• Title/Summary/Keyword: Endpoints

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Excess zinc uptake in Paronychiurus kimi(Collembola) induces toxic effects at the individual and population levels

  • Son, Jino;Lee, Yun-Sik;Kim, Yongeun;Wee, June;Ko, Euna;Cho, Kijong
    • Korean Journal of Environmental Biology
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    • v.37 no.3
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    • pp.335-342
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    • 2019
  • The purpose of this study was to investigate the toxic effects of zinc in collembolan Paronychiurus kimi at the individual (survival and juvenile production) and population (population growth and age structure) levels after 28 days of exposure in artificially spiked soil. These toxic effects were interpreted in conjunction with the internal zinc concentrations in P. kimi. The EC50 value for juvenile production based on the total zinc concentration was 457 mg Zn kg-1 dry soil, while the LC50 value for adult survival and ri=0 value for population growth were within the same order of magnitude (2,623 and 1,637 mg Zn kg-1 dry soil, respectively). Significant differences in adult survival, juvenile production, and population growth compared with the control group were found at concentrations of 1,500, 375, and 375 mg Zn kg-1 dry or higher, respectively, whereas significant differences in the age structure, determined by the proportion of each age group in the population, were observed in all treatment groups. It appeared that the internal zinc level in P. kimi was regulated to some extent at soil zinc concentrations of ≤375 mg Zn kg-1 dry soil, but not at high soil zinc concentrations. These results indicate that, despite zinc being regulated by P. kimi, excess zinc exceeding the regulatory capacity of P. kimi can trigger changes in the responses at the individual and population levels. Given that population dynamics are affected not only by individual level but also by population level endpoints, it is concluded that the toxic effects of pollutants should be assessed at various levels.

Does Epidural Naloxone Reduce Side Effects of Epidural Morphine without Reversing Analgesia? (Morphine과 Naloxone의 경막외 동반 투여가 Morphine의 제통효과와 부작용에 미치는 효과)

  • Choi, Jong-Ho;Lee, Jai-Min;Kim, Tae-Hyun
    • The Korean Journal of Pain
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    • v.11 no.1
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    • pp.47-53
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    • 1998
  • Background: Epidural coadministration of opioids and local anesthetics has provided excellent analgesia during postoperative period. However, it is usually associated with the occurance of many side effects which were induced by epidural morphine. Low dose of intravenous naloxone has been known to reduce morphine-induced side effects without reversing analgesia, but the effect of epidural naloxone has not been defined in human study. Therefore we evaluated side effects and analgesia when naloxone was administered via epidural route. Methods: Eighty patients having epiduro-general anesthesia for hysterectomy were randomly assigned to one of four study groups. As a mean of postoperative pain control, all received 2 mg of epidural morphine bolusly at 1 hr before the end of surgery and continuous epidural infusion was started by Two-day Infusor containing morphine 4 mg in 0.125% bupivacaine 100 ml with either none of naloxone(Group 1, n=20), 2 ug/kg/day of naloxone(Group 2, n=20), 3 ug/kg/day of naloxone(Group 3, n=20) or 4 ug/kg/day of naloxone(Group 4, n=20). Study endpoints included visual analog scales(VAS) for pain, severity of nausea, itching, somnolence and respiratory depression. They were assessed at 2, 4, 8, 16, 32, and 48 hr postoperatively. Results: VAS for pain showed significant difference in Group 4 compared with Group 1 at all of the evaluation time. Itching score decreased significantly in Group 3 and 4 after 8 hr postoperatively and nausea score decreased significantly in Group 3 after 4 hr postoperatively. Alertness score decreased significantly in Group 3 and 4 especially in early postoperative period. Conclusion: This study suggests that epidural naloxone reduce morphine-induced side effects in dose-dependent fashion without reversal of the analgesic effect of epidural morphine.

