亚砷酸联合全反式维甲酸治疗急性早幼粒细胞白血病16例疗效观察

目的:观察亚砷酸(As2O3)与全反式维甲酸(ATRA)联合治疗初发急性早幼粒细胞白血病(APL)的疗效和不良反应.方法:As2O3联合ATRA治疗初治APL患者16例,As2O30.1%注射液10ml加入5%葡萄糖溶液500ml静脉点滴,持续4h,1次/d;ATRA40-60mg/d,分2次口服,观察完全缓解(CR)率,获得CR所需时间、不良反应.结果:15例患者获得CR,CR率93.8%,获得缓解时间(27.3±3.6)d,没有发现明显的不良反应.结论:As2O3,联合ATRA治疗初发APL患者疗效好,能缩短CR的时间,长期CR时间需要进一步观察.     

全反式维甲酸联合亚砷酸治疗急性早幼粒细胞白血病疗效观察

目的:观察全反式维甲酸(ATRA)联合三氧化二砷(As2O3)治疗急性早幼粒细胞白血病(APL)患者的疗效。方法:应用ATRA联合As2O3治疗初治APL共39例,ATRA 40mg/d分2次口服;As2O30.1%注射液10ml加入0.9%氯化钠溶液250ml静脉滴注,持续4-6h,1次/d。根据外周血白细胞计数,维甲酸综合征以及肝功能变化调整ATRA和As2O3的剂量。缓解后巩固治疗:DA(柔红霉素+阿糖胞苷)方案或HA(高三尖杉酯碱+阿糖胞苷)方案交替治疗4-6个疗程,ATRA与As2O3交替治疗。结果:39例初治患者中,仅2例因剧烈头痛(排除脑出血)退出,其余37例均达到CR,CR率94.87%(37/39),取得CR的平均时间是(26.9±4.3)d,均无早期复发并持续完全缓解,联合用药的不良反应患者均能耐受,毒副作用未增加。结论:ATRA联合As2O3治疗初治APL具有疗效好,达CR时间短,不良反应少,无病生存时间长的优点。     

全反式维A酸联合三氧化二砷治疗初治急性早幼粒细胞白血病17例

 目的 观察全反式维A酸（ATRA）联合三氧化二砷（As2O3）治疗初治急性早幼粒细胞白血病（APL）的完全缓解率（CR）。方法 ATRA 25 mg·m-2·d-1,As203 0.16 mg·kg-1·d-1联合治疗APL直至CR。根据外周血白细胞计数、维A酸综合征以及肝功能变化调整ATRA和As2O3的剂量。观察CR率、获得CR所需的时间、不良反应及近期缓解时间。结果 17例初次治疗APL患者早期死亡1例,16例获得CR,CR率94.1 %（16／17）,获得CR的平均时间为（28.4±5.7）d。85 %（12／14）患者在治疗开始后出现白细胞升高;53 %（9／17）患者出现肝功能异常,多在减量或停用后1周内恢复。至今16例获得CR的患者仍处于CR状态（1 ~ 25个月）。结论 ATRA联合 As2O3治疗初治APL疗效好,不良反应少,有条件的患者可考虑作为首选诱导缓解方案。     

全反式维甲酸联合三氧化二砷治疗急性早幼粒细胞白血病29例观察

目的　观察全反式维甲酸 (ATRA)联合三氧化二砷 (As2 O3 )治疗急性早幼粒细胞白血病 (APL)的临床疗效、作用特点及毒副作用。方法　As2 O3 注射液 0 .16mg/ (kg·d) ,ATRA 2 5mg/ (m2 ·d)联合治疗初治APL 2 9例 ,根据外周血白细胞计数、维甲酸综合征以及肝功能变化调整ATRA和As2 O3 的剂量。治疗过程中每周检查血象、骨髓像 ,随机检查凝血纤溶指标和肝、肾功能、心电图。结果　治疗初治APL 2 9例 ,1例因并发颅内出血而早期死亡 ,其余 2 8例均达到CR ,完全缓解率 96.6% ,平均缓解时间 ( 2 6.3± 4.1)天。结论　As2 O3 联合ATRA治疗APL的CR率高 ,达CR时间缩短 ,不良反应少。     

