螺内酯联合胺碘酮治疗阵发性心房颤动110例

<正>本研究观察螺内酯与胺碘酮联合治疗非瓣膜病阵发心房颤动的临床效果和对左心房内径大小的影响,发现螺内酯与胺碘酮联合治疗阵发性心房颤动维持窦性心律的效果优于单用胺碘酮,同时可抑制左心房结构重构并能延缓左心房的扩大,现报告如下。1资料与方法 1.1临床资料:选择2011年1月至2014年9月我院门诊及住院的非瓣膜病阵发性心房颤动患者110例,男性56例,女性54例,年龄33~85岁。将110例患者按就诊顺序分为单用     

联合用药对阵发性心房颤动患者疗效观察

目的 观察联合应用小剂量胺碘酮、螺内酯与厄贝沙坦对非瓣膜病阵发性心房颤动患者窦性心律的维持,对左心房内径、脑钠肽以及安全性的影响.方法 将142例非瓣膜病阵发性心房颤动按就诊顺序随机分为胺碘酮组(n=47),胺碘酮加螺内酯组(n=47),胺碘酮、厄贝沙坦、螺内酯组(联合用药组,n=48),3组均服用胺碘酮,胺碘酮加螺内酯组在应用胺碘酮基础上加用螺内酯,联合用药组在应用胺碘酮、螺内酯基础上加用厄贝沙坦,观察3组治疗6、12、18个月后的左心房内径、脑钠肽变化以及治疗3、6、12、18、24个月后的窦性心律维持率和安全性.结果 治疗6个月后3组左心房内径、脑钠肽值差异无统计学意义,但12个月后胺碘酮加螺内酯组、联合用药组的左心房内径、脑钠肽值明显小于胺碘酮组(P＜0.05),联合用药组左心房内径、脑钠肽值明显小于胺碘酮加螺内酯组(P＜0.05);治疗3、6个月后胺碘酮组窦性心律维持率低于胺碘酮加螺内酯组、联合用药组,治疗6个月后胺碘酮组和联合用药组之间差异有统计学意义(P＜0.05),治疗12个月后胺碘酮加螺内酯组、联合用药组的窦性心律维持率明显大于胺碘酮组(P＜0.05),联合用药组窦性心律维持率明显大于胺碘酮加螺内酯组(P＜0.05).结论 胺碘酮、螺内酯联合治疗非瓣膜病阵发性心房颤动维持实性心律的疗效优于单用胺碘酮,并能延缓左心房的扩大和脑钠肽值的升高,在胺碘酮、螺内酯基础上加用厄贝沙坦则使上述疗效进一步加强.

Abstract：

Objective To observe the effect and safety of amiodarone, spironolactone and irbesartan on sinus rhythm, left atrial internal diameter and brain natruretic peptide(BNP) for patients with nonvalvular paroxysmal atrial fibrillation(AF). Methods One hundred and forty-two patients with nonvalvular paroxysmal atrial fibrillation were divided into amiodarone group(n=47), amiodarone plus spironolactone group (n = 47 ) and amiodarone spironolactone plus irbesartan group ( Combined treatment group, n = 48 ). Three groups were treated with amiodarone.Amiodarone plus spironolactone group was treated with spironolactone in addition. Combined treatment group was treated with irbesartan based on amiodarone and spironolactone. Left atrial internal diameter and BNP were observed after 6 months, 12 months, 18 months respectively and the rate of maintenance of sinus rhythm was observed after 3months, 6 months, 12 months, 18 months, 24 months respectively. The safety of drugs was observed during this study. Results After 6 months treatments, left atrial internal diameter and BNP of three groups was no difference but left atrial internal diameter and BNP of amiodarone plus spironolactone group and Combined treatment group was less than that of amiodarone group after 12 months ( P ＜ 0.05 ). left atrial internal diameter and BNP of combined treatment group was less than those of amiodarone plus spironolactone group after 12 months ( P ＜ 0.05 ). After 3and 6 months treatments, the rate of maintenance of sinus rhythm of amiodarone group was lower than that in amiodarone plus spironolactone group and combined treatment group, but there was no statistically significance difference between amiodarone group and amiodarone plus spironolactone group, amiodarone plus spironolactone group andCombined treatment group. The rate of maintenance of sinus rhythmia of amiodarone group was statistically lower than that in combined treatment group (P＜0.05). After 12 months, The rate of mainterance of sinus rhythmia of amiodarone plus spironolactone group and Combined treatment group was more than that of amiodarone group (P＜0.05 ), and that of group Ⅲ was more than that of amiodarone plus spironolactone group ( P ＜ 0.05 ). Conclusions Therapeutic results of mainterance of sinus rhythmia is better with amiodarone plus spironolactone than with amiodarone lonely, and treatment with amiodarone plus spironolactone can suspend the enlargement of left atrial. This influence will strengthen if treated with irbesartan based on amiodarone and spironolactone.     

