氯诺昔康超前镇痛的临床研究

目的:探讨新的非甾体类抗炎药氯诺昔康的超前镇痛作用.方法:60例接受单纯全麻的开胸、胸椎、腰椎手术患者分为三组,Ⅰ和Ⅱ组患者术中不再使用其他静脉镇痛药物,Ⅲ组患者麻醉前静脉注射氯诺昔康8mg,如手术时间超过4h,则术中追加氯诺昔康4mg,所有患者术毕即开始静脉自控镇痛(PCIA),Ⅰ组配方:芬太尼浓度为5μg·mL-1,咪唑达仑0.1mg·mL-1,总容量200mL;Ⅱ,Ⅲ组配方:在Ⅰ组配方基础上加氯诺昔康0.16mg·mL-1,总容量不变.观察所有患者术毕清醒、术后12,24,48h的VAS评分、血压、心率及脉搏血氧饱合度(SPO2)和术后48h的镇痛药总用量、患者按压(bolus)的总次数与实际进药次数以及两者之间的比值(即D/D比值),记录患者对镇痛效果的满意度.结果:Ⅱ和Ⅲ组在术后PCA泵中加入氯诺昔康可显著降低VAS评分和减少患者主动按压的次数和D/D值以及对阿片类药物(芬太尼)的需求量;Ⅲ组患者麻醉前及术中静脉注射氯诺昔康,与Ⅰ和Ⅱ组相比,术后患者VAS评分显著降低,对阿片类药需要量显著减少.结论:麻醉手术前静脉注射氯诺昔康8mg有超前镇痛效应,氯诺昔康在静脉PCA中作为基础镇痛药或称背景镇痛药辅助阿片类药物用于术后镇痛,可显著提高镇痛效果.     

氯诺昔康在妇科腹腔镜术后镇痛中的应用

目的 观察妇科腹腔镜患者术后单次使用氯诺昔康的24h镇痛作用。方法 将妇科腹腔镜择期手术患者90例随机分为A组（氯诺昔康8mg）、B组（氯诺昔康16mg）和c组（对照组），每组30例，A，B组均在术毕注射氯诺昔康．采用视觉模拟法（VAS评分）分别于术后1，4，8，24h作痛觉评分，并记录有无恶心等副作用及术后24h内使用镇痛药物的总次数。结果 使用氯诺昔康的两组患者术后24h内VAS评分显著低于对照组（P〈0．05），B组使用镇痛药的次数明显低于对照组（P〈0．05）。结论妇科腹腔镜术毕单次静脉注射8mg或16mg氯诺昔康可有效缓解术后疼痛，16mg组的镇痛作用更强，且均无明显的不良反应。     

氯诺昔康与帕瑞昔布钠在下肢骨科手术术后镇痛效果的比较

目的比较氯诺昔康、帕瑞昔布钠联合阿片类镇痛药对下肢骨折手术患者术后镇痛效果。方法 90例拟行胫骨骨折手术患者均使用腰硬联合麻醉,根据术后镇痛方式不同随机分为三组：C组（对照组）手术结束后常规接上电子静脉镇痛泵镇痛。L组（氯诺昔康组）手术结束前静脉输注氯诺昔康8mg,连接电子静脉镇痛泵。镇痛泵中加入氯诺昔康32mg,其余配方同C组。P组（帕瑞昔布钠组）在手术结束后常规接上电子镇痛泵镇痛,回病房后肌肉注射注射帕瑞昔布钠40mg,术后继续给予40mg帕瑞昔布钠q12h,至术后48h。静脉镇痛泵的配方同C组。镇痛不足时由病房医生根据患者疼痛情况给予哌替啶50mg肌肉注射。记录三组术后4、8、12、24、36、48h的疼痛评分及副作用。记录三患者术后24h镇痛泵的芬太尼用量、按压总次数和有效次数。结果术后各个观察时点NRS评分C组和L组均显著高于P组（P〈0.01）,术后各个观察时点NRS评分C组与L组差异没有显著性（P〉0.05）。术后镇痛泵按压次数和24h芬太尼用量C组和L组均显著大于P组（P〈0.05）。结论对于术后中、重度疼痛的患者帕瑞昔布钠复合阿片类静脉镇痛较氯诺昔康能获得较为满意的镇痛效果。     

