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Favorable Outcome in Elderly Asian Patients with Metastatic Renal Cell Carcinoma Treated with Everolimus: The Osaka Urologic Oncology Group

  • Inamoto, Teruo;Azuma, Haruhito;Nonomura, Norio;Nakatani, Tatsuya;Matsuda, Tadashi;Nozawa, Masahiro;Ueda, Takeshi;Kinoshita, Hidefumi;Nishimura, Kazuo;Kanayama, Hiro-Omi;Miki, Tsuneharu;Tomita, Yoshihiko;Yoshioka, Toshiaki;Tsujihata, Masao;Uemura, Hirotsugu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1811-1815
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    • 2014
  • Background: In clinical trials with no upper age limit, the proportion of older patients is usually small, probably reflecting the more conservative approach adopted by clinicians when treating the elderly. An exploratory analysis of elderly patients in the RECORD-1 Trial showed that patients ${\geq}$ 65 y.o. had superior median PFS than overall RECORD-1 population (5.4 months and 4.9 months, respectively). We investigated the efficacy, relative benefit and safety of Everolimus (EVE) as sequential therapy after failure of VEGFr-TKI therapy for older patients with metastatic renal cell cancer (mRCC), in daily practice. Materials and Methods: 172 consecutive IRB approved patients with mRCC (median age 65, M:F 135/37, 78% clear cell) who received salvage EVE at 39 tertiary institutions between October 2009 and August 2011 were included in this analysis. Some 31% had progressed on sunitinib, 22% on sorafenib, 1% on axitinib, 41% on sequential therapy, and 5% had received other therapy. Patients with brain metastases were not included and 95% of the patients had a ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1. Previous radiotherapy was an exclusion criterion, but prior chemotherapy was permitted. Adequate organ function and hematologic parameters were mandatory. EVE administration was approved by the institutional review board at each participating institution and signed informed consent was obtained from all patients. Results: Median time of the whole cohort to last follow-up was 3.5 months (range 0.4-15.2 months). Forty four percent were continuing to take EVE at last followup. There were 86 (50%) patients ${\geq}$ 65 y.o. and 86 (50%) <65 y.o. The percentage of patients who showed PR/SD was higher in the older group than in the younger one (5.9%/61.2% vs 1.2%/46.5%, respectively). Median survival of older patients was also significantly longer (3.5 +/- 0.31 vs 3.1 +/- 0.34, hazard ratio=0.45, CI; 0.255-0.802). Analysis using Cox regression model adjusted for gender, PS, number of metastases, site of metastases, histology, smoking history and age detected an association between age and PFS (p=0.011). The frequency of adverse events in elderly patients treated with EVE was no greater than that in younger patients, although such toxicity may have had a greater impact on their quality of life. Conclusions: Older patients should not generally be excluded from accepted therapies (mTOR inhibitors after failure of VEGFr-TKI therapy) for mRCC.

Development and Research on a Functional Hydrolyzed Whey Protein Powder Product with Sialic Acid as a Marker Compound - II. Repeated 90-day Oral Administration Toxicity Test using Rats Administered Whey Protein Powder containing Highly Concentrated Sialic Acid (23%) produced by Enzyme Separation and Solvent Enrichment Method - (Sialic Acid를 지표성분으로 하는 유청가수분해단백분말의 기능성식품 개발연구 - II. 효소분리 용매정제로 고농도 Sialic Acid가 함유된 유청가수분해단백분말(23%)의 랫드를 이용한 90일 반복경구투여 독성시험 평가 연구 -)

