紫杉醇脂质体联合奈达铂治疗晚期非小细胞肺癌17例

［摘要］目的观察紫杉醇脂质体联合奈达铂治疗晚期非小细胞肺癌(NSCLC)的近期疗效和毒副作用。方法17例晚期NSCLC患者采用紫杉醇脂质体135 mg•（m2） 1 ,静脉滴注3 h,第1天;联合奈达铂80 mg•（m2） 1 ,静脉滴注,第2天,21 d为1个周期,化疗2～6个周期。结果17例患者均可评价近期疗效：完全缓解1例,部分缓解4例,稳定 3例,进展9例。毒副作用主要为血液学毒副作用,以白细胞和血小板减少为主;非血液学毒副作用中恶心呕吐、肝功能轻度损伤、脱发例数较多。结论紫杉醇脂质体联合奈达铂方案治疗晚期非小细胞肺癌疗效较好,毒副作用可以耐受。     

培美曲塞联合奥沙利铂治疗晚期非小细胞肺癌30例

摘要目的探讨培美曲塞联合奥沙利铂对晚期非小细胞肺癌患者疗效以及对血清糖类抗原（CA）125与癌胚抗原（CEA）的影响。方法晚期非小细胞肺癌患者60例,按入组编号随机分为治疗组与对照组,每组30例。治疗组应用培美曲塞500 mg•（m2）－1,静脉滴注,第1天;奥沙利铂120 mg•（m2）－1,静脉滴注,第1天,每3周重复;对照组应用吉西他滨1 000～1 250 mg•（m2）－1,静脉滴注,第1,8天;奥沙利铂120 mg•（m2）－1,静脉滴注,第1天,每3周重复。2个疗程后,比较两组患者瘤灶、生活质量（体质量、卡氏评分）、CA125和CEA水平变化。结果两组患者有效率及瘤灶稳定率均差异无统计学意义（P＞0.05）。治疗组和对照组体质量分别为（74.06±5.28）,（67.94±5.03） kg;卡氏评分分别为（84.63±8.26）,（76.85±7.94）分（均P＜0.05）;化疗后两组患者CA125及CEA水平均明显下降（P＜0.05或P＜0.01）,且治疗组较对照组下降更明显（P＜0.05）。结论培美曲塞联合奥沙利铂治疗晚期非小细胞肺癌疗效肯定,不仅能提高患者生活质量,还能降低血清CA125和CEA水平,是一安全有效的化疗选择。摘要目的探讨培美曲塞联合奥沙利铂对晚期非小细胞肺癌患者疗效以及对血清糖类抗原（CA）125与癌胚抗原（CEA）的影响。方法晚期非小细胞肺癌患者60例,按入组编号随机分为治疗组与对照组,每组30例。治疗组应用培美曲塞500 mg•（m2）－1,静脉滴注,第1天;奥沙利铂120 mg•（m2）－1,静脉滴注,第1天,每3周重复;对照组应用吉西他滨1 000～1 250 mg•（m2）－1,静脉滴注,第1,8天;奥沙利铂120 mg•（m2）－1,静脉滴注,第1天,每3周重复。2个疗程后,比较两组患者瘤灶、生活质量（体质量、卡氏评分）、CA125和CEA水平变化。结果两组患者有效率及瘤灶稳定率均差异无统计学意义（P＞0.05）。治疗组和对照组体质量分别为（74.06±5.28）,（67.94±5.03） kg;卡氏评分分别为（84.63±8.26）,（76.85±7.94）分（均P＜0.05）;化疗后两组患者CA125及CEA水平均明显下降（P＜0.05或P＜0.01）,且治疗组较对照组下降更明显（P＜0.05）。结论培美曲塞联合奥沙利铂治疗晚期非小细胞肺癌疗效肯定,不仅能提高患者生活质量,还能降低血清CA125和CEA水平,是一安全有效的化疗选择。     

左乙拉西坦治疗儿童多发性抽动症38例

目的观察左乙拉西坦治疗儿童多发性抽动症的疗效与安全性。方法70例多发性抽动症患儿随机分为治疗组38例和对照组32例,治疗组给予左乙拉西坦口服,20 mg•kg－1•d－1,1周内逐步增加到30～40 mg•kg－1•d－1,最大剂量2 000 mg•d－1,平分两次服药;对照组给予氟哌啶醇口服,0.03 mg•kg－1•d－1,每1～2周增加0.025～0.050 mg•kg－1•d－1,最大0.15 mg•kg－1•d－1。采用《耶鲁抽动症整体严重程度量表》（YGTSS）及《副作用量表》（TESS）,于治疗后第8周末及第16周末评价疗效与不良反应。结果治疗第8,16周末,治疗组运动抽动评分显著低于对照组（均P＜0.05）,治疗16周末治疗组发声抽动评分显著低于对照组（P＜0.05）,治疗组TESS总分均显著低于对照组（均P＜0.05）。结论左乙拉西坦治疗儿童多发性抽动症疗效优于氟哌啶醇,不良反应较轻。     

