• Title/Summary/Keyword: Refractory

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Intracranial Pressure and Cerebral Blood Flow Monitoring after Bilateral Decompressive Craniectomy in Patients with Acute Massive Brain Swelling (급성 중증 뇌종창 환자의 양측성 감압개두술 후 뇌압 및 뇌혈류 측정)

  • Yoo, Do-Sung;Kim, Dal-Soo;Huh, Pil-Woo;Cho, Kyoung-Suck;Park, Chun-Kun;Kang, Joon-Ki
    • Journal of Korean Neurosurgical Society
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    • v.30 no.3
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    • pp.295-306
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    • 2001
  • Objectives : The management of massive brain swelling remains an unsolved problem in neurosurgical field. Despite newly developed medical and pharmacological therapy, the mortality and morbidity due to massive brain swelling remains high. According to many recent reports, surgical decompression with dura expansion is superior to medical management in patients with massive brain swelling. We performed surgical treatment on the first line of treatment, and followed medical management in case with refractory increased intracranial pressure(ICP). To show the quantitative effect of decompressive surgery on the intracranial pressure, we performed ventricular puncture and checked the ventricular ICP continuously during the decompressive surgery and postoperative period. Materials and Methods : Fifty-one patients with massive brain swelling, undergoing bilateral decompressive craniectomy with dura expansion, were studied in this study. In all patients, ventricular puncture was performed at Kocher's point on the opposite side of massive brain swelling. The ventricular pressure was monitored continuously, during the bilateral decompression procedures and postoperative period. Results : The initial ventricular ICP were varied from 13mmHg to 112mmHg. Immediately after the bilateral craniectomy, mean ventricular ICP decreased to $53.1{\pm}15.8%$ of the initial ICP(ranges from 5mmHg to 87mmHg). Dura opening decreased mean ICP by additional 36.7% and made the ventricular pressure $16.4{\pm}10.5%$ of the initial pressure (ranges from 0mmHg to 28mmHg). Postoperatively, ventricular pressure was lowered to $20.2{\pm}22.6%$(ranged from 0mmHg to 62.3mmHg) of the initial ICP. The ventricular ICP value during the first 24 hours after decompressive surgery was found to be an important prognostic factor. If ICP was over 35mmHg, the mortality was 100% instead of additional medical(barbiturate coma therapy and hypothermia) treatments. Conclusion : Bilateral decompression with dura expansion is considered an effective therapeutic modality in ICP control. To obtain favorable clinical outcome in patients with massive brain swelling, early decision making on surgical management and proper patient selection are mandatory.

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Role of the MDM2 Promoter Polymorphism (-309T>G) in Acute Myeloid Leukemia Development

  • Cingeetham, Anuradha;Vuree, Sugunakar;Jiwatani, Sangeeta;Kagita, Sailaja;Dunna, Nageswara Rao;Meka, Phanni Bhushann;Gorre, Manjula;Annamaneni, Sandhya;Digumarti, Raghunadharao;Sinha, Sudha;Satti, Vishnupriya
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2707-2712
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    • 2015
  • Background: The human homologue of the mouse double minute 2 (MDM2) gene is a negative regulator of Tp53. MDM2-309T>G a functional promoter polymorphism was found to be associated with overexpression thereby attenuation of Tp53 stress response and increased cancer susceptibility. We have planned to evaluate the possible role of MDM2-309T>G polymorphism with risk and response to chemotherapy in AML. Materials and Methods: A total of 223 de novo AML cases and 304 age and sex matched healthy controls were genotyped for the MDM2-309T>G polymorphism through the tetra-primer amplification refractory mutation system (ARMS)-PCR method. In order to assess the functional relationship of -309T>G SNP with MDM2 expression level, we quantified MDM2 mRNA in 30 primary AML blood samples through quantitative RT-PCR. Both the (-309T>G) genotypes and the MDM2 expression were correlated with disease free survival (DFS) rates among patients who have achieved complete remission (CR) after first induction chemotherapy. Results: MDM2-309T>G polymorphism was significantly associated with AML development (p<0.0001). The presence of either GG genotype or G allele at MDM2-309 confered 1.79 (95% CI: 1.12-2.86; p<0.001) and 1.46 fold (95%CI: 1.14-1.86; p= 0.003) increased AML risk. Survival analysis revealed that CR+ve cases with GG genotype had significantly increased DFS rates (16months, p=0.05) compared to CR+ve TT (11 months) and TG (9 months) genotype groups. Further, MDM2 expression was also found to be significantly elevated in GG genotype patients (p=0.0039) and among CR+ve cases (p=0.0036). Conclusions: The MDM2-309T>G polymorphism might be involved in AML development and also serve as a good prognostic indicator.

