晚期结直肠癌三种化疗方案的成本-效果分析

目的:探讨晚期结直肠癌不同化疗方案临床疗效和经济学效果。方法:92例晚期结直肠癌患者,根据不同治疗方案分为3组。FOLFOX方案:奥沙利铂85 mg·m-2,iv,d1;亚叶酸钙200 mg·m-2,iv,d1～2;氟尿嘧啶400 mg·m-2,iv,d1～2,600 mg·m-2·d-1,44 h持续静脉点滴,d1～2。14 d为一周期。FOLFIRI方案:伊立替康180 mg·m-2,iv,d1;亚叶酸钙200 mg·m-2,iv,d1～2;氟尿嘧啶400 mg·m-2,iv,d1～2,600 mg·m-2·d-1,44 h持续静脉点滴,d1～2。14 d为一周期。XELOX方案:卡培他滨2 000 mg·m-2·d-1,po,d1～14;奥沙利铂130 mg·m-2,iv,d1。21 d为一周期。运用药物经济学成本-效果分析方法,对3组治疗方案进行分析和评价。结果:FOLFOX方案、FOL- FIRI方案、XELOX方案的有效率分别为40．0％,48．6％,11．8％。化疗一个疗程住院费用分别为4 704．60元、11 167．25元、6 387．97元。在FOLFOX方案的基础上,每增加一个单位效果,FOLFIRI方案和XELOX方案所追加的成本分别为751．47元和-59．69元。结论:根据本研究结果表明,FOLFOX方案为晚期结直肠癌化疗的较好方案。     

奥沙利铂联合5-氟尿嘧啶及亚叶酸钙治疗晚期胃癌31例临床分析

目的观察奥沙利铂（LOHP）联合5-氟尿嘧啶（5．Fu）和亚叶酸钙（cF）治疗晚期胃癌的疗效及不良反应。方法经组织病理学细胞学证实的31例晚期胃癌患者，采用奥沙利铂135mg／m2，静脉滴注3h，第1天；亚叶酸钙200mg／m2静脉滴注2h，第1～5天；随后5-FU500mg／m2便携式微量泵持续静脉滴注（CIV）18h，第1～5天。21d为一周期，每例患者至少完成三个周期化疗。完成三周期后一月作疗效评定及不良反应观察。按WHO标准评价近期疗效和不良反应。结果入组的31例晚期胃癌患者，CR2例（6．5％），PR14例（45．2％），NC10例（32．3％），PD5例（16％），RR为51．6％，生活质量改善率达到74．2％。全组患者无化疗相关死亡。结论奥沙利铂联合亚叶酸钙和5．氟尿嘧啶连续静滴的方案治疗晚期胃癌疗效较好，不良反应轻，值得临床推广验证。     

多西紫杉醇联合奥沙利铂、卡培他滨治疗晚期胃癌的疗效观察

目的:观察多西紫杉醇联合奥沙利铂、卡培他滨治疗晚期胃癌的临床疗效和毒副反应。方法:选择不能手术或手术后复发的晚期胃癌患者80例,随机分为试验组和对照组,各40例。试验组采用多西紫杉醇60mg·m-2,静脉滴注,第1天;奥沙利铂130mg·m-2,静脉滴注,第1天;卡培他滨800mg·m-2,口服,bid,第1～14天。对照组采用顺铂20mg·m-2,静脉滴注,第1～5天;5-氟尿嘧啶500mg·m-2,静脉滴注,第1～5天。2组均以21d为1个周期。至少2周期后评价疗效及毒副反应。结果:试验组40例患者有38例可评价疗效,有效率为55.3%,中位疾病进展时间(TTP)为6.6个月,中位总体生存时间(OS)为11.3个月。对照组40例均可评价疗效,有效率42.5%,中位TTP为5.1个月,中位OS为8.9个月。2组差异无统计学意义(P>0.05)。毒副反应主要为骨髓抑制、消化道反应、外周神经毒性,大部分患者可以耐受。结论:多西紫杉醇联合奥沙利铂、卡培他滨治疗晚期胃癌疗效肯定,毒副反应可耐受,可作为主要治疗方案。     

奥沙利铂、亚叶酸钙联合5-氟尿嘧啶持续静脉滴注治疗晚期胃癌的临床疗效分析

目的探讨奥沙利铂联合5-氟尿嘧啶持续静脉滴注对胃癌术后辅助化疗的临床疗效。方法经组织病理学证实的45例晚期胃癌患者,采用奥沙利铂135mg/m2加入5%葡萄糖注射液500 mL中静脉滴注3h,第1天;亚叶酸钙200mg/m2加入5%葡萄糖注射液250mL中静脉滴注2h,第1～5天;5-氟尿嘧啶(5-Fu)500mg/m2以微量泵进行24h持续静脉滴注,第1～5天。21d为一周期,每一例患者至少完成3个周期化疗。3个周期化疗结束后按WHO标准评价近期疗效和不良反应。结果入组的45例晚期胃癌患者,CR 3例(6.67%),PR 20例(44.44%),NC 15例(33.33%),PD 7例(15.56%),RR为51.11%,生活质量改善率达到72.35%。全组患者无化疗相关死亡。结论奥沙利铂、亚叶酸钙联合5-氟尿嘧啶持续静脉滴注治疗晚期胃癌疗效较好,不良反应轻,在临床中值得推广。     

