植入冠脉支架患者择期非心脏手术的围术期抗血小板治疗方案探究

植入冠脉支架患者正在逐渐成为接受择期非心脏手术(non-cardiac surgery,NCS)的患者中不可忽视的一个群体.既往心脏疾病、冠脉支架以及抗血小板药物使这类患者在围术期面临着血栓形成和出血的双重风险.制定适宜的围术期抗血小板治疗方案将有助于降低风险,保障患者安全.本文将围绕目前支架患者择期NCS围术期抗血小...     

The clinical use of oral sulfonylureas in the management of non-insulin dependent diabetes mellitus (NIDDM)

Eighty percent of Americans afflicted with diabetes mellitus have Type II or non-insulin dependent diabetes mellitus (NIDDM). Impaired or defective insulin secretion and insulin resistance are universal pathophysiologic findings. Management involves attention to diet, exercise, and commonly the use of insulin and/or oral sulfonylureas. Currently there are six marketed first and second generation agents available for use in the United States. Although the newer agents are more potent, they all share a similar mechanism of action. These agents can only be effective if the patient has retained beta cell secretory function. Pharmacokinetic and pharmacodynamic differences may make the newer agents, glyburide and glipizide, preferred in the management of Type II diabetes mellitus. The combined use of insulin and oral sulfonylureas may be useful for the patient exhibiting persistent fasting hyperglycemia despite maximal oral drug therapy. The precise role for combination therapy and optimal patient characteristics awaits further study.     

Topical treatments for onychomycosis: a historical perspective

Topical treatment of onychomycosis, in contrast to systemic oral therapy, allows the patient to apply medication directly to the affected area, thereby decreasing the potential for adverse events and drug interactions. Historically, several topical antifungal agents have been used in the treatment of onychomycosis; however, the evidence for their effectiveness is based on very limited data or anecdotal reports. Recently, the development of new, effective topical agents has renewed interest in this form of therapy. As clinical experience with newer topical agents expands, they may be found to be an effective option for the treatment of onychomycosis.     

Cephalosporin antibiotic agents

The cephalosporins are a group of antibiotic agents that have been available now for 20 years. Three classes, or generations, of cephalosporins are recognized. The newer third-generation drugs have wider spectra of antibacterial activity; because of this attribute and their ability to achieve high bactericidal titres in CSF these newer compounds constitute an advance in antibiotic therapy by providing safe and effective treatment for Gram-negative bacillary meningitis. The earlier cephalosporins provide cheap, useful and convenient prophylaxis for vascular and orthopaedic operations near the inguinal area. Comparative trials with other broad-spectrum agents need to be performed before the true place of the third-generation agents in anti-infective therapy and prophylaxis is finally determined.     

Case of ischemic colitis in a young adolescent associated with triphasic hormonal contraceptive therapy: a case report and review of the literature

There has been speculation that third generation hormonal contraceptives may be less prone to inducing clotting than the earlier generation products. We present a case of colonic ischemia in a young adolescent receiving pharmacotherapy with a third-generation hormonal contraceptive. Ischemic colitis is an uncommon adverse effect in young adolescents associated with hormonal contraception, especially the third generation agents. We believe this case to be the second-youngest patient reported with ischemic colitis due to this therapy. Clinical vigilance is recommended for women presenting with abdominal pain, with or without hematochezia, who are receiving hormonal contraceptive therapy. Since their introduction in the early 1960's, the combination hormonal contraceptives have been utilized by millions of women for both contraceptive and non-contraceptive purposes. Although a variety of adverse effects can be experienced by individuals taking these agents, it has been demonstrated that these agents are associated with an increased risk of venous and arterial thromboses. Publications more consistently report on the cardiovascular-, pulmonary-, peripheral vascular-, or cerebrovascular-based thrombotic events associated with these agents. During the past several decades changes have been incorporated in the dose and types of compounds included in the combination hormonal contraceptive products in an attempt to reduce the risk of coagulation and other adverse effects. Less common and less frequently publicized are the gastrointestinal-based thrombotic events that result in ischemia and presents as severe abdominal pain, with or without hematochezia. We report an uncommon case of reversible colonic ischemia in who we believe to be the second-youngest adolescent female reported in the literature (youngest aged 16 years) to have this diagnosis associated with the use of a newer, third-generation oral combination hormonal contraceptive (Naranjo scale of 7; Probable).     

