诱导化疗联合放疗42例中晚期鼻咽癌近期疗效观察

目的探讨亚叶酸钙、5-氟尿嘧啶（5-Fu）、顺铂方案诱导化疗联合放射治疗中晚期鼻咽癌的近期疗效。方法随机抽取2004年1月至2008年1月局部中晚期鼻咽癌（T3、T4）,单纯放疗组（简称单放组）42例,诱导化疗联合放疗组（简称联合组）42例,共84例。在放疗前,联合组用亚叶酸钙、5-Fu、顺铂方案诱导化疗2周期。放疗开始均采用面颈联合野和下半颈切线野常规分割,DT36Gy后鼻咽部采用CT定位适形放疗和全颈切线野放疗,总剂量鼻咽部70～72Gy,颈部淋巴结阳性65～70Gy,淋巴结阴性60～65Gy。结果放疗结束后6个月,鼻咽部原发灶完全缓解率（CR）：单放组为66．67％（28／42）,联合组为90．48％（38／42）（Pd0．05）;颈部淋巴结CR：单放组为61．90％（26／42）,联合组为85．71％（36／42）（P〈0．05）。早期反应主要为白细胞下降和口腔黏膜炎,患者均可耐受。结论诱导化疗联合放疗治疗中晚期鼻咽癌近期疗效较好,不良反应少,患者耐受性好。     

鼻咽癌三维适形放射治疗的临床研究

目的探讨鼻咽癌三维适形放射治疗的疗效及毒副作用。方法112例初治鼻咽癌患者随机分为两组：A组（n=56）为三维适形放射治疗组（3DCRT）,13组（n=56）为常规放射治疗组（CFRT）,两组均辅以相同的化学治疗：DDP（60mg／m2,d1）＋5-FU（500mg／m2,d1～5）,每4周为1程,共3个疗程。放疗于第一程化疗结束后立即执行。放疗总剂量（DT）：A组为72～76Gy,7．2～7．6周;B组为66～72Gy,6．6～7。2周。观察对比两组患者治疗后原发灶消退情况、颈淋巴结消退情况和放疗毒副反应。结果112例病人均完成治疗。放疗结束后3个月,原发灶消退情况：A组完全缓解率（CR）为96．4％（54／56）,B组CR为82．1％（46／56）：颈淋巴结消退情况,A组CR为100％（56／56）,B组CR为96．4％（54／56）。放疗毒副反应：口腔粘膜反应A组比B组程度轻,骨髓抑制、皮肤反应及胃肠道反应等,两组比较程度相当。结论鼻咽癌三维适形放射治疗,跟常规治疗比较,在可以不增加放疗毒副作用的前提下提高放疗剂量,从而提高了局部控制率。     

放、化疗综合治疗N2N3期鼻咽癌的临床分析

目的 探讨治疗N2、N3期鼻咽癌的方式。方法 132例N2、N3期鼻咽癌随机分为放化疗组和单放组,两组放疗均采用6mv-x线常规分割照射,鼻咽部剂量为68～86Gy／6.8～9周,颈部淋巴结转移灶剂量为64～80Gy／6.4～8N。放化疗组在放疗前1周开始以5Fu＋DDP联合化疗,之后间隔3周重复,共四个周期。结果 放化疗组和单放组近期鼻咽部肿瘤完全消退率分别为92.1％和86.3％（P〉0．05）;颈部淋巴结转移灶完全消退率为89．3％和61．2％（P〈0．05）。两组3、5年鼻咽肿瘤控制率分别是76．8％和45．4％（P〈0．05）,65．9％和47．2（P〈0．05）;两组颈部淋巴结转移灶控制率分别是65.1％和41．9％（P〈0．05）,59.3％和37．2％（P〈0、05）;两组3、5年的远处转移率分别是22．5％和43.8％（P〈0．05）,27.1％和48．9％（P〈0．05）：两组3、5年生存率分别是65．4％和30、6％（P〈0．05）,45.8％和22．9％（P〈0．05）。放化组的消化道反应、血液毒性均高于单放组（P〈0.05）,但病人可以耐受。结论 放化疗综合治疗N2、N3期鼻咽癌有助于提高短、中期生存率,减少局部复发和远处转移。     

