皮质激素治疗57例SARS患者的不良反应

目的:观察糖皮质激素治疗SARS患者出现的不良反应。方法:将98例SARS患者分为激素治疗组和对照组,激素治疗组57例,对照组41例。激素治疗组按照用药剂量分为<160mg·d-1(16例)、≥160,<320mg·d-1(35例)、≥320mg·d-1(6例)三组;按照用药疗程分为<20d(19例)、≥20d(38例)两组,并分析比较激素治疗组和对照组产生的不良反应。结果:激素组与对照组比较,发生低钾血症分别为43.9%和26.8%,血糖升高分别为45.6%和22%,继发细菌感染分别为31.6%和14.6%,减量过程中体温再次升高分别为38.6%和17.1%,胸片示炎症加重分别为21.1%和7.3%。激素组不良反应的发生率有随剂量、疗程的增加而增加的趋势。结论:激素治疗SARS患者有引起低钾血症、血糖升高、继发细菌感染的可能,激素减量过程中可出现病情反复。     

SARS患者激素治疗与继发感染关系的探讨

目的:探讨传染性非典型肺炎(SARS)患者使用糖皮质激素治疗与继发感染的关系。方法:对我院2003年3月26日至5月24日住院治疗的253例非典型肺炎患者的血、尿、便、痰等标本进行细菌培养,对培养结果依据糖皮质激素使用情况分类进行统计分析。结果:253例患者标本中共分离出致病菌80株。79例未使用激素者,继发感染率7.6%;174例使用糖皮质激素治疗者,继发感染率为19.0%。其中普通型SARS的继发感染率为12.9%,重症SARS的继发感染率25.9%,使用糖皮质激素小剂量患者的感染率为10.3%,中大剂量患者的感染率为23.3%。结论:SARS患者使用糖皮质激素治疗出现的继发感染率要高于未使用激素者,随着糖皮质激素使用剂量的增加,患者继发感染的几率也在增加;重症患者使用糖皮质激素后更易引起继发感染。因此,在治疗SARS病人中应注意合理使用激素。     

榄香烯乳注射液耐受性试验Ⅰ期临床研究

目的:探讨榄香烯乳剂注射液的不良反应,探索最大耐受剂量,为Ⅱ期临床研究推荐最佳剂量。方法:设置6个剂量组,每组入选3例患者。初始剂量750 mg·d-1,递增幅度250 mg,最高剂量2 000 mg·d-1。采用持续静脉滴注,qd,每周连续给药5 d,休息2d,28 d为一周期。按照世界卫生组织(WHO)抗肿瘤药物常见毒性反应分级标准及加拿大通用毒性评价标准(NCIC-CTC)评价不良反应,并初步观察疗效。结果:19例患者参加了临床试验,主要不良反应为三酰甘油及胆固醇水平升高,其余可见非感染性发热、消化道反应、白细胞下降等。不良反应与剂量升高无相关趋势。直到2 000 mg·d-1仍没有摸索到最大耐受剂量。根据耐受及生存情况,1 250 mg·d-1为合理使用剂量。结论:榄香烯乳剂注射液耐受性良好,结合生存情况,临床推荐1 250 mg·d-1为Ⅱ期临床使用剂量。     

两性霉素B联合抗结核药物治疗结核性脑膜炎合并隐球菌性脑膜炎的疗效观察

目的:观察两性霉素B联合抗结核药物治疗结核性脑膜炎合并隐球菌性脑膜炎的临床疗效。方法:将52例结核性脑膜炎合并隐球菌性脑膜炎患者随机均分为治疗组和对照组。2组患者均采用抗结核、降颅内高压、应用激素、保肝等综合治疗。治疗组在综合治疗的基础上给予两性霉素B注射剂,以1mg·kg-1·d-1为首次剂量逐渐递增治疗;对照组在综合治疗的基础上给予氟康唑注射剂200mg·kg-1·d-1,首次剂量加倍。2组均治疗45d,均于治疗期间每周复查脑脊液蛋白量。结果:治疗后治疗组脑脊液蛋白量下降至正常率为84.6%,对照组为57.7%,2组比较差异有统计学意义(P<0.05)。治疗组有5例(19.2%)、对照组有4例(15.4%)发生不良反应,2组比较差异无统计学意义(P>0.05)。结论:两性霉素B联合抗结核药物治疗结核性脑膜炎合并隐球菌性脑膜炎可明显降低脑脊液蛋白量,且不良反应少。     

厄贝沙坦治疗轻中度原发性高血压的临床研究

目的　评价国产厄贝沙坦治疗轻中度原发性高血压的有效性及安全性。方法　采用随机双盲平行对照的临床设计 ,将5 7例轻中度原发性高血压病患者分成试验组 (厄贝沙坦组 ) 2 7例和对照组 (缬沙坦组 ) 30例 ,起始剂量分别为 75mg·d-1和80mg·d-1,2周后如DBP仍≥ 90mmHg ,则加量至 15 0mg·d-1和 16 0mg·d-1,疗程 4周。结果　试验组与对照组血压均明显下降。试验组总有效率 86 .6 % ,不良反应发生率 7.4 %。对照组总有效率 93.3% ,不良反应发生率 10 .0 %。两组疗效和不良反应发生率均无显著性差异。结论　国产厄贝沙坦是一种安全有效的治疗轻、中度原发性高血压的药物 ,其降压效果和不良反应均与缬沙坦相似     