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Efficacy of Aprepitant for Nausea in Patients with Head and Neck Cancer Receiving Daily Cisplatin Therapy

  • Ishimaru, Kotaro;Takano, Atsushi;Katsura, Motoyasu;Yamaguchi, Nimpei;Kaneko, Ken-ichi;Takahashi, Haruo
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9627-9630
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    • 2014
  • Background: Although efficacy of aprepitant for suppressing emesis associated with single-dose cisplatin has been demonstrated, there are limited data on the antiemetic effect of this oral neurokinin-1 receptor antagonist during daily administration of cisplatin. Accordingly, we investigated the efficacy and safety of aprepitant in patients with head and neck cancer (HNC) receiving combination therapy with cisplatin and 5-FU (FP therapy). Materials and Methods: Twenty patients with HNC were prospectively studied who received a triple antiemetic regimen comprising granisetron ($40{\mu}g/kg$ on Days 1-4), dexamethasone (8 mg on Days 1-4), and aprepitant (125 mg on day 1 and 80mg on days 2-5) with FP therapy (cisplatin $20mg/m^2$ on days 1-4; 5-FU $400mg/m^2$ on days 1-5) (aprepitant group). We also retrospectively studied another 20 HNC patients who received the same regimen except for aprepitant (control group). Results: For efficacy endpoints based on nausea, the aprepitant group showed significantly better results, including a higher rate of complete response (no vomiting and no salvage therapy) for the acute phase (p=0.0342), although there was no marked difference between the two groups with regard to percentage of patients in whom vomiting was suppressed. There were no clinically relevant adverse reactions to aprepitant. Conclusions: This study suggested that a triple antiemetic regimen containing aprepitant is safe and effective for HNC patients receiving daily cisplatin therapy.

Temozolomide during and after Radiotherapy for Newly Diagnosed Glioblastomas : A Prospective Multicenter Study of Korean Patients

  • Joo, Jin-Deok;Chang, Jong-Hee;Kim, Jeong-Hoon;Hong, Yong-Kil;Kim, Young-Hoon;Kim, Chae-Yong
    • Journal of Korean Neurosurgical Society
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    • v.52 no.2
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    • pp.92-97
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    • 2012
  • Objective : This study was performed to determine the safety and outcome of concurrent chemoradiotherapy (CCRT) and adjuvant chemotherapy with temozolomide for Korean patients with a newly diagnosed glioblastoma. Methods : Patients were recruited from four institutions between 2004 and 2007. The patients received fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks and daily temozolomide, followed by 6 cycles of adjuvant temozolomide. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS), response, and safety. Results : A total of 103 patients were enrolled in this study. Ninety-six patients (93%) completed the CCRT and 54 patients (52%) received 6 cycles of adjuvant temozolomide. The response rate was 73% (53/73) and the tumor control rate was 92% (67/73). Of the 96 patients who completed the CCRT, the median OS was 18.0 months and the 1- and 2-year OS rates were 74 and 38%, respectively. The median PFS was 10.0 months and the 1- and 2-year PFS rates were 33 and 16%, respectively. The only significant prognostic factor of survival was the extent of surgical resection (p<0.05). CCRT resulted in grade 3 or 4 hematologic toxic effects in 8% of patients. No opportunistic infections were noted. Conclusion : This study is the first prospective multi-institutional report of CCRT and adjuvant chemotherapy with temozolomide for patients with a newly diagnosed glioblastoma in Korea. The current protocol may prolong the survival of Korean patients with a glioblastoma and may be tolerable in terms of toxicity.

Chemical Classification Based on Environmental and Health Toxicity and Implementation for GHS (화학물질의 독성에 근거한 분류체계 및 GHS 도입을 위한 대응방안)

  • Lim Young-Wook;Yang Ji-Yeon;Lee Yong-Jin;Shim Dong-Chun
    • Environmental Analysis Health and Toxicology
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    • v.21 no.2 s.53
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    • pp.197-208
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    • 2006
  • The hazards of chemicals can be classified using classification criteria that are based on physical, chemical and ecotoxicological endpoints. These criteria may be developed be iteratively, based on scientific or regulatory processes. A number of national and international schemes have been developed over the past 50 years, and some, such as the UN Dangerous Goods system or the EC system for hazardous substances, are in widespread use. However, the unnecessarily complicated multiplicity of existing hazard classifications created much unnecessary confusion at the user level, and a recommendation was made at the 1992 Rio Earth summit to develop a globally harmonized chemical hazard classification and compatible labelling system, including material safety data sheets and easily understandable symbols, that could be used for manufacture, transport, use and disposal of chemical substances. This became the globally harmonized system for the Classification and Labelling of Chemicals (GHS). The developmental phase of the GHS is largely complete. Consistent criteria for categorizing chemicals according to their toxic, physical, chemical and ecological hazards are now available. Consistent hazard communication tools such as labelling and material safety data sheets are also close to finalizations. The next phase is implementation of the GHS. The Intergovernmental Forum for Chemical Safety recommends that all countries implement the GHS as soon as possible with a view to have the system fully operational by 2008. When the GHS is in place, the world will finally have one system for classification of chemical hazards.