诱导化疗联合后程超分割放射治疗中晚期鼻咽癌的临床研究

目的 探讨诱导化疗联合后程超分割放疗在中晚期鼻咽癌治疗中的应用价值。方法 126例Ⅲ、Ⅳa期鼻咽癌被随机分为诱导化疗联合后程超分割放疗组（治疗组）64例和常规放疗组（对照组）62例,治疗组先行二个周期PF／CF方案化疗,常规分割放疗剂量达40Gy后改为超分割放疗。对照组采用常规分割放疗。结果 原发病灶和颈部转移病灶对化疗均有较高的反应率（有效率分别为79．7％和81．3％;治疗组颈部淋巴结CR率高于对照组（P〈0．05）;治疗组1、3、5年生存率和无瘤生存率似高于对照组,但统计学处理差异不显著。治疗组复发率明显低于对照组（P〈0．05）,平均复发时间明显长于对照组（P〈0．001）。远处转移情况两组相似。治疗组急性放射反应明显大于对照组,但远期后遗症发生率相似。结论 大剂量PF／CF方案诱导化疗联合后程超分割放疗能提高局部控制率,有可能提高中晚期鼻咽癌的远期生存率,治疗中急性放射反应明显加重,但未增加远期后遗症发生率。二个周期化疗未能减少远处转移率。     

重组人红细胞生成素结合高低氧对中晚期髓质型食管癌的放疗增敏作用

目的探讨重组人红细胞生成素（rhEPO）结合高低氧对中晚期髓质型食管癌放射治疗（放疗）的增敏作用及不良反应。方法将62例欲接受放疗的中晚期髓质型食管癌患者随机分为试验组和对照组。试验组：在放疗前1周给予rhEPO30000U，皮下注射，每周1次，至放疗结束。放疗用6MVX射线进行外照射，DT1．8～2．0Gy／次，每周5次，前后两野对穿照射DT38～40Gy后，再两斜野对穿照射DT20～30Gy，中位剂量为DT64Gy。放疗过程中吸人高低氧。对照组单纯放疗，其射野和剂量同试验组，中位剂量为DT66Gy。结果放疗DT20Gy时，试验组完全消退率（CR）为10％，对照组CR为6．5％（P〉0．05）；放疗DT40Gy时，试验组CR为33．3％，对照组CR为16．1％（P〉0．05）；放疗结束时，试验组CR为53．3％，对照组CR为25．8％（P〈0．05）；放疗结束1个月后，试验组CR为66．7％，对照组CR为35．5％（P〈0．05）。放疗结束时，Hb升高值试验组为17g／L．对照组为一3g／L（P〈0．05）；放疗结束1个月后，Hb升高值为试验组14g／L，对照组为2g／L（P〈0．05）。两组的血液学毒性发生率分别为33．3％和61．3％，差异有统计学意义。结论rhEPO结合高低氧对中晚期髓质型食管癌有明显的放射增敏作用，血液学毒性较对照组轻微，并可预见能延长患者的远期生存，值得临床上进一步试用推广。rhEPO停用后1个月内仍有改善患者贫血的作用。     

放化疗联合治疗晚期非小细胞肺癌50例临床分析

目的比较同步放化疗和序贯放化疗的临床效果和毒性反应，探讨非小细胞肺癌化疗和放疗的顺序和时机。方法50例Ⅲ期非小细胞肺癌患者分为两组，序贯组（A组24例）先化疗后放疗；同步组（B组26例）放疗和化疗同时进行。序贯组为诱导化疗3个周期后开始放疗，放疗结束后再化疗1个周期，同步组为化疗同时开始放疗。两组患者放疗技术和剂量相同．总剂量为60GY／6周。化疔方案TP方案：紫杉醇135mg／m^2＋顺铂（DDP）80mg／m^2第1天。结果结束治疗．序贯组和同步组缓解率分别为70．8％、80．7％，两组比较差异无统计学意义（P〉0．05）。1、2、3年生存率A组分别为65％、25％、15％，B组为67％、43％、32％，差异无统计学意义（P〉0．05）。Ⅲ～Ⅳ度放射性食管炎的发生率分别为8．3％和23．1％（P〈0．05）；Ⅲ～Ⅳ度白细胞下降发生率分别为25．0％和61．5％（P〈0．05）。结论同步放化疗是治疗晚期非小细胞肺癌的一种较好的治疗方法。     

