氯诺昔康在术后患者静脉吗啡自控镇痛中的作用

目的:观察氯诺昔康单次静注在术后患者静脉吗啡自控镇痛中的辅助作用.方法:90例行中上腹部手术的患者随机分为三组,术后均采用患者静脉吗啡自控镇痛.M组:术毕缝皮时开启镇痛泵.L1组:术毕缝皮时静注氯诺昔康8mg,然后开启镇痛泵.L2组:术毕缝皮时及术后6h各静注氯诺昔康8mg,术毕开启镇痛泵.术后24h和48h随访,采用视觉模拟评分法(VAS)和Keele疼痛描述四分法(VRS)评估镇痛效果,并记录不良反应.结果:各组VAS及VRS差异均无显著性.吗啡总药量、患者自控镇痛(PCA)按压次数和有效次数方面,M组最多,L2组最少,两组间比较有显著性差异(P<0.05).第1次PCA按压的时间M组最早,L2组最晚,最后1次PCA按压的时间L2组最早,M组最晚,按压的总间隔时间M组最长,L2组最短,L2组与L1组和M组相比差异有显著性(P<0.05).恶心的发生以M组最多,L2组最少,头晕的发生则相反.结论:术后患者静脉吗啡自控镇痛时分次加用氯诺昔康8mg可以提高镇痛效果,减少吗啡用量,降低恶心呕吐等不良反应.     

氯诺昔康对术后病人镇痛中吗啡的节俭作用

目的:探讨氯诺昔康用于术后病人自控静脉镇痛吗啡的节俭作用.方法:选择AsAJ-Ⅱ级择期行上腹部手术的患者69例,随机分成3组,术后均采用病人自控静脉吗啡镇痛.M组:术毕缝皮时开启镇痛泵.L2组:术毕开启镇痛泵.术毕缝皮时及术后8h各静脉注射氯诺昔康8 mg.L3组:术毕开启镇痛泵,术毕缝皮时、术后8h及术后16 h各静脉注射氯诺昔康8 mg.镇痛药液配制如下:吗啡0.25mg/ml,背景输注速度1 ml/h,病人自控量(PCA)4 ml,锁定时间5 min.术后4、24、48 h随访,采用视觉模拟评分法(VAS)评估镇痛效果,并记录镇痛药物用量和不良反应.结果:各组24 h和48 h VAS评分差异无显著性(P>0.05).24 h和48 h吗啡总量、PCA按压次数和有效次数M组最多.L2其次,L3组最少,M组分别与L2组、L3组相比差异有显著性(P<0.01).恶心呕吐和嗜睡的发生以M组最多,L2组和L3组均较少.头晕的发生3组相同.结论:氯诺昔康用于术后病人自控静脉镇痛,能够节俭吗啡的用量,减少吗啡的不良作用,提高术后镇痛质量.     

氯诺昔康和吗啡用于骨科术后病人自控镇痛的比较

目的：比较氯诺昔康和吗啡用于骨科术后病人自控镇痛(PCA)的安全性和有效性。方法：120例ASAⅠ～Ⅱ级硬膜外麻醉行股骨骨折手术的病人，随机分为氯诺昔康组(L组)和吗啡组(M组)。术毕给负荷剂量L组氯诺昔康0．1mg/kg，M组吗啡0．1mg／kg，随后L组氯诺昔康32mg加生理盐水至100ml，M组吗啡40mg加生理盐水至100ml，分别加入镇痛泵药池，背景输注为2ml／h，PCA量为0．5ml，锁定时间为10分钟。观察记录镇痛效果及发生的不良反应。结果：L组和M组镇痛效果差异无显著性，M组恶心、呕吐、皮肤瘙痒及尿潴留发生率明显高于L组。结论：氯诺昔康用于骨科术后PCA的镇痛效果与吗啡接近而不良反应发生率明显低于吗啡，适用于PCA。     