胺碘酮联合贝那普利治疗阵发性心房颤动疗效观察

目的了解胺碘酮联合贝那普利对阵发性心房颤动复律及复律后窦性心律维持的影响。方法将78例阵发性房颤患者随机分成二组,分别给予胺碘酮、胺碘酮加贝那普利治疗,疗效观察12个月。结果治疗6个月后窦性心律维持及左房内径无统计学意义(P>0.05),治疗12个月后两组窦性心律维持及左心房内径有统计学意义(P<0.05)。结论胺碘酮与贝那普利联合治疗阵发性房颤,维持窦性心律的疗效优于单用胺碘酮,并能延缓左心房扩大。     

厄贝沙坦与胺碘酮联合治疗阵发性心房颤动疗效观察

目的评价厄贝沙坦与小剂量胺碘酮联合治疗心功能正常的阵发性房颤的长期疗效。方法将142例阵发性房颤随机分为胺碘酮组（n=72）、胺碘酮＋厄贝沙坦组（n=72），治疗随访时间为18个月，研究的一级终点为房颤复发，比较两组治疗后窦性心律的维持率以及治疗前后6、12、18个月左心房内径。结果治疗12个月后，胺碘酮组左心房内径大于胺碘酮联合厄贝沙坦组（P〈0．05）。试验终点时单用胺碘酮组窦性心律维持率为58．04％，联合用药组为84．06％，两组比较差异有统计学意义（P〈0．05）。结论胺碘酮联合厄贝沙坦在维持窦性心律作用优于胺碘酮，且能抑制左心房的扩大。     

雷米普利和替米沙坦与胺碘酮联用治疗阵发性心房颤动的临床观察

目的探讨雷米普利和替米沙坦与小剂量胺碘酮联用对心功能正常的阵发性心房颤动（房颤）维持窦性心律的长期疗效。方法将180例阵发性房颤患者完全随机分为胺碘酮组（A组,61例）、胺碘酮＋雷米普利组（B组,59例）、胺碘酮＋替米沙坦组（C组,60例）,随访2年,比较3组治疗后6、12、18、24个月的窦性心律维持率以及治疗前、后的左心房内径。结果治疗12个月后,A组左心房内径大于B、C组（P〈0．05）,A组窦性心律维持率明显低于B、C组（P〈0．05）。试验终点时,A组的窦性心律维持率为58．62％,B组为77．78％,C组为78．57％（P〈0．05）。结论胺碘酮分别与雷米普利和替米沙坦配伍治疗阵发性房颤维持窦性心律具有相同的疗效,但优于单用胺碘酮,并能抑制左心房的扩大。     

胺碘酮联合厄贝沙坦和阿托伐他汀治疗130例阵发性心房颤动患者的临床疗效观察

目的观察胺碘酮联合厄贝沙坦、阿托伐他汀治疗阵发性房颤的临床疗效。方法将130例阵发性房颤患者随机分为两组：胺碘酮加阿托伐他汀组（对照组）65例;在对照组用药基础上加用厄贝沙坦组（治疗组）65例。观察两组患者治疗后的窦性心律维持率及治疗前、治疗后6、12、18个月后左心房内径（LA）的变化情况。结果两组治疗后窦性心律维持率均较治疗前显著改善,差异有统计学意义（P〈0.05）,但组间比较,差异无统计学意义（P〉0.05）,治疗12个月后治疗组窦性心律维持率明显大于对照组（P〈0.05）;治疗6个月后两组左心房内径差异无统计学意义,但18个月后治疗组的左心房内径较明显小于对照组（P〈0.05）。结论胺碘酮联合厄贝沙坦、阿托伐他汀治疗阵发性心房颤动,其维持窦性心律的疗效优于胺碘酮联合阿托伐他汀,并能延缓左心房的扩大。     