氯诺昔康对心内直视手术后患者自控镇痛效应的影响

目的：观察氯诺昔康对心内直视手术后患者自控镇痛效应的影响。方法：将30例心内直视手术患者随机分为氯诺昔康组和吗啡组,每组各15例。镇痛药为吗啡1mg/mL,参数设置为：负荷剂量1mg,持续输注剂量0.5mg/h,单次给药剂量1mg,锁定时间10min,每4h最大限量20mg。应用PCA泵的同时,氯诺昔康组静脉注射首剂氯诺昔康8mg,首剂药物后12、24和36h,静脉注射氯诺昔康8mg;吗啡组在四时间点均注射生理盐水。镇痛开始后12、24、36和48h记录疼痛VAS评分,PCA需求按压次数和有效按压次数,药物用量,镇静程度评分;术后各种并发症及不良反应发生率;记录镇痛满意度NRS评分。结果：两组患者各时间点安静痛和咳嗽痛评分差异无统计学意义（P〉0.05）。镇静程度评分、PCA需求按压次数、有效按压次数及药物用量氯诺昔康组显著低于吗啡组（P〈0.05）。两组患者氯诺昔康组恶心发生率显著低于吗啡组（P〈0.05）,其他术后各种并发症及不良反应发生率差异无统计学意义（P〉0.05）。两组患者对镇痛满意度评分、在ICU停留时间及手术后住院时间差异无统计学意义（P〉0.05）。结论：氯诺昔康可安全有效地应用于心内直视手术后患者术后镇痛,并减少吗啡用量。     

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.     

单次帕瑞昔布钠对曲马多术后镇痛效果的影响

目的观察术毕单次应用帕瑞昔布钠是否改善曲马多的镇痛效果。方法 60例择期腹部手术患者随机均分为两组:T组术毕实施曲马多患者自控静脉镇痛(PCIA);TP组PCIA前静脉注射帕瑞昔布钠40mg。PCIA:术毕前30min静脉注射曲马多1.5mg/kg和昂丹司琼8mg;术毕接镇痛泵(曲马多15mg/kg、昂丹司琼16mg稀释至100ml)。记录术后4、24及48h的VAS疼痛评分、Ramsay镇静评分、舒适度评分(BCS)、追加镇痛药人数、镇痛泵按压次数和不良反应发生情况。结果与T组相比,TP组术后24h的VAS、术后4h追加镇痛药人数,术后4、24和48h镇痛泵按压次数均明显减少(P<0.05)。两组均无严重不良反应。结论曲马多PCIA前加用帕瑞昔布钠可改善曲马多术后镇痛效果。     

氯诺昔康联合小剂量氯胺酮 预防开颅患者术后疼痛的疗效观察

［摘要］目的探讨氯诺昔康联合小剂量氯胺酮对开颅患者术后镇痛疗效和安全性。方法将择期开颅患者42例随机均分为Ⅰ、Ⅱ、Ⅲ组，每组14例。3组患者均用咪达唑仑+异丙酚+芬太尼+维库溴铵静脉诱导后行气管插管，术中以吸入异氟醚和持续静脉注射异丙酚，间断给维库溴铵麻醉。Ⅰ组患者术前静脉注射氯诺昔康8 mg，同时静脉注射氯胺酮0.2 mg·kg 1，术后追加氯诺昔康8 mg；Ⅱ组患者只在术后给氯诺昔康8 mg；Ⅲ组患者未行镇痛。记录各患者的手术时间、全麻苏醒时间；观察并记录手术后3，6，18，24 h各时点的视觉模拟（VAS）评分及镇静评分；记录各组患者术后恶心、呕吐程度和发生率。结果3组患者手术时间、全麻苏醒时间无显著差别；Ⅰ、Ⅱ组患者镇痛优良率分别为85.2%，72.3%（P＜0.05），术后3，6 hⅠ组与Ⅱ组VAS评分差异无显著性，但Ⅰ组术后18 h VAS评分明显低于Ⅱ组（P＜0.05）；术后3，6，18 hⅠ组、Ⅱ组术后VAS评分均显著低于Ⅲ组（P＜0.05），但术后24 h各组患者VAS评分差异无显著性；术后各组恶心、呕吐程度及发生率差异无显著性；各组镇静评分差异无显著性。结论氯诺昔康伍用小剂量氯胺酮具有良好的镇痛作用，且不影响意识状态，是用于开颅患者的一种较理想的术后镇痛方法。     

