Pemetrexed has demonstrated clinical activity in non-small cell lung cancer (NSCLC) as well as other solid tumors. It transports into the cells via reduced folate carrier (RFC) and is polyglutamated by folypolyglutamate synthetase (FPGS). Pemetrexed directly inhibits several folate-dependent enzymes such as thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). We investigated the effects of genetic variations and the expression of RFC, FPGS, TS and DHFR enzymes on drug sensitivity to pemetrexed in NSCLC cells. Polymorphisms in RFC, FPGS, and DHFR were genotyped in four NSCLC cells - A549, PC14, HCC-1588, and H226. Real-time RT-PCR and Western blot was performed to evaluate mRNA transcripts and protein of these genes. The cytotoxicity of pemetrexed was measured by SRB assay. In PC14 and H226 cells, increased mRNA expressions of RFC and FPGS were associated with higher cytotoxicity to pemetrexed. 2R/2R genotype of TS and its increased mRNA expression were associated with drug resistance to pemetrexed in A549 cells, whereas 3R/3R genotype in TS with decreased mRNA expression was associated with higher sensitivity in H226 cells. After pemetrexed treatment, an inverse change of DHFR mRNA and protein expression was found. The strongest linkage disequilibrium (LD) was discovered between-1726C>T and -1188A>C SNP of DHFR gene. Our findings suggest the cytotoxic effect of pemetrexed may be associated with genetic polymorphisms and the expression level of genes involved in pemetrexed metabolisms in NSCLC cells.
Pulmonary artery banding (PAB) in the functional univentricular heart (UVH) is a palliative procedure for staging toward the Fontan procedure; however, it is known to be a risk factor. Material and method: The records of all 37 patients with functional UVHs who underwent surgical palliation using PAB between September 1989 and August 1999 were reviewed retrospectively. We investigated the aortic arch obstruction, the development and progression of subaortic stenosis after PAB, and risk factor of mortality according to surgical method. Result: In 37 neonates and infants with single ventricular physiology, aortic arch obstruction was combined in 7. There were 6 early deaths (16.2%) after PAB and 3 late deaths (8.1%) after Fontan operation. The actuarial overall survival including early mortality at 3 and 5 years were 80.7$\pm$6.6%, 72.2$\pm$8.2% respectively. Among 31 patients who survived PAB, 27 patients (87.1 %) could become candidates for Fontan operation; 22 patients (71.0%) completed Fontan operation with 3 deaths and 5 were waiting bidirectional cavopulmonary shunt(BCPS) or Fontan operation (follow-up mean 4.5 year, minimal 2 year). Subaortic stenosis developed in 8 patients after PAB (8/29, 27.6%); 3 cases in the patients without arch anomaly (3/22, 13.6%) and 5 in those with arch anomaly (5/7, 71.4%). The subaortic stenosis was managed with Damus-Kaye-Stansel procedure (DKS) in 6 patients without operative mortality and conal septum resection in 2 without long-term survivor. Analysis of risk factors established that aortic arch obstruction was strongly associated with subaortic stenosis (p<0.001). The only risk factor of late mortality was Fontan procedure without staged palliation by BCPS (p=0.001). Conclusion: PAB is effective as an initial palliative step in functional UVH. And the high risk group of patients with aortic obstruction can undergo effective short-term PAB as an initial palliative step, with subsequent DKS for subaortic stenosis. This strategy, initial PAB and careful surveillance, and early relief of subaortic stenosis can maintain acceptable anatomy and hemodynamics for later Fontan procedures.