胺碘酮联合厄贝沙坦治疗阵发性房颤

目的 观察小剂量胺碘酮与厄贝沙坦(科苏)联合治疗阵发房颤的临床疗效.方法 将144例阵发性房颤随机分为胺碘酮组(Ⅰ组,n=71),胺碘酮加厄贝沙坦组(Ⅱ组,n=73),计算两组治疗后6个月,12个月,18个月的左心房内径及治疗后3个月,6个月,12个月,18个月,24个月的窦性,心律维持率.结果 治疗6个月后两组左心房内径无显著差异,但12个月后两组有显著差异(P＜0.05);治疗后3个月,6个月Ⅰ组窦律维持率低于Ⅱ组,但无显著差异,而治疗12个月后两组有显著差异(P＜0.05).结论 胺碘酮与厄贝沙坦联合治疗阵发性心房颤动维持窦性心律的疗效优于单用胺碘酮,并能延缓左心房的扩大.     

胺碘酮与依那普利联合治疗阵发性心房颤动的临床研究

目的评价胺碘酮与依那普利联合治疗阵发性心房颤动（房颤）的临床疗效。方法将129例阵发性房颤随机分为胺碘酮组（Ⅰ组,n=64）和胺碘酮联合依那普利组（Ⅱ组,n=65）,治疗随访时间为1年,研究终点为房颤发作。比较两组治疗前、治疗后的左心房内径。计算两组治疗后窦性心律维持率。结果两组患者治疗前后左心房内径比较：治疗前分别为（35．21±1．76）mm、（35．84±1．69）mm,治疗后分别为（38．76±2．14）mm、（36．27-I-1．91）mm,治疗后IⅠ组患者左房内径明显小于Ⅰ组。两组患者窦性心律维持率的比较：治疗结束时,Ⅰ组患者窦性心律维持率为62．3％,Ⅱ组患者窦性心律维持率80．6％,两组患者比较有显著性差异。结论胺碘酮与依那普利联合治疗阵发性房颤维持窦性心律的疗效优于单用胺碘酮,对延缓左心房扩大有一定作用。     

胺碘酮联合缬沙坦预防房颤复发及心房重构疗效分析

目的探讨胺碘酮联合缬沙坦预防房颤复发及心房重构的疗效。方法86例阵发性房颤患者随机分为对照组40例与观察组46例,对照组给予胺碘酮口服,观察组接受胺碘酮联合缬沙坦联合治疗1年。比较2组房颤复发率、窦性心律维持率、房颤负荷及左心房内径的改变。结果治疗后3及6个月,2组窦性心律维持率差异无统计学意义（ P ＞0 R．05）,治疗后9个月观察组窦性心律维持率显著高于对照组（ P ＜0．05）;治疗12个月观察组与对照组房颤复发率分别为13．0％和42．5％,差异有统计学意义（ P ＜0．05）;与对照组相比,观察组治疗后12个月左心房内径显著小于对照组（ P ＜0．05）,房颤负荷显著低于对照组（ P ＜0．05）。结论胺碘酮联合缬沙坦能有效地预防阵发性房颤复发,改善心房重构。     

胺碘酮联合螺内酯对持续性心房颤动转复后维持窦性心律的疗效分析

目的探讨并分析胺碘酮联合螺内酯对持续性心房颤动转复后维持窦性心律的治疗效果。方法92例持续性心房颤动患者,随机分为对照组和观察组,各46例。对照组患者给予胺碘酮治疗,观察组患者给予胺碘酮联合螺内酯治疗。比较两组患者临床疗效;治疗前后左房内径、收缩压(SBP)、舒张压(DBP);治疗后1、6、12个月窦性心律维持率。结果观察组治疗总有效率93.48%高于对照组的65.22%,差异具有统计学意义(P<0.05)。治疗后,两组左房内径、SBP、DBP均低于本组治疗前,且观察组低于对照组,差异均具有统计学意义(P<0.05)。治疗后6、12个月,观察组窦性心律维持率分别为80.43%、84.78%,均高于对照组的54.35%、52.17%,差异具有统计学意义(P<0.05)。结论临床上治疗持续性心房颤动患者时,采用胺碘酮联合螺内酯治疗,能够有效维持患者转复后的窦性心律,效果显著,安全性高,有较高的推广价值。     

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.     

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.     