抗血小板药物的多效性研究进展

冠状动脉粥样硬化性心脏病(coronary atherosclerotic heart disease, CAD)是由冠状动脉发生动脉粥样硬化而引起血管腔狭窄或阻塞,造成心肌缺血缺氧或发生坏死。抗血小板药物在CAD治疗中占据首要地位,目前常用于临床治疗的抗血小板药物分别是口服环氧化酶-1（COX-1）抑制剂、口服P2Y12受体抑制剂以及磷酸二酯酶抑制剂。抗血小板药物除抗血小板聚集,还具有抗炎、抗动脉硬化、抗癌、改善冠状动脉痉挛、改善内皮功能等作用。本文就阿司匹林、氯吡格雷、替格瑞洛、双嘧达莫以及西洛他唑的多效性进行综述。     

Fish bone-induced hepatic abscess: medical treatment

We report a case of a 59-year-old man admitted for acute myocardial infarction. He subsequently spiked a high-grade fever on the second day after percutaneous coronary intervention. Computed tomography imaging of the abdomen revealed a hepatic abscess secondary to gastrointestinal perforation by a fish bone. Medical therapy with antibiotics was preferred over surgical drainage of the hepatic abscess in view of the fact that the patient was on dual antiplatelet agents. The hepatic abscess was completely resolved with conservative antimicrobial therapy. Antimicrobial therapy appears to be a viable option in selected patients with hepatic abscess secondary to fish bone perforation, especially if they have contraindications to surgery.     

Update in rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by polyarticular symmetrical arthritis. Inflammatory mediators targeting joint structures produce joint inflammation with pain, functional loss, joint destruction and permanent deformity. Currently, no cure for RA exists but the increasing use of combination therapy and immunomodulatory agents has led to improved quality of life and long-term outlook for many of these patients. While traditionally employed therapies have provided limited disease suppression, advances in our understanding of the molecular pathogenesis of RA have resulted in new therapies targeting very specific components of the inflammatory process. These new treatments have shown very promising results with improved efficacy and an overall decreased toxicity profile. This review provides an overview for practicing clinicians of the current immunosuppressive therapies in RA with an emphasis on newer biological agents regarding their mechanisms of action, efficacy, side effects and monitoring recommendations. Developing therapeutics will be briefly discussed.     

Antithrombotic and antiplatelet therapies in relation to risk stratification in patients with non-ST elevation acute coronary syndrome: insights from the Sino-Global Registry of Acute Coronary Events

Background Antithrombotic and antiplatelet therapies have been proposed to treat non-ST elevation acute coronary syndrome （NSTEACS）, yet limited information is available about their applications from a multicenter ＂real-world＂ clinical procedure, especially in China. This study was undertaken to characterize the use of antithrombotic and antiplatelet agents in relation to the risk levels of the NSTEACS patients who were enrolled in Sino-Global Registry of Acute Coronary Events （GRACEs） registry study. Methods We analyzed the data from 618 Chinese NSTEACS patients stratified into low-（n=151）, intermediate-（n=233）, and high-risk groups （n=-234） based on GRACE risk scores. The baseline characteristics, clinical presentations, antithrombotic and antiplatelet agents were recorded and compared among the three groups. Results The administration rates of low-molecular-weight heparins （LMWHs） （86.08%） and thienopyridines （85.92%） were higher whereas the administration rate of glycoprotein Ⅱb/Ⅲa inhibitor （1.78%） was much lower than those reported previously. Meanwhile, within the first 24 hours of admission, the use of heparin/LMWHs in the high-risk group was more than that in the intermediate- and low-risk groups （73.50% vs 63.09% vs 55.63%, P=0.001）. Furthermore, the combination of antithrombotic and antiplatelet medications showed no significant differences in all groups. Conclusions In the ＂real world＂ practice of China, the antithrombotic and antiplatelet therapies on NSTEACS are well adherent to the current guidelines except for several gaps, such as the very low use of glycoprotein Ⅱb/Ⅲa inhibitor. Moreover, these antithrombotic and antiplatelet treatments usually tend to be underused for the high-risk ones.     

