以国产草酸铂为主的化疗方案治疗中晚期大肠癌

目的　研究草酸铂联合 5 氟尿嘧啶、甲酰四氢叶酸钙 (OXP、5 FU/CF)方案化疗 ,治疗中晚期大肠癌的近期疗效和毒副作用。方法　草酸铂 (OXP) 1 0 0mg·m- 2 静脉滴注 2h ,第一天 ;甲酰四氢叶酸钙 (CF) 2 0 0mg·m- 2 静脉滴注 2h后推注 5 氟尿嘧啶 (5 FU) 4 0 0mg·m- 2 ,后续 5 FU60 0mg·m- 2 静脉持续输注 2 2h ,第 1、2天。每 3周重复 ,行 4周期 (8周 )治疗后判定疗效。结果　入组观察 1 5例 ,其中行原发灶切除者 8例 ,未切除者 7例。可评价疗效者 1 3例 ,其中完全有效 (CR) 2例 (1 5 .4% ) ,部分有效 (PR) 5例 (38.5 % ) ,稳定 (SD) 5例 ,进展 (PD) 2例。总有效率 (ORR) 53 .8% (7/1 3) ,初治ORR为 66 .7% (4/6)高于复治ORR42 .8% (3/7) ,但无统计学差异 (P >0 .0 5)。中位无进展期 (mTTP) 5个月 ,中位总生存期 (mos) 8个月。 1 3例中不良反应为 3～ 4度者 5例 (38.5 % ) ,其中白细胞减少 2例 (1 5 .4% ) ,血小板减少、恶心呕吐及转氨酶增高者各 1例 (7.7% )。无化疗相关死亡。结论　OXP、5 FU/CF方案化疗治疗中晚期大肠癌的近期疗效好 ,毒副作用低而且安全     

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.     

FOLFOX4方案治疗晚期胃癌的临床观察

目的 观察奥沙利铂(L-OHP)联合氟尿嘧啶(5-Fu)、亚叶酸钙(CF)组成的FOLFOX4方案治疗晚期胃癌的疗效及不良反应.方法 26例晚期胃癌患者接受FOLFOX4方案化疗:L-OHP 85 mg·m-2静脉滴注2 h,第1天;CF 200 mg·m-2静脉滴注2 h,第1,2 天;5-Fu 400 mg·m-2...     

亚叶酸钙加氟尿嘧啶联合奥沙利铂治疗晚期胃癌26例

目的 :探讨亚叶酸钙加氟尿嘧啶 (5 Fu)持续 72h滴注联合奥沙利铂治疗晚期 /转移性胃癌的临床疗效和毒副作用。方法 :共入选 2 6例。治疗方案为 :在每周期的d1,静脉滴注奥沙利铂 130mg·m-2 ;d1～d3静脉滴注亚叶酸钙 2 0 0mg·m-2 ·d-1;在d1静脉滴注亚叶酸钙结束后 ,静脉注射 5 Fu 0 .75 g ,然后静脉滴注 5 Fu 3.0g·m-2 ,持续 72h(d1～d3)。 4周为 1个周期 ,每例患者至少应用 2个周期。结果 :2 6例晚期胃癌患者获CR 2例 ,PR9例 ,有效率 4 2 .3%。毒副作用主要为骨髓抑制、口腔黏膜炎、腹泻 ,无严重神经损害。结论 :此方法治疗晚期 /转移性胃癌疗效好 ,安全性高。     

奈达铂联合氟尿嘧啶治疗晚期鼻咽癌的临床观察

目的:观察奈达铂(NDP)联合氟尿嘧啶(5-FU)治疗晚期鼻咽癌的近期疗效和安全性。方法:将我院2005年-2011年42例晚期鼻咽癌患者随机均分为治疗组和对照组,治疗组采用NDP80～100mg·m-2,静脉滴注,d1;5-FU600mg·m-2,d1～5。对照组采用顺铂(CDDP)30mg·m-2,静脉滴注,d1～3;5-FU600mg·m-2,d1～5。2组均3周为1个周期,治疗2个周期后评价近期疗效及不良反应。结果:治疗组与对照组的有效率分别为61.90%和38.10%,治疗组明显优于对照组,差异有统计学意义(P<0.05)。与对照组比较,治疗组消化道不良反应、肝肾毒性轻微,差异有统计学意义(P<0.05)。结论:NDP联合5-FU治疗晚期鼻咽癌近期疗效及安全性较好。     

FOLFOX方案治疗30例晚期胃癌疗效观察

目的：观察每二周高剂量亚叶酸钙（CF）／氟脲嘧啶（5－FU）与草酸铂（L－OHP）方案（FOLFOX方案）治疗晚期胃癌的临床疗效和毒副反应。方法：采用高剂量CF／5－FU／L－OHP深静脉输注方案（CF200mg.m^2-1.d^-1，静滴2小时，第1、2天；5-FU400mg.m^2-1.d^-1,静推，第1天，5－FU1600mg.m^2-1.d^-1，静滴22小时，第1、2天；L－OHP130mg.m^2-1.d^-1，静脉输注4小时，第1天），化疗方案以14天为1周期，重复4周期后间隔1个月评定疗效。结果：全组30例，总有效率为53．3％，18例初治组的有效率为61．11％，其中CR1例。12例复治组的有效率为41．7％，初治组中位缓解期为5个月。复治组的中位缓解期为3个月。Ⅱ、Ⅲ度口腔炎发生率为26．7％，7例出现手足综合征，血液学毒性轻微。结论：每二周高剂量CF／5－FU／L－OHP方案是治疗晚期胃癌有效安全的化疗方案。     