Early Clinical Experience with Sutureless Aortic Valve Replacement for Severe Aortic Stenosis

  • Kim, Do Jung;Kim, Hyo-Hyun;Lee, Shin-Young;Lee, Sak;Chang, Byung-Chul
    • Journal of Chest Surgery
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    • v.51 no.1
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    • pp.1-7
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    • 2018
  • Background: Sutureless aortic valve replacement (SU-AVR) has been developed as an alternative surgical treatment for patients with symptomatic severe aortic stenosis (AS). The aim of this study was to evaluate the clinical outcomes of SU-AVR through an assessment of hemodynamic performance and safety. Methods: From December 2014 to June 2016, a total of 12 consecutive patients with severe AS underwent SU-AVR. The endpoints were overall survival and valve-related complications (paravalvular leakage, valve thrombosis, migration, endocarditis, and permanent pacemaker implantation). The mean follow-up duration was $18.1{\pm}8.6months$. Results: The mean age of the patients was $77.1{\pm}5.8years$ and their mean Society of Thoracic Surgeons score was $9.2{\pm}17.7$. The mean cardiopulmonary bypass and aortic cross-clamp times were $94.5{\pm}37.3$ minutes and $54.9{\pm}12.5minutes$, respectively. Follow-up echocardiography showed good prosthesis function with low transvalvular pressure gradients (mean, $13.9{\pm}8.6mm\;Hg$ and peak, $27.2{\pm}15.0mm\;Hg$) at a mean of $9.9{\pm}4.2months$. No cases of primary paravalvular leakage, valve thrombosis, migration, or endocarditis were reported. A new permanent pacemaker was implanted in 1 patient (8.3%). The 1-year overall survival rate was $83.3%{\pm}10.8%$. Conclusion: Our initial experience with SU-AVR demonstrated excellent early clinical outcomes with good hemodynamic results. However, there was a high incidence of permanent pacemaker implantation compared to the rate for conventional AVR, which is a problem that should be solved.

Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy

  • Safdieh, Joseph J.;Schwartz, David;Weiner, Joseph;Weiss, Jeffrey P.;Rineer, Justin;Madeb, Isaac;Rotman, Marvin;Schreiber, David
    • Radiation Oncology Journal
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    • v.32 no.3
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    • pp.179-186
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    • 2014
  • Purpose: To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. Materials and Methods: The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. Results: The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). Conclusion: In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.

Esophageal tolerance to high-dose stereotactic radiosurgery

  • Lee, Bo Mi;Chang, Sei Kyung;Ko, Seung Young;Yoo, Seung Hoon;Shin, Hyun Soo
    • Radiation Oncology Journal
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    • v.31 no.4
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    • pp.234-238
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    • 2013
  • Purpose: Esophageal tolerance is needed to guide the safe administration of stereotactic radiosurgery (SRS). We evaluated comprehensive dose-volume parameters of acute esophageal toxicity in patients with spinal metastasis treated with SRS. Materials and Methods: From May 2008 to May 2011, 30 cases in 27 patients with spinal metastasis received single fraction SRS to targets neighboring esophagus. Endpoints evaluated include length (mm), volume (mL), maximal dose (Gy), and series of dose-volume thresholds from the dose-volume histogram (volume of the organ treated beyond a threshold dose). Results: The median time from the start of irradiation to development of esophageal toxicity was 2 weeks (range, 1 to 12 weeks). Six events of grade 1 esophageal toxicity occurred. No grade 2 or higher events were observed. $V_{15}$ of external surface of esophagus was found to predict acute esophageal toxicity revealed by multivariate analysis (odds radio = 1.272, p = 0.047). Conclusion: In patients with spinal metastasis who received SRS for palliation of symptoms, the threshold dose-volume parameter associated with acute esophageal toxicity was found to be $V_{15}$ of external surface of esophagus. Restrict $V_{15}$ to external surface of esophagus as low as possible might be safe and feasible in radiosurgery.

