• 약학회지
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• 제54권4호
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• pp.270-281
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• 2010

Total parenteral nutrition (TPN) is necessary to neonates in neonatal intensive care unit (NICU) for survival and growth because of impossible of enteral feeding. Long-term TPN can be associated with a broad spectrum of hepatobiliary disorder, ranging from mild hepatic dysfunction to severe end-stage liver disease. Cholestasis developed most commonly in neonate, ursodeoxycholic acid (UDCA) is widely used in adult with cholestatic and non-cholestatic liver diseases but there have been limited data on the effects in neonate with PNAC. This study was performed retrospectively to review all medical histories of the total 30 neonates with was administrated UDCA for treatment to parenteral nutrition associated cholestasis (PNAC) at Chungbuk National University Hospital NICU from April 2002 to December 2008. UDCA was administrated at bilirubin is over 2 mg/dl. The criterias for drug evaluation were included hepatic biochemical marker such as direct bilirubin, total bilirubin, AST, ALT, ALP and GGT, TPN therapy period, cholestasis development period, UDCA treatment period, UDCA dosage and adverse effect. In the results, Post-UDCA treatment significant was decreased direct bilirubin, total bilirubin, AST and ALP (p<0.05), and was decreased GGT (p>0.05) and slightly was increased ALT (p>0.05). Reffective timect biDCA was appear at mean $10.5{\pm}1.3$ days, iDCA administration period was mean $64.4{\pm}5.9$ days, cholestasis period was mean $71.9{\pm}6.4$ days and UDCA dosage was mean $22.9{\pm}0.9$ mg/kg/day. Common adverse effects is diarrhea, 5 patients arised mild diarrhea but it possible also related with increased enteral feeding. In conclusion, iDCA can decrease direct bilirubin that major parameter t bcholestasis and oher hepatic biochemical makers. UDCA is effective on PNAC without any serious side effect and cost-effective. Although no greatly shortening cholestasis period, but can protect to develop into severe liver disease and other complication or death. Based on these result, UDCA is recommended for treatment of cholestasis at direct bilirubin is over 2 mg/dl.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6275-6281
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• 2014

Nasal-type extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a highly invasive cancer with a poor prognosis. More effective and safer treatment regimens for ENKL are needed. Pegaspargase (PEG-Asp) has a similar mechanism of action to L-asparaginase (L-Asp), but presents lower antigenicity. The aim of the present research was to evaluate the safety profile and the latent efficacy of a PEG-Asp-based treatment regimen in patients with ENKL. Data collected from 20 patients with histologically confirmed ENKL, admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to August 2013, were included in the study. All patients received $2500IU/m^2$/IM PEG-Asp on day 1 of every 21-day treatment cycle. Patients received combination chemotherapy with CHOP (n=5), EPOCH (n=7), GEMOX (n=7) or CHOP with bleomycin (n=1). After 2-5 treatment cycles (median, 4 cycles) of PEG-Asp-based chemotherapy, five patients (25%) showed a complete response (CR), and the overall response rate (ORR) was 60%. Grade 3/4 neutropenia occurred in fourteen patients (70%). Grade 3 alanine aminotransferase (ALT) elevation was observed in two. Grade 1-2 non-hematological toxicity consisted of activated partial thromboplastin time (APTT) elongation (n=9), hypofibrinogenemia (n=6), hypoproteinemia (n=17), hyperglycemia (n=3), and nausea (n=6). No allergic reactions were detected. No treatment related death was reported. Our results suggested that PEG-Asp-based chemotherapy presented an acceptable tolerance and a potential short-term outcome in patients with nasal-type ENKL.