PLF、PFM方案治疗放疗后复发或转移鼻咽癌的临床研究

目的本临床研究采用以铂类加5-氟尿嘧啶(5-FU)为主的PLF、PFM方案治疗放疗后复发或转移鼻咽癌,探讨这两个方案在晚期鼻咽癌治疗中的价值及晚期鼻咽癌的预后因素。方法对入选晚期鼻咽癌进行非随机分组,一组采用PLF方案治疗醛氢叶酸(CF,200mg·m-2,d1)静脉滴注2h加5-FU0.5g静脉推注及5-FU3.0g·m-2持续48h滴注联合DDP(25mg·m-2,d1-3)静脉滴注;另一组采用PFM方案治疗DDP(25mg·m-2,d1-3)静脉滴注加5-FU(0.4g·m-2,d1-5)静脉滴注联合PYM(5mg·m-2,d1、3、5)肌注。结果共有48例病人入选,全组总有效率为63.83%,两组有效率分别为76.92%、47.62%(P=0.066);主要的不良反应为恶心呕吐、脱发、口腔粘膜炎、白细胞下降、血红蛋白下降等,PLF方案组恶心呕吐发生率显著低于PFM方案组(P=0.032);中位随访时间为10个月,全组中位生存期为11个月,两组的中位生存期分别为12、9个月(P=0.3691);在预后方面,治疗前血红蛋白<10g·L-1、年龄≥65岁是预后不良的相关因素(P值分别为0.001、0.030)。结论PLF方案的近期疗效、生存期有优于PFM方案的趋势,且毒副作用也较轻,可作为晚期鼻咽癌化疗的标准一线治疗。治疗前血红蛋白水平、年龄是影响预后的相关因素。     

利妥昔单抗联合CHOP方案治疗弥漫大B细胞性淋巴瘤的多中心临床研究(英文)

目的 :观察利妥昔单抗联合环磷酰胺、长春新碱、多柔比星及泼尼松 (CHOP方案 )治疗新诊断的弥漫性大B细胞性淋巴瘤 (DLBL)的临床疗效。　方法 :2 0 0 2年 4月至 2 0 0 3年 2月 ,共 5 2例病人进入本研究。化疗采用标准的CHOP方案 :d 1,环磷酰胺 6 0 0mg·m- 2 ,长春新碱 1.4mg·m- 2 ,多柔比星 2 5mg·m- 2 ,泼尼松 6 0mg·m- 2 × 5d ,每 3wk一个疗程 ,共 6个疗程。利妥昔单抗静脉滴注剂量为 375mg·m- 2 ,于化疗第一个疗程前 2d开始 ,每周输注 1次 (连续输注 ) ,连续 4次 (标准剂量 )或 6次 (增强剂量 ) ;或于每疗程的CHOP方案化疗前 2d输注 ,每 3周 1次 (间隔输注 ) ,输注 4次 (标准剂量 )或 6次 (增强剂量 )。结果 :5 0例病人进入临床疗效评估 ,6 0 %获得完全缓解 ,总有效率为 10 0 %。其中 ,34例AnnArbor分期为Ⅲ期或Ⅳ期的病人有15例获得完全缓解 ,完全缓解率为 4 4%。 5 0例病人共随访了 (8±s 5 )wk ,2～ 30wk ,病人 16wk的无病生存 (PFS)率为 87%。标准剂量组和增强剂量组疗效无显著差异 ,连续输注和间隔输注疗效差异亦无显著意义 (P >0 .0 5 )。所有病人在治疗过程中对本方案均能较好耐受 ,主要的不良反应为输注相关的不良反应 (32 % )和化疗相关的血液学不良反应 (2 0 % )。　结论 :利妥昔单?     

奥沙利铂联合氟尿嘧啶、亚叶酸钙治疗晚期胃癌的临床观察

目的：观察奥沙利铂（oxaliplatin,L—OHP）联合氟尿嘧啶（fluorouracil,Fu）、亚叶酸钙（calcium folimate,CF）治疗晚期胃癌的近期疗效和毒副反应。方法：48例晚期胃癌患者均经病理学证实。化疗方案为L—OHP100mg／m。静脉滴注2h第1天,CF200mg／m^2静脉滴注2h,第1～2天,FU2400mg／m。持续静脉泵入46h。每3～4周重复,2个周期后评效。结果：48例患者均可评效。完全缓解（CR）2例,部分缓解（PR）16例,稳定20例,进展10例,有效率（CR＋PR）37．5％,临床受益率79．17％,中位疾病进展时间（TFP）5．8个月,中位生存期9．1个月。1年生存率54．17％。主要毒副反应为恶心呕吐、骨髓抑制及轻度的外周神经系统病变。结论：L—OHP联合FU、CF方案治疗晚期胃癌疗效较好,毒副反应轻,值得临床推广。     

紫杉醇联合顺铂、5-氟尿嘧啶治疗晚期食管癌近期疗效观察

目的 观察紫杉醇联合顺铂(DDP)加亚叶酸钙(CF)和5-氟尿嘧啶(5-FU)方案治疗晚期食管癌的近期疗效及安全性.方法 观察55例晚期食管癌患者,PTX 135～175 mg·m-2,静脉滴注3 h,d1,DDP 20 mg·m-2 d1～d4、CF 0.2g·m-2 d2～d3、5-FU 2.0g·m-2持续静滴4...     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

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.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.