氯诺昔康用于上腹部手术术后镇痛的临床研究

目的:观察氯诺昔康用于上腹部手术术后镇痛的疗效及安全性.方法:40例上腹部手术患者,随机分为三组:L组8例,术后使用氯诺昔康自控镇痛PCA泵(1mg·次-1,24h限量40mg),M组16例,使用吗啡PCA泵(1mg·次-1,48h限量80mg),C组16例,手术结束时静注氯诺昔康8mg,术后48h氯诺昔康32mg持续静脉输注,同时应用吗啡PCA泵(1mg·次-1,48h限量80mg).观察48h记录术后4,8,12,24,48h各组VAS评分、吗啡用量及不良反应.结果:三组中L组术后镇痛效果差,12h时VAS仍高达(50.3±4.5)分,故12h后均加用吗啡镇痛.术后各时段M组与C组镇痛效果均相似,而吗啡用量C组(27.3±10.7)mg·48h-1,明显少于M组(41.3±16.3)mg·48h-1.C组和M组术后胃肠道不良反应发生率相似.结论:单独氯诺昔康不能控制上腹部术后剧烈疼痛,与吗啡联合应用可很好的缓解疼痛,而且可以减少34%吗啡用量.     

氯诺昔康用于开腹手术后患者的自控镇痛

目的:研究氯诺昔康(可塞风)用于开腹手术后患者的自控镇痛临床效果以及对血糖和血皮质醇的影响.方法:45例择期行全麻下开腹手术患者,随机分为氯诺昔康组(L组)、芬太尼组(F组)和氯诺昔康 芬太尼组(C组)行术后镇痛.观察镇痛、镇静效果和测定麻醉前和术后24h时静脉血皮质醇、血糖浓度变化.结果:三组患者术后VAS评分无明显差异(P>0.05);F组术后6h时的镇静评分明显高于L组和C组(P<0.05);三组患者术后24h时的血皮质醇浓度升高无明显差异(P>0.05).结论:氯诺昔康用于开腹手术后患者的自控镇痛临床效果确切,可以作为术后镇痛的较佳选择.     

氯诺昔康与曲马多联合吗啡用于术后静脉镇痛的疗效对比

目的:评价氯诺昔康与曲马多连续静脉输入联合吗啡预先硬膜外输注应用于术后镇痛的效果和安全性.方法:44例ASA Ⅰ～Ⅲ在硬膜外阻滞麻醉或腰硬联合阻滞麻醉下行腹部、脊柱、下肢手术的患者随机均分为氯诺昔康组和曲马多组,每组22例.两组均于麻醉后,切皮前以吗啡1～2mg注入硬膜外腔,手术结束前半小时采用一次性静脉输注泵持续输注氯诺昔康0.6mg·2mL-1·h-1(氯诺昔康组);曲马多16.6mg·2mL-1·h-1(曲马多组).两组输注泵内加用氟哌利多5mg,用生理氯化钠溶液稀释至96mL(48h用量).观察并记录术后4,8,12,24,48h各组各时点的VAS分值及不良反应.结果:两组镇痛效果均为良好或基本满意,但在术后12h和48h的VAS评分以曲马多组为高(P<0.05、P<0.01).两组恶心呕吐、头晕、嗜睡等并发症以曲马多组为多,差异有显著性(P<0.01),均未出现呼吸循环抑制、皮肤瘙痒等并发症.氯诺昔康与曲马多的总使用量之比为0.04∶1.结论:氯诺昔康能安全、有效应用于术后镇痛,其镇痛效果优于曲马多,联合吗啡硬膜外预先镇痛能提高其镇痛效果,减少各自药物的用量及降低并发症的发生率.     

氯诺昔康复合吗啡用于开胸手术后患者自控镇痛的比较

目的:比较氯诺昔康、吗啡、氯诺昔康复合吗啡用于开胸手术后,患者自控镇痛(PCA)的有效性和安全性.方法:择期开胸手术患者45例分三组,每组15例.PCA药物配伍为:A组吗啡50mg,B组氯诺昔康40mg,C组吗啡30mg 氯诺昔康24mg,溶于100mL生理氯化钠溶液.PCA工作方式采用持续背景剂量(2mL·h-1)配合单次按压剂量(1mL),锁定时间30min.采用视觉模拟评分(VAS),记录每个患者术后的疼痛程度;同时记录48h内总的按压次数以及可能出现的不良反应.结果:B组患者在术后各时间点的VAS评分稍高于A、C两组,但没有统计学差异(P>0.05).观察期间B组和C组患者恶心、呕吐的发生率明显低于A组(P<0.05),B和C两组间则没有统计学差异.结论:氯诺昔康用于开胸手术后PCA镇痛效应与吗啡相近,都能达到很好的镇痛作用.相对于单独应用吗啡或氯诺昔康,两者联合应用,术后镇痛效果相同,恶心、呕吐等不良反应少.     

