鞘内镇痛在顽固性癌痛患者的应用

目的探讨鞘内镇痛用于顽固性癌痛患者的临床效果及安全性。方法晚期顽固性癌痛患者50例采用持续鞘内镇痛,镇痛药物分别为吗啡+布比卡因(A组,25例)和吗啡(B组,25例)。比较治疗前后静息/运动VAS疼痛评分,记录吗啡用量,评估生活质量和不良反应。结果与治疗前相比,两组患者镇痛期间VAS疼痛评分均降低(P<0.05),A组患者的运动VAS疼痛评分较B组更低(P<0.05)。A组每日吗啡用量为(4.17±1.25)mg,少于B组的(8.34±1.48)mg(P<0.05)。A组患者的生活质量总评分为(80.24±6.71)分,高于B组的(67.82±6.03)分(P<0.05)。A组镇痛相关的不良反应发生率低于B组(4.00%vs.20.00%)(P<0.05)。结论与单一吗啡比较,持续鞘内输注吗啡联合布比卡因对顽固性癌痛的镇痛效果较好,能减少吗啡的用量和不良反应。     

剖宫产术后鞘内注射不同剂量吗啡镇痛的疗效观察

目的探讨剖宫产术后鞘内注射不同剂量吗啡镇痛的效果及不良反应,优化吗啡鞘内注射的临床剂量。方法将我院96例行剖宫产的产妇随机分组,每组24例,患者均采用腰-硬联合麻醉(CESA)。鞘内注药:A组:0.5%的罗哌卡因15mg;B组:0.5%的罗哌卡因15mg+吗啡0.3mg;C组:0.5%的罗哌卡因15mg+吗啡0.6mg;D组:0.5%的罗哌卡因15mg+吗啡1.2mg。观察镇痛效果及不良反应。结果 B组、C组的VAS疼痛评分均显着高于A、D组,差异有统计学意义(P<0.05),在镇痛效果上C组与B组镇痛效果满意,C组在各时段均优于B组的镇痛作用。在不良反应上,吗啡用量越少,不良反应亦越少。结论鞘内注射吗啡镇痛用于剖宫产术,可减少局麻药用量,术后镇痛效果满意,不良反应少,是一种安全有效的术后镇痛方法。     

经皮下输注装置鞘内吗啡镇痛的疗效及经济学评价

目的：评估经皮下输注装置鞘内输注吗啡治疗癌性疼痛的有效性和经济性。方法：收集2017年4月至2018年4月采用经皮下输注装置鞘内吗啡输注治疗的32例晚期癌痛病例,统计患者的疼痛程度、住院时长和住院费用等一般信息,评价鞘内镇痛对癌痛患者疼痛程度、日常生活能力和镇痛药物用量的影响,分析患者鞘内镇痛前后每日镇痛所需费用的变化,以及鞘内镇痛前后每日镇痛费用的差额与住院费用平衡所需时长。结果：行鞘内镇痛术的癌痛患者平均疼痛持续时间为（10.6±9.7）月,平均住院时长和住院费用分别为（13.0±5.8）d和（48 237.0±11 137.0）元。鞘内镇痛能够显著降低癌痛患者的疼痛程度（VAS评分：6.81±0.16 vs.2.69±0.22）、镇痛药物用量[（105.94±23.04）mg vs.（1.62±0.44）mg]和每日镇痛费用[（211.71±99.31）元vs.（5.62±0.15）元],但对患者的日常生活能力没有显著的改善作用（68.75±25.84）vs.（65.47±25.09）。鞘内镇痛前后每日镇痛费用的差额与住院费用抵消所需要的平衡时间为（515.87±325.56）d。结论：经皮下输注装置鞘内吗啡镇痛能够有效治疗晚期癌痛,减少镇痛药物用量和每日镇痛费用,但不能改善患者的生活质量和降低癌痛患者的总镇痛费用。     