Predictive and Prognostic Biomarkers for Patients Treated with Anti-EGFR Agents in Lung Cancer: A Systemic Review and Meta-Analysis

  • Wang, Ying;Qu, Xiao;Shen, Hong-Chang;Wang, Kai;Liu, Qi;Du, Jia-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4759-4768
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    • 2015
  • Background: Several studies have investigated predictive and prognostic biomarkers for patients treated with anti-epidermal growth factor receptor (EGFR) agents in lung cancer. However, the conclusion is controversial. Materials and Methods: A meta-analysis was conducted to evaluate the associations of mutant K-ras, PIK3CA and PTEN deficiency with the efficacy of anti-EGFR agents in lung cancer. The primary endpoint was objective response rate (ORR). The secondary endpoints were overall survival (OS) and progression-free survival (PFS). Results: A total of 61 studies were included in the final meta-analysis. The result showed that K-ras mutation was a good predictor for ORR (RR=0.42, 95%CI, 0.33-0.55, p=0.000) and an effective prognostic marker for OS (HR=1.37, 95%CI, 1.15-1.65, p=0.001) and PFS (HR=1.33, 95%CI, 1.05-1.69, p=0.019). However, PTEN deficiency or PIK3CA mutation did not show any significance predictive value for ORR (PTEN, RR=0.82, 95%CI, 0.56-1.19, p=0.286; PIK3CA, RR=1.08, 95%CI, 0.17-6.66, P=0.938). And PTEN deficiency or expression of PIK3CA did not show significance prognostic value for OS (PTEN, HR=0.88, 95%CI, 0.31-2.46,P=0.805; PIK3CA, HR=0.79, 95%CI: 0.23-2.68, P=0.706). Conclusions: Our meta-analysis showed that K-ras mutation may be an effective predictor in lung cancer patients treated with anti-EGFR agents. Whereas, the predictive and prognostic value of PTEN deficiency and PIK3CA mutation need to be further investigated.

The Effect of E.G.F. and Human Follicular fluid on the Maturation of Mouse Oocytes in in vitro Culture (생쥐난의 체외 배양에서 인간난포액과 표피 성장 인자가 난성숙에 미치는 영향)

  • Min, Bu-Kie
    • Clinical and Experimental Reproductive Medicine
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    • v.20 no.2
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    • pp.157-160
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    • 1993
  • The human follicular f1uids(F.F.) may be considered to contribute the maturation of the oocytes on the in vitro culture. To investigate the effects of epidermal growth factor (E.G.F.), which is present in mature and immature follicular fluids, we had experiments of mouse oocytes maturation in vitro. The endpoints assayed were rated as percentage of oocytes undergoing germinal vesicle breakdown(G.V.B.D.) and polar body(P.B.) formation at 12 hours after in vitro culture. The rates of G.B.B.D. were 87% in mature F.F. 68% in immature F.F. and 78% in Ham's F-10 medium respectively. And overall the mature F.F. seem to stimulate on in vitro oocyte maturation compared with either immature F.F. or Ham's F-10 medium. As the concentration of addition of E.G.F. in immature F.F., the rates of G.V.B.D. and P.B. formation were 82 %, 23% in addition with 2 ng/ml while 84%, 32% in addition with 4 ng/ml respectivly. And at the concentration of addition of E.G.F. in Ham's F-10 media as well, the rates of G.V.B.D. and P.B. formation were 84%, 40% and 82%, 44% in addition with each 2ng, 4ng. AccordinglY there was no influence on the oocytes maturation at the addition of E.G.F. to each immature F.F. and Ham's F-10 medium. In conclusion, the E.G.F. is not able to induce oocyte maturation independent of it's effects in immature F.F. and Ham's F-10 media.

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