氯诺昔康超前镇痛对腹腔镜胆囊切除术后镇痛的影响

目的探讨氯诺昔康超前镇痛对腹腔镜下胆囊切除患者术后镇痛的影响。方法选择腹腔镜下胆囊切除术患者80例,随机分为氯诺昔康超前镇痛组（A组）和氯诺昔康术后镇痛组（B组）,每组40例。所有患者均采用静脉全身麻醉：芬太尼、维库溴铵复合异丙酚血浆靶控输注。两组患者分别在麻醉诱导前10分钟和手术结束时静注氯诺昔康0．2mg／kg,术毕拔管清醒后均采用芬太尼0．5μg／kg用于术后镇痛。采用VAS评分法评估患者术后0、1、2、4、8、12、24小时疼痛程度并记录需追加芬太尼镇痛患者的时间间隔及追加次数;记录手术时间、麻醉苏醒时间及不良反应等情况。结果A组患者在术后0、1、2、4、8、12、24小时VAS评分均低于B组（P〈0．05）,且术后24小时内需追加芬太尼镇痛的患者明显少于B组（0：22．7％;P〈0．05）。两组患者手术时间、麻醉苏醒时间及不良反应发生率差异无统计学意义（P〉0．05）。结论氯诺昔康0．2mg／kg超前镇痛可以产生较好的术后镇痛效果,同时可减少阿片类药物的应用。     

氯诺昔康与曲马多在骨科术后患者自控静脉镇痛中的应用

目的:探讨氯诺昔康、曲马多与芬太尼配伍用于患者自控静脉镇痛(PCIA)的镇痛效果比较.方法:60例各类骨科术后中等以上疼痛患者随机分为两组(每组30例),试验组(L组)用芬太尼 氯诺昔康,对照组(T组)用芬太尼 曲马多.芬太尼用量0.02mg·kg-1,根据患者体重计算芬太尼总用量后,分别用8mg氯诺昔康或100mg曲马多替代0.1mg芬太尼.在L组中芬太尼与氯诺昔康各占一半,T组中芬太尼与曲马多各占一半.镇痛泵背景剂量2mL·h-1,PCIA剂量2mL·次-1,锁定时间15min.依据VAS评分标准分别测定术后4,16,24,36,50h的疼痛值,并观察两组在恶心、呕吐等方面不良反应,最后记录镇痛结束时患者对镇痛效果的总体评价.结果:两组镇痛效果VAS评分无显著差异(P>0.05),L组恶心呕吐等不良反应少于T组.结论:氯诺昔康和曲马多分别与芬太尼配伍用于PCIA镇痛效果无显著差异.氯诺昔康在恶心呕吐等不良反应方面优于曲马多.     

氯诺昔康复合吗啡对腭咽成形术后镇痛效果的临床观察

[摘要] 目的 对比观察氯诺昔康复合吗啡对腭咽成形术患者自控镇痛(PCA)的有效性和安全性。方法 40例腭咽成型术患者随机分为氯诺昔康组(L组)和吗啡组(M组),每组20例。PCA泵的镇痛药为吗啡1 mg／ml;同时L组于术毕和术后12、24、和36h静脉注射氯诺昔康．每次8mg;M组在相应时点注射生理盐水,记录镇痛12、24、36和48 h VAS评分及镇静程度评分;PCA需求按压次数、有效按压次数及药物用量;术后不良反应发生率和镇痛治疗总体满意度。结果两组患者各时点安静痛和咳嗽痛VAS评分差异无统计学意义;镇静程度评分、PCA需求按压次数、有效按压次数及药物用量L组显著低于M组(P<0.05);L组恶心、呕吐发生率显著低于M组(P<0.05);镇痛效果总体满意度两组间差异无统计学意义。结论 氯诺昔康用于腭咽成形术镇痛效果确切、安全有效,且可减少吗啡用量,降低恶心。呕吐的发生率。     

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.