Inhibition of synaptosomal uptake of amino acid transmitters by diamines

Reports of the inhibitory effects of diaminocarboxylic acids on the uptake of amino acid transmitters led the present authors to examine the effects of simple aliphatic diamines on the synaptosomal uptake of glutamate, aspartate, GABA and glycine. The diamines studied were the series from ethylenediamine through to 1,7-diaminoheptane; DL-2,4-diaminobutyric acid (DABA) was also tested for comparative purposes. The greatest inhibition seen was on the uptake of glycine and GABA. Weaker effects on uptake were seen with glutamate, while aspartate was unaffected. The patterns of inhibition for glycine and GABA were similar and the effects were dose-dependent. 1,2-Diaminopropane was the most inhibitory, followed by ethylenediamine and 1,7-diaminoheptane. The reported inhibitory effects of DL-2,4-diaminobutyric acid on the uptake of GABA and glutamate were confirmed; comparable inhibition of the uptake of glycine and aspartate was seen but the effects on GABA were most potent. Inhibition of the uptake of GABA by 1,2-diaminopropane was approximately one fifteenth that reported for DL-2,4-diaminobutyric acid. The inhibition by diamine of the uptake of glycine and GABA can provide an explanation of the depressant effects of diamines, seen after ventricular administration; however, the excitotoxic effects of the diamines 1,3-diaminopropane through to 1,7-diaminoheptane could not be explained by the present results.     

Inhaled therapeutics for prevention and treatment of pneumonia

The lungs are the most common site of serious infection owing to their large surface area exposed to the external environment and minimum barrier defense. However, this architecture makes the lungs readily available for topical therapy. Therapeutic aerosols include those directed towards improving mucociliary clearance of pathogens, stimulation of innate resistance to microbial infection, cytokine stimulation of immune function and delivery of antibiotics. In our opinion inhaled antimicrobials are underused, especially in patients with difficult-to-treat lung infections. The use of inhaled antimicrobial therapy has become an important part of the treatment of airway infection with Pseudomonas aeruginosa in cystic fibrosis and the prevention of invasive fungal infection in patients undergoing heart and lung transplantation. Cytokine inhaled therapy has also been explored in the treatment of neoplastic and infectious disease. The choice of pulmonary drug delivery systems remains critical as air-jet and ultrasonic nebulizer may deliver sub-optimum drug concentration if not used properly. In future development of this field, we recommend an emphasis on the study of the use of aerosolized hypertonic saline solution to reduce pathogen burden in the airways of subjects infected with microbes of low virulence, stimulation of innate resistance to prevent pneumonia in immunocompromised subjects using cytokines or synthetic pathogen-associated molecular pattern analogues and more opportunities for the use of inhaled antimicrobials. These therapeutics are still in their infancy but show great promise.     

Recommandations de bon usage des carbapénèmes

Carbapenems are being increasingly used because of the widespread dissemination of antibiotic resistance among Gram-negative bacilli, especially of extended-spectrum beta-lactamases; this increasing use raises the concern of loss of activity for this antimicrobial class following the emergence of carbapenemases. The current guideline from the Anti-infective drugs Committee of the Assistance publique-Hôpitaux de Paris (AP–HP) group emphasizes the careful and limited use of carbapenems, comparing the respective characteristics of the four available molecules, and specifies their indications in clinical hospital practice, with possible alternatives.     

Antifungal drugs in pregnancy: a review

The use of any medication in pregnant women requires careful consideration of benefit to the mother versus risk posed to the fetus. Fungal infections are not uncommon in pregnant women; in fact, the incidence of certain infections such as Candida vaginitis is increased in this patient population. A variety of antimycotic agents are currently available to treat systemic or mucocutaneous fungal infections. Many of these agents are capable of penetrating the placental barrier and entering fetal cord blood, therefore adverse effects of these agents on the fetus are a valid concern. The use of topical azoles for the treatment of superficial fungal infections is safe and efficacious. However, there are some data suggesting a dose-related increase in the risk of teratogenicity associated with the use of systemic azoles. Amphotericin B remains the drug of choice for the treatment of systemic fungal infections in pregnancy. There are serious risks of fetal malformations associated with the use of griseofulvin, ketoconazole, voriconazole, flucytosine and potassium iodide. These drugs are contraindicated in pregnancy. There are insufficient data regarding the use of caspofungin in pregnancy. This article will review available data regarding the safety of antifungal drug use in pregnant women.     

