brain Metastases 
Journal of Korean Medical Science  2013;28(2):205-212.
We retrospectively analyzed the prognostic factors on overall survival (OS) in patients with brain metastasis (BM) and evaluated the role of combined primary tumor and extracranial metastasis (ECM) status as a constituent factor for prognostic index. This study involved 897 patients with BMs who underwent radiotherapy between April 2003 and December 2009. Among the clinical parameters, multivariate analysis showed that age, Karnofsky performance status (KPS), combined primary tumor and ECM status, number of BMs, and treatment group were significant prognostic factors for OS (P < 0.05). To compare the discriminatory ability of 5 prognostic indices, i.e., recursive partitioning analysis (RPA), basic score for BMs (BSBM), score index for radiosurgery (SIR), graded prognostic assessment (GPA), and modified GPA including the combined primary tumor and ECM status (mGPA), the Akaike information criteria (AIC) were calculated. The mGPA showed the lowest AIC value, followed by RPA, GPA, SIR, and BSBM, in that order. It is implicated that modified score of pre-existing factors (i.e., age and KPS) and addition of the combined primary tumor and ECM status to the prognostic index can improve its discriminatory ability and the combined primary tumor and ECM status may be useful as one of constituent factors for prognostic index.
doi:10.3346/jkms.2013.28.2.205
PMCID: PMC3565131  PMID: 23400308
Brain Metastasis; Prognostic Index; Radiotherapy
6.  Utilization of evidence-based treatment in elderly patients with chronic heart failure: using Korean Health Insurance claims database 
Background
Chronic heart failure accounts for a great deal of the morbidity and mortality in the aging population. Evidence-based treatments include angiotensin-2 receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACE-I), beta-blockers, and aldosterone antagonists. Underutilization of these treatments in heart failure patients were frequently reported, which could lead to increase morbidity and mortality. The aim of this study was to evaluate the utilization of evidence-based treatments and their related factors for elderly patients with chronic heart failure.
Methods
This is retrospective observational study using the Korean National Health Insurance claims database. We identified prescription of evidence based treatment to elderly patients who had been hospitalized for chronic heart failure between January 1, 2005, and June 30, 2006.
Results
Among the 28,922 elderly patients with chronic heart failure, beta-blockers were prescribed to 31.5%, and ACE-I or ARBs were prescribed to 54.7% of the total population. Multivariable logistic regression analyses revealed that the prescription from outpatient clinic (prevalent ratio, 4.02, 95% CI 3.31–4.72), specialty of the healthcare providers (prevalent ratio, 1.26, 95% CI, 1.12–1.54), residence in urban (prevalent ratio, 1.37, 95% CI, 1.23–1.52) and admission to tertiary hospital (prevalent ratio, 2.07, 95% CI, 1.85–2.31) were important factors associated with treatment underutilization. Patients not given evidence-based treatment were more likely to experience dementia, reside in rural areas, and have less-specialized healthcare providers and were less likely to have coexisting cardiovascular diseases or concomitant medications than patients in the evidence-based treatment group.
Conclusions
Healthcare system factors, such as hospital type, healthcare provider factors, such as specialty, and patient factors, such as comorbid cardiovascular disease, systemic disease with concomitant medications, together influence the underutilization of evidence-based pharmacologic treatment for patients with heart failure.
doi:10.1186/1471-2261-12-60
PMCID: PMC3468388  PMID: 22849621
Congestive heart failure; Drug utilization evaluation; Elderly; Type 2 angiotensin receptor antagonists; Angiotensin-converting enzyme antagonists; Beta-adrenergic blockers
7.  Overlapping Medication Associated with Healthcare Switching among Korean Elderly Diabetic Patients 
Journal of Korean Medical Science  2011;26(11):1461-1468.
This study was performed to describe the patterns of healthcare switching with overlapping use of anti-diabetic medication in the elderly using the Korea Health Insurance Review and Assessment Service's claims data. The study subjects were ambulatory elderly diabetic patients (ICD-10, E10-14) receiving at least one oral anti-diabetic drug or insulin, and visiting healthcare facilities more than two times between January and December 2005. A total of 457,975 elderly diabetic ambulatory care patients were identified. The mean of visiting frequencies was 9.0 ( ± 3.6) and switching frequencies was 1.5 ( ± 0.8) during 2005. Switching group consisted of 33% of total study subject. Healthcare switching was common in female patients who were older, and had treated polytherapy more in rural areas. The movement among primary care medical services was very common among the patients in the switching group (52.6%). A statistically significant correlation was observed between the healthcare switching and concomitant drug use (rho = 0.96), and overlapping days (rho = 0.57). The use of overlapping anti-diabetic medication increased with the extent of healthcare switching. Further, frequent switching of healthcare between primary clinics was observed. Efforts should be made to establish continuity for the elderly diabetic patients with the identification of frequent switching with overlapping medication.