香菇多糖联合GP方案治疗晚期非小细胞肺癌25例

目的评价香菇多糖联合吉西他滨和顺铂（GP方案）治疗晚期非小细胞肺癌（NSCLC）的近期疗效及对患者生活质量的影响。方法将51例ⅢB和Ⅳ期NSCLC患者随机分为治疗组25例和对照组26例,均给予吉西他滨1 000 mg•（m2）－1,第1,8天静脉滴注;顺铂25 mg•（m2）－1,第2～4天静脉滴注。21 d为1个周期,两个周期后评价疗效。治疗组同时给予香菇多糖2 mg＋ 5%葡萄糖注射液或0.9%氯化钠注射液250 mL,第1,4天静脉滴注。两组化疗前均给予5 羟色胺受体拮抗药预防性止吐,并常规给予水化利尿处理。结果两组QLQ C30生活质量评分均较治疗前升高,治疗组整体生活质量评分显著高于对照组,乏力较对照组显著改善（P＜0.05）;两组QLQ LC 13肺癌相关症状（咳嗽、呼吸困难、胸痛）评分较治疗前均下降;治疗组细胞免疫功能较治疗前无变化,对照组免疫功能下降,两组治疗后比较差异有统计学意义（P＜0.05）;对照组白细胞减少多于治疗组。结论香菇多糖联合GP方案化疗治疗晚期非小细胞肺癌可有效控制NSCLC进展,减轻化疗不良反应,预防患者细胞免疫功能损伤,明显改善患者的生活质量。     

哌罗匹隆治疗首发精神分裂症32例

目的探讨哌罗匹隆治疗首发精神分裂症的临床疗效及安全性。方法64例首发精神分裂症患者,随机分为治疗组和对照组各32例。治疗组给予哌罗匹隆,起始剂量12 mg•d－1,逐渐增加到治疗剂量,最大48 mg•d－1,平均（28.00±9.59） mg•d－1;对照组给予阿立哌唑,起始剂量5 mg•d－1,逐渐增加到治疗剂量,最大30 mg•d－1,平均（18.33±7.90） mg•d－1。疗程8周。两组治疗期间必要时使用苯二氮类药物和抗胆碱能药物。于用药前及用药后1,2,4,8周分别采用阳性与阴性症状量表和临床总体印象量表评定药物疗效,副作用量表评定不良反应。结果治疗8周后,治疗组有效率84.38%,对照组有效率87.50%,两组疗效差异无统计学意义。治疗组锥体外系不良反应少于对照组（P＜0.05）,两组头痛、嗜睡、体质量增加、恶心、呕吐、口干、心动过速或过缓、肝功能异常等不良反应差异无统计学意义。结论哌罗匹隆治疗精神分裂症疗效与阿立哌唑相当,不良反应明显少于阿立哌唑。     

重组人血管内皮抑素联合化学治疗药物治疗晚期胰腺癌21例

目的观察重组人血管内皮抑素注射液联合化学治疗药物治疗晚期胰腺癌的近期疗效。方法将晚期胰腺癌患者39例分成两组。治疗组21例于治疗第1～14天连续给予重组人血管内皮抑素7.5 mg•（m2） 1＋0.9%氯化钠注射液500 mL缓慢静脉滴注,qd;第1～8天给予吉西他滨835 mg•（m2） 1＋0.9%氯化钠注射液100 mL,30 min内静脉滴注完,qd;第1天给予奥沙利铂85 mg•（m2） 1＋5%葡萄糖注射液500 mL,2 h内静脉滴注完,qd。21 d为一个周期,一般治疗2～4个周期。对照组18例第1和8天给予吉西他滨835 mg•（m2） 1＋0.9%氯化钠注射液100 mL,30 min静脉滴注完,qd;第1天给予奥沙利铂85 mg•（m2） 1＋5%葡萄糖注射液500 mL,2 h静脉滴注完,qd。21 d为1个周期,至少治疗2个周期。两组患者每天静脉滴注前30 min静脉注射格拉司琼30 mg。结果两组实体瘤疗效：治疗组CR、PR、SD、PD分别为1,11,8,1例;对照组CR、PR、SD、PD分别为0,4,10,4例。治疗组PR高于对照组。临床受益：治疗组14例,对照组8例,两组差异性不大。两组不良反应包括骨髓抑制、恶心、呕吐等,发生不良反应差异无显著性。结论重组人血管内皮抑素注射液联合GEMOX方案治疗晚期胰腺癌可以提高近期疗效。     