盐酸羟考酮注射液用于重度吗啡耐药癌痛治疗的临床观察

目的观察盐酸羟考酮注射液对重度吗啡耐药癌痛的治疗效果。方法 37例重度吗啡耐药癌性疼痛患者,停止口服吗啡,改用盐酸羟考酮注射液给予患者自控性静脉镇痛,记录患者用药前及用药后1、4、7 d的VAS、KPS、QOL评分及不良反应发生情况。结果患者用药后各时间点VAS、KPS、QOL评分明显改善(P<0.01);患者换药4 d后瘙痒、恶心、便秘等不良反应明显减轻(P<0.05)。结论盐酸羟考酮注射液可以迅速、有效、安全地治疗重度吗啡耐药的癌性疼痛患者。     

鞘内吗啡联合皮下自控术后镇痛的效果观察

目的:比较鞘内吗啡镇痛、皮下自控镇痛以及鞘内吗啡联合皮下自控镇痛在术后镇痛中的临床效果。方法:研究对象为300例行剖宫产术患者,ASA(美国麻醉医师协会)～级。随机分为鞘内吗啡镇痛组(A组)、皮下自控镇痛组(B组)和鞘内吗啡联合皮下自控镇痛组(C组),每组100例。A组鞘内吗啡0.6 mg,B组术终前接皮下自控镇痛泵,C组鞘内吗啡0.4 mg+皮下自控镇痛(镇痛泵于术后12 h开启)。记录三组术后4,8,12,24,48 h各时点疼痛视觉模拟评分法(VAS)和恶心、呕吐、皮肤瘙痒以及呼吸抑制等不良反应的发生情况。结果:术后8,12 h的VAS评分A组明显低于B组,术后24,48 h的VAS评分B组明显低于A组,C组的VAS评分于术后8,12 h明显低于B组,术后24,48 h明显低于A组。结论:鞘内吗啡、皮下自控镇痛均能产生良好的术后镇痛效果,将鞘内吗啡与皮下镇痛联合应用优于二者单独使用时的镇痛效果,并可减少各自用药量及不良反应的发生。     

吗啡联合氯胺酮持续静脉泵入用于控制癌痛的临床观察

目的探讨吗啡联合氯胺酮持续静脉泵入治疗癌性疼痛的临床效果及其安全性。方法选取晚期癌痛患者86例,随机分为吗啡组（对照组）和吗啡联合氯胺酮组（观察组）,每组43例。2组均采用静脉持续泵入镇痛液的方法控制癌痛,对照组：吗啡100mg4-氟哌利多5mg＋0．9％氯化钠溶液至100ml,观察组：吗啡100mg＋氯胺酮50mg＋氟哌利多5mg＋0．9％氯化钠溶液至100ml。分别在安装止痛泵后30min、1、3、5、24、48h采用视觉模拟评分法（VAS）评估疼痛程度,统计2组治疗过程中不良反应。结果治疗后2组各时间点VAS评分与治疗前相比差异有统计学意义（P〈0．05）,2组患者疼痛均明显缓解;2组间各时间点VAS评分比较差异无统计学意义（P〉0．05）,但观察组吗啡用量显著少于对照组（P〈0．05）;观察组生活质量评分显著低于对照组（P〈0．05）;不良反应：观察组恶心呕吐、便秘、皮肤瘙痒等不良反应发生率显著低于对照组（P〈0．05）,而呼吸抑制、幻觉发生率比较差异无统计学意义（P〉0．05）。结论氯胺酮辅助吗啡持续静脉泵入具有用量小、镇痛作用强、不良反应小等优点,适合治疗晚期顽固性癌痛．．     

术前硬膜外应用氯胺酮对术后镇痛的影响

目的观察术前应用氯胺酮对术后镇痛的作用。方法选择90例妇产科手术病人,随机分为两组,每组45人,实验组在术前行氯胺酮30mg注入硬膜外腔,对照组注入生理盐水。两组术后均行PCEA镇痛,记录疼痛出现的时间,术后3、6、9、12、16、24小时VAS评分,24小时镇痛液的用药及不良反应。结果实验组术后疼痛出现的时间明显延长(P<0.05);术后16小时及24小时两组VAS评分有统计学意义(P<0.05);两组24小时内吗啡用量有统计学意义(P<0.05);不良反应两组无明显差异。结论术前硬膜外腔应用氯胺酮能加强吗啡术后镇痛的效果。     