doi:10.3346/jkms.2011.26.11.1461
PMCID: PMC3207049  PMID: 22065902
Elderly People; Diabetes Mellitus; Healthcare Seeking Behaviour; Prescribing Pattern; Co-medication; Delivery of Health Care; Referral and Consultation; National Health Insurance
8.  A population-based case-crossover study of polyethylene glycol use and acute renal failure risk in the elderly 
AIM: To evaluate the possibility of an association between polyethylene glycol (PEG) and acute renal failure (ARF) in elderly patients using a health insurance claims database.
METHODS: We conducted a population-based case-crossover study using information obtained from Korean Health Insurance Review and Assessment Service (HIRA) claims from January 1, 2005 to December 31, 2005 (Seoul, Korea). The study population consisted of elderly patients who received PEG prior to experiencing their first ARF-related hospitalization from April 1, 2005 to December 31, 2005. For each patient, one case and two control periods were matched. PEG use in a 2- or 4-wk window period prior to hospitalization for ARF was compared with PEG use in two earlier 2- or 4-wk control window periods. Conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% CI, adjusting for concomitant uses of diuretics, angiotensin converting enzyme inhibitors, non-steroidal anti-inflammatory drugs, antibiotics, anti-cancer drugs, and contrast media.
RESULTS: Within the HIRA database which contained 1 093 262 elderly patients, 1156 hospitalized ARF cases were identified. Among these cases, PEG was prescribed to 17 (1.5%) patients before hospitalization. The adjusted ORs when applying the 2- and 4-wk window periods were 0.4 (95% CI: 0.03-5.24) and 2.1 (95% CI: 0.16-27.78), respectively.
CONCLUSION: No increased risk of ARF was found in elderly PEG users. However, based on the limited number of study subjects, further analysis should be performed to confirm these results.
doi:10.3748/wjg.v17.i5.651
PMCID: PMC3040338  PMID: 21350715
Polyethylene glycol; Acute renal failure; Adverse drug reaction; Health insurance claims database; Case-crossover
9.  Condom Use and Prevalence of Genital Chlamydia trachomatis Among the Korean Female Sex Workers 
Epidemiology and Health  2010;32:e2010008.
OBJECTIVES
Since 2004, availability of resources for preventing sexually transmitted diseases in Korean female sex workers (FSWs) has decreased because of strict application of a law against prostitution. This study is to evaluate the condom use and prevalence of Chlamydia trachomatis among FSWs in Korea.
METHODS
We performed a cross-sectional study of FSWs from 15 major sex work sites in Korea from June to November 2008, using convenience sampling. Self-administered questionnaires and urine samples were collected after all participants' written informed consent. Urine samples were analyzed with PCR at a single central laboratory.
RESULTS
Among 1,086 FSWs who consented to study participation, data from 999 FSWs were appropriate for analysis. C. trachomatis prevalence was 12.8% (95% CI: 10.7-14.9%). Younger age increased risk for C. trachomatis. Whereas majority of FSWs (71.0%) answered high self confidence in condom negotiation, the proportion of FSWs who always used condoms last month was only 23.7%. However, practicing regular condom use showed significant protection against chlamydia infection, not self confidence in condom negotiation.
CONCLUSION
In Korea, FSWs were not practicing enough self-protection at work with a high prevalence of C. trachomatis. Education for constant practice of protection against sexually transmitted diseases is needed, especially for younger FSWs.
doi:10.4178/epih/e2010008
PMCID: PMC2984866  PMID: 21191461
Chlamydia trachomatis; Condom use; Sex worker
10.  A Case of Huge Thrombus in the Aortic Arch with Cerebrovascular Embolization 
Pedunculated thrombus in the aortic arch that is associated with cerebral infarction is very rare requires prompt diagnosis and treatment to prevent occurrence of another devastating complication. Transesophageal echocardiography is useful for detecting source of embolism including aortic thrombi. The treatment options of aortic thrombi involves anticoagulation, thrombolysis, thromboaspiration, and thrombectomy. Here we report a case of huge thrombus in the aortic arch, resulting in acute multifocal cerebellar embolic infarct in patient without any risk factors for vascular thrombosis. Thrombi in the aortic arch were diagnosed by transesophageal echocardiography and treated with anticoagulants successfully.
doi:10.4250/jcu.2009.17.4.148
PMCID: PMC2889393  PMID: 20661342
Aortic thrombus; Echocardiography
11.  Multi-Indication Carbamazepine and the Risk of Severe Cutaneous Adverse Drug Reactions in Korean Elderly Patients: A Korean Health Insurance Data-Based Study 
PLoS ONE  2013;8(12):e83849.