  • Noh, Hye-Ji;Cho, Hyang-Hyun;Kim, Hee-Kyong;Koh, Hong-Bum
    • Journal of Dairy Science and Biotechnology
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    • v.34 no.2
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    • pp.117-135
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    • 2016
  • The present study was performed to develop a functional raw food material from hydrolyzed whey protein powder (23%-GNANA) medication containing sialic acid as a marker compound that is naturally occurring at 7% concentration in GMP (glycomacropeptide). GMP is used worldwide in foodstuffs for babies and infants and is obtained from the milk protein as safe food. While the purpose of our detailed evaluation was aimed to assess preliminary NOAEL values for and above 2,000 mg/kg/day, a clinical dose allowance for 23%-GNANA (as per characteristic of a functional health product, a highly refined test substance of 23% (v/v) sialic acid combined in GMP), at the same time we also wanted to assess the safety of GMP hydrolyzate lacking sialic acid but with identical properties as GMP. Animal safety evaluation was conducted using 23%-GNANA as the test substance, produced from hydrolyzed whey protein powder (product name: HELICOBACTROL-23; provided by Medinutrol Inc. [Korea]; composed of 23% sialic acid and GMP protein) after isolating the sialic acid using enzymes approved as food additives, with GMP as a raw material, and subsequently increasing the content of xx up to 23% through 80% (v/v) ethanol soaking and concentrating, in accordance with GLP Guideline. The animal safety evaluation mentioned above was made on the basis of toxicity in SPF Sprague-Dawley female and male rats dosed with 10 mL of the test substance diluted to 0, 1,250, 2,500, and 5,000 mg/kg directly into their stomachs for 90 d. This was determined in terms of the general symptoms and animal viability, weight and amount of feed intake, eye examination, uracrasia tests, hematological and blood biochemical disorder tests, blood coagulation test, abnormal intestine weight, abnormalities during postmortem and histopathological examinations. Statistical significance was set at P<0.05. Based on the toxicity determination, a certain minor effect associated with the test substance was observed in male rats with no major effects of the tested substance, in comparison with the control group dosed with sterilized water. Nevertheless, the NOAEL value, evaluated as per toxicity criteria, was verified as 5,000 mg/kg/day (P<0.05). Similarly, for female rats, a certain minor effect associated with the test substance was observed in 5,000 mg/kg/day dosed group, with no major effect, yet the NOAEL value (as assessed as per toxicity criteria) was determined to be 5,000 mg/kg/day (P<0.05), which was the same as for male rats. Accordingly, the NOAEL values of the test substances for all female and male rats were finally verified as 5,000 mg/kg/day (P<0.05). In conclusion, it was determined that the 23%-GNANA test substance exceeds 2,000 mg/kg/day, the clinical allowance characteristic for functional health food, and was finally evaluated to cause no safety concerns when used as a raw material in functional health food production, which was the ultimate goal of the present study.

The effects of superovulatory doses of pregnant mare serum gonadotropin on uterine microenvironment of the rat (다배란 용량의 임마혈청성 고나도트로핀(PMSG)이 랫트의 자궁내 미세환경에 미치는 영향)

  • Yun, Young-won
    • Korean Journal of Veterinary Research
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    • v.34 no.4
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    • pp.745-757
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    • 1994
  • Superovulatory treatment with exogenous gonadotropins adversely affects the uterus through the disruption of the delicate balance of ovarian steroids (estrogens, progestins, androgens). To examine the uterine effects of this treatment, 189 rats were given 4IU, 20IU or 40IU pregnant mare',s serum gonadotropin(PMSG) at 28 days of age and sacrificed every 24h until day 10(D10) post injection. Long term uterine effects were examined in 12 rats treated with 4IU or 40IU PMSG and killed on D30. Adult rat uteri were examined to provide a reference for comparisons. Morphological and histological changes of control (4IU) uteri mimicked those of the adult on a comparable time-course form D2 to D5. Administration of superovulatory doses(20IU, 40IU) of PMSG produced stromal hypertrophy by D2 and focal papillary hyperplasia of the luminal epithelia by D3. Levels of $17{\beta}$-estradiol following 20IU and 40IU PMSG treatment were significantly(p<0.05, p<0.005) elevated above those of controls after D1. Androgen levels of both groups(20IU, 40IU) significantly p<0.05, p<005 increased from baseline on D1 and were maximum between D2 and D3. In the 20IU PMSG group, the hyperplasia gradually regressed after D3 and was absent by D10. The hyperplasia in the 40IU PMSG group, however, had become extensive by D6. It is suspected that preceding elevated levels of estrogen may be responsible for this progressive change. On D 4, the levels of $17{\beta}$-estradiol reached a maximum, which was significantly(p<0.001) greater than both the controls and 20IU PMSG-treated rats. Between D6 and D10, the hyperplasia in 40IU PMSG-treated rats partially regressed. Examination of uteri from D30 revealed no evidence of the hyperplasia. It is suggested that previous exposure to high levels of estrogen and androgens, secondary to superovulation, is possible cause for the observed hyperplasia.