血栓形成与中药防治

血栓形成是导致心、脑及外周血管疾病发病和死亡的主要病理环节。抗栓治疗在心脑血管疾病治疗中占重要地位。目前使用的抗栓药物包括抗血小板药、抗凝剂和溶栓剂。尽管取得了良好疗效,但同时出现的出血等不良反应以及抗血小板药物抵抗现象在一定程度上限制了药物的临床应用。寻找抗血小板以外的多途径抗栓是未来的研究方向之一。中药具有多靶点、多环节且不良反应小等优势,因此在预防血栓前状态研究方面备受关注。     

新型抗血小板药物研究进展

心脑血管血栓疾病是导致人类死亡的主要病因之一,而抗血小板治疗则是主要的治疗手段。阿司匹林与氯吡格雷是目前抗血小板治疗的标准组合,但两药合用导致的出血发生率增加、以及日益受到关注的阿司匹林和氯吡格雷抵抗,使得现有抗血小板治疗难以满足临床需要。文中就现有口服抗血小板药物治疗的局限性及一些新型抗血小板药物的研究进展作一综述。     

抗血小板聚集药在缺血性脑卒中的应用

缺血性脑卒中(IS)是危害人类健康的第二大"杀手"。抗血小板治疗在IS的一级和二级预防中具有重要的作用。目前市场上有很多类抗血小板聚集药物,都被广泛用于IS预防,治疗方案各异。研究发现在IS的一级预防中,主要推荐使用的是阿司匹林,而在IS的二级预防中,第一治疗应当给予联用阿司匹林和双嘧达莫,或者单用氯吡格雷。现就抗血小板聚集的药物在预防IS的主要研究进展予以综述,以寻找抗血小板聚集药预防IS的最佳治疗方案。     

New drugs for the treatment of epilepsy: a practical approach

The availability of new antiepileptic drugs has broadened the spectrum of medical treatment options in epilepsy. The new agents, together with established drugs, offer substantial choice for doctors treating patients with focal or generalised epilepsy. The newer antiepileptic drugs are not necessarily more effective but usually better tolerated than the traditional agents, mainly because of favourable pharmacokinetic profiles and fewer interactions. Because treatment options have increased, drug therapy can now be tailored to the requirements of individual patients. Nevertheless, significant safety and efficacy issues continue to exist and there is a need for the development of even better agents. This review describes the clinical use of the new antiepileptic drugs, but focuses in particular on monotherapy, the treatment of generalised seizures, teratogenicity, and the cognitive side effect profile of the newer compounds.     

抗血小板药物抵抗的研究进展

抗血小板药物从20世纪60年代问世一直应用至今,是治疗心血管疾病、预防血栓事件的主要手段。随着药物的广泛应用,人们发现,部分接受抗血小板药物治疗的患者仍然发生血栓事件,被称为"抗血小板药物抵抗"。这一现象与药物的剂量、药物间的相互作用、基因的多态性、基础血小板的反应性、药物吸收的个体差异、患者依从性等多个因素密切相关。联合使用药物或加大剂量是目前最主要应对药物抵抗的措施,但也增加了出血并发症的危险。     

Plasma exchange in thrombotic thrombocytopenic purpura

Three patients were recently treated for thrombotic thrombocytopenic purpura (TTP). One presented with toxic shock syndrome; TTP developed but promptly responded to a regimen of antiplatelet agents, steroids and plasma exchange. In another the manifestations of TTP developed after presentation with hypertension and abdominal pain. This patient responded to a similar regimen but required extended treatment before remission could be maintained with medications alone. In the third patient the full TTP syndrome appeared after several days of plasma exchange treatment for hemolyticuremic syndrome. He did not respond. It is suggested that TTP may present in many forms initially, that microangiopathic hemolysis may be a late manifestation and that the optimal therapy is not known.     

