弥漫性结缔组织病并发弥漫性肺泡出血12例临床分析

目的分析总结弥漫性结缔组织病(CTD)合并弥漫性肺泡出血(DAH)的临床资料,提高对该病的认识。方法回顾分析深圳市人民医院2005年7月至2012年9月确诊的12例弥漫性CTD并发DAH患者的临床表现、实验室检查、诊治经过和转归。结果 DAH主要表现是咯血、胸闷、呼吸困难、血红蛋白下降;X线胸片、高分辨率CT可出现新发的肺部浸润影。弥漫性CTD合并DAH的患者中,系统性红斑狼疮(SLE)8例,显微镜下多血管炎(MPA)2例,肉芽肿性多血管炎(GPA)2例;诊断DAH时的年龄:SLE(26±8)岁,MPA分别为12岁和42岁,GPA为51岁和57岁;诊断DAH时的病程:SLE(18±14)d,其中有3例SLE患者以DAH为首发症状,另外有1例MPA患者也以DAH为首发症状;SLE合并DAH时SLE疾病活动指数(SLEDAI)评分为(18±5)分,抗核抗体呈高滴度,MPA/GPA患者核周型抗中性粒细胞胞质抗体(p-ANCA)/胞质型抗中性粒细胞胞质抗体(c-ANCA)分别呈阳性;9例患者发生明确感染;共有9例患者接受了激素冲击治疗,10例应用免疫抑制剂,7例行机械通气,2例行血液透析,所有患者病程中均使用抗生素。有1例患者死亡。结论 DAH与弥漫性CTD原发病的活动性密切相关,容易导致呼吸衰竭和肺部感染。弥漫性CTD合并DAH病死率高,应早期诊断,早期治疗。     

全反式维甲酸诱导联合化疗治疗急性早幼粒细胞白血病并发症的护理评价

目的对全反式维甲酸(ATRA)诱导联合化疗治疗急性早幼粒细胞白血病(APL)所引发的并发症的护理进行探讨与分析。方法本研究共纳入研究对象20例,均为2011年1月至2014年1月收治的APL患者,给予所有患者ATRA+蒽环类药物化疗治疗。结果 20例患者均出现并发症,其中11例为弥漫性血管内凝血,6例为粒细胞缺乏,3例为维甲酸综合征。通过对病情严密观察以及有效的护理之后,完全缓解的有19例,占95%,死亡的有1例,占5%。结论针对APL患者,运用ATRA+蒽环类药物化疗进行治疗,能够提高完全缓解率,但也容易出现并发症。这就要求护理人员运用科学的护理措施,准确判断并及时处理。     

急性早幼粒细胞白血病缓解后治疗的随访观察

目的 :观察经全反式维甲酸 (ATRA)诱导治疗取得完全缓解 (CR)的急性早幼粒细胞性白血病 (APL)的缓解后治疗的疗效。方法 :34例经ATRA治疗取得CR的APL患者 ,随机分为二组进行缓解后治疗 ,化疗组 1 6例 ,CR后予HA、DA等方案定期巩固化疗 ,持续 3a～ 4a停药 ;化疗与ATRA交替治疗组 1 8例 ,CR后采用化疗与ATRA每月交替方案进行治疗 ,持续 3a～ 4a停药。结果 :随访 1 3个月～ 85个月 ,复发 8例 ,复发率 2 3 5 %,其中化疗组复发 5例 ,复发率 31 3%,化疗与ATRA交替治疗组复发 3例 ,复发率 1 6 7%,总生存例数 2 8例 ,总生存率 (OS) 82 4 %,其中化疗组生存 1 2例 ,OS 75 %,生存 3a以上 8例 ,化疗与ATRA交替治疗组生存 1 6例 ,OS 88.9%,生存 3a以上 1 1例 ,两组复发率及OS无显著性差异 (P >0 0 5 ) ,复发后 6例接受重新诱导治疗 ,4例取得第二次CR(CR2 ) ,CR2 率 6 6 7%。结论 :APLCR后予积极治疗 ,可减少患者复发率 ,延长患者生存期。CR后采用化疗与ATRA交替治疗方案 ,与单用化疗巩固治疗比较 ,复发率低、生存率高 ,但无统计学意义。APL复发后重新诱导治疗 ,仍可取得CR2 ,但CR2 期较短。     

32例早幼粒细胞白血病治疗的临床疗效观察

目的 探讨三氧化二砷(AS2O3)、全反式维甲酸(ATRA)联合化疗方案对治疗急性早幼粒细胞白血病(APL)的疗效.方法 32例APL患者经联合诱导后,再对其进行巩固、维持治疗.结果 32例患者持续缓解率(CCR)为87.5%,5年预计OS和RFS分别为92.3%、88.2%未发现严重不良反应.结论 APL完全缓解患者巩固强化治疗后用ATRA、AS2O3与化疗联合维持治疗,总体生存率高,安全性好,值得临床推广.     