奥沙利铂引起的溶血性贫血

奥沙利铂 ( oxaliplatin)为一种新型的第三代顺铂类化合物 ,是治疗晚期结肠直肠癌的有效药物 ,单用或与氟尿嘧啶和叶酸合用均具有极好的安全性。本文报道 1例患者使用奥沙利铂治疗后 ,产生致命性急性溶血。患者女性 ,年龄 66岁 ,1 996年 3月因结肠直肠腺癌转移为非切除性肝转移瘤进行化疗。每天用奥沙利铂 1 0 0 mg·m- 2 ,叶酸 2 0 0 mg·m- 2 ,5-氟尿嘧啶推注 ( bolus) 4 0 0 mg· m- 2 ,5-氟尿嘧啶 2 2 h连续输注 60 0 mg·m- 2 ,每 2周连用 2 d。 4 1个疗程后 ,血红蛋白、胆红素和血清乳酸脱氢酶活性 ( LDH,n<2 50 )浓度分别为 1 1 9g…     

奥沙利铂联合方案治疗晚期胃癌的临床疗效

目的　研究奥沙利铂(L OHP)与氟尿嘧啶(5 FU)、亚叶酸钙(CF)联合化疗方案治疗晚期胃癌的近期疗效及不良反应。方法　2 0 0 2年6月至2 0 0 4年6月2 4例晚期胃癌患者入组本次临床试验。入组病例接受L OHP联合5 FU及CF治疗方案:d1,L OPH 130mg·m-2 ,ivgtt;d1～5 ,CF 2 0 0mg·m-2 ,ivgtt;d1～5 ,5 FU 5 0 0mg·m-2 ,ivgtt×6h ,2 1d为一个周期,至少完成3周期。分别观察其近期疗效及不良反应。结果　近期疗效判定参照WHO实体瘤疗效评价标准;不良反应按实体瘤(1981年)NCI分级标准。全组2 4例患者总有效率(CR +PR)为5 0 % (12 / 2 4 ) ;主要不良反应为轻度骨髓抑制、消化道反应及外周神经毒性。结论　L OHP联合化疗方案治疗晚期胃癌疗效确切,不良反应能耐受     

奥沙利铂与5-氟尿嘧啶及亚叶酸钙联合治疗晚期胃癌21例观察

目的 观察奥沙利铂、亚叶酸钙／5-氟尿嘧啶治疗晚期胃癌的近期疗效和不良反应。方法 21例晚期胃癌，采用奥沙利铂60mg／m^2静滴第1、第8天，亚叶酸钙100mg／m^2／5-氟尿嘧啶500mg／m^2静滴第1～5天，28天为一周期，至少连用2周期后评价疗效及毒副反应。结果 21例中CR0例(0／21)，PR10例(10／21)，CR PR47．6％(10／21)，毒性反应为感觉神经毒性54．1％，消化道反应38．2％。结论 奥沙利铂、亚叶酸钙／5-氟尿嘧啶联合治疗晚期胃癌疗效肯定，不良反应少，值得应用。     

奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期结直肠癌的临床研究

目的:观察奥沙利铂联合氟尿嘧啶、亚叶酸钙的联合化疗方案对晚期结直肠癌的临床疗效和毒副反应。方法:35例晚期结直肠癌患者采用联合化疗方案:奥沙利铂130m g/m2,静脉滴注3小时,第1天;5氟-尿嘧啶500m g/m 2,静脉滴注,第1~5天;亚叶酸钙200m g/m2,静脉滴注,第1~5天。21天为一个周期。结果:完全缓解(CR)1例,部分缓解(PR)14例,总有效率(CP+PR)为42.9%。主要不良反应为骨髓抑制、消化道反应和神经毒性。结论:奥沙利铂联合氟尿嘧啶、亚叶酸钙的化疗方案对晚期结直肠癌疗效较好,不良反应可以耐受。     

奥沙利铂联合亚叶酸钙和替加氟时辰化疗治疗晚期胃肠癌的临床研究

目的比较奥沙利铂联合亚叶酸钙和替加氟时辰化疗方案与常规化疗方案治疗晚期胃肠癌的近期疗效和不良反应。方法63例晚期胃肠癌患者随机分为时辰化疗组(给予奥沙利铂、亚叶酸钙、替加氟栓)31例与常规化疗组(给予奥沙利铂、亚叶酸钙、氟尿嘧啶)32例,21d为1个周期,2个周期后评定2组的近期疗效和不良反应。结果时辰化疗组与常规化疗组的有效率分别为77·4%、43·8%(P<0·05),KPS评分显效率分别为87·1%、50·0%(P<0·05),不良反应发生率分别为13·7%、29·8%(P<0·05)。结论奥沙利铂联合亚叶酸钙和替加氟的时辰化疗方案有效率高,不良反应少。     

紫杉醇联合氟尿嘧啶/甲酰四氢叶酸钙治疗21例晚期胃癌的疗效观察

目的观察紫杉醇加氟尿嘧啶/甲酰四氢叶酸钙联合方案(TCP)治疗晚期胃癌的近期疗效及不良反应.方法TCP方案中紫杉醇135～175 mg·m-2静滴3 h,每21 d一次;甲酰四氢叶酸钙200mg·m-2静滴2 h;氟尿嘧啶针400mg·m-2快速静注,继后氟尿嘧啶2.4～3.6 g·m-2持续静脉滴注22 h,21 d为一周期,完成2～3个周期后判定,以WHO标准评价近期疗效和毒性反应,有效病例4周后确认.结果全组21例患者中完全缓解1例,部分缓解7例,稳定9例,进展4例,总有效率(CR+PR)为38.3%.主要不良反应为血液学毒性、恶心、呕吐和脱发、口腔黏膜炎.结论紫杉醇和氟尿嘧啶/甲酰四氢叶酸钙治疗晚期胃癌有效且不良反应可以耐受.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.