Totally Laparoscopic Total Gastrectomy for Early Gastric Cancer: An Initial Experience (조기위암으로 진단된 환자에서의 전복강경하 위전절제술의 초기 경험)

  • Lee, Jeong-Seon;Lee, Han-Hong;Kim, Jin-Jo;Park, Seung-Man
    • Journal of Gastric Cancer
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    • v.10 no.1
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    • pp.26-33
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    • 2010
  • Purpose: We wanted to evaluate the technical feasibility and safety of totally laparoscopic total gastrectomy (TLTG) for treating early gastric cancer. Materials and Methods: The medical records of 11 consecutive patients who underwent TLTG after being diagnosed with early gastric cancer at Incheon St. Mary's Hospital, The Catholic University of Korea from February 2005 to September 2009 were retrospectively reviewed and their clinicopathologic characteristics and the surgical results wereinvestigated. Results: The mean operation time was $385.6{\pm}94.1$ minutes, the mean time for creating an intracorporeal anastomosis was $97.5{\pm}60.0$ minutes and the mean number of the harvested lymph nodes was $46.6{\pm}15.4$ The mean number of days after operation until starting a liquid diet was the $6.1{\pm}7.6^{th}$ postoperative day and the mean hospital stay after surgery was $14.2{\pm}11.9$ days. There was no case of open conversion, but there were 2 cases of intraoperative complication and 3 cases of postoperative complication. There was one case of postoperative mortality. The patient suffered from thrombocytopenia of an unknown cause, which was refractory to platelet transfusion, on $4^{th}$ postoperative day and the patient died of intraabdominal bleeding on the $6^{th}$ postoperative day. Conclusion: TLTG was a technically feasible and relatively safe procedure. However, a long time for creating the intracoproeal anastomosis and a long operation time are still problems to be solved.

An Analysis of the Existing Guidelines and Clinical Trials for the Development of the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD) (위식도역류질환 한약제제 임상시험 가이드라인 개발을 위한 관련 국내 가이드라인 분석 및 기존 한약임상시험과의 비교)

  • Han, Ga-jin;Leem, Jung-tae;Kim, Jin-sung;Lee, Jun-hee
    • The Journal of Internal Korean Medicine
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    • v.37 no.1
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    • pp.90-108
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    • 2016
  • Objectives: This study aimed to learn what should be considered in the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD) by analyzing the existing guidelines and clinical trials.Methods: The development committee searched the existing guidelines for herbal medicinal products or GERD. Then, clinical trials related to GERD using herbal medicine were selected. The chosen trials were analyzed in terms of their inclusion and exclusion of participants, intervention, comparators, outcome, and trial design. Then, we compared the results of the analysis according to the regulations and guidelines of the Ministry of Food and Drug Safety to suggest the issues that we will have to consider when developing the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD).Results: As a result, few guidelines for GERD and clinical trials with herbal medicinal products were located in the national institution homepage. In addition, 8 articles were found using the following combination of search terms: “Gastroesophageal reflux disease”, “GERD”, “herbal medicine”, “herbal therapy”, “Korean Medicine”, “Traditional Chinese Medicine”, and “TCM”. Even though all trials had their own unique research questions, all studies were performed using a randomization method. Most trials included participants with reflux esophagitis, but two trials targeted proton pump inhibitor-refractory GERD. The type of intervention varied, such as decoction, granules, and capsules. Additionally, individualized herbal medicines were used in two studies. Comparators were diverse, such as placebo, Western medicine, and electro-acupuncture. The most frequently used outcome for efficacy was the effectiveness rate. In addition, the outcome for evaluating quality of life, esophageal mucosa and pressure, esophageal acid reflux, and recurrence rates were used. Safety was investigated by recording adverse events and carrying out laboratory tests.Conclusions: We identified some issues by reviewing the existing guidelines and comparing them with clinical trials for GERD and herbal medicinal products. These results will be utilized for developing the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD).