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A Study on the Reality and Improvement of Autonomous Police System in Jeju Special Self-Government Province (제주자치경찰 시스템의 실태와 발전모델에 관한 연구)

  • Cho, Chul-Ok
    • Korean Security Journal
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    • no.14
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    • pp.485-516
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    • 2007
  • Jeju Special Self-Government Province adopted an autonomous police system for the first time since 60 years in Korean police. The purpose of autonomous police system is to offer a police service to be suitable in regional conditions. But Jeju autonomous police system for nearly one year after adoption is criticized to be established on the ground of political reason but not local decentralization. Actually Jeju autonomous police has not a clear cut jurisdiction and operation scope because of the jurisdiction duplication between national and autonomous police. The original task is confined on environment and sightseeing so on given to administration police for local self-government. So criminal investigation authority on general crimes is not to Jeuju autonomous police on account of special judicial police. First, it is the structural rationalization of Jeju autonomous police system. It speaks that Jeju provincial police bureau and police station have to be as national police institution, on the other hand, patrol district station and police box have to be as autonomous police institution. Of course, functional division has to be followed. National police performs managing all the assembly and demonstration by the management law on assembly and demonstration including the suppression against any large scale demonstration and disturbance, also the investigation on serious crimes just as international crimes and broaden area crimes including all the felony. Together national police performs the duty concerned to all the foreign affairs and national securities in along with the investigation on traffic accidents. On the other hand, autonomous police performs the function for citizen's life safety as crime prevention and the enforcement on the violation against police operation law, together the traffic management and the regulation on traffic violations. and the investigation on minor crime as simple violence or petty larceny including the management on local big events. Second, the budgetary of autonomous police is rationalized by the share of budgeting between Korean government and Jeju special self-government province. Third, urgent arrest authority on general crime and the rights of claims for the summary trial on minor crimes are given to autonomous police. Of course, this problem is resolved naturally in case of giving the investigation rights to autonomous police on minor crimes.

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Analytical Method for MCPA Residue in Brown Rice and Rice Straw by HPLC/UVD (HPLC/UVD를 이용한 현미와 볏짚 중 MCPA의 잔류분석방법 확립)

  • Yoo, Ki-Yong;Kang, Dae-Won;Choi, Yong-Hwa;Han, Seong-Soo
    • Korean Journal of Weed Science
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    • v.30 no.4
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    • pp.361-370
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    • 2010
  • This study was carried out to establish the analytical method of MCPA residue in brown rice and rice straw by HPLC/UVD. When MCPA was extracted from sample under the pH 3.6 by adding acetone 200 mL and 1N-HCl 100 mL, the extraction efficiency was high by 87%. And purification efficiency was high by 83% when 5 mL of 1% methanol/acetonitrile was eluated by the florisil Sep-pak cartridge column. From spiking of $0.1{\mu}g\;mL^{-1}$ and $0.25{\mu}g\;mL^{-1}$ of MCPA to control sample, respectively, average recovery rate of MCPA in brown rice was 96.0% and 94.9% and that in rice straw was 92.5% and 88.2%, respectively. Precision of experiment was very high by relative standard deviation of 1.5% to 5.7%. In brown rice and rice straw treated with bentazone+MCPA (11+1.2%) of 30 kg and 60 kg per ha at 30 days after rice transplanting, respectively, maximum residue limit was under $0.05{\mu}g\;mL^{-1}$ of the recommended rate of Korean Food and Drug Administration. From the above results, the analytical procedure of MCPA in plants such as hydrolysis, saponification and derivatization were ommited, and retention time was faster and recovery rate was higher than the existed results of HPLC/UVD. Therefore, these results were greatly improved and seemed to be usefully applied for residue analysis of MCPA in plants.