Lee Jeong Ryul;Choi Chang Hyu;Min Sun Kyung;Kim Woong Han;Kim Yong Jin;Rho Joon Ryang;Bae Eun Jung;Noh Chung I1;Yun Yong Soo
Journal of Chest Surgery
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v.38
no.8
s.253
/
pp.538-544
/
2005
Background: Pulmonary artery banding (PAB) is an initial palliative procedure for a diverse group of patients with congenital cardiac anomalies and unrestricted pulmonary blood flow. We proved the usefulness of PAB through retrospective investigation of the surgical indication and risk analysis retrospectively. Material and Method: One hundred and fifty four consecutive patients (99 males and 55 females) who underwent PAB between January 1986 and December 2003 were included. We analysed the risk factors for early mortality and actuarial survival rate. Mean age was $2.5\pm12.8\;(0.2\sim92.7)$ months and mean weight was $4.5\pm2.7\;(0.9\sim18.0)\;kg$. Preoperative diagnosis included functional single ventricle $(88,\;57.1\%)$, double outlet right ventricle $(22,\;14.2\%)$, transposition of the great arteries $(26,\;16.8\%)$, and atrioventricular septal defect $(11,\;7.1\%)$. Coarctation of the aorta or interrupted aortic arch $(32,\;20.7\%)$, subaortic stenosis $(13,\;8.4\%)$ and total anomalous pulmonary venous connection $(13,\;8.4\%)$ were associated. Result: The overall early mortality was $22.1\%\;(34\;of\;154)$, The recent series from 1996 include patients with lower age $(3.8\pm15.9\;vs.\;1.5\pm12.7,\;p=0.04)$ and lower body weight $(4.8\pm3.1\;vs.\;4.0\pm2.7,\;p=0.02)$. The early mortality was lower in the recent group $(17.5\%;\;16/75)$ than the earlier group $(28.5\%;\;18/45)$. Aortic arch anomaly (p=0.004), subaortic stenosis (p=0.004), operation for subaortic stenosis (p=0.007), and cardiopulmonary bypass (p=0.007) were proven to be risk factors for early death in univariate analysis, while time of surgery (<1996) (p=0.026) was the only significant risk factor in multivariate analysis. The mean time interval from PAB to the second-stage operation was $12.8\pm10.9$ months. Among 96 patients who survived PAB, 40 patients completed Fontan operation, 21 patients underwent bidirectional cavopulmonary shunt, and 35 patients underwent biventricular repair including 25 arterial switch operations. Median follow-up was $40.1\pm48.9$ months. Overall survival rates at 1 year, 5 years and 10 years were $81.2\%\;65.0\%,\;and\;63.5\%$ respectively. Conclusion: Although it improved in recent series, early mortality was still high despite the advances in perioperative management. As for conventional indications, early primary repair may be more beneficial. However, PA banding still has a role in the initial palliative step in selective groups.
Staple closure of bronchial stump was compared with manual suture closure among 100 cases of pneumonectomy during the recent 5-year period, We have reviewed the incidence of bronchpleural fistula between autosutured group and manual sutured group. Material and Method: During the recent 5-year period, 100 patients underwent pneumonectomy at Hanyang University Hospital. Staple closure of bronchial stump was performed in 65 patients and manual suture in 35 patients. There were 55 males and 10 females in the autosutured group, and 26 males and 9 females in manual sutured group, which showed no significant statistical difference between the two groups. The mean ages of patients for autosutured group and manual sutured group were 56.7$\pm$10.3 years and 61.4$\pm$9.2 years, respectively, which showed no significant statistical difference between the two groups. There were 38 cases of left pneumonectomy and 27 cases of right pneumonectomy in autosutured group, and 22 cases of left pneumonectomy and 13 cases of right pneumonectomy in manual sutured group. There were 53 cases of malignancy and 12 cases of benign imflammatory disease in autosutured group, and 27 cases of malignancy and 7 cases of benign imflammatory disease in manual sutured group. Result: The incidence of bronchopleural fistula was 6.1% in autosutured group and 5.7% in manual sutured group. The incidence of other postoperative complication between the two groups showed no significant statistical difference. Conclusion: The incidence of bronchopleural fistula between autosutured group and manual sutured group was not different stastically. Both method for closure of bronchial stump can be performed in pneumonectomy.