• Radiation Oncology Journal
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• 제37권3호
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• pp.176-184
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• 2019

Purpose: It is unclear whether adding concurrent chemotherapy (CT) to definitive radiotherapy (RT) following induction CT is a tolerable and cost effective treatment for non-small-cell lung cancer (NSCLC) patients aged 70 years or older with comorbidities. This study evaluated the actual clinical outcomes between concurrent chemoradiotherapy (CCRT) and RT alone following induction CT or not in patients (≥70 years) in a single institution's clinical practice. Materials and Methods: A total of 82 patients with unresectable stage III NSCLC between 2004 and 2016 were retrospectively analyzed. Their treatment tolerance and clinical outcomes such as overall survival (OS), locoregional recurrence (LRR), treatment toxicities and distant metastasis (DM) were evaluated. Early mortality rates were also evaluated as 4-month mortality after RT. Results: Fifty-four patients received CCRT and 28 patients received RT alone. Induction CT before RT was performed for 68.5% and 50.0% in CCRT and RT alone groups. Treatment tolerance was significantly worse in CCRT (p = 0.046). The median survival was 21.1 and 18.1 months for CCRT and RT alone, which was not statistically significant. LRR and DM were also not different. Most early deaths after CCRT were attributed to non-cancer-related mortality. Acute esophagitis of grade ≥2 occurred more following CCRT (p = 0.017). In multivariate analysis, a Charlson Comorbidity Index (CCI) of ≥5 and a weight loss of ≥5% after RT were associated with poor OS. The factors adversely affecting 4-month survival were a CCI of ≥5 and CCRT. Conclusion: There were no significant differences in OS, LRR, and DM between CCRT and RT alone treatment in elderly patients. However, there was a poorer tolerance and higher incidence of acute esophagitis in the CCRT group. Specifically, when the patients had a CCI of ≥5, RT alone seems to be reasonable with a low probability of early death.

• 동의생리병리학회지
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• 제20권1호
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• pp.163-170
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• 2006

Nardostachyos Rhizoma (N. Rhizoma) belonging to the family Valerianaceae has been anti-arrhythmic effect, and sedation to the central nerve and a smooth muscle. We reported that the water extract of N. Rhizoma induced apoptotic cell death and differentiation in human promyelocytic leukemia (HL-60) cells. Cytotoxicity of N. Rhizoma was detected only in HL-60 cells (IC50 is about 200 ${\mu}g/ml$). The cytotoxic activity of N. Rhizoma in HL-60 cells was increased in a dose-dependent manner. We used several measures of apoptosis to determine whether these processes were involved in N. Rhizoma-induced apoptotic cell death. The high-dose (200 ${\mu}g/ml$) treatment of N. Rhizoma to HL-60 cells showed cell shrinkage, cell membrane blobbing, apoptotic bodies, and the fragmentation of DNA, suggesting that these cells underwent apoptosis. Treatment of HL-60 cells with N. Rhizoma time-dependently induced activation of caspase-3, caspase-8, and caspase-9 and proteolytic cleavage of poly(ADP-ribose) polymerase. Also, we investigated the effect of N. Rhizoma on cellular differentiation and proliferation in HL-60 cells. Differentiation and proliferation of HL-60 cells was determined through expression of CD11b and CD14 surface antigens using flow cytometry and nitroblue tetrazolium (NBT) assay, and through analysis of cell cycle using propidium iodide assay, respectively. N. Rhizoma induced the differentiation of HL-60 at the low-dose (100 ${\mu}g/ml$) treatment, as shown by increased expression of differentiation surface antigen CD11b, but not CDl4 and increased reducing activity of NBT. When HL-60 cells were treated with N. Rhizoma at concentration of $50{\mu}g/ml\;and\;100{\mu}g/ml$, NBT-reducing activities induced approximately 1.5-fold and 20.0-fold as compared with the control. In contrast, HL-60 cells treated with the N. Rhizoma-ATRA combination showed markedly elevated levels of 26.3-fold at $50{\mu}g/ml$ N. Rhizoma-0.1 ${\mu}M$ ATRA combination and 27.5-fold at 50 ${\mu}g/ml$ N. Rhizoma-0.2 ${\mu}M$ ATRA combination than when treated with N. Rhizoma alone or ATRA alone. It may be that N. Rhizoma plays important roles in synergy with ATRA during differentiation of HL-60 cells. DNA flow-cytometry indicated that N. Rhizoma markedly induced a G1 phase arrest of HL-60 cells. N. Rhizoma-treated HL-60 cells increased the cell population in G1 phase from 32.71% to 42.26%, whereas cell population in G2/M and S phases decreased from 23.61% to 10.33% and from 37.78% to 33.98%, respectively. We examined the change in the $p21^{WAF1/Cip1}\;and\;p27^{Kip1}$ proteins, which are the CKIs related with the G1 phase arrest. The expression of the CDK inhibitor $p27^{Kip1},\;but\;not\;p21^{WAF1/Cip1}$ were markedly increased by N. Rhizoma. Taken together, these results demonstrated that N. Rhizoma induces apoptotic cell death through activation of caspase-3, and potently inhibits the proliferation of HL-60 cells via the G1 phase cell cycle arrest in association with $p27^{Kip1}$ and granulocytic differentiation induction .