Thrombolytic Therapy for Thrombosis of Prosthetic Mitral Valve - A Case Report - (인공 승모판막에 생긴 혈전의 혈전용해 치료 - 1례 보고 -)

  • Kang, Shin-Kwang;Kim, Si-Wook;Won, Tae-Hee;Ku, Kwan-Woo;Na, Myung-Hoon;Yu, Jae-Hyun;Lim, Seung-Pyung;Lee, Young;Jeong, Jin-Ok
    • Journal of Chest Surgery
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    • v.35 no.11
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    • pp.826-830
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    • 2002
  • Prosthetic valve thrombosis(PVT) may be a life-threatening complication requiring prompt intervention. This is a case report of thrombolytic therapy for thrombosis of prosthetic mitral valve. A 47 year-old male admitted to the emergency room for abrupt onset of dyspnea. He had undergone mitral valve replacement(On-Ⅹ valve, 29mm) for mitral stenosis 8 months ago. The patient's international normalized ratio(INR) on admission was 1.09. The mechanical clicks were muffled and rales were heard in both lung fields. A transesophageal echocardiography(TEE) revealed prosthetic valve thrombosis with increased transvalvular pressure gradient(34 mmHg). The patient's condition needed to intubation for mechanical ventilation due to hemodynamic compromise, however his wife and relatives refused the surgical intervention due to financial problems. The patient was transferred to the cardiac care unit and we decided to perform thrombolytic therapy. A bolus of 1,500,000 IU of urokinase was given, followed by a drip of 1,500,000 IU for 1 hour. The patient did not improved hemodynamically; therefore, we gave 100 mg of tissue plasminogen activator(t-PA) for over 2 hours. During that time mechanical clicks were audible and hemodynamics of the patient improved progressively. A TEE showed disappearance of thrombus and decreased pressure gradient(1.7 mmHg) after 6 hours of thrombolytic therapy. The patient was recovered without any neurologic sequale and was discharged with administration of warfarin.

Effect of Aprotinin on Changes in Plasma Thromboxane $B_2$ and Endothelin-1 Concentratin after Extracorporeal Circulation (체외순환후 혈중 Thromboxane $B_2$와 Endothelin-1 농도 변화에 미치는 Aprotinin의 효과)

  • Lim, Cheong;Yun, Tae-jin;Kim, Yeon-seung;Kim, Seung-hoo;Lee, Jae-dam;Rho, Joon-Ryang;Song, Meong-Gun
    • Journal of Chest Surgery
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    • v.33 no.3
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    • pp.221-229
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    • 2000
  • Background: Thromboxane A2 and endothelin-1 are the potent vasoconstrictors affecting pulmonary pathophysiology in response to whole body inflammatin following CPB. Aprotinin, as an antiiflammatory agent, may decrease the release of such vasoactive substance from pulmonary tissues, preventing pulmonary hypertension after cardiopulmonary bypass. Material and Method: Ten mongrel dogs(Bwt. ac. 20kg) were subjected to cardioupulmonary bypass for 2 hours and postbypass pulmonary vascular resistance(0, 1, 2, 3 hours) were compared with prebypass level. The dogs were divided into 2 groups; control group(n-5) and aprotinin group(n=5). In the aprotinin group, aprotinin was administered as follows; 50,000 KIU/kg mixed in pump priming solution, 50,000 KIU/kg prebypass intravenous infusion over 30 minutes, 10,000 KIU/kg/hour postbypass continuous infusion. Prebypass and postbypass 0, 1, 2, 3 hour pulmonary vascular resistance were measured. At prebypass and postbypass 0, 90, 180 minutes, blood samples were obtained from pulmonary arterial and left atrial catherers for the assay of plasma thromboxane B2 a stable metabolite of thromboxane A2, and endothelin-1 concentrations. Result: The ratios of pustbypass over prebypass pulmonary vascular at postbypass 0, 1, 2, 3 hours were 1.28$\pm$0.20, 1.82$\pm$0.23, 1.90$\pm$0.19, 2.14$\pm$0.18 in control group, 1.58$\pm$0.18, 1.73$\pm$0.01, 1.66$\pm$0.10, 1.50$\pm$0.08 in aprotinin group ; the ratios gradually increased in control group while decreased or fluctuated after postbypass 1 hour in aprotinin group. There was statistically significant difference between control group and aprotinin group at postbypass 3 hours(P=0.014). Pulmonary arterial plasma concentration of thromboxane B2(pg/ml) at prebypass, postbypass 0, 90, 180 minutes were 346.4$\pm$61.9, 529.3$\pm$197.6, 578.3$\pm$255.8, 493.3$\pm$171.3 in control group, 323.8$\pm$118.0, 422.6$\pm$75.6, 412.3$\pm$59.9, 394.5$\pm$154.0 in aprotinin group. Left atrial concentrations were 339.3$\pm$89.2, 667.0$\pm$65.7, 731.2$\pm$192.7, 607.5$\pm$165.9 in control group, 330.0$\pm$111.2, 468.4$\pm$190.3, 425.4$\pm$193.6, 4.7.3$\pm$142.8 in aprotinin group. These results showed decrement of pulmonary thromboxane A2 generation in aprotinin group. Pulmonary arterial concentrations of endothelin-1(fmol/ml) at the same time sequence were 7.84$\pm$0.31, 13.2$\pm$0.51, 15.0$\pm$1.22, 16.3$\pm$1.73 in control group, 7.76$\pm$0.12, 15.3$\pm$0.71, 22.6$\pm$6.62, 14.9$\pm$1.11 in aprotinin group. Left atrial concentrations were 7.61$\pm$17.2, 57.1$\pm$28.4, 18.9$\pm$18.2, 31.5$\pm$20.5 in control group, 5.61$\pm$7.61, 37.0$\pm$26.2, 28.6$\pm$21.7, 37.8$\pm$30.6 in aprotinin group. These results showed that aprotinin had no effect on plasma endothelin-1 concentration after cardiopulmonary bypass. Conclusion: Administration of aprotinin during cardiopulmonary bypass could attenuate the increase in pulmonary vascular resistance after bypass. Inhibition of pulmonary thromboxane A2 generation was thought to be one of the mechanism of this effect. Aprotinin had no effect on postbypass endothelin-1 concentration.