FP与DP方案同步放化疗治疗中晚期宫颈癌的临床疗效比较

目的 探讨顺铂＋氟尿嘧啶(FP方案)和顺铂＋多西紫杉醇(DP方案)同步放射治疗和化学治疗(放、化疗)中晚期宫颈癌的临床疗效和毒性反应. 方法125例经病理学或细胞学确诊的Ⅱb～Ⅳa期宫颈癌患者,随机分为FP组65例及DP组60例. FP组:顺铂40 mg&#8226;(m2)^-1第1～4天静脉滴注,氟尿嘧啶1.0 mg&#8226;(m2)^-1第1～5天静脉滴注,28 d为1 个周期,共用2个周期. DP组:多西紫杉醇135 mg&#8226;(m2)^-1,第1天静脉滴注;顺铂40 mg&#8226;(m2)^-1,第1～4天静脉滴注,28 d为1个周期,共用2个周期. 对两组的临床疗效和不良反应进行对比观察. 结果 FP组近期有效率为78.5%,DP组为91.7%,两组差异有统计学意义(P<0.05). FP组和DP组中位生存时间分别为32.4和31.7个月,2 a生存率分别为84.6%和86.7%,差异无统计学意义(P>0.05). 两组不良反应相似,均以骨髓抑制、胃肠道反应为主,发生率及程度差异无统计学意义(P>0.05),可耐受. 结论 FP方案和DP方案治疗中晚期宫颈癌均具有较好的耐受性和疗效,不良反应可以耐受. DP方案近期效果较FP方案更好,缓解率更高,可作为中晚期宫颈癌较理想的化疗方法之一.     

奎硫平与奥氮平治疗老年期精神分裂症比较

目的比较奎硫平与奥氮平治疗老年精神分裂症的疗效和安全性。方法将60例老年精神分裂症患者随机分为两组各30例,治疗前均进行1周药物清洗。两组分别给予奎硫平或奥氮平口服。奎硫平起始剂量50 mg&#8226;d－1,逐渐加量至100～400 mg&#8226;d－1,平均（320.2±80.5） mg&#8226;d－1;奥氮平起始剂量2.5 mg&#8226;d－1,渐加量至5～15 mg&#8226;d－1,平均（10.1±5.4） mg&#8226;d－1。疗程8周,采用阳性与阴性症状量表及治疗中出现的症状量表评定疗效和不良反应。结果治疗8周后两组阳性与阴性症状量表评分均较治疗前显著下降。奎硫平组显效率70.0%,有效率90.0%;奥氮平组显效率73.3%,有效率93.3%,差异无统计学意义。奎硫平组的锥体外系反应、嗜睡、体质量增加均明显低于奥氮平组（P＜0.01）;奎硫平组头晕、便秘、口干亦低于奥氮平组（P＜0.05）。结论奎硫平与奥氮平对老年期精神分裂症均有较好的疗效,奎硫平安全性更高。     

环孢素与甲泼尼龙及丙种球蛋白联合治疗重型再生障碍性贫血27例

摘要目的观察环孢素与甲泼尼龙、丙种球蛋白联合治疗重型再生障碍性贫血（SAA）的疗效。方法SAA患者54例,随机分为治疗组和对照组各27例。对照组单用雄激素常规联合方案治疗,治疗组在对照组治疗基础上加用环孢素（3.5～12.0 mg&#8226;kg－1&#8226;d－1,3个月）、大剂量甲泼尼龙（1 000 mg&#8226;d－1,逐渐减至60 mg&#8226;d－1）及大剂量丙种球蛋白（20 g&#8226;d－1）治疗。观察两组疗效及血液各指标变化情况。结果治疗组和对照组治疗总有效例数分别为21,14例（P＜0.05）;治疗组治疗后血常规各项指标较对照组均明显上升（P＜0.05）;两组治疗过程中均未见严重不良反应。结论环孢素、甲泼尼龙及丙种球蛋白联合雄激素治疗SAA疗效显著,不良反应少,值得临床推广应用。     

艾司西酞普兰与文拉法辛治疗难治性抑郁症的对照研究

目的 探讨艾司西酞普兰对难治性抑郁症患者的疗效和安全性. 方法 68例难治性抑郁症的住院患者随机分为治疗组和对照组各34例, 治疗组给予艾司西酞普兰,起始剂量10 mg&#8226;d^-1,早餐后服,根据病情调整10～20 mg&#8226;d^-1,平均剂量（16.62±3.65） mg&#8226;d^-1. 对照组给予文拉法辛缓释剂,起始剂量75 mg&#8226;d^-1,早餐后服用,7～10 d加至治疗量150～225 mg&#8226;d^-1,平均剂量（175.54±20.50） mg&#8226;d^-1. 两组疗程均6周. 采用汉密尔顿抑郁量表（HAMD）评定疗效,不良反应和安全性采用不良反应量表（TESS）及实验室检查评定. 结果 有效率和痊愈率治疗组分别为58.8%,20.6%;对照组分别为61.8%,23.5%;两组比较差异无显著性（P＞0.05）. TESS评定显示,两组不良反应发生率差异无显著性（P＞0.05）. 结论 艾司西酞普兰治疗难治性抑郁症的疗效与文拉法辛相似,起效快,不良反应较轻.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.

     

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.     

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.