氯诺昔康与曲马多合用对开胸术术后止痛的疗效

目的:选用氯诺昔康配合曲马多连续静脉输注用于开胸手术患者的术后止痛,观察其止痛效果及不良反应,评估其在胸科术后止痛的价值.方法:90例开胸手术患者,随机分为三组,氯诺昔康 曲马多组(L组),曲马多组(T组)和硬膜外吗啡组(M).每组30例,L组与T组药物均采用曲马多20mg·kg-1 氟哌利多0.1mg·kg-1 生理氯化钠溶液配成100mL,以2mL·h-1速度输注.L组在切皮前和关胸时各用氯诺昔康8mg静注,而T组不用氯诺昔康.M组药物采用吗啡0.12mg·kg-1 0.15%罗哌卡因100mL,行硬脊膜外腔输注.镇痛效果用4点疼痛分级以及VAS进行评估.结果:在8和28h时段,L组VAS评分低于T组(P<0.05).在28和48h时段,L组的4点疼痛分级低于M组(P<0.01).皮肤瘙痒在L组和T组无一例发生,M组有3例(3/30).恶心呕吐发生率三组比较无统计学意义.结论:开胸术后,采用氯诺昔康联合曲马多静脉输注止痛,可等效于硬脊膜外腔吗啡的止痛效果,同时不增加不良反应.     

氯诺昔康、右美沙芬与吗啡协同镇痛作用的临床观察

目的:观察小剂量氯诺昔康、右美沙芬复合小剂量吗啡用于上腹部手术后镇痛的效果.方法:择期上腹部手术患者45例,术后使用100mL一次性镇痛泵.所用药物为分别为吗啡50mg(吗啡组,n=14)、吗啡30mg 右美沙芬15mg(右美沙芬组,n=14)、吗啡30mg 氯诺昔康16mg(氯诺昔康组,n=14)和吗啡30mg(对照组,n=6).记录术后3,6,24,48h疼痛视觉模拟评分(VAS)、Ramsay镇静评分、活动后VAS评分和48h内使用吗啡总量并记录可能出现的不良反应.结果:术后6和24h吗啡组、氯诺昔康组VAS明显低于对照组,右美沙芬组6h明显低于对照组.术后6和24h吗啡与氯诺昔康组活动后VAS明显低于对照组,而右美沙芬组与对照组差异无显著性,且在6h显著高于吗啡组.各组术后镇静评分无差异.术后48h吗啡总量吗啡组明显高于其他3组,氯诺昔康与右美沙芬组低于对照组.术后恶心呕吐病例吗啡组明显高于其他3组.右美沙芬组1例眩晕,吗啡组1例皮肤瘙痒,未发现其他不良反应.结论:小剂量非阿片类药物氯诺昔康与右美沙芬与吗啡联合应用可增加吗啡的镇痛效果.     

氯诺昔康用于食管癌术后镇痛的临床研究

目的:评价氯诺昔康用于食管癌术后镇痛的效果及安全性.方法:选择行食管癌根治术患者60例,接受术后镇痛治疗(PCIA),随机分为L组和T组.L组使用氯诺昔康64mg·48h-1,T组使用曲马多800mg·48h-1.结果:两组于使用PCIA后4,12,24,36,48h的VAS疼痛评分、PHS术后疼痛评分无显著性差异(P＞0.05).镇静度评分:12h以后T组高于L组(P<0.05).术后镇痛不良反应的发生率L组低于T组,两组相比有显著性差异(P<0.05).总体评价L组优于T组.结论:氯诺昔康用于食管癌术后镇痛安全有效,满意度优于曲马多.     

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.     

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.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.