全反式维A酸联合三氧化二砷治疗急性早幼粒细胞白血病的临床观察

 目的 观察全反式维A酸（ATRA）与三氧化二砷（As2O3）联合治疗急性早幼粒细胞白血病（APL）的疗效和毒副作用。方法 As2O3联合ATRA治疗初治和复发APL患者12例,As2O3 0.1 %注射液10 ml加入5 %葡萄糖溶液500 ml静脉滴注,持续4 ~ 5 h,1次／d, 28 d为一疗程。ATRA 25 mg·m-2·d-1,分3次口服,根据外周血白细胞计数、 维A酸综合征以及肝功能变化调整As2O3和ATRA的剂量。结果 11例均达完全缓解（CR）,获得CR的平均时间为（28.2±4.5）d,未发现严重毒副反应。结论 As2O3联合ATRA治疗初发及复发APL患者疗效好, 能缩短CR的时间。     

小剂量三氧化二砷、维A酸双诱导并化疗序贯治疗急性早幼粒细胞白血病远期疗效观察

 目的 探讨三氧化二砷（As2O3）联合全反式维A酸（ATRA）双诱导治疗急性早幼粒细胞白血病（APL）的近期疗效及化疗序贯治疗的远期疗效观察。方法 对51例APL患者应用As2O3联合ATRA双诱导治疗;对其中47例CR患者采用DA,HA,MDAra-C,As2O3序贯巩固治疗。结果 51例APL患者47例获CR,CR率92.2 %。47例CR患者中,42例生存至今,生存时间8 ~ 83个月,中位生存时间41.2个月。 结论 As2O3联合ATRA诱导治疗APL完全缓解率高,毒副作用小,结合化疗及As2O3序贯治疗,复发率低,长生存率高。     

全反式维甲酸联合三氧化二砷及蒽环类药物治疗急性早幼粒细胞白血病44例

 目的　探讨全反式维甲酸（ATRA）与三氧化二砷（As2O3）联合蒽环类药物（ATC）治疗初治急性早幼粒细胞白血病（APL）的疗效和不良反应。方法　44例初发APL患者均符合FAB分型诊断标准,其中25例行荧光原位免疫杂交（FISH）检查PML-RARα融合基因均为阳性。均以ATRA+As2O3双诱导,白细胞＞15×109／L时,加用ATC,达完全缓解（CR）后,每月以ATC联合阿糖胞苷（Ara-C）化疗1个疗程,共3个疗程,继以ATC联合化疗、ATRA、As2O3序贯。观察其疗效和不良反应。结果　44例APL患者,早期死亡1例（诱导治疗1周死于弥漫性血管内凝血并颅内出血）,43例达CR,CR率97.73 %,获得CR的时间（27.3±5.2）d,43例目前均持续CR,25例初诊时PML-RARα融合基因阳性者,巩固化疗结束时均转为阴性,治疗过程中无严重不良反应发生。结论　ATRA与 As2O3联合ATC治疗APL效果满意,不良反应少。     

全反式维甲酸、三氧化二砷、化疗联合治疗急性早幼粒细胞白血病疗效观察

 目的　评估全反式维甲酸（ATRA）、三氧化二砷（As2O3）、化疗联合治疗初诊急性早幼粒细胞白血病（APL）的疗效和患者不良反应。方法　对40例采用ATRA、As2O3、化疗三联疗法治疗的APL患者的临床资料进行回顾性分析,观察其疗效及不良反应。结果　总体CR率92.5 %（37／40）,完全缓解所需中位时间27（22～61）d;白细胞≥10×109／L组CR率72.7 %（8／11）,白细胞＜10×109／L组CR率100 %（29／29）,差异有统计学意义（χ2＝8.550,P＝0.004）;治疗过程中无严重不良反应,仅1例发生维甲酸综合征。结论　ATRA、As2O3、化疗联合应用可作为APL患者的首选治疗方案。     

维甲酸联合三氧化二砷及化疗治疗急性早幼粒细胞白血病21例

 目的 观察全反式维甲酸（ATRA）联合三氧化二砷（As2O3）及小剂量DA方案化疗治疗急性早幼粒细胞白血病（APL）的疗效和患者不良反应。方法 采用ATRA联合As2O3及小剂量DA方案化疗对21例APL患者进行治疗观察,其中初治APL 15例,经ATRA治疗未缓解2例,ATRA治疗完全缓解（CR）后复发4例,ATRA 25 mg·m-2·d-1,分2～3次口服;As2O3 0.1％注射液10 ml加入5 ％葡萄糖溶液500 ml静脉滴注,持续4～5 h;治疗2周左右时加用DA方案化疗（D：柔红霉素30～40 mg·m-2·d-1×3 d,A：阿糖胞苷50～100 mg m-2·d-1×7 d）,观察CR率、获得CR所需时间、患者不良反应。结果 19例患者获得CR,CR率90.5 ％,获得缓解的时间（28.4±3.6）d,未发现明显的不良反应。结论 ATRA联合As2O3及小剂量化疗治疗APL患者疗效好,能缩短CR的时间,改善高白细胞综合征。     