Bioavailabilities of rectal and oral methadone in healthy subjects

AIMS: Rectal administration of methadone may be an alternative to intravenous and oral dosing in cancer pain, but the bioavailability of the rectal route is not known. The aim of this study was to compare the absolute rectal bioavailability of methadone with its oral bioavailability in healthy humans. METHODS: Seven healthy subjects (six males, one female, aged 20-39 years) received 10 mg d(5)-methadone-HCl rectally (5 ml in 20% glycofurol) together with either d(0)-methadone intravenously (5 mg) or orally (10 mg) on two separate occasions. Blood samples for the LC-MS analyses of methadone and it's metabolite EDDP were drawn for up to 96 h. Noninvasive infrared pupillometry was performed at the same time as blood sampling. RESULTS: The mean absolute rectal bioavailability of methadone was 0.76 (0.7, 0.81), compared to 0.86 (0.75, 0.97) for oral administration (mean (95% CI)). Rectal absorption of methadone was more rapid than after oral dosing with Tmax values of 1.4 (0.9, 1.8) vs. 2.8 (1.6, 4.0) h. The extent of formation of the metabolite EDDP did not differ between routes of administration. Single doses of methadone had a duration of action of at least 10 h and were well tolerated. CONCLUSIONS: Rectal administration of methadone results in rapid absorption, a high bioavailability and long duration of action. No evidence of presystemic elimination was seen. Rectal methadone has characteristics that make it a potential alternative to intravenous and oral administration, particularly in cancer pain and palliative care.     

《儿科阿奇霉素注射使用的快速建议指南》临床问题与结局指标的调查分析

目的:通过总结《儿科阿奇霉素注射使用的快速建议指南》临床问题与结局指标的前期调查结果,与指南专家评估结果进行对比,探讨开展该工作的意义。方法:通过电子问卷,对临床一线医务人员进行调查,调查内容主要包括参与者的基本信息、对指南拟纳入的临床问题(5分制)和结局指标(9分制)进行重要程度评分以及补充。计算各题平均分,采用变异系数表示一致性,采用Wilcoxon秩和检验,对比参与者和专家评估结果,对补充的内容进行描述性分析。结果:共纳入155位参与者的调查结果,各年龄段、文化程度和职称等均有分布。结果显示,注射用阿奇霉素的用法用量(4.56分)和有效性指标(7.28分)最受关注,特殊人群用药(42.71%)和安全性(34.52%)的一致性较差;与专家评估对比分析显示,对于大部分问题和指标,前期调研和专家评估的评分差异无显著性,专家评估的变异系数更低;共收集有效补充15条,最终将新生儿的使用问题纳入。结论:在指南制订前期,有必要对临床问题和结局指标进行广泛调查,收集并分析评估和补充意见,这对指南专家组的评估具有一定的参考意义。     

Current concepts of the actions of paracetamol (acetaminophen) and NSAIDs

There is much uncertainty about the mechanism of action of paracetamol (acetaminophen). It is commonly stated that, unlike the non-steroidal anti-inflammatory drugs (NSAIDs), it is a weak inhibitor of the synthesis of prostaglandins. This conclusion is made largely from studies in which the synthesis of prostaglandins was measured in homogenized tissues. However, in several cellular systems, paracetamol is an inhibitor of the synthesis of prostaglandins with IC₅₀ values ranging from approximately 4 μM to 200 μM. Paracetamol is not bound significantly to plasma proteins and therefore the concentrations in plasma can be equated directly with those used in in vitro experiments. After oral doses of 1 g, the peak plasma concentrations of paracetamol are approximately 100 μM and the plasma concentrations are therefore in the range where marked inhibition of the synthesis of prostaglandins should occur in some cells. Paracetamol is metabolized by the peroxidase component of prostaglandin H synthase but the relationship of this to inhibition of the cyclooxygenase or peroxidase activities of the enzyme is unclear. Paracetamol is also metabolized by several other peroxidases, including myeloperoxidase, the enzyme in neutrophils which is responsible for the production of hypochlorous acid (HOCl). The metabolism of paracetamol by myeloperoxidase leads to the decreased total production of HOC1 by both intact neutrophils and isolated myeloperoxidase, even though the initial rate of production of HOC1 is increased. The IC₅₀ value, derived from inhibition of the total production of HOC1 by isolated myeloperoxidase, is 81 μM. Several NSAIDs inhibit functions of neutrophils in media containing low concentrations of protein but their effects, in contrast to that of paracetamol, are generally produced only at concentrations greater than those of the unbound drug in plasma during treatment with the NSAIDs. However, neutrophils isolated during treatment with NSAIDs, such as piroxicam, ibuprofen and indomethacin show decreased function. Paracetamol has little or no anti-inflammatory activity by itself but may potentiate the clinical activity of NSAIDs in the treatment of rheumatoid arthritis.