局部复发鼻咽癌调强放疗的临床结果和预后因素分析

目的：探讨局部复发鼻咽癌调强放疗的临床结果和预后因素。方法接受放疗的鼻咽癌局部复发患者72例，再程放疗pGTV总剂量50～75创．5 Gy（中位剂量为65 Gy），每次分割剂量1．85～2．4 Gy（中位2．1 Gy）。其中52例患者同时给予化疗。结果截止到随访结束，26例患者死亡，病死率为36．11％。影响因素COX回归分析，其中首程放疗方式、再程放疗总剂量是影响患者生存率的独立因素（ P ＜0．05）。首程放疗方式、再程放疗总剂量影响患者预后的系数方面分别为0．626（95％CI0．372～0．863， P ＝0．008）与0．539（95％CI0．463～0．774， P ＝0．002）。结论 IMRT可有效治疗局部复发性鼻咽癌，能够有效提高肿瘤患者的局部控制率，值得临床推广。     

顺铂联合5-氟尿嘧啶治疗41例晚期鼻咽癌疗效观察

目的评价PF方案（顺铂及5-氟尿嘧啶）以不同给药方法治疗肝、肺转移晚期鼻咽癌患者的疗效及毒副反应。方法回顾性研究41例接受PF方案治疗鼻咽癌肝、肺转移病例。按不同给药方法分为两组：A组22例,5-Fu 3.0g／m^2 120小时持续静脉输注;B组19例,5-Fu 00mg／m^2 5天间断静脉输注。所有患者至少接受两个疗程化疗。结果A组有效率86％。（CR3例,PR16例）,B组有效率52％（CR1例,PR9例）具有统计学意义（P〈0．05）。毒副反应多为Ⅰ°～Ⅱ°。两组比较无统计学意义（P〉0．05）。结论PF方案5-Fu持续静脉输注法治疗晚期鼻咽癌疗效优于5-Fu间断静脉输注法。     

NP及FP方案诱导化疗同步适形调强放疗治疗局部晚期鼻咽癌

目的：评价NP及FP方案诱导化疗＋同步适形调强放疗治疗局部晚期鼻咽癌的毒副作用和疗效。方法经病理学或细胞学证实的局部晚期鼻咽癌患者81例,采用数字表法随机分为两组。观察组采用NP方案诱导化疗：长春瑞滨（NVB）25～30 mg/m2,第1、8天;顺铂（DDP）75 mg/m2,分为第1～3天。对照组：PF方案诱导化疗,DDP 75 mg/m2,分为第1～3天;氟尿嘧啶（ Fu）750 mg/m2第1～5天,均每3周重复,化疗2～4周期,化疗结束后进行同步放化疗。观察组同步化疗：NVB 25～30 mg/m2,DDP 40 mg第1、8、22、29、43、51天,对照组同步化疗：Fu 750 mg/m2,DDP 25/m2第1、8、22、29、43、51天。同时给予同步鼻咽＋颈部适形调强放疗。结果随访率为100％,观察组与对照组Ⅲ～Ⅳ度血液学毒性累计：白细胞减少47．5％与24.4％（χ2＝4．73,P＜0．05）。Ⅲ～Ⅳ度急性黏膜反应10％与20％。5年无局部区域复发生存率85．0％与65．9％（χ2＝4．05,P＜0．05）。5年总生存85．0％与68．3％（χ2＝3．18,P＜0．05）。结论 NP较FP方案诱导化疗＋同步适形调强放疗治疗局部晚期鼻咽癌局部控制率高,5年无复发生存率高,毒副作用可耐受,远期毒性低。     

单纯放疗及同期放化疗治疗中晚期鼻咽癌的临床对比研究

目的比较单纯放疗与同期放化疗治疗中晚期鼻咽癌的临床效果及安全性。方法回顾性分析我院收治的120例中晚期鼻咽癌患者的临床资料,根据治疗方法的不同分为4组：A组（单纯放疗）、B组（放疗联合紫杉醇同期化疗）、C组（放疗联合替加氟同期化疗）、D组（放疗联合紫杉醇＋替加氟化疗）,每组各30例患者。比较各组的近期治疗总有效率、5年总生存率及治疗过程中不良反应的发生情况。结果 B、C、D组的治疗总有效率和5年总生存率均明显高于A组;A组患者各项毒副反应的发生率均明显低于同期B、C、D组;D组发生毒副反应的比率明显高于B、C组;B组和C组发生毒副反应的比率无显著性差异（P〉0.05）。结论同期放化疗治疗中晚期鼻咽癌的临床效果优于单纯放疗,单一或联合药物同期放化疗的临床效果相当,但单一药物同期放化疗的安全性更高,值得临床推广应用。     

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.

     

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.     

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.     

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.     

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.