快速、持续、充分——梗死相关动脉血流再灌注之重要性

近20年来,急性心肌梗死(AMI)的诊断和治疗取得了长足的进展,根据临床实用的原则分为ST段抬高和非ST段抬高两类。对于ST段抬高的AMI(STEMI),其治疗主要目的是梗死相关动脉血流和心肌的快速、完全、持续性再灌注恢复,溶栓和机械性冠脉血流的恢复可改善左室功能,缩小梗死范围,降低死亡率。但无论溶栓或冠脉内介入治疗,早期快速的血运重建至关重要。早期冠脉再通对STEMI预后的影响STEMI患者初始治疗的主要目的是早期冠脉再灌注恢复,从胸痛发作到有效治疗的时间间隔,是决定患者早期和晚期临床预后的重要因素。GISSI研究为安慰剂对照…     

急性冠脉综合征抗栓治疗的进展

急性冠状动脉综合征(ACS)为冠心病急性发病的临床表现,其发病机理主要是因斑块破裂继发血栓形成所致,临床类型包括ST段抬高急性心肌梗死(AMI)以及无ST段抬高AMI和不稳定型心绞痛(UA),后两者常被称为无ST段抬高ACS。ST段抬高AMI约80%～90%最终演变为Q波性AMI,无ST段抬高AMI中约80%演变为非Q波性AMI。ST段抬高AMI1.溶栓治疗在无条件进行经皮冠状动脉介入治疗(PCI)的医院,溶栓治疗仍是首选治疗,在AMI发病3小时内行溶栓治疗,其梗死相关血管的再通率高,死亡率明显降低,其临床疗效与直接介入治疗相当。因此发病在3个小时内到…     

ST段再抬高对急性心肌梗死溶栓患者近期预后的影响

目的：探讨急性心肌梗死（AMI）静脉溶栓治疗后ST段再抬高对患者近期预后的影响。方法：将首发98例患者按静脉溶栓治疗后心电图有无ST段再抬高分为ST段再抬高组（A组）和ST段无再抬高组（B组），比较两组危险因素、再灌注心律失常、心功能、梗死后心绞痛及并存疾病等。结果：两组伴发糖尿病、原发性高血压及吸烟比较，无统计学意义（P〉0．05）；两组梗死部位、再灌注心律失常、心功能分级、梗死后心绞痛比较，无统计学意义（P〉0．05）。结论：AMI静脉溶栓治疗后短暂的ST段再抬高可作为心肌再灌注成功的一种临床表现，对患者近期预后无不良影响。     

急性心肌梗死溶栓治疗中ST段再抬搞的意义

目的探讨急性心肌梗死静脉溶栓治疗中ST段再抬高产生的原因和意义。方法通过回顾性分析42例首发急性心肌梗死患者,按静脉溶栓治疗中有无ST段再抬高分为观察组和对照组两组,比较两组间伴发疾病、再通率、并发症发生的情况、梗死后心绞痛,进行分析。结果静脉溶栓治疗时ST段再抬高与患者合并糖尿病、高血压、高血脂症及再灌注损伤有关;根本原因是冠脉存在多只病变及梗死血管狭窄程度重所致。     

右室受累或未受累的急性下壁心肌梗死应用溶栓疗法的结果

此项研究旨在评价链激酶治疗对右室受累(RVI)的大面积或小面积下壁急性心肌梗死(AMI)病人预后的影响。 方法　应用水蛙素改善溶栓(HIT-4)治疗522例下壁AMI病人。通过在基础心电图上 V_4 R导联 ST段抬高≥0.1mV评价左室受累,并根据ST段降低程度评价梗死大小:小面积 AMI=总计ST段抬高≤0.8 mV和心前区无 ST段降低(小ST);大面积AMI=心前区有ST段降低或总计ST段升高>0.8 mV(大 ST)。187例病人进行 90分冠脉造影检查。 结果169例(32%)病人有RVI。RVI的30天心脏性病死率(5.9%比2.5%)较高是与便死面积较大有关,与RVI无关。关于…     

