复方苦参注射液联合多西他赛治疗一线化疗失败非小细胞肺癌患者的疗效

[目的]探讨复方苦参注射液联合多西他赛对一线化疗失败非小细胞肺癌(NSCLC)患者的疗效及血清肿瘤标记物的影响.[方法]80例一线化疗失败的NSCLC患者随机分为观察组(复方苦参注射液+多西他赛)与对照组(多西他赛),比较两组近期疗效、不良反应、治疗前后血清肿瘤标记物水平及细胞免疫功能变化,并随访统计两组总生存期(OS)、无进展生存期(PFS).[结果]观察组近期有效率和疾病控制率分别为25.00%(10/25)和62.50%(25/40),明显高于对照组的10.00%(4/40)和37.50%(15、40),且差异有显著性(P<0.05);两组各不良反应发生率比较差异无显著性(P>0.05);与治疗前比较,两组治疗后血清癌胚抗原(CEA)、糖类抗原-125(CA-125)、细胞角蛋白19片段(CYFRA21-1)水平均显著下降(P<0.05),且观察组治疗后上述指标均显著低于对照组(P<0.05);观察组中位OS、PFS分别为13.50个月、9.00个月,明显长于对照组的10.20个月、7.40个月,且差异有显著性(P<0.05).[结论]复方苦参注射液联合多西他赛能明显降低NSCLC患者血清肿瘤标记物,改善机体细胞免疫功能,延长OS、PFS,且不增加毒副反应.     

甘氨双唑钠与紫杉醇在中晚期非小细胞肺癌放射治疗中增敏疗效比较

目的比较甘氨双唑钠（CMNa）与紫杉醇（PaclitaxelTAX）在中晚期非小细胞肺癌放射治疗中增敏疗效及不良反应。方法首程治疗96例中晚期非小细胞肺癌患者均给予放疗,根据化疗方式分为甘氨双唑钠组、紫杉醇组及对照组。甘氨双唑钠组,甘氨双唑钠的给药方案：氯化钠溶液i00ml＋CMNal．0g静脉滴注,每周3次;紫杉醇组,紫杉醇60mg静脉滴注,每周1次;对照组仅行单纯放射治疗。结果甘氨双唑钠组和紫杉醇组在有效率、放疗增敏比与对照组比较,差异有统计学意义（P〈0．05）。甘氨双唑钠组和紫杉醇组比较差异无统计学意义（P〉0．05）,消化道、血液系统不良反应差异有统计学意义（P〈0．05）。结论甘氨双唑钠与紫杉醇放射增敏疗效差异无统计学意义,但都优于单纯放疗组。甘氨双唑钠组消化道、血液系统不良反应发生率低于紫杉醇组。     

利拉鲁肽对缺氧/复氧诱导的乳鼠心肌细胞损伤的影响

[目的]观察新型降糖药物利拉鲁肽对缺氧/复氧(H/R)诱导的乳鼠心肌细胞损伤的影响.[方法]将体外培养Wistar大鼠乳鼠心肌细胞进行分组:单纯H/R组(A组)、利拉鲁肽组+H/R组(B组)、正常对照组(C组),将A,B两组细胞同时进行H/R损伤,复氧后分别检测3组的乳酸脱氢酶(LDH)、丙二醛含量(MDA)、超氧化酶歧化酶(SOD)活性及各组心肌细胞凋亡率.[结果]A组与C组比较,其细胞培养液中LDH、MDA含量、细胞凋亡率均增加,SOD活性降低,且差异有显著性(P＜0.01).与A组相比,B组LDH、MDA含量、细胞凋亡率则明显降低(P＜0.01),但仍高于C组,且差异有显著性(P＜0.01);SOD活性较A组增高,差异亦有显著性(P＜0.01).[结论]H/R可以造成心肌细胞的损伤,增加细胞的凋亡;利拉鲁肽作为胰高血糖素样肽-1类似物,其直接作用于心肌细胞,可减轻H/R造成的心肌细胞损伤,抑制心肌细胞的凋亡,具有潜在的心脏保护作用.     