全反式维甲酸联合三氧化二砷治疗急性早幼粒细胞白血病疗效分析

 目的　比较全反式维甲酸（ATRA）联合三氧化二砷（As2O3）双诱导与ATRA单药诱导治疗初发急性早幼粒细胞白血病（APL）的临床疗效。方法　我院收治的APL患者51例,分别采用ATRA联合As2O3双诱导、ATRA单药诱导治疗方案治疗4周以上,比较两组患者的完全缓解（CR）率和达CR的时间。结果　ATRA联合As2O3双诱导组和ATRA单药诱导组的CR率分别为83.3 %（20／24）和96.3 %（26／27）,差异无统计学意义（χ2＝1.44,P＞0.05）。ATRA联合As2O3双诱导组达到CR的时间[（36.8±6.12）d]明显短于ATRA单药诱导组的时间[（45.1±8.14）d],差异有统计学意义（t＝4.075,P＜0.05）,且不良反应少,更易于控制。结论　ATRA联合As2O3双诱导方案能缩短APL患者达到CR的时间,较ATRA单药诱导治疗具有更好疗效。     

大剂量甲氨蝶呤联合顺铂治疗骨肉瘤的临床研究

目的:观察以大剂量甲氨蝶呤(MTX)联合顺铂(PDD)治疗骨肉瘤的疗效及毒副反应。方法:40例骨肉瘤患者均有组织病理学或细胞学诊断及可评价客观指标。采用大剂量MTX6～8g/m2d1,静脉滴注6h,使用后4h配合甲酰四氢叶酸钙(CF)解救14～17次;PDD60～80mg/m2d8,21天为1周期,2周期评价疗效。化疗期给予水化、碱化及利尿处理并配合MTX的血药浓度监测。结果:CR10.0%,PR62.5%,SD12.5%,PD15.0%,有效率(CR PR)为72.5%。并且初治组疗效高于复治组(P<0.05),Ⅱ期疗效高于Ⅲ期(P<0.05)。不良反应主要为肝功能损害(52.5%)、皮疹(12.5%)、口腔粘膜炎(25.0%)和白细胞减少(20.0%)。结论:HDMTX联合PDD治疗骨肉瘤疗效肯定,耐受性好,值得临床推广使用。     

Multifunctional anti-angiogenic activity of the cyclic peroxide ANO-2 with antitumor activity

Our focus was to develop an anti-angiogenic drug possessing the inhibitory activity of urokinase-type plasminogen activator (u-PA) production. During preliminary screening, the effects of 13 ozonides on the inhibition of u-PA production in human fibrosarcoma HT-1080 cells and on the inhibition of angiogenesis on chicken embryonic chorioallantoic membranes were determined. Of the ozonides tested, 9 inhibited in vitro u-PA production of HT-1080 cells and 7 of these 9 exhibited strong anti-angiogenic activity. Interestingly, 6 of the 13 ozonides also inhibited cathepsin B activity. 1-Phenyl-1, 4-epoxy-1H,4H-naphtho[1,8-de][1, 2]dioxepin (ANO-2) potently inhibited cathepsin B (IC(50) = 0.47 microM) as well as u-PA production. Consequently, ANO-2 was selected for further study. ANO-2 inhibited tube formation by human umbilical vein endothelial cells cultured on Matrigel while exhibiting no cytotoxicity. Additionally, in vivo administration of ANO-2 inhibited angiogenesis induced by mouse Sarcoma-180 cells tested using the mouse dorsal air sac assay. Moreover, ANO-2 also suppressed primary tumor growth and reduced the number of pulmonary metastases caused by Lewis lung carcinoma cells in mice. These in vitro and in vivo activities indicate that ANO-2 has considerable potential as a new and potent anti-angiogenic drug that inhibits both u-PA production and enzymatic activity of cathepsins, indicating that ANO-2 may be a multifunctional inhibitor of angiogenesis.     