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Preschool and Day-care Center Teacher's Attitude to Nutrition and Relationships between Their Educational Background and Nutrition Knowledge -Centered on the Kyongnam Area- (유치원 및 어린이집 교사의 어린이 영양에 대한 태도 및 교육 배경과 영양지식과의 관련성에 관한 연구 -강남지역을 중심으로-)

  • 신동주
    • The Korean Journal of Food And Nutrition
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    • v.10 no.2
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    • pp.219-227
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    • 1997
  • This research aims to reveal the attitude of day-care center and preschool teachers to nutrition, while understanding the influence of their experience of participation in nutrition education programs or taking nutrition courses in school days on the degree of their nutrition knowledge scores. The 204 subjects answered the questionnaire by a self-administration method from April 3 through April 30, 1997. Following are the results of this study : The teachers thought higher of social life(50.5%) and health life(37.3%) among the 5 item of child's living guidance. 58.8% answered 'necessary' and 36.3% 'very necessary' about nutrition education in one's childhood. As to the participation in nutrition education programs, 28.4% answered 'without fail' and 55.9% 'will try'. About the meaning of the meal time, 55.4% regarded it as an occasion for the child's socialization and 30.9% as an opportunity of nutrition education. Looking into their nutrition knowledge scores in four parts, 5 points each, the average totaled 10.9$\pm$3.0 : basic nutrition as 2.7$\pm$1.2, child's nutrition as 3.0$\pm$1.2, food and cookery as 2.4$\pm$1.2, food storage and hygiene as 2.8$\pm$0.8. Those teachers who had some experience of participation in nutrition education programs earned 11.0$\pm$3.1, while the rest scored 10.3$\pm$2.7-no significant difference. On the other hand, those teachers who had experience of taking nutrition courses received in school days 11.1$\pm$2.9, whereas the rest got 10.6$\pm$3.2-no significant difference.

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Quality and Affecting Factor of Care for Patients Hospitalized with Pneumonia (폐렴 입원환자 진료과정의 질적 수준과 이에 영향을 미치는 요인: 임상질지표를 중심으로)