As users environments change, users primary needs for homepages also change more complicatedly. Today, users do not only want usability for homepages, but also to feel appropriate emotional experiences. Despite users needs, users do not always experience appropriate emotions that are conveyed by designers through homepage. I In this research paper, we analyzed the related factors with the emotional quality, which means the degree that users feel target emotions intended by designers. For analyzing factors related with the emotional quality, three hypotheses were verified; the factor of an emotion, the factor of users and the factor of designers. As the factor of emotions, the first hypothesis is that unclear emotional dimensions in users minds are related with the emotional quality. The second hypothesis, as the factor of users, is that the diversity of users experiences by same homepage is related with the emotional quality. The third hypothesis, as the factor of designers, is that the appropriate selection of design elements is related with the emotional quality. In the previous research, we selected the basic 13 emotional dimensions and 30 representative emotional words based on the statistical results and evaluations by professional designers. For this research, we conducted an experiment and user survey. In the experiment, we asked 30 designers to design homepages focusing on the typical emotion that was presented by a researcher. Based on the designing process and user evaluation, we performed statistical analyses: ANOVA with Tukey post hoc method and Factor Analysis. We found the discrepancy between the emotions that designers intend and the actual emotions that users experienced from homepages. From the result of analysis, we know that the factor of users and the factor of designers related with the emotional qualities, but the factor of emotions did not. The definiteness of emotions did not relate with the emotional quality. However, the diversity of emotions that users feel seeing the same homepages and design elements that designers chose for conveying target emotion related with the emotional quality.
Background: T-cell mediated cellular immunity has been suggested as an important mechanism in mycobacterial infection and imbalance between helper/inducer and suppressor/cytotoxic T-cell has been suggested as an important immunological abnormality in the pathogenesis of tuberculosis in human. Method: To determine whether there is any difference in T-cell mediated immunity in the pathogenesis of pulmonary and extra pulmonary tuberculosis, total numbers of WBC&lymphocytes were counted and helper/inducer and suppressor/cytotoxic cells were calculated by flow cytometry. Blastogenesis after stimulation with Concanavalin-A, Phytohemagglutinin and PPD were measured by $^3H$-thymidine uptake. PPD skin test was performed as an in vivo test. Results: 1)There was no significant difference in the size of PPD skin test between pulmonary and extrapulmonary tuberculosis groups. 2)Number of total lymphocytes significantly decreased in tuberculosis patients compared with healthy control group. But there was no significant difference between pulmonary and extrapulmonary tuberculosis groups. 3) Number of HLA-DR and Interleukin-2 receptor (+) cells were significantly increased in tuberculosis patients. But there was no significant difference between pulmonary and extra pulmonary tuberculosis groups. 4) There was no significant difference in the numbers of WBC, $T_3$, $T_4$ and $T_8$ lymphocytes and $T_4/T_8$ ratio between tuberculosis patients and healthy controls. 5) There was no significant difference in the blastogenesis after stimulation with specific and non-specific blastogens between tuberculosis patients and healthy controls. 6) The percentage and absolute number of $T_4$ lymphocyte were significantly correlated with the size of PPD skin test. (r=0.689 and 0.598). Conclusion: From these results, it is concluded that there was no difference in T-cell mediated immunity between pulmonary and extra pulmonary tuberculosis group. But, because it is suspected that there might be some difference in the role of T-cell mediated immunity in the pathogenesis of pulmonary and extra pulmonary tuberculosis or even among the extrapulmonary tuberculosis patients, further studies would be required.