急性心肌梗死溶栓治疗中ST段再抬搞的意义

目的探讨急性心肌梗死静脉溶栓治疗中ST段再抬高产生的原因和意义。方法通过回顾性分析42例首发急性心肌梗死患者，按静脉溶栓治疗中有无ST段再抬高分为观察组和对照组两组，比较两组间伴发疾病、再通率、并发症发生的情况、梗死后心绞痛，进行分析。结果静脉溶栓治疗时ST段再抬高与患者合并糖尿病、高血压、高血脂症及再灌注损伤有关；根本原因是冠脉存在多只病变及梗死血管狭窄程度重所致。     

急性心肌梗死患者及时建立静脉溶栓通道护理对策

治疗心肌梗死（AMI）的首要目标是尽快给予再灌注治疗，而开通梗死相关血管与发病到溶栓开始的时间密切相关，即溶栓越早，溶栓挽救的心肌就越多，患者从溶栓的获益也越多，所以尽量缩短发病至入院和入院至溶栓开始的时间，而静脉溶栓治疗简便易行，目前是基层医院采用的主要治疗手段，即所有在症状发作后12h内就诊的有ST段抬高的患者，若无禁忌证均考虑溶栓，发病虽〉12h，但仍有进行性胸痛和ST段抬高也考虑溶栓，而溶栓前的准备工作争分夺秒是保证AMI溶栓的快速实施。     

ST段抬高程度对急性心肌梗死患者早期预后的影响

目的 探讨不同程度ST段抬高对急性心肌梗死(AMI)患者早期预后的影响.方法 分组对比ST段抬高最大幅度、ST段抬高总导联数、ST段抬高总和对AMI患者30 d病死率、心力衰竭、心律失常、再梗、梗死后心绞痛的发生率及一年内心血管事件的影响.结果 ST段抬高幅度越大,ST段抬高导联数越多,ST段抬高总和越大,其30 d病死率、心力衰竭、心律失常发生率越高(P＜0.05);梗死后心绞痛、一年内心血管事件和30d再梗发生率也升高,但差异未达到统计学意义(P＞0.05).结论 AMI患者ST段抬高幅度越大.ST段抬高导联数越多,ST段抬高总和越大,早期预后越差.     

ST段抬高急性冠脉综合征抗栓治疗的现状和进展

ST段抬高急性冠脉综合征(STE-ACS)即ST段抬高急性心肌梗死(STEMI)的现代治疗策略是“尽早、充分、持续开通梗死相关血管”(即再灌注治疗),已被所有专家认可。当我们不断推荐溶栓和急诊经皮冠状动脉介入治疗(PCI)治疗的同时,应该强调抗栓治疗是基础,包括抗血小板治疗和抗凝治疗。     

急性ST段抬高型心肌梗死溶栓治疗的疗效与安全性

对于急性ST段抬高型心肌梗死患者,早期的再灌注治疗能有效开通梗死相关血管,减少心肌损伤,促进心功能的恢复。本文就近年来急性ST段抬高型心肌梗死溶栓治疗的发展进行综述,分析心肌梗死溶栓治疗的优势和需要解决的问题。     

Susceptibility to erythromycin of anaerobes of the genera Bacteroides, Fusobacterium, Sphaerophorus, Veillonella, Clostridium, Corynebacterium, Peptococcus, Peptostreptococcus

The minimal inhibitory concentrations (MIC) of erythromycin were determined by broth dilution tests for 313 anaerobic strains, most of which were clinical isolates. All the gram-positive anaerobes tested (84 Peptococcaceae, including 21 Peptostreptococcus anaerobius and 15 Peptococcus variabilis; 65 Corynebacterium acnes and 29 Clostridium strains, including 13 C. perfringens) were sensitive (MIC values 0.012 through 3.12 microgram erythromycin/ml); so were 111 cultures of gram-negative anaerobes (52 Bacteroides fragilis, 12 B. thetaiotaomicron, 7 B. vulgatus, 13 B. oralis, 4 B. melaninogenicus, 10 Sphaerophorus necrophorus, 2 Veillonella sp., 11 members of other species). Erythromycin at concentrations of 6.25 through 200.0 microgram/ml was active against 24 strains (1 B. fragilis, 4 Fusobacterium fusiforme, 9 Sph. freundi, 10 Sph. varius). The present results are compared to the limited number of reports existing with regard to the susceptibility of anaerobes to erythromycin.     