  • Moon, Sangjun;Lee, Jin-Seok;Kim, Yoon;You, Sun-Ju;Choi, Yun-Kyoung;Suh, Soo Kyung;Kim, Yong-Ik
    • Tuberculosis and Respiratory Diseases
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    • v.66 no.4
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    • pp.300-308
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    • 2009
  • Background: The quality of care for patients with community acquired pneumonia needs to be improved; the factors affecting this care need to be analyzed. The objectives of this study were used to measure the performance of care processes of for patients with pneumonia and to determine those patient and hospital characteristics are associated with quality care. Methods: The analysis was performed using data from 21 hospitals that had over 500 beds for 1,001 patients, who were sampled randomly. All patients were born before 31 December 1989, and discharged between the two months' August 2006 and October 2006. Performance process indicators were measured by respective hospital, and multivariate logistic regression was used to calculate associations between patients and hospital characteristics using 4 process indicators. Results: Performance rates in timely assessment of oxygenation assessments and blood cultures, correct administration of antibiotic medications, and blood culture performed prior to initial antibiotics were 69.4%, 79.1%, 82.5% and 60.5%, respectively. Age had a positive affect on oxygenation assessment within 24 hours. Bed number, number of nurses per bed, annual number of emergency department visits, average percentage of beds filled, location and arrival time, and site were factors associated with process indicators. Conclusion: It is necessary to make up for the weak points in the process of care for patients with community acquired pneumonia, by enforcing quality assurance. To reduce performance rate variation among hospitals, improvement in care protocols is required for hospitals that have poor quality of care levels.

A Study of Job Satisfaction and Related Factors of the National Hospital Nurses (국립병원 간호사의 직무만족과 관련요인 연구)

  • Suh Gil-Hee;Kim Ok-Hee
    • Journal of Korean Public Health Nursing
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    • v.7 no.2
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    • pp.53-66
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    • 1993
  • By this time, a few of previous studies of factors related to separation from their jobs and job satisfaction only have dealt with the separation rate. the cause of separation and related factors that induce job satisfaction and incentive factors, the actualities of morale some suggestions for reduction of the separation rate. This study is attempted to determine factors that have effect on job satisfaction of national hospital nurses. and to proide information and materials for the development of the administration of nursing through the appreciation of factors influencing on job satisfaction between isolated ward nurses and general ward nurses working at national hospitals. 185 nurses of national hospitals responsed th this study, and were divided into two groups. Group 1: 57 nurses working at isolated wards for tuberculosis patients and Group 2 : 128 nurses at general wards. Relevant data were collected from August, 5, 1992 through August 20, 1992. The questionnaire consisted of 8 genalized items and 4 items concerning job satisfaction. The collected data were processed with SPSS, and the relationship among vaviables was analyzed by means of $X^2-test$, Pearson Correlation, Multiple Regression. The results of this study are as follows: 1. There is no significant difference between two groups in terms of generalized items. Age distributions show $44.3\%$ under the category of less than 34. and $55.7\%$ under the category more than 35, $19.3%$ was single and $74.6\%$ was married respectively. 2. $79.4\%$ of the nurses have the desire to have in-service education under the satisfactory physical environments such as welfare system, accommodating structures and facilities, instruments or management systems of the hospital, but under the category of unsatisfactory circumstances, $60.3\%$ have the intention of having in- service education. The concern in terms of in-service education shows statistically significant difference between two groups $(X^2=8.85,\;p<0. 05)$. This result accepts the hypothesis that good physical environments could intensify interests in service education. 3. The extent of satisfaction related to psychological environments is heightend according to good physical environments. In result, the hypothesis that the extent of satisfaction in terms of physical environments could raise satisfaction about psychological environment is accepted. 4. In the light of the extent of satisfaction about physical environments, $33.3\%$ of isolated ward nurses are satisfied with physical environments, but only $11.7\%$ of general ward nurses are satisfied. $(X^2=10.88,\; p<0.01)$. This result shows that the satisfaction degree about phusicalenvironments of isolated war nurses was higher than that of general ward nurses in spite of high physical and psychological risks due to exposure to infection. Consequently. the hypothesis was rejected that the satisfaction degree about physical environments would be lower in isolated ward nurses than in general ward nurses. 5. The fact that $87.7%$ of isolated ward nurses took interest in service education and $53.19\%$ of general ward nurses took interest in service education demonstrats that isolated ward nurse have more interest in service education than gerneral ward nurses. The result shows that the hypothesis is accepted that isolated ward nurses would have mor interests in service education than general ward nurses. 6. In the extent of satisfaction about physical environments such as morale human relationship promotion, there is no significant difference between two groups in terms of statistics. The hypothesis is rejected that satisfaction about psychologic environments would be high in isolated ward nurses than in general ward nurses. In conclusion. factors influencing on job satisfaction are considered to have effect on. another, and also interdisciplinary amelioration of factors accompanied with systematic inter cooperative investigation is necessary.

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