加巴喷丁联合吗啡治疗顽固性癌痛的临床效果

目的观察加巴喷丁对顽固性癌痛患者的镇痛效果。方法 46例癌症患者分别采用吗啡(M组,22例)和吗啡联合加巴喷丁(MG组,24例)镇痛。M组患者根据疼痛VAS评分递加吗啡镇痛;MG组口服加巴喷丁900mg/d的同时再根据镇痛情况服用吗啡。给药1、2、4周时进行VAS疼痛评分及镇痛效果评定,记录吗啡使用剂量及服药4周后的镇痛相关不良反应。结果镇痛期间,两组VAS疼痛评分均低于治疗前(P<0.01),镇痛优良率达79.17%~90.91%。随着治疗时间的延长,M组吗啡用量明显增加(P<0.05或P<0.01),MG组吗啡用量与初始量仅稍有增加(P>0.05)。治疗的第2、4周,MG组吗啡使用量小于M组(P<0.05)。两组治疗相关主要不良反应为便秘、尿潴留、恶心呕吐、皮肤瘙痒和嗜睡等;两组近期不良反应发生率相仿(59.09%vs.62.50%)(P>0.05)。结论复合应用加巴喷丁和吗啡能有效缓解顽固性癌痛,并可以明显减少吗啡需要量。     

探讨吗啡联合氯胺酮皮下自控镇痛治疗顽固性中、重度癌痛的作用

目的探讨吗啡联合氯胺酮皮下自控镇痛治疗顽固性中、重度癌痛的作用。方法接收在我院的中、重度癌痛患者一共有82例,随机分为研究组、对照组,对照组对患者采取吗啡皮下自控镇痛进行治疗,研究组对患者采取小剂量氯胺酮联合吗啡皮下自控镇痛进行治疗,对比两组患者临床治疗以后的镇痛效果和不良反应。结果研究组治疗后的48h VAS评分明显低于对照组,其之间的差异具有统计学意义(P<0.05);研究组患者的吗啡用量为31.25 mg,对照组患者的吗啡用量为56.42 mg,研究组患者的吗啡用量明显低于对照组,其之间的差异具有统计学意义(P<0.05);研究组患者的不良反应发生率明显低于对照组,其之间的差异具有统计学意义(P<0.05)。结论顽固性中、重度癌痛患者采取吗啡联合氯胺酮皮下自控镇痛进行治疗,可以取得良好的镇痛效果,同时不良反应相对比较少,具有临床推广价值。     

氟比洛芬酯对胃癌根治术后吗啡用量及患者肠功能恢复的影响

目的:探讨氟比洛芬酯对胃癌根治术后吗啡用量及患者肠功能恢复的影响。方法:102例胃癌根治术患者按随机数字表法分为对照组和观察组,各51例。对照组患者给予常规硬膜外吗啡自控镇痛泵镇痛,观察组患者在此基础上分别于术前及术后24 h静脉注射氟比洛芬酯50 mg。观察并记录两组患者疼痛视觉模拟评分法(VAS)评分、舒适度评分法(BCS)评分、吗啡用量及肠功能恢复情况。结果:两组患者术后48 h VAS评分、BCS评分比较差异均无统计学意义(P>0.05),但观察组患者吗啡用量明显少于对照组,差异有统计学意义(P<0.05);观察组患者术后肠鸣音恢复时间与第1次肛门排气时间均显著早于对照组,且观察组患者术后恶心呕吐发生率明显低于对照组,差异有统计学意义(P<0.05)。结论:胃癌根治术患者应用氟比洛芬酯协同吗啡镇痛可在达到相同镇痛效果的基础上减少吗啡用量,降低吗啡的不良反应,并且有利于患者术后肠功能恢复。     

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.