全反式维甲酸联合砷剂、化疗治疗急性早幼粒细胞白血病的疗效观察

目的探讨全反式维甲酸(ATRA)联合砷剂、化疗治疗急性早幼粒细胞白血病(APL)疗效.方法采用ATRA、砷剂、化疗交替治疗5个周期.结果9例APL均获完全缓解(CR),并持续无病生存9～38个月.结论ATRA联合砷剂、化疗是治疗APL理想方案.     

全反式维甲酸与亚砷酸联合化疗对急性早幼粒细胞白血病高危患者的疗效

目的观察全反式维甲酸(ATRA)与亚砷酸(ATO)联合化疗对急性早幼粒细胞白血病(APL)患者的疗效。方法回顾性分析86例不同危险分级的初治APL患者的临床资料。根据治疗前白细胞和血小板数将APL患者分为低、中、高危三组。采用ATRA+ATO+蒽环类药诱导缓解,蒽环类药+阿糖胞苷巩固治疗,ATRA+ATO+甲氨蝶呤(MTX)[部分加用6-巯基嘌呤(6-MP)]维持治疗。结果治疗后,完全缓解(CR)率高达95.3%(82/86)。中位随访37个月,高危组和中低危组无事件生存率及中枢神经系统累积复发率差异均无统计学意义(P>0.05)。维持治疗单用MTX者或MTX+6-MP者CR率均为100%。结论 APL患者尤其是高危患者可以从ATO+ATRA+化疗中受益;该方案作为初治APL的一线治疗方案优势明显。     

Outcomes of treating high-risk acute promyelocytic leukemia with all-trans retinoic acid combined with arsenic trioxide

目的 观察全反式维甲酸(ATRA)与亚砷酸(ATO)联合化疗对急性早幼粒细胞白血病(APL)患者的疗效.方法 回顾性分析86例不同危险分级的初治APL患者的临床资料.根据治疗前白细胞和血小板数将APL患者分为低、中、高危三组.采用ATRA+ATO+蒽环类药诱导缓解,蒽环类药+阿糖胞苷巩固治疗,ATRA+ ATO+甲氨蝶呤(MTX)[部分加用6-巯基嘌呤(6-MP)]维持治疗.结果 治疗后,完全缓解(CR)率高达95.3％(82/86).中位随访37个月,高危组和中低危组无事件生存率及中枢神经系统累积复发率差异均无统计学意义(P＞0.05).维持治疗单用MTX者或MTX+6-MP者CR率均为100％.结论 APL患者尤其是高危患者可以从ATO +ATRA+化疗中受益;该方案作为初治APL的一线治疗方案优势明显.     

维甲酸联合三氧化二砷治疗初发APL的临床疗效观察

目的:探讨全反式维甲酸(ATRA)和三氧化二砷(As2O3)治疗初发急性早幼粒细胞白血病(APL)的疗效和不良反应。方法:对16例初治病人给予ATRA联合As2O3以诱导缓解,完全缓解(CR)后用DA(D:柔红霉素,A:阿糖胞苷)、HA(H:高三尖杉酯碱,A:阿糖胞苷)和中剂量Ara-C(阿糖胞苷)方案巩固化疗,维持治疗方案用ATRA、MTX(甲氨蝶呤)和As2O3依次序贯治疗。结果:16例患者均获CR,其中15例目前仍保持CR状态,持续CR的时间8～46个月,l例因为皮肤浸润复发而死亡。结论:ATRA联合As2O3诱导缓解治疗APL以及维持治疗阶段以ATRA、As2O3、MTX序贯治疗,不良反应无显著增加,不仅能提高CR率,缩短达到CR的时间,并可降低复发率,有助于延长APL患者的持续缓解时间及无病生存时间。     

全反式维甲酸治疗59例急性早幼粒细胞白血病致维甲酸综合征临床分析

目的　探讨全反式维甲酸(ATRA)治疗急性早幼粒细胞白血病(APL)发生维甲酸综合征(RAS)的临床规律、治疗及预防方法。方法　对59例初发APL患者行ATRA治疗过程中,发生与不发生白细胞增高与RAS的关系、临床特征及RAS的治疗方法进行观察。结果　59例APL患者在ATRA治疗后,WBC＞20.0×10     

18例急性早幼粒细胞白血病序贯治疗临床观察

目的观察亚砷酸(AS2O3),全反式维甲酸(ATRA)联合化疗方案序贯治疗成人急性早幼粒细胞白血病(APL)的疗效。方法 18例APL患者,采用ATRA及亚砷酸(出现高白细胞淤积症时,给予柔红霉素)联合进行诱导,巩固及维持治疗,并定期检测PML_RARa融合基因。结果完全缓解(CR)率为87.5%,达CR中位时间为26d,并于巩固治疗期间采用AS2O3与ATRA及蒽环类药物交替进行,并于以维持治疗,总疗程为3年。目前已12例停药,13例患者每3个月检测PML-RARa融合基因均为(-),3例处于维持治疗阶段。仅2例患者未达CR因脑出血死亡。结论 AS2O3与ATRA联合化疗治疗成人APL的疗效较满意。     

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.     

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.