• Journal of Preventive Medicine and Public Health
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• 제11권1호
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• pp.123-127
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• 1978

The major objective of this research is to identify those hospital characteristics that best explain cost variation among hospitals and to formulate linear models that can predict hospital costs. Specific emphasis is placed on hospital output, that is, the identification of diagnosis related patient groups (DRGs) which are medically meaningful and demonstrate similar patterns of hospital resource consumption. A casemix index is developed based on the DRGs identified. Considering the common problems encountered in previous hospital cost research, the following study requirements are estab-lished for fulfilling the objectives of this research: 1. Selection of hospitals that exercise similar medical and fiscal practices. 2. Identification of an appropriate data collection mechanism in which demographic and medical characteristics of individual patients as well as accurate and comparable cost information can be derived. 3. Development of a patient classification system in which all the patients treated in hospitals are able to be split into mutually exclusive categories with consistent and stable patterns of resource consumption. 4. Development of a cost finding mechanism through which patient groups' costs can be made comparable across hospitals. A data set of Medicare patients prepared by the Social Security Administration was selected for the study analysis. The data set contained 27,229 record abstracts of Medicare patients discharged from all but one short-term general hospital in Connecticut during the period from January 1, 1971, to December 31, 1972. Each record abstract contained demographic and diagnostic information, as well as charges for specific medical services received. The 'AUT-OGRP System' was used to generate 198 DRGs in which the entire range of Medicare patients were split into mutually exclusive categories, each of which shows a consistent and stable pattern of resource consumption. The 'Departmental Method' was used to generate cost information for the groups of Medicare patients that would be comparable across hospitals. To fulfill the study objectives, an extensive analysis was conducted in the following areas: 1. Analysis of DRGs: in which the level of resource use of each DRG was determined, the length of stay or death rate of each DRG in relation to resource use was characterized, and underlying patterns of the relationships among DRG costs were explained. 2. Exploration of resource use profiles of hospitals; in which the magnitude of differences in the resource uses or death rates incurred in the treatment of Medicare patients among the study hospitals was explored. 3. Casemix analysis; in which four types of casemix-related indices were generated, and the significance of these indices in the explanation of hospital costs was examined. 4. Formulation of linear models to predict hospital costs of Medicare patients; in which nine independent variables (i. e., casemix index, hospital size, complexity of service, teaching activity, location, casemix-adjusted death. rate index, occupancy rate, and casemix-adjusted length of stay index) were used for determining factors in hospital costs. Results from the study analysis indicated that: 1. The system of 198 DRGs for Medicare patient classification was demonstrated not only as a strong tool for determining the pattern of hospital resource utilization of Medicare patients, but also for categorizing patients by their severity of illness. 2. The wei틴fed mean total case cost (TOTC) of the study hospitals for Medicare patients during the study years was $11,27.02 with a standard deviation of $117.20. The hospital with the highest average TOTC ($1538.15) was 2.08 times more expensive than the hospital with the lowest average TOTC ($743.45). The weighted mean per diem total cost (DTOC) of the study hospitals for Medicare patients during the sutdy years was $107.98 with a standard deviation of $15.18. The hospital with the highest average DTOC ($147.23) was 1.87 times more expensive than the hospital with the lowest average DTOC ($78.49). 3. The linear models for each of the six types of hospital costs were formulated using the casemix index and the eight other hospital variables as the determinants. These models explained variance to the extent of 68.7 percent of total case cost (TOTC), 63.5 percent of room and board cost (RMC), 66.2 percent of total ancillary service cost (TANC), 66.3 percent of per diem total cost (DTOC), 56.9 percent of per diem room and board cost (DRMC), and 65.5 percent of per diem ancillary service cost (DTANC). The casemix index alone explained approximately one half of interhospital cost variation: 59.1 percent for TOTC and 44.3 percent for DTOC. Thsee results demonstrate that the casemix index is the most importand determinant of interhospital cost variation Future research and policy implications in regard to the results of this study is envisioned in the following three areas: 1. Utilization of casemix related indices in the Medicare data systems. 2. Refinement of data for hospital cost evaluation. 3. Development of a system for reimbursement and cost control in hospitals.