Background: Thoracic trauma is one of the leading causes of morbidity and mortality in developing countries. A rib fracture that is secondary to blunt thoracic trauma is an important indicator of the severity of the trauma. The purpose of study was to determine the morbidity and mortality rates and the management of rib fractures. Material and Method: We performed a retrospective study that involved all the blunt trauma patients with rib fractures, excluding those that were transferred to other hospital within 3 days, that were seen at our hospital between May 2002 and December 2008. Of the 474 admitted patients, 454 met the inclusion criteria. There were 356 male and 98 females, and their overall mean age was 53 years (range: 5~90 years). The outcome parameters included the mechanism of injury, the number of fractured ribs, the length of stay in the ICU, the Injury Severity Score (ISS), the length of the hospital stay, the pulmonary complications and the mortality. Result: The mechanism of trauma included traffic accidents in 189 (41.7%) cases, slipping down in 103 (22.7%) cases, falls in 85 (18.7%) cases, cultivator accidents in 30 (6.6%) cases, industrial accidents in 32 (7.0%) cases and assault in 15 (3.3%) cases. Intrathoracic injury was noted such as hemothorax in 269 (59.3%) cases, pneumothorax in 144 (31.7%) cases, pulmonary contusion in 95 (20.9%) cases, subcutaneous emphysema in 29 (6.4%) cases and great vessel injury in 5 (0.1%) cases. Conservative treatment was administered to most of the patients. Tube thoracostomy was administered in 234 (51.5%) cases, whereas thoracotomy was performed in 18 (4.0%) cases. The mean duration of thoracostomy was $5.2{\pm}6.2$ days. Most of the cases with rib fracture were treated in wards and their mean duration of hospital stay was $22.5{\pm}20$ days. The mean Injury Severity Score (ISS) was $14.8{\pm}10.9$ (range: 3~75). The mortality rate was calculated to be 4.8% (n=22). The main factors correlated with an adverse outcome were the number of ribs fractured, the duration of thoracostomy and pulmonary disease. Industrial insurance affected the length of hospitalization. Pulmonary contusion and the Injury Severity Score (ISS) affected the mortality. Conclusion: Rib fractures are a indicator of severe injury. Because of the complication and associated injuries, we believe these patients should be admitted for evaluation and treatment. Recent studies on the impact of rib fractures after blunt trauma have shown that patients as young as 40 years of age demonstrate increased morbidity and mortality with similar injuries as compared to that of older patients. The ISS and pulmonary contusion influenced the mortality rate. Patients with isolated rib fractures should be hospitalized if the number of fractured ribs is one or more.
Modern businesses are adopting new technologies to serve their markets better as well as to improve efficiency and productivity. The advertising industry has continuously experienced disruptions from the traditional channels (radio, television and print media) to new complex ones including internet, social media and mobile-based advertising. This case study focuses on proposing intelligent advertising business model in Seoul's metro network. Seoul has one of the world's busiest metro network and transports a huge number of travelers on a daily basis. The high number of travelers coupled with a well-planned metro network creates a platform where marketers can initiate engagement and interact with both customers and potential customers. In the current advertising model, advertising is on illuminated and framed posters in the stations and in-car, non-illuminated posters, and digital screens that show scheduled arrivals and departures of metros. Some stations have digital screens that show adverts but they do not have location capability. Most of the current advertising media have one key limitation: space. For posters whether illuminated or not, one space can host only one advert at a time. Empirical literatures show that there is room for improving this advertising model and eliminate the space limitation by replacing the poster adverts with digital advertising platform. This new model will not only be digital, but will also provide intelligent advertising platform that is driven by data. The digital platform will incorporate location sensing, e-commerce, and mobile platform to create new value to all stakeholders. Travel cards used in the metro will be registered and the card scanners will have a capability to capture traveler's data when travelers tap their cards. This data once analyzed will make it possible to identify different customer groups. Advertisers and marketers will then be able to target specific customer groups, customize adverts based on the targeted consumer group, and offer a wide variety of advertising formats. Format includes video, cinemagraphs, moving pictures, and animation. Different advert formats create different emotions in the customer's mind and the goal should be to use format or combination of formats that arouse the expected emotion and lead to an engagement. Combination of different formats will be more effective and this can only work in a digital platform. Adverts will be location based, ensuring that adverts will show more frequently when the metro is near the premises of an advertiser. The advertising platform will automatically detect the next station and screens inside the metro will prioritize adverts in the station where the metro will be stopping. In the mobile platform, customers who opt to receive notifications will receive them when they approach the business premises of advertiser. The mobile platform will have indoor navigation for the underground shopping malls that will allow customers to search for facilities within the mall, products they may want to buy as well as deals going on in the underground mall. To create an end-to-end solution, the mobile solution will have a capability to allow customers purchase products through their phones, get coupons for deals, and review products and shops where they have bought a product. The indoor navigation will host intelligent mobile-based advertisement and a recommendation system. The indoor navigation will have adverts such that when a customer is searching for information, the recommendation system shows adverts that are near the place traveler is searching or in the direction that the traveler is moving. These adverts will be linked to the e-commerce platform such that if a customer clicks on an advert, it leads them to the product description page. The whole system will have multi-language as well as text-to-speech capability such that both locals and tourists have no language barrier. The implications of implementing this model are varied including support for small and medium businesses operating in the underground malls, improved customer experience, new job opportunities, additional revenue to business model operator, and flexibility in advertising. The new value created will benefit all the stakeholders.