Safety assessment of poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate as used in cosmetics

Poloxamers are polyoxyethlyene, polyoxypropylene block polymers. The impurities of commercial grade Poloxamer 188, as an example, include low-molecular-weight substances (aldehydes and both formic and acetic acids), as well as 1,4-dioxane and residual ethylene oxide and propylene oxide. Most Poloxamers function in cosmetics as surfactants, emulsifying agents, cleansing agents, and/or solubilizing agents, and are used in 141 cosmetic products at concentrations from 0.005% to 20%. Poloxamers injected intravenously in animals are rapidly excreted in the urine, with some accumulation in lung, liver, brain, and kidney tissue. In humans, the plasma concentration of Poloxamer 188 (given intravenously) reached a maximum at 1 h, then reached a steady state. Poloxamers generally were ineffective in wound healing, but were effective in reducing postsurgical adhesions in several test systems. Poloxamers can cause hypercholesterolemia and hypertriglyceridemia in animals, but overall, they are relatively nontoxic to animals, with LD(50) values reported from 5 to 34.6 g/kg. Short-term intravenous doses up to 4 g/kg of Poloxamer 108 produced no change in body weights, but did result in diffuse hepatocellular vacuolization, renal tubular dilation in kidneys, and dose-dependent vacuolization of epithelial cells in the proximal convoluted tubules. A short-term inhalation toxicity study of Poloxamer 101 at 97 mg/m(3) identified slight alveolitis after 2 weeks of exposure, which subsided in the 2-week postexposure observation period. A short-term dermal toxicity study of Poloxamer 184 in rabbits at doses up to 1000 mg/kg produced slight erythema and slight intradermal inflammatory response on histological examination, but no dose-dependent body weight, hematology, blood chemistry, or organ weight changes. A 6-month feeding study in rats and dogs of Poloxamer 188 at exposures up to 5% in the diet produced no adverse effects. Likewise, Poloxamer 331 (tested up to 0.5 g/kg day(-1)), Poloxamer 235 (tested up to 1.0 g/kg day(-1)), and Poloxamer 338 (at 0.2 or 1.0 g/kg day(-1)) produced no adverse effects in dogs. Poloxamer 338 (at 5.0 g/kg day(-1)) produced slight transient diarrhea in dogs. Poloxamer 188 at levels up to 7.5% in diet given to rats in a 2-year feeding study produced diarrhea at 5% and 7.5% levels, a small decrease in growth at the 7.5% level, but no change in survival. Doses up to 0.5 mg/kg day(-1) for 2 years using rats produced yellow discoloration of the serum, high serum alkaline phosphatase activity, and elevated serum glutamicpyruvic transaminase and glutamic-oxalacetic transaminase activities. Poloxamers are minimal ocular irritants, but are not dermal irritants or sensitizers in animals. Data on reproductive and developmental toxicity of Poloxamers were not found. An Ames test did not identify any mutagenic activity of Poloxamer 407, with or without metabolic activation. Several studies have suggested anticarcinogenic effects of Poloxamers. Poloxamers appear to increase the sensitivity to anticancer drugs of multidrug-resistant cancer cells. In clinical testing, Poloxamer 188 increased the hydration of feces when used in combination with a bulk laxative treatment. Compared to controls, one study of angioplasty patients receiving Poloxamer 188 found a reduced myocardial infarct size and a reduced incidence of reinfarction, with no evidence of toxicity, but two other studies found no effect. Poloxamer 188 given to patients suffering from sickle cell disease had decreased pain and decreased hospitilization, compared to controls. Clinical tests of dermal irritation and sensitization were uniformly negative. The Cosmetic Ingredient Review (CIR) Expert Panel stressed that the cosmetic industry should continue to use the necessary purification procedures to keep the levels below established limits for ethylene oxide, propylene oxide, and 1,4-dioxane. The Panel did note the absence of reproductive and developmental toxicity data, but, based on molecular weight and solubility, there should be little skin penetration and any penetration of the skin should be slow. Also, the available data demonstrate that Poloxamers that are introduced into the body via routes other than dermal exposure have a rapid clearance from the body, suggesting that there would be no risk of reproductive and/or developmental toxicity. Overall, the available data do not suggest any concern about carcinogenesis. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used, and at what concentration, indicates a pattern of use. Based on these safety test data and the information that the manufacturing process can be controlled to limit unwanted impurities, the Panel concluded that these Poloxamers are safe as used.     