• 한국수산과학회지
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• 제32권6호
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• pp.791-797
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• 1999

Kluyveromyces fragilis (ATCC 36534)와 Candida utilis (ATCC 9950) 균주를 사료 첨가제와 rotifer 먹이로서 가치를 평가하기 위해 성장 단계별 및 세포벽의 화학처리에 따른 영양가를 분석하여 비교하였다. 조단백질 함량은 K. fragilis가 $48.2\~58.5\%$로 C. utilis의 $25.9\~43.4\%$보다 높은 경향을 보였고, 조지방 함량은 K. fragilis 및 C. utilis모두 $0.1\~1.6\%$로 매우 낮은 수준이었다. 조섬유의 함량은 두 효모에서 $0.6\~3.3\%$의 범위로 낮은 수준이었으며, protoplasted 효모의 경우는 다소 낮아지는 경향을 보였다. 효모종류에 따라 아미노산 조성이 다소 차이를 보였는데, Asp, Gly, Pro, Leu, Lys 및 Val은 K. fragilis가 C. utilis보다 그 함량이 높았으며, Glu 및 Arg은 C. utilis가 상대적으로 더 높은 경향을 보였다. 성장 단계별 아미노산 조성은 특별한 변화 경향이 없었으며, 세포 외벽을 처리한 protoplasted K. fragilis와 C. utilis의 Glu, Gly 및 Asg은 처리전보다 낮아지는 경향이었고, Leu, Phe 및 Val의 함량은 다소 높아진 것으로 나타났다. K. fragilis 및 C. utilis의 지방산은 대부분 $C_{18}$ 이하의 포화 또는 불포화산으로 구성되어 있었는데, 주로 $C_{16-18}$의 지방산들은 early log 또는 log phase에서 death phase로 갈수록, 그리고 protoplast에서 낮아지는 반면에 $C_{10-12}$와 같은 저급 지방산들은 증가하는 경향을 보였다. K. fragilis 및 C. utilis의 early log phase에서는 ATP 함량이 검출되지 않았지만, 그 후 단계 (log - death phase)에서 각각 증가하는 경향을 보였다 ADP 함량은 K. fragilis에서 early log phase 이후 단계부터 증가하였고, 세포막을 처리한 protoplast 상태에서는 높은 수준을 유지하였지만, C. utilis의 경우는 성장이 진행됨에 따라 감소하는 경향을 보였으며, protoplast 상태에서는 그 함량이 낮아지는 경향을 보였다. AMP 함량은 두 균주 모두 early log phase에서 낮은 수준이었지만, 그 후 단계에서는 높은 함량을 유지하였으며, protoplast 상태에는 검출되지 않았다 IMP 함량은 두 균주 모두 log phase에서 가장 높은 값을 보였으며, protoplast 상태에서는 낮은 값을 보였다. Inosine 함량은 K. fragilis의 성장이 진행됨에 따라 증가되었고, C. utilis에서는 K. fragilis보다 높은 경향이었으며, log phase에서 최대값을 보였다. 성장 단계별로 이들의 핵산관련물질의 총량은 두 균주 모두 early log phase에서 가장 낮은 값을 보였으며, 각 성장 단계별로 K. fragilis가 C. utilis보다 높은 값을 유지하였고. protoplast 상태에서는 C. utilis가 더 높은 값을 나타내었다.