托吡酯与丙戊酸钠对照治疗成人癫痫124例

目的:观察托吡酯及丙戊酸钠单药对照治疗新诊断的成人癫痫患者的疗效及耐受性。方法:入组患者124例,其中试验组60例,起始剂量25 mg·d-1,qd,对照组64例,起始剂量丙戊酸钠200 mg·d-1,bid。根据患者发作情况及药物不良反应调整剂量,观察药物的疗效及耐受性,以达最佳或最终剂量。通过比较2组患者治疗前后的月平均发作次数和退出试验的病例比例评价药物的总体疗效。结果:观察时间试验组(8．10±6．44)个月,对照组(14．16±11．75)个月。最佳或最终剂量范围试验组50～300 mg·d-1。对照组200～1500 mg·d-1。两组总有效率分别为78．33％及59．38％,两组比较差异有显著性(P=0．0383)。试验组和对照组分别有2例和1例因不良反应退出或换药。结论:托吡酯单药治疗成年新诊断癫痫患者的疗效好于丙戊酸钠,具有较好的安全性和耐受性。     

49例地高辛中毒原因分析

目的分析地高辛中毒的原因,为临床合理使用提供依据。方法分析49例地高辛中毒患者的临床资料。结果中毒者平均年龄为(59.6±13.1)岁。43例血药浓度为1.8~3.7μg·L-1,6例大于5μg·L-1。用药剂量0.125mg·d-9例,0.25mg·d-125例,0.375mg·d-110例,0.5mg·d-1例,0.75mg·d-12例,>0.75mg·d-11例。40例合并用药配伍药物有去乙酰毛花苷、利尿剂、抗心律失常药、硝酸酯类血管紧张素转换酶抑制剂、钙拮抗剂、血脂调节药、抗感染药等。结论剂量、患者年龄、病理生理状况以及药物相互作用与地高辛中毒有关。及时监测血药浓度,调整用药剂量,对防止中毒非常重要。     

奥氮平与氯丙嗪治疗精神分裂症阳性症状的临床疗效比较

目的 :观察奥氮平治疗精神分裂症阳性症状的疗效及安全性。方法 :采用随机临床对比研究。奥氮平组 31例 (男性 14例 ,女性 17例 ) ,剂量范围 5～ 2 0mg·d- 1;氯丙嗪组 2 7例 (男性 14例 ,女性 13例 ) ,剂量范围为 2 5～ 6 0 0mg·d- 1。结果 :奥氮平组治疗精神分裂症的显效率为 6 1% ,有效率为80 % ;而氯丙嗪组的显效率为 33% ,有效率为 5 2 % ,奥氮平组的临床疗效显著优于氯丙嗪组 (P <0 .0 5 )。奥氮平组的不良反应较少 ,未发现锥体外系不良反应及直立性低血压。结论 :奥氮平是一有效而安全的非典型性抗精神病药物 ,对精神分裂症阳性症状有效     

卡马西平引起药疹的特征分析

［摘要］目的研究卡马西平所致药疹的临床特征。方法分析由马西平所致药疹住院的8例患者的临床资料，包括用药原因、潜伏期、皮肤和黏膜损害特点、系统损害特点及对治疗的反应等。结果8例患者的平均潜伏期为（13.9±5.9） d；重症多形性红斑（SEM）、重症多形性红斑并发大疱性表皮松解症（SEM/ TEN）各3例，轻症多形性红斑（MEM）、大疱性表皮松解症（TEN）各1例；成人重症药疹易出现肝肾等内脏损害；对糖皮质激素反应较差的重症药疹患者并用大剂量静脉用丙种球蛋白（IVIG）疗效较理想； 在7例重症药疹患者中有5例糖皮质激素的有效剂量等效于泼尼松平均为1.5 mg·kg-1·d-1。 结论卡马西平所致药疹的潜伏期平均约为2周；多数患者在短期内可进展成重症药疹；及时停药和使用足量的糖皮质激素可能是阻止患者向TEN或SEM/ TEN发展的关键；等效的泼尼松1.2～2.0 mg·kg-1·d-1的激素用量或并用较大剂量IVIG疗效较好， 且在4周内未出现明显糖皮质激素不良反应。     

托吡酯治疗脑梗死性癫32例

目的评价托吡酯治疗脑梗死性癫患者的疗效与安全性。方法将52例脑梗死性癫患者随机分为治疗组32例和对照组20例，治疗组给予托吡酯片口服，每次25 mg·d-1， bid，持续7 d，以后按每周25～50 mg·d-1的量逐渐增加，依临床疗效调整剂量，最大剂量为375～500 mg·d 1；对照组给予卡马西平片口服，每次0.1 g，tid，逐渐加量，依临床疗效调整剂量，最大剂量为1.0～1.2 g·d 1。两组观察期均为20周。结果治疗组总有效率（84.4%）明显高于对照组（60.0%）（P＜0.05）。治疗组中小面积梗死的总有效率（95.5%）明显高于大面积梗死患者（60.0%）（P＜0.05）。治疗组不良反应发生率21.9%，对照组不良反应发生率40.0%，不良反应均随着治疗时间的延长而消失。结论托吡酯单药治疗脑梗死性癫患者疗效较好，安全，尤其对小面积脑梗死型癫疗效较好。     

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.