早期高危宫颈癌术后同步放化疗和序贯放化疗的对比研究

目的：对早期高危宫颈癌术后同步放化疗与序贯放化疗的疗效和毒副作用进行比较。方法：６８例早期高危宫颈癌术后患者随机分成同步放化疗组（３５例）及序贯放化疗组（３３例）。同步放化疗组放疗同时予以顺铂（ＤＤＰ）＋亚叶酸钙（ＣＦ）＋氟尿嘧啶（５ ＦＵ）化疗,放疗结束后再行辅助化疗;而序贯放化疗组先仅行放疗,结束后再行辅助化疗。治疗结束后定期复查,评估疗效和毒副作用,并进行对比。结果：同步组和序贯组中位生存时间分别为７０.３个月和６４.６个月（Ｐ＝０.０４７）。两组３年和５年局部无进展生存率分别为９３.８％、８７.５％和９２.１％、８０.９％;３年和５年总生存率分别为９６.８％、９０.６％和９６.１％、８５.０％（Ｐ＝０.０４９）。两组主要毒副反应为放射性直肠炎和骨髓抑制,但患者经治疗后均可耐受。结论：同步放化疗治疗早期高危宫颈癌术后患者,疗效优于序贯放化疗,且安全性较好。     

两种蒽环类化疗药物不良反应的对照分析

目的　观察分析临床两种常用蒽环类化疗药物的不良反应 ,为临床合理用药提供依据。方法　对照分析43例恶性肿瘤患者化疗过程中不良反应的发生情况。结果　脱发方面吡柔比星与阿霉素存在显著差异 ,消化道反应及骨髓抑制方面无统计学差异 ,由于累积剂量有限 ,所以心脏毒性方面未做分析。结论　患者对吡柔比星的耐受情况优于阿霉素 ,而且治疗组生活质量高于对照组     

15例脊髓空洞症放射治疗疗效分析

目的：探讨放射治疗对脊髓空洞症的治疗作用。方法：回顾性分析1993年3月至2001年月该院共收治的15例脊髓空洞症患者的疗效，采用钴60或6MV X线或电子束照射，剂量21.6Gy，分次量为1.2Gy／次，每周5次。结果：完全恢复（CR）2例，好转（PR）8例，有效率66．7％，稳定（SD）3例，进展（PD）2例，全组均无明显放疗反应。结论：放射治疗是脊髓空洞症的一种重要的治疗方法，合并Chiari畸形及病程较长者疗效较差。     

Incidence of Colorectal Cancer in Selected Countries of Latin America: Age-Period-Cohort Effect

Objective: To estimate Age-Period-Cohort effects on colorectal, colon and rectal cancer incidence rates in Latin American countries covered by high quality Population-Based Cancer Registries. Methods: A trend study was performed using data from Cancer Incidence in Five Continents. Age-Period-Cohort effects were estimated by Poisson regression for individuals aged between 20 and 79 years with colorectal, colon and rectal cancers informed by Population-Based Cancer Registries from 1983 to 2012 in Cali (Colombia); from 1983 to 2007 in Costa Rica; and from 1988 to 2012 for both Goiânia (Brazil) and Quito (Ecuador). Goodness of fit model was tested using the deviance of the models. Results: Age effect was statistically significant for both sexes in all Population-Based Cancer Registries areas and the curves slope reached peaks in the older age groups. There were cohort effects on the incidence rates for colorectal, colon and rectal cancers in all Population-Based Cancer Registries areas, except for women in Quito. Regarding the period effect, an increased ratio rate was observed in men (1.26, 95%CI 1.17 to 1.35) and women (1.23, 95%CI, 1.15 to 1.32) in Goiânia, between 2003 and 2007. Conclusions: In Latin America, age effect was observed on incidence rates for colorectal, colon and rectal cancers. Besides, birth cohort effect was identified for recent cohorts in both genders for colorectal, colon and rectal cancers in Cali and Goiânia, and cohort effect for colorectal and colon cancers in both genders in Costa Rica; while in Quito a cohort effect was only observed for rectal cancer among men. Period effect was observed in Goiânia with increased ratio rate in 2003-2007.     