上海中心城区幽门螺杆菌菌株原发性耐药的调查

背景：在全球范围内幽门螺杆菌（H．pylori）菌株对甲硝唑、克拉霉素和阿莫西林耐药的发生率正在不断增加。目的：了解H．pylori对甲硝唑、克拉霉素和阿莫西林的原发耐药情况。方法：2005年12月～2006年6月间因消化不良来上海市静安区中心医院行胃镜检查，除外大环内酯类、青霉素类抗生素和甲硝唑服药史，并经尿素酶试验初步确认H．pylori感染的患者．取其胃黏膜活检标本行体外微需氧培养，经生化、涂片检查鉴定为典型的H．pylori．经转代选择其中生长发育良好的菌株36株。应用E-test试纸测定其对甲硝唑、克拉霉素和阿莫西林的敏感性。结果：36株H．pylori菌株中，对甲硝唑、克拉霉素和阿莫西林的原发性耐药率分别为44-4％、8．3％和2．8％：甲硝唑耐药菌株分布与性别、年龄以及所患的胃十二指肠疾病种类无明显相关性。结论：有必要定期检测或调查本地H．pylori对抗生素的敏感性，以监测在根除H．pylori时应用“检测和治疗”策略的效果，提高根除H．pylori的疗效。     

抗菌药物临床应用管理架构、技术支持体系与策略

抗菌药物管理是一个世界性难题,本文对抗菌药物管理的各个方面,包括其定义、目标、组织架构、技术支持体系、管理策略等进行详细阐述,同时就我国目前抗菌药物管理工作存在的问题进行剖析.我国应学习和借鉴国际经验,结合自身情况的复杂性进行实践、研究和创新.     

Editorial: The CARD15 gene mutation in Crohn disease

Background: The immunosuppressive effects of thiopurine drugs are mainly mediated through their intracellular metabolism into active 6-thioguanine nucleotide (6-TGN) metabolites, which are incorporated into DNA. Erythrocyte 6-TGN (E-6TGN) levels have been proposed as an instrument for monitoring treatment. The aim of the study was to use erythrocyte E-6TGN, methylated mercaptopurine (MeMP) metabolites, and thiopurine methyltransferase (TPMT) measurements in a clinical setting to determine the clinical outcome in relation to thiopurine metabolism. Methods: Fifty-five adult patients with inflammatory bowel disease were included in a prospective study and followed for 6 months. Metabolite levels were measured and correlated to outcome and AZA/6-MP dose. Results: The E-6TGN level was significantly related to the TPMT genotype (P?=?0.008). Patients in disease remission had higher E-6TGN levels than patients with disease activity both at baseline (P?&;lt;?0.05) and after 6 months (P?=?0.02). Active disease was more frequent among subjects with E-6TGN?≤??125?nmol/mmol Hb at baseline (P?=?0.04), but not at 6 months. AZA/6-MP drug dose was positively correlated to E-MeMP levels (r [Formula: See Text]?=?0.48; P?&;lt;?0.001) and E-MeMP/E-6TGN ratio (r [Formula: See Text]?=?0.41; P?=?0.002). Dose changes were positively correlated with the changes in E-MeMP levels (P?=?0.01) and E-MeMP/E-6TGN ratio (P?=?0.03). Conclusions: E-6TGN level was the only factor in this study related to disease activity, while there was no relationship between AZA/6-MP dose and E-6TGN levels. This finding illustrates the clinical usefulness of E-6TGN monitoring in the evaluation of treatment intensity.     

Ethanol-enhanced cytotoxicity of alkylating agents

BACKGROUND: Although ethanol itself is not genotoxic, chronic alcohol consumption increases the risk of neoplastic disease. The mechanism by which ethanol exerts a cocarcinogenic effect is not well established, and the aim of this study was to determine whether exposure to ethanol increased the cytotoxicity of known carcinogens. METHODS: To assess cell survival, the ability of Chinese hamster A10 cells, which express alcohol dehydrogenase, to form colonies was determined after exposure to ethanol and other substances, including both genotoxicants and non-DNA-reactive cytotoxic agents. RESULTS: 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) is an alkylating agent that forms covalent bonds with DNA. The cytotoxicity of MNNG at concentrations of 0.17 to 0.68 microM was markedly enhanced when cells were also treated with 50 mM ethanol. When combined with 0.34 microM MNNG, concentrations of ethanol as low as 2 mM exacerbated the toxicity of this alkylating agent. When these experiments were repeated in the presence of 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, pretreatment with ethanol did not affect the toxicity of MNNG. When ethanol treatment was combined with exposure to other carcinogens, as well as agents that do not directly damage DNA, the cytotoxicity of the DNA-reactive agents 4-nitroquinoline-N-oxide, mitomycin C, and 6-chloro-9-(3-[2-chloroethyl]aminopropylamino)-2-methoxyacridine was modestly enhanced, and that of a second alkylating agent, ethyl methanesulfonate, was markedly increased. CONCLUSIONS: The results are consistent with impairment of DNA repair processes, particularly base excision repair, by acetaldehyde, as a mechanism by which ethanol increases the genotoxicity of certain genotoxic agents.     