Lack of Association of the NPAS2 Gene Ala394Thr Polymorphism (rs2305160:G>A) with Risk of Chronic Lymphocytic Leukemia

  • Rana, Sobia;Shahid, Adeela;Ullah, Hafeez;Mahmood, Saqib
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7169-7174
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    • 2014
  • Background: NPAS2 is a product of the circadian clock gene. It acts as a putative tumor suppressor by playing an important role in DNA damage responses, cell cycle control and apoptosis. Chronic lymphocytic leukemia (CLL) appears to be an apoptosis related disorder and alteration in the NPAS2 gene might therefore be directly involved in the etiology of CLL. Here, the Ala394Thr polymorphism (rs2305160:G>A) in the NPAS2 gene was genotyped and melatonin concentrations were measured in a total of seventy-four individuals, including thirty-seven CLL cases and an equal number of age- and sex-matched healthy controls in order to examine the effect of NPAS2 polymorphism and melatonin concentrations on CLL risk in a Pakistani population. Materials and Methods: Genotyping of rs2305160:G>A polymorphism at NPAS2 locus was carried out by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Melatonin concentrations were determined by enzyme linked immunosorbent assay (ELISA). Statistical analysis was performed using Statistical Package for Social Sciences software. Results: Our results demonstrated no association of the variant Thr genotypes (Ala/Thr and Thr/Thr) with risk of CLL. Similarly, no association of rs2305160 with CLL was observed in either females or males after stratification of study population on a gender basis. Moreover, when the subjects with CLL were further stratified into shift-workers and non-shift-workers, no association of rs2305160 with CLL was seen in either case. However, significantly low serum melatonin levels were observed in CLL patients as compared to healthy subjects (p<0.05). Also, lower melatonin levels were seen in shift-workers as compared to non-shift-workers (p<0.05). There was no significant difference (p>0.05) in the melatonin levels across NPAS2 genotypes in all subjects, subjects with CLL who were either shift workers or non-shift-workers. General Linear Model (GLM) univariate analysis revealed no significant association (p>0.05) of the rs2305160 polymorphism of the NPAS2 gene with melatonin levels in any of the groups. Conclusions: While low melatonin levels and shift-work can be considered as one of the risk factors for CLL, the NPAS2 rs2305160 polymorphism does not appear to have any association with risk of CLL in our Pakistani population.

Radiation therapy for gastric mucosa-associated lymphoid tissue lymphoma: dose-volumetric analysis and its clinical implications

  • Lim, Hyeon Woo;Kim, Tae Hyun;Choi, Il Ju;Kim, Chan Gyoo;Lee, Jong Yeul;Cho, Soo Jeong;Eom, Hyeon Seok;Moon, Sung Ho;Kim, Dae Yong
    • Radiation Oncology Journal
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    • v.34 no.3
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    • pp.193-201
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    • 2016
  • Purpose: To assess the clinical outcomes of radiotherapy (RT) using two-dimensional (2D) and three-dimensional conformal RT (3D-CRT) for patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma to evaluate the effectiveness of involved field RT with moderate-dose and to evaluate the benefit of 3D-CRT comparing with 2D-RT. Materials and Methods: Between July 2003 and March 2015, 33 patients with stage IE and IIE gastric MALT lymphoma received RT were analyzed. Of 33 patients, 17 patients (51.5%) were Helicobacter pylori (HP) negative and 16 patients (48.5%) were HP positive but refractory to HP eradication (HPE). The 2D-RT (n = 14) and 3D-CRT (n = 19) were performed and total dose was 30.6 Gy/17 fractions. Of 11 patients who RT planning data were available, dose-volumetric parameters between 2D-RT and 3D-CRT plans was compared. Results: All patients reached complete remission (CR) eventually and median time to CR was 3 months (range, 1 to 15 months). No local relapse occurred and one patient died with second primary malignancy. Tumor response, survival, and toxicity were not significantly different between 2D-RT and 3D-CRT (p > 0.05, each). In analysis for dose-volumetric parameters, $D_{max}$ and CI for PTV were significantly lower in 3D-CRT plans than 2D-RT plans (p < 0.05, each) and $D_{mean}$ and V15 for right kidney and $D_{mean}$ for left kidney were significantly lower in 3D-CRT than 2D-RT (p < 0.05, each). Conclusion: Our data suggested that involved field RT with moderate-dose for gastric MALT lymphoma could be promising and 3D-CRT could be considered to improve the target coverage and reduce radiation dose to the both kidneys.