Percutaneous nephrolithotomy in patients on chronic anticoagulant/antiplatelet therapy

Percutaneous nephrolithotomy (PCNL) is an integral component in the management of large volume renal stone disease either as monotherapy or in combination with shock wave lithotripsy. Stone disease in patients on chronic anticoagulation/antiplatelet therapy, however, poses a difficult scenario. Bleeding is a major concern for any patient undergoing PCNL. We retrospectively analyzed our series of patients with renal calculi who were on chronic anticoagulant therapy and who underwent PCNL. We reviewed the case records of patients undergoing PCNL during the period from January 2005 to December 2011. We analyzed the changes in preoperative and postoperative hemoglobin, serum creatinine, and clotting parameters, as well as intraoperative and postoperative bleeding and thromboembolic complications. During the 5-year study period, a total of 36 patients (30 males and 6 females) with a mean age of 46.33±9.96 years (range, 29-61 years) who were on chronic anticoagulant/antiplatelet therapy underwent PCNL for urolithiasis. The mean size of the stone was 6.40±1.98 cm(2) (range, 2.8-9 cm(2)). The mean operating time was 62.08±10.10 min. The bleeding was successfully managed in all patients and the anticoagulant/antiplatelet agents were restarted after an appropriate duration. The mean rise in serum creatinine at discharge was 0.05±0.03 mg/dl and the mean fall in serum hemoglobin was 1.63±0.77 g/dl. At 3 months after surgery, the stone-free rate was 100%. With careful preoperative care and regulation of anticoagulation/antiplatelet therapy and appropriate intraoperative management, PCNL can be performed safely and successfully in properly selected patients with renal calculi who are on chronic anticoagulant/antiplatelet therapy.     

质量控制活动规范急性ST段抬高型心肌梗死早期抗栓治疗的效果观察

目的 探索将质量控制活动(QC)活动用于管理急性心肌梗死(AMI)早期抗血小板药物规范使用的实施方法 ,并观察其对预后的影响.方法 成立QC小组,遵循:计划-执行-检查-处理(PDCA)循环的方法 ,对急性ST段抬高型心肌梗死(STEMI)早期使用双联抗血小板药物的情况及患者预后进行现状调查,找到药物使用过程中存在的主...     

In vitro activity of some newer quinolone compounds

The quinolones are a group of antimicrobial agents that act by inhibiting bacterial DNA gyrases, enzymes essential in DNA replication. Several newer quinolone agents have been introduced recently. These are broad spectrum agents which may be administered orally. In-vitro susceptibility testing of five quinolone agents namely norfloxacin, pefloxacin, enoxacin, ofloxacin and ciprofloxacin against recent clinical bacterial isolates at the General Hospital Kuala Lumpur was performed. The results confirm the broad spectrum and high activity of these agents against these isolates which included Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. The quinolones would provide valuable alternatives in the treatment of infections caused by organisms resistant to the more commonly used antibiotics.     

Immunosuppressive therapy in children

The treatment of auto-immune diseases is evolving and newer agents become available. This review will outline treatment options in children with auto-immune disorders. Treatment with current corticosteroids and azathioprine works in majority but issues of intolerance and incomplete response arise, which led to window of newer immunosuppressants including mycophenolate mofetil, cyclosporine, tacrolimus, sirolimus, and various antibodies of human and animal origin. The newer agents have been studied in fewer numbers of children, so they are not first-line treatment yet but do have a clear role in patients with intolerance or incomplete response to standard therapy.     