Kim Tae-Hyun;Yang Dae-Sik;Kim Chul-Young;Choi Myung-Sun
Radiation Oncology Journal
/
v.18
no.2
/
pp.85-91
/
2000
Purpose : The aim of this study is to look for the possible efficacy of postoperative external irradiation for incompletely resected meningiomas. Methods and Materials : From August 198: to January 1997, forty-four patients with intracranial meningioma were treated by postoperative external irradiation. Of the 44 meningiomas, 18 transitional, 13 meningotheliomatous, 6 hemangiopericytic, 4 atypical, 2 fibroblastic and 1 malignant meningioma were identified. We classified all patients into two groups by the histology. The benign group was consisted of the meningotheliomatous, transitional and fibroblastic types. The malignant group was consisted of the atypical, hemangiopericytic and malignat types. In the means of surgery, 37 patients were resected incompletely and 7 patients were managed by biopsy only. After surgery, all patients were received postoperative external irradiation. Radiotherapy was deliverd using Co-60 or 4 MV photon beam to a total dose of 50 to 65 Gy (mean dose 57.4 Gy) with a 1.8 to 2 Gy per fraction. The median follow-up was 48 months (range : 21 $\~$ 101 months). Multivariate analysis of the Influence by age, sex, location, histology and radiation dose on local control has been done using Cox's proportional hazard model. Results : 5-year local control rate was 93.8$\%$ for the benign histology and 51.8$\%$ for the malignant histology (p=0.0110) and overall local control rate at 5 years was 87.4$\%$. The analysis of the prognostic factors, such as age, sex, location, and radiation dose were not significant except for the histology. Conclusion : Adjuvant postoperative external irradiation appears to be significantly improved local control in the patients with incompletely resected meningiomas.
Syenite is not a common rock, unlike granitic rocks formed the major component of the continental crust. The aim of this study is to decipher the occurrences and detailed descriptive characteristics of the syenite distributed in Sancheong area, and to investigate the petrogenesis of the syenitic magma based on geochemical study. The dominant minerals in syenite are alkali feldspar (usually orthoclase and rarely microcline), plagioclase, amphibole, biotite, and quartz. Syenites are found in a wide variety of colors. The anhedral hornblende and biotite filling the boundary of feldspar and quartz indicate that the hydrous minerals were crystallized lately, and that water was insufficient at the beginning of crystallization in magma. According to the analysis of mineral composition, amphibole in syenite is mostly ferro-edenite, and the pressure is calculated as 3.3~4.9 kb with 11.9~17.3 km of emplacement depth. Biotite and pyroxene are plotted in the region of annite and hedenbergite, respectively. Based on petrochemical studies of major elements, syenite belongs to alkaline series, metaluminous, and I-type. On the other hand, the variation patterns of trace and rare earth elements of syenite differ from the patterns of diorite and granite. In the geochemical characteristics, syenite is different from gabbro-diorite spatially adjacent to syenite, as well as granite. These results suggest that each rock has been generated from the different sources of magma. Additionally, based on the experimental data, the syenitic magma can be formed (1) by the partial melting at a high pressure and dry system, (2) when the initial crystallization minerals to be residue with migration of the residual melts separated from the ascending cotectic magma (3) when fluorine compositions to be plentiful in the protolith and/or at depth of the magma. Based on the petrographic characteristics of the syenite, Sancheong syenitic magma may have been formed by partial melting in a dry system.
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