HPLC法测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱

目的 采用高效液相色谱（HPLC）法同时测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱10种活性成分。方法 采用InerSustain AQ-C₁₈色谱柱（250 mm×4.6 mm,5 μm）,流动相A：乙腈–无水乙醇（80∶20）,流动相B：0.1%磷酸溶液,梯度洗脱,检测波长220 nm,体积流量1.0 mL/min,柱温30℃,进样量10 μL。结果 木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱分别在2.69～134.50、1.95～97.50、0.63～31.50、0.86～43.00、11.95～597.50、0.59～29.50、6.08～304.00、4.85～242.50、1.66～83.00、19.79～989.50 μg/mL线性关系良好（r≥0.999 3）;平均回收率分别为99.11%、98.23%、96.95%、97.78%、100.02%、97.21%、99.66%、99.52%、98.81%、100.08%,RSD值分别为1.04%、1.23%、1.37%、1.65%、0.70%、1.28%、0.65%、0.81%、1.11%、0.63%。结论 建立的HPLC法可用于抗妇炎胶囊中10种活性成分的测定,作为抗妇炎胶囊质量控制方法。     

Strength of drug habits: For heroin,morphine, methadone,alcohol, barbiturates,pentobarbital, benzedrine,cocaine, and marijuana

The drug habits for 78 confirmed opiate addicts were studied on eight scales from the Process Association Test of Addiction (PATA) for many drug names. Through cluster analysis eight stages of addiction were defined: “to be clean”, “to learn about drugs”, “to hustle”, “to chip” (also “to be high”), to be psychologically dependent or “to need a shot”, “to be hooked”, “to kick a habit” and “to be in treatment”. Associations stimulated by the words heroin and morphine were very similar over the eight stages of addiction in opiate addicts. The subjects were especially inclined to associate morphine and heroin with the most severe level of addiction, “to be hooked”. Associations to both methadone and cocaine were elevated at the “hooked” stage, but in other respects associations to these drugs were opposite. Thus, associations to cocaine were focused on the stage of psychological dependence and the lower intermediate stage of addiction, “to chip” and “to be high”, whereas associations to methadone suggested a turning away from addiction as indicated by avoidance associations (“to come down” and “to kick a habit”) as well as associations to “treatment” and “to be clean”. Marijuana, Benzedrine, “goofball” (barbiturates) and alcohol habits were prominent at an intermediate stage of addiction (“to chip” and “to be high”). Avoidance associations were common for Benzedrine and “goofballs” (also pentobarbital) but not for marijuana or alcohol. “Hustling” associations were frequent for marijuana but not for alcohol.     