Antiplatelet effect of aspirin in patients with coronary artery disease

Cardiovascular disease is the number one cause of death globally, and atherothrombosis is the underlying cause of most cardiovascular events. Several studies have shown that antiplatelet therapy, including aspirin (acetylsalicylic acid), reduces the risk of cardiovascular events and death. However, it is well-known that many patients experience cardiovascular events despite treatment with aspirin, often termed "aspirin low-responsiveness". This fact has caused considerable debate: does biochemical aspirin low-responsiveness have prognostic value? Can low-responders be reliably identified? And if so, should antithrombotic treatment be changed? Is the whole discussion of antiplatelet drug response merely a result of low compliance? Compliance should be carefully optimised, before evaluating the pharmacological effect of a drug. It is well-known that cardiovascular disease is multifactorial, and, therefore, total risk reduction is not feasible. Aetiological factors to the variable platelet inhibition by aspirin seem to include genetic factors, pharmacological interactions, smoking, diabetes mellitus, and increased platelet turnover. It is a captivating thought that antiplatelet therapy may be improved by individually tailored therapy based on platelet function testing. Ongoing studies are challenging the current one-size-fits-all dosing strategy, but the preceding evaluation of platelet function assays has not been adequate. The overall objective of this thesis was to evaluate the reproducibility of and aggreement between a number of widely used platelet function tests and to explore the importance of platelet turnover for the antiplatelet effect of aspirin in patients with coronary artery disease. In the intervention studies (studies 1, 3, and 4), optimal compliance was confirmed by measurements of serum thromboxane, which is the most sensitive assay to confirm compliance with aspirin. In study 1, platelet function tests widely used to measure the antiplatelet effect of aspirin were evaluated in healthy individuals and patients with coronary artery disease. Pharmaco-specific metabolites were measured in urine and serum to investigate the pharmacodynamic effect of aspirin and to enable the comparison with the more global tests of platelet function. Based on repeated duplicate measurements, we evaluated the reproducibility of each test. We found that reproducibility of the classical reference method was not impressive and that the newer, so-called point-of-care tests differed markedly on reproducibility. With coefficients of variation of about 3%, the VerifyNow Aspirin test was clearly the most reproducible test - even after correction of the official scale, which begins at about 350 aspirin reaction units and, therefore, results in artificially low coefficients of variation. Among the platelet function tests investigated, Multiplate was most sensitive for aspirin treatment. In study 2 we performed the hitherto largest study of newly released, immature platelets as a marker of platelet turnover. The study population included healthy individuals, patients with stable coronary artery disease, and patients with acute coronary syndromes. The main finding was an increased fraction of immature platelets in patients with ST-segment myocardial infarction, indicating an increased platelet turnover. Smoking and type 2 diabetes were identified as independent determinants of platelet turnover. In study 3 we explored the relationship between platelet turnover and the antiplatelet effect of aspirin in patients with stable coronary artery disease. The study results support the hypothesis that an increased platelet turnover reduces the antiplatelet effect of aspirin. The main findings were: 1) platelet turnover correlated with platelet aggregation measured by Multiplate and with sP-selectin, a marker of platelet activation. 2) Patients with diabetes mellitus type 2 had reduced antiplatelet effect of aspirin compared with patients without diabetes. 3) Widely used platelet function tests differ with respect to dependence on platelet parameters, including platelet count. 4) Smoking, diabetes mellitus type 2, and thrombopoietin were identified as independent determinants of platelet turnover. 5) The relative fraction of immature platelets has been employed in most previous studies, but in stable patients the absolute immature platelet count does not seem dependent on the total platelet count, and it has a stronger correlation with both platelet activation measured by sP-selectin and with platelet aggregation during treatment with aspirin. In study 4 we investigated platelet turnover and the antiplatelet effect of aspirin in a nested case-control study on patients with previous definite stent thrombosis. Patients with stent thrombosis were compared with patients without stent thrombosis, with whom they were matched at a 1:2 ratio with respect to risk factors for stent thrombosis: age, sex, stent type, and indication for percutaneous coronary intervention. The study showed that patients with previous stent thrombosis have reduced antiplatelet effect of aspirin and a tendency towards increased platelet turnover. In conclusion, widely used platelet function tests markedly differ on reproducibility, and the agreement between tests is relatively poor. An increased platelet turnover as suggested by the presence of newly formed immature platelets is important for the antiplatelet effect of aspirin, and, perhaps also for the development of acute coronary thrombosis. In the future, individually tailored antiplatelet therapy may potentially improve the benefit-risk ratio of antiplatelet therapy.