Ondansetron and tropisetron in the control of nausea and vomiting in children receiving combined cancer chemotherapy

Ondansetron (Zofron, Glaxo) and tropisetron (Navoban, Sandoz) are selective serotonin (5HT ) 3 antagonists that have proven very effective in the prevention of vomiting and nausea in adults and children receiving cancer chemotherapy. This study compared the efficacy of the two agents in the prevention of vomiting and nausea in children receiving chemotherapy for solid tumors and blood malignancies. A total of 23 children were studied in 205 chemotherapeutic cycles (116 oneday regimens and 89 multiple-day regimens). In 102 chemotherapeutic cycles the children received ondansetron as an antiemetic agent in a dose of 5 mg/m 2 30 min before chemotherapy was given and then 4 mg/m 2 every 8 h IV (group A) and in 103 cycles they received tropisetron in one dose of 0.2 mg/kg 24 h 1 IV (max dose 5 mg) 30 min before cytotoxic drugs administration every day they received chemotherapy (group B). The response was defined as complete in the absence of nausea and vomiting per 24 h of chemotherapy, as partial given the presence of 1-4 events of vomiting and/or nausea less than 5 h per 24 h, and as failure if there were more than 4 events of vomiting and/or nausea for more than 5 h per 24 h of chemotherapy. The response of the two groups was studied independently and depending on the degree of emetogenicity of the chemotherapeutic agents, which were divided into mildly, moderately, and highly emetogenic. The comparison of the two groups not taking into consideration the emetogenicity of the chemotherapeutic agents showed that ondansetron was more effective in 1-day regimens ( P = . 023 ), whereas the two agents were equally effective in multiple-day regimens ( P = . 2 ). The statistical analysis depending on the emetogenicity of the chemotherapeutic agents showed increased efficacy of ondansetron in mild ( P = . 017 ) and moderately emetogenic chemotherapeutic agents, whereas there was no difference in the highly emetogenic drug group. Ondansetron is found to be more effective than tropisetron in controlling acute nausea and vomiting in children receiving mild and moderately emetogenic chemotherapeutic drugs, although there is no difference in the efficacy of both antiemetic agents when highly emetogenic drugs are administered.     

On catalepsy and catatonia and the predictability of the catalepsy test for neuroleptic activity

The neuroleptic agents peromide and spiroxatrine induced an immobility in the rat which, in appearance, more resembled morphine catatonia than haloperidol catalepsy. Therefore, in a attempt to differentiate the behavioural states termed catalepsy and catatonia, haloperidol and morphine were closely compared using drug interaction and brain lesion studies.Atropine abolished or reduced the effects of haloperidol, peromide and spiroxatrine but not morphine, whilst morphine and spiroxatrine were similarly modified by nalorphine. The spiroxatrine effect was completely abolished by atropine and nalorphine combined. The cholinergic agent RS 86 synergised with haloperidol, peromide and spiroxatrine but not with morphine.Lesion of the dopaminergic extrapyramidal and/or mesolimbic innervation, of the caudate-putamen, globus pallidus and nucleus amygdaloideus centralis each reduced or abolished haloperidol, peromide and spiroxatrine catalepsy/catatonia. In contrast, morphine catatonia was only partially reduced by ablating the mesolimbic input, and was potentiated by lesions destroying the extrapyramidal/mesolimbic innervation, caudate-putamen and globus pallidus. Morphine catatonia was more susceptible to inhibition by the amygdaloid lesions than the catalepsy/catatonia induced by the other agents tested.     

Adventitious agents and smallpox vaccine in strategic national stockpile

In keeping with current standards, we urge that old smallpox vaccines that were made in animal skin and are still a key part of our strategic national stockpile be tested for adventitious infectious agents. The advisory especially applies to viruses that have the potential for zoonotic transmission to human vaccine recipients.