Objective
To evaluate the risk of severe cutaneous adverse drug reactions (SCAR) after exposure to multi-indication antiepileptic drugs for in Korean elderly patients.
Methods
We used a nationwide database from the Korean Health Insurance Review and Assessment Service claims constructed for the monitoring of drug utilization among the entire Korean elderly population from January 2005 to June 2006. We identified cases of SCARs among inpatients aged ≥65 years and those newly diagnosed with erythema multiforme according to the International Classification of Diseases, 10th revision code (L51). Each case was matched to four controls for gender, age, and the first hospitalization date as the index date. The use of carbamazepine, gabapentin, lamotrigine, topiramate, phenobarbital, phenytoin, and valproate during a 60-day period before the index date was compared. A conditional logistic regression analysis was performed to calculate the odds ratios (OR) and 95% confidence intervals (CI) of SCARs for antiepileptic drug.
Results
We identified 286 cases of SCAR and 1,144 matched controls. Among the 25 patients who were prescribed antiepileptic drugs within 60 days of the index date. There were 11 cases (3.8%) of severe ocular manifestations, and most elderly patients were first-time or short-term users of antiepileptic drugs. Among the 10 cases of carbamazepine use, only 2 cases were prescribed carbamazepine for seizure. All antiepileptic drugs were associated with an increased SCAR risk (adjusted OR = 3.42, 95% CI: 1.75–6.63). The SCAR risk was highest in patients treated with carbamazepine (adjusted OR = 10.39, 95% CI: 2.64–40.86, for multi-indication; adjusted OR = 6.84, 95% CI: 1.55–30.10, for neuropathic pain).
Conclusion
Carbamazepine use was associated with a nearly 10-fold increase in severe cutaneous drug reactions in Korean elderly patients. This association was consistently high with SCAR patients who received carbamazepine for neuropathic pain.
doi:10.1371/journal.pone.0083849
PMCID: PMC3877105  PMID: 24391836
12.  Human Monoclonal Antibodies against Glucagon Receptor Improve Glucose Homeostasis by Suppression of Hepatic Glucose Output in Diet-Induced Obese Mice 
PLoS ONE  2012;7(12):e50954.
Aim
Glucagon is an essential regulator of hepatic glucose production (HGP), which provides an alternative therapeutic target for managing type 2 diabetes with glucagon antagonists. We studied the effect of a novel human monoclonal antibody against glucagon receptor (GCGR), NPB112, on glucose homeostasis in diet-induced obese (DIO) mice.
Methods
The glucose-lowering efficacy and safety of NPB112 were investigated in DIO mice with human GCGR for 11 weeks, and a hyperinsulinemic-euglycemic clamp study was conducted to measure HGP.
Results
Single intraperitoneal injection of NPB112 with 5 mg/kg effectively decreased blood glucose levels in DIO mice for 5 days. A significant reduction in blood glucose was observed in DIO mice treated with NPB112 at a dose ≥5 mg/kg for 6 weeks, and its glucose-lowering effect was dose-dependent. Long-term administration of NPB112 also caused a mild 29% elevation in glucagon level, which was returned to the normal range after discontinuation of treatment. The clamp study showed that DIO mice injected with NPB112 at 5 mg/kg were more insulin sensitive than control mice, indicating amelioration of insulin resistance by treatment with NPB112. DIO mice treated with NPB112 showed a significant improvement in the ability of insulin to suppress HGP, showing a 33% suppression (from 8.3 mg/kg/min to 5.6 mg/kg/min) compared to the 2% suppression (from 9.8 mg/kg/min to 9.6 mg/kg/min) in control mice. In addition, no hypoglycemia or adverse effect was observed during the treatment.
Conclusions
A novel human monoclonal GCGR antibody, NPB112, effectively lowered the glucose level in diabetic animal models with mild and reversible hyperglucagonemia. Suppression of excess HGP with NPB112 may be a promising therapeutic modality for the treatment of type 2 diabetes.
doi:10.1371/journal.pone.0050954
PMCID: PMC3513295  PMID: 23226550

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