Continual Reassessment Method in Phase I Clinical Trials for Leukemia Patients (백혈병환자 대상의 제1상임상시험 연속재평가방법)

  • Lee, Joo-Hyoung;Song, Hae-Hiang
    • Communications for Statistical Applications and Methods
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    • v.18 no.5
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    • pp.581-594
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    • 2011
  • The traditional method of 3+3 standard design and model-based Bayesian continual reassessment method (CRM) are commonly used in Phase I clinical trials to identify the maximal tolerated dose(MTD) of a new drug. In this paper we review clinical examples of Phase I trials that were carried out in patients with refractory or relapsed leukemia and myelodysplastic syndrome. The recently proposed 3+1+1 design and rolling-6 design can shorten the trial duration, when a very slow accrual of patients with a simple 3+3 standard design may result in the untimely termination of trials. Too conservative approaches in determining the dose levels in Phase I clinical trials can leave clinical investigators unable to accurately determine the MTD. When determining future patient doses, the designs that use a time-to-event CRM can cooperate late toxicities by accounting for the proportion of the observation period of each enrolled patient. With the CRM design, simulations under different scenarios during the trial are important in detecting the under- or over-estimation of the initial estimate of the dose-limiting toxicity rate for each dose level. We present the advantages and drawbacks of the designs used in Phase I clinical trials for leukemia patients.

Combined Heart and Kidney Transplantation in Patient with Postpartum Cardiomyopathy and Renal Failure (분만 후 발생한 심근병증 및 만신신부전 환자의 심장-신장 동시이식 수술 체험 1예)

  • Lee Seung-Cheol;Hahm Shee-Young;Kim Jae-Joong;Han Duck-Jong;Song Meong-Gun
    • Journal of Chest Surgery
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    • v.39 no.9 s.266
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    • pp.714-717
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    • 2006
  • Heart and kidney transplantation has made great progress in the modern era. Coupled with the growing successes in individual solid organ transplantation, there has also been an increase in the number of multiple organ transplants, such as heart-kidney transplantation. This trend has been in part due to a better understanding of immunobiology, advances in surgical technique and postoperative care, and an often-common pathologic association between dual-organ failure. This pathologic course is representative for end-stage heart failure leading to secondary renal dysfunction or failure, or for end-stage renal failure as a cause for (uremic) cardiomyopathy. However, refractory cardiac failure has long been considered a contraindication to kidney transplantation. Additionally, cardiac transplantation has been denied for patients with end-stage renal disease. Over recent years, combined heart-kidney transplantation has been offered to select patients who were once denied transplantation. We report the first experience of combined heart-kidney transplantation with one year follow-up results.