宫颈癌根治术合适手术范围及疗效的研究

我院1973～1985年作宫颈癌根治术441例,其中84例术时进行切除范围的测量。Ⅰ_b期42例,Ⅱ_a期36例,Ⅱ_b期6例。切除主韧带8～14cm~2,宫骶韧带12～19cm~2,阴道旁2.5～5.9cm~2,阴道2～3.5cm。5年、10年存活率较多切除者高,即切除范围扩大存活率未见增加而略有降低。但经统计学检验差异无显著性(P均>0.05)。提示上述切除范围对Ⅰ_b期、Ⅱ_a期是合适的。本组随访率100.0％。5年存活率94.05％,其中Ⅰ_b期95.24％,Ⅱ_a期94.44％,Ⅱ_b期5/6。术后尿潴留占11.91％(10/84),输尿管阴道瘘占2.38％(2/84)。本文对手术合适的切除范围、降低术后并发症、提高对淋巴结转移的疗效及Ⅱ~b期手术问题进行了讨论。     

Effect of chronically-administered secretin on the nude mouse

Secretin plays an important role in the growth regulation of certain cancers in vitro. The nude mouse is a suitable model for evaluation of the effects of this hormone on tumor xenografts in vivo, but little is known about long-term actions of secretin in this species. We investigated the impact of chronically administered synthetic porcine secretin in the nude mouse. Six groups of mice (eight animals each) received twice-daily intraperitoneal injections of saline or secretin at 0.5, 5, 50, 500, or 5,000 micrograms/kg for 14 days. Body weight and general health were unaffected by exogenous secretin, and no apparent behavioral effects were observed. Seven abdominal organs were examined at necropsy and all were histologically normal. The only organ that showed a weight change was the pancreas (13% decrease at the highest secretin dose). This was accompanied by decreases in DNA and RNA content, indicating pancreatic hypoplasia. Secretin administration caused changes in DNA and/or RNA content (but not protein content or weight) in liver, small bowel, cecum, and large bowel. No effect of secretin on stomach or kidney was observed. Our work demonstrates the safety of frequent injections of pharmacologic doses of secretin in this frail animal and suggests that the nude mouse is an appropriate model for the in vivo study of tumor growth regulation by secretin.     

Flexure dose: the low-dose limit of effective fractionation

Total radiation dose often can be increased without subsequent increases in the severity of tissue injury by using reduced doses per fraction. The flexure dose, df, is defined as the largest fractional dose for which further fractionation produces no significant change in the total dose required to reach a specified effect level. Thus, df is clinically relevant in that it represents the limit of effective dose fractionation. For those tissues in which injury reflects depletion of a critical proportion of target cells, the flexure dose is a measure of the extent of the initial, nearly linear portion of the dose-survival curve. More generally, the flexure dose is a measure of the extent of the initial, nearly linear portion of a dose-response curve in organized tissue, whatever its relationship to clonogenic target cells might be. Several quantitative expressions for df are derived. The characteristic common to these is that each defines the flexure dose as a multiple of the ratio alpha/beta of the parameters of the linear-quadratic model of cell survival or dose response, where the multiple is a measure of experimental or statistical resolution. These multiples tend to fall within a limited range, thereby defining the "region of flexure" via the inequality 0.05 (alpha/beta) less than or equal to df less than or equal to 0.15 (alpha/beta). Estimates of the region of flexure are presented for a variety of normal and neoplastic tissues.     

Antimicrobial susceptibility and the in vitro postantibiotic effects of vancomycin and ciprofloxacin against Bacillus cereus isolates

Background: Vancomycin and ciprofloxacin were often used in the therapy of infections associated with Bacillus cereus.

Methods: Four B. cereus food and clinical isolates were chosen for determination of time–kill curves and postantibiotic effects (PAE) of ciprofloxacin and vancomycin.

Results: According to the minimum inhibition concentration (MIC), breakpoints defined by CLSI for Staphylococcus spp. were all four strains intermediate for vancomycin (MIC?=?4?μg/ml) and sensitive to ciprofloxacin (MIC?=?0.2?μg/ml) except the strain Bc63 resistant to the last antimicrobial (MIC?=?1.6?μg/ml). The lowest CFU values of tested strains were reached after 3–5?hours of exposure to 4?× MIC of vancomycin, and after 6–7?hours exposure to 10?× MIC of ciprofloxacin. The maximum reduction of the CFU in the presence of vancomycin and ciprofloxacin was about 2.46 log₁₀ and 2.48 log₁₀, respectively. The average duration of the PAE of vancomycin and ciprofloxacin was 0.94 and 1.60?hours, respectively. The statistically significant differences between PAEs induced with 3?× MIC, 4?× MIC and 8?× MIC of vancomycin were observed (P?Conclusions: The differences in PAE duration were strain and antimicrobial dependent.