• Tuberculosis and Respiratory Diseases
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• 제56권5호
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• pp.450-464
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• 2004

연구배경 : FHIT 유전자의 homozygous deletion과 이와 관련된 mRNA 발현 이상, 단백질의 발현 결손은 폐암에서 매우 높은 빈도로 관찰되고 있다. 일부 연구에 의하면 FHIT 유전자를 폐암 세포 내에 이입시켰을 때 apoptosis가 유발되었고, 세포 주기의 이상 소견이 관찰되었으며, 종양형성 능력이 억제됨이 관찰되었다. 하지만 아직까지 FHIT 단백질의 기능에 대한 지식은 미진한 상태이다. 본 연구에서는 FHIT 유전자를 폐암 세포에 이입시켰을 때 유발되는 apoptosis의 기전을 규명하고자 하였다. 방 법 : FHIT 유전자가 결손된 NCI-H358 세포주에 FHIT 유전자를 stable transfection 시킨 후, cisplatin 혹은 paclitaxel을 가하고 apoptosis가 항진되어 나타나는가를 DAPI staining과 flow cytometry로 관찰해 보았다. 또한 이 과정에서 나타나는 caspase system의 변화와 Bcl-2 family의 변화를 Western blotting으로 조사해 보았다. 결 과 : FHIT를 발현시킨 세포에서는 cisplatin 혹은 paclitaxel을 투여하였을 때 유의하게 생존율이 감소하였으며, 이는 apoptosis 증가에 의한 것으로 확인 되었다. 이 과정에서 FHIT가 발현된 세포는 caspase-3, caspase-7의 활성화가 유의하게 증가되었으며, Bcl-2와 Bcl-xL 발현은 유의하게 감소하고 Bax와 Bad 발현은 유의하게 증가하였다. 결 론 : FHIT가 발현된 폐암 세포에 항암제를 투여하였을 때 유의하게 증가한 apoptosis는 caspase system과 Bcl-2 family의 활성화와 관련되어 있다.

• Journal of Korean Neurosurgical Society
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• 제61권4호
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• pp.478-484
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• 2018

Objective : Cerebrovascular disease (CVD) was the third most common cause of death in South Korea in 2014. Evidence from abroad suggests that comprehensive stroke centers play an important role in improving the mortality rate of stroke. However, surgical treatment for CVD is currently slightly neglected by national policy, and there is still regional imbalance in this regard. For this reason, we conducted a survey on the necessity of, and the requirements for, establishing regional comprehensive cerebrovascular surgery centers (CCVSCs). Methods : This investigation was performed using the questionnaire survey method. The questionnaire was consisted with two sections. The first concerned the respondent's opinion regarding the current status of demand and the regional imbalance of cerebrovascular surgery in South Korea. The second section asked about the requirements for establishing regional CCVSCs. We sent the questionnaire to 100 board members of the Korean Society of Cerebrovascular Surgeons. Results : Most experts agreed that cerebrovascular surgery patients were concentrated in large hospitals in the capital area, and 83.6% of respondents agreed that it was necessary to alleviate the regional imbalance of cerebrovascular surgery. With regards to personnel, over 90% of respondents answered that at least two neuro-vascular surgeons and two neuro-interventionists are necessary to establish a CCVSC. Regarding facilities, almost all respondents stated that each CCVSC would require a neuro-intensive care unit and hybrid operating room. The survey asked the respondents about 13 specific neurovascular surgical procedures and whether they were necessary for a regional CCVSC. In the questions about the necessity of cerebrovascular surgical equipment, all seven pieces of equipment were considered essential by all respondents. A further five pieces of equipment were considered necessary on site: computed tomographic angiography, magnetic resonance angiography, conventional angiography, surgical microscope, and surgical navigation. Our results may provide a basis for future policy regarding treatment of cerebrovascular disease, including surgery. Conclusion : Raising the comprehensiveness of treatment at a regional level would lower the national disease burden. Policies should be drafted regarding comprehensive treatment including surgery for cerebrovascular disease, and related support plans should be implemented.