Simultaneous measurement of bupivacaine, etidocaine, lidocaine, meperidine, mepivacaine, and methadone

A gas-liquid chromatographic method for the simultaneous measurement of bupivacaine, etidocaine, lidocaine, meperidine, mepivacaine, and methadone in serum is described. The drugs and the internal standard, prilocaine, are extracted from 1 ml of serum. The procedure involves a two-step extraction and injection of the extract into a gas chromatograph equipped with a 10-ft OV-11 glass column and a nitrogen-phosphorus detector. The temperature gradient program results in a run time of 16 min and retention times for meperidine, prilocaine (internal standard), lidocaine, etidocaine, mepivacaine, methadone, and bupivacaine of 3.8, 5.4, 6.0, 8.7, 11.0, 11.7, and 14.8 min, respectively. Standard curves for all drugs were linear over the 80 to 2,000-ng/ml range and recovery of all components averaged 97 +/- 2% with the lowest detection limit of 10 ng/ml for all drugs except meperidine and methadone, which were 20 ng/ml. The within-day coefficients of variation ranged from 12 to 8% at 500 ng/ml. The day-to-day coefficients of variation of the slope and intercept values ranged from 2 to 0% and 130 to 3%, respectively. Response factors of the nitrogen-specific collector varied with the drug analyzed and resulted in peak area variation at constant offset and attenuation of 30%. This method is intended and adequate for therapeutic monitoring of chronically treated pain patients who are being given various combinations of local anesthetic and/or narcotic agents.     

New antiretroviral drugs: a review of the efficacy,safety, pharmacokinetics,and resistance profile of tipranavir,darunavir, etravirine,rilpivirine, maraviroc,and raltegravir

Background: The introduction and approval of new antiretroviral agents in the US and Canada bring new opportunities and new challenges. Arguably, for the first time ever, clinicians have the drugs necessary to achieve the goal of suppressing HIV RNA to levels less than 50 copies/mL in even the most treatment-experienced patients and in those with extensive drug-limiting resistance mutations. However, the use of these new agents is complicated by many drug–drug interactions and – to some extent – pre-existing mutations. To derive maximum durability from the use of these newer drugs, a thorough understanding of their indications and limitations is critical. Objective: To thoroughly review the six most recently approved or soon-to-be-approved antiretroviral drugs in the US and Canada: tipranavir, darunavir, etravirine, rilpivirine, maraviroc, and raltegravir. Methods: Discussion of the indications for, and pharmacokinetics, resistance profile, activity, toxicity, and clinical trials results of, the six new agents. Results/conclusions: These six new agents have resulted in marked progress towards the goal of being able to provide HIV-infected individuals with the drugs necessary to achieve decades of durable suppression of HIV without substantial toxicity.     

Disposition of fluvastatin, an inhibitor of HMG-COA reductase, in mouse, rat, dog, and monkey

The physiological disposition of fluvastatin, a potent inhibitor of hydroxymethylglutaryl-CoA reductase and thus cholesterol synthesis, has been studied in the mouse, rat, dog, and monkey using 14C- or 3H-labeled drug. Oral doses of fluvastatin were absorbed at a moderate to rapid rate. The extent of absorption was dose-independent and was essentially complete in all four species studied. However, the drug was subject to extensive presystemic hepatic extraction followed by direct excretion via the bile, thus minimizing the systemic burden and yielding high liver/peripheral tissue concentration gradients for fluvastatin and its metabolites. Only at high doses far exceeding the intended human daily dose of ca 0.6 mg kg-1 did fluvastatin bioavailability approach unity, apparently due to saturation of the first-pass effect. Dose-normalized blood levels of fluvastatin and total radioactivity were higher in the dog than in the other species, suggesting a smaller distribution volume in the former. Fluvastatin was partially metabolized before excretion, the extent of metabolism being smallest in the dog and greatest in the mouse. The half-life of intact fluvastatin ranged from 1-2h in the monkey to 4-7h in the dog. Regardless of the dose or dose route, the administered radioactivity was recovered predominantly in feces, with the renal route accounting for less than 8 per cent of the dose. No tissue retention of radioactivity was observed, and material balance was essentially achieved within 96h after dosing.