LPCVD로 성장된 텅스텐 게이트의 물리.전기적 특성 분석

  • 노관종;윤선필;황성민;노용한
    • Proceedings of the Korean Vacuum Society Conference
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    • 1999.07a
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    • pp.151-151
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    • 1999
  • 금속-산화막-반도체(MOS) 소자를 이용하는 집적회로의 발전은 게이트 금속의 규격 감소를 필요로 한다. 규격감소에 따른 저항 증가가 중요한 문제점으로 대두되었으며, 그동안 여러 연구자들에 의하여 금속 게이트에 관련된 연구가 진행되어 왔다. 특히 저항이 낮으며 녹는점이 매우 높은 내화성금속(refractory metal)인 텅스텐(tungsten, W)이 차세대 MOS 소자의 유력한 대체 게이트 금속으로 제안되었다. 텅스텐은 스퍼터링(sputtering)과 화학기상 증착(CVD) 방식을 이용하여 성장시킬 수 있다. 스퍼터링에 의한 텅스텐 증착은 산화막과의 접착성은 우수한 반면에 증착과정 동안에 게이트 산화막(SiO2)에 손상을 주어 게이트 산화막의 특성을 열화시킬 수 있다. 반면, 화학기상 증차에 의한 텅스텐 성장은 스퍼터링보다 증착막의 저항이 상대적으로 낮으나 산화막과의 접착성이 좋지 않은 문제를 해결하여야 한다. 본 연구에서는 감압 화학기상 증착(LPCVD)방식을 이용하여 텅스텐 게이트 금속을 100~150$\AA$ 두께의 게이트 산화막(SiO2 또는 N2O 질화막)위에 증착하여 물리 및 전기적 특성을 분석하였다. 물리적 분석을 위하여 XRD, SEM 및 저항등이 증착 조건에 따라서 측정되었으며, 텅스텐 게이트로 구성된 MOS 캐패시터를 제작하여 절연 파괴 강도, 전하 포획 메커니즘 등과 같은 전기적 특성 분석을 실시하였다. 특히 텅스텐의 접착성을 증착조건의 변화에 따라서 분석하였다. 텅스텐 박막의 SiO2와의 접착성은 스카치 테이프 테스트를 실시하여 조사되었고, 증착시의 기판의 온도에 민감하게 반응하는 것을 알 수 있었다. 또한, 40$0^{\circ}C$ 이상에서 안정한 것을 볼 수 있었다. 텅스텐 박막은 $\alpha$$\beta$-W 구조를 가질 수 있으나 본 연구에서 성장된 텅스텐은 $\alpha$-W 구조를 가지는 것을 XRD 측정으로 확인하였다. 성장된 텅스텐 박막의 저항은 구조에 따라서 변화되는 것으로 알려져 있다. 증착조건에 따른 저항의 변화는 SiH4 대 WF6의 가스비, 증착온도에 따라서 변화하였다. 특히 온도가 40$0^{\circ}C$ 이상, SiH4/WF6의 비가 0.2일 경우 텅스텐을 증착시킨 후에 열처리를 거치지 않은 경우에도 기존에 발표된 저항률인 10$\mu$$\Omega$.cm 대의 값을 얻을 수 있었다. 본 연구를 통하여 산화막과의 접착성 문제를 해결하고 낮은 저항을 얻을 수 있었으나, 텅스텐 박막의 성장과정에 의한 게이트 산화막의 열화는 심각학 문제를 야기하였다. 즉, LPCVD 과정에서 발생한 불소 또는 불소 화합물이 게이트의 산화막에 결함을 발생시킴을 확인하였다. 향후, 불소에 의한 게이트 산화막의 열화를 최소화시킬 수 있는 공정 조건의 최저고하 또는 대체게이트 산화막이 적용될 경우, 개발된 연구 결과를 산업체로 이전할 수 있는 가능성이 높을 것을 기대된다.

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A New Rhabdovirus (HRV-like) Isolated in Korea from Cultured Japanese Flounder Paralichthys olivaceus (양식산 넙치로부터 HRV-like Rhabdovirus의 분리)

  • Oh, Myung-Joo;Choi, Tae-Jin
    • Journal of fish pathology
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    • v.11 no.2
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    • pp.129-136
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    • 1998
  • In March 1997, a new rhabdovirus was isolated from moribund cultured Japanese flounder Paralichthys olivaceus in sea water tank and cage culture systems in Kyung-Nam and Chun-Nam province, Korea. At temperature $15^{\circ}C$ the virus replicated and induced cytopathic effects (CPE), which progressed to eventual cytolysis, in susceptible cell lines, including RTG-2 and EPC. The CHES-214 cell line was refractory. Virus particles were bullet-shaped and measured $70nm{\times}100$ to 150 nm in size. The isolate was sensitive to pH 3, to diethyl ether, and to heat ($50^{\circ}C$ 5 min, $60^{\circ}C$ 1 min). Viral replication was not inhibited by $10^{-4}$ M 5-iododeoxyuridine. Virus infectivity was reduced by anti-HRV (8401-H) rabbit serum, but can not reduced by antisera against infectious hematopoietic necrosis virus (IHNV), chum salmon reovirus (CSV), retrovirus of salmonid (RVS) and infectious pancreatic necrosis virus (IPNV). HRV virus antigen was detected by fluorescent antibody test (FAT) in the cytoplasm of infected EPC cell. Purified isolates virions were composed of: polymerase (L), glycoprotein (G), nucleoprotein (N) and 2 matrix proteins (M1 and M2). Based upon their relative mobilities, the estimated molecular weights of the proteins were: L, 160 kDa; G, 55 kDa; N, 45 kDa; M1, 26 kDa; and M2, 22 kDa.

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