• Tuberculosis and Respiratory Diseases
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• 제75권1호
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• pp.9-17
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• 2013

Background: In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome. There have been a few reports of its effect in combination with anticancer drugs. We performed this study to investigate whether erlotinib, an epidermal growth factor receptor inhibitor, or rapamycin, an mammalian target of rapamycin (mTOR) inhibitor, is effective in combination therapy with monensin in non-small cell lung cancer cells. Methods: NCI-H1299 cells were treated with rapamycin or erlotinib, with or without monensin pretreatment, and then subjected to growth inhibition assay, apoptosis analysis by flow cytometry, and cell cycle analysis on the basis of the DNA contents histogram. Finally, a Western blot analysis was done to examine the changes of proteins related to apoptosis and cell cycle control. Results: Monensin synergistically increases growth inhibition and apoptosis induced by rapamycin or erlotinib. The number of cells in the sub-$G_1$ phase increases noticeably after the combination treatment. Increase of proapoptotic proteins, including bax, cleaved caspase 3, and cleaved poly(ADP-ribose) polymerase, and decrease of anti-apoptotic proteins, bcl-2 and bcl-xL, are augmented by the combination treatment with monensin. The promoters of cell cycle progression, notch3 and skp2, decrease and p21, a cyclin-dependent kinase inhibitor, accumulates within the cell during this process. Conclusion: Our findings suggest that concurrent autophagy inhibition could have a role in lung cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6257-6261
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• 2012

Objective: To investigate the safety and efficacy of transcatheter arterial chemoembolization (TACE), combined with portal vein embolization (PVE), and high intensity focused ultrasound (HIFU) sequential therapy in treating patients with hepatocellular carcinoma (HCC). Methods: Patients with inoperative HCC were treated by two methods: in the study group with TACE first, then PVE a week later, and then TACE+PVE every two months as a cycle, after 2~3 cycles finally HIFU was given; in the control group only TACE+PVE was given. Response (CR+PR), and disease control rate (CR+PR+SD), side effects, overall survival and time to progress were calculated. Results: Main side effects of both groups were nausea and vomiting. No treatment related death occurred. In the study group, 32 patients received TACE for overall 67 times, PVE 64 times, and HIFU 99 times; on average 2.1, 2 and 3.1 times for each patient, respectively. In the control group, 36 patients were given TACE 78 times and PVE 74 times, averaging 2.2 and 2.1 times per patient. Effective rate: 25.0% in study group and 8.3% in control group (p>0.05). Disease control rates were 71.9% and 44.4%, respectively (p<0.05). In patients with portal vein tumor thrombus, the rate reduced over 1/2 after treatment was 69.2%(9/13) in the study and 21.4%(3/14) in the control group (p<0.05). Rate of AFP reversion or decrease over 1/2 was 66.7%(16/24) in study and 37%(10/27) (p<0.05) in control group. Median survival time: 16 months in study and 10 months in control group. PFS was 7months in study and 3 months in control group. Log-rank test suggested that statistically significant difference exists between two groups (p=0.024). 1-, 2- and 3-year survival rates were 56.3%, 18.8% and 9.3% in study, while 30.6%, 5.6% and 0 in control group, respectively, with statistically significant difference between two groups (by Log-rank, p = 0.014). Conclusions: The treatment of TACE+PVE+HIFU sequential therapy for HCC increases response rate, prolong survival, and could thus be a safe and effective treatment for advanced cases.