Scanning electron microscopic assessment of coating irregularities and their precursors in unexpanded durable polymer‐based drug‐eluting stents

Objectives : To assess and quantify coating irregularities on unexpanded and expanded durable polymer‐based drug‐eluting stents (DES) to gain insights into the origin of coating irregularities. Background: Previous scanning electron microscopy (SEM) studies in various expanded DES revealed differences in frequency and size of coating irregularities between DES types and specific distribution patterns, however, the origin of these irregularities is unclear. Methods: We assessed at bench side a total of 1,200 SEM images obtained in 30 DES samples (15 expanded and 15 unexpanded) of Cypher Select Plus, Taxus Liberté, Endeavor, Xience V, and resolute. Results: For most coating irregularities seen on expanded DES (72%; 23/32), a matching irregularity (n = 18/23) and/or its precursor (n = 11/23) was observed in unexpanded DES. Unexpanded Cypher select showed (small) crater lesions and cracks together with precursors of “peeling.” On unexpanded Taxus Liberté, thinning of polymer, small bare metal areas, wrinkles, and one precursor type were found. Unexpanded endeavor showed cracks, small bare metal areas, crater lesions, and precursors of the latter. Unexpanded Xience V and resolute mainly revealed crater lesions and their precursors. On unexpanded versus expanded DES, there was no difference in measured frequency of coating irregularities and precursors (P = ns) with the exception of more bare metal areas on expanded Taxus Liberte (P = 0.01). Conclusions : Most coating irregularities, or the potential to develop them, are inherent to the unexpanded DES. Important determinants of the formation of coating irregularities may be the stent geometry and the physical properties of the coating, while stent‐balloon interaction plays no major role. © 2011 Wiley Periodicals, Inc.     

抗结核药物引起的副作用综合报告

目的了解各种抗结核药物引起的副作用并掌握一般处理原则。方法直接或间接证明６２例中由抗结核药物引起的副作用，观察并分析各种副作用分布情况、出现时间及表现形式。结果过敏反应频度占副作用的首位，共３７例，占６０％；严重副反应绝大多数由利福霉素类引起；副作用出现时间多为服药后２个月以内；药物服用过量易导致副反应发生；多种药物可同时或相继产生严重副作用。结论一旦发生严重药物副作用，必须立即停药，及时治疗，否则后果严重；利福霉素类药停药后再服，有可能加重过敏反应程度，故要详细询问既往用药情况，对有肝炎史、酗酒史、药物过敏史和年老体弱者用药过程中要严密观察；对多种药物过敏者，无论反应轻重，以快停药、早脱敏为原则；必须确定过敏原时，要使用常量的１／１０以下，并制定应急处理措施，严重过敏者不应进行重复验证     

Spontaneous remission of hepatitis B virus reactivation during direct‐acting antiviral agent‐based therapy for chronic hepatitis C

The administration of direct‐acting antiviral agents (DAAs) to treat hepatitis C virus (HCV) infection has been reported to cause hepatitis B virus (HBV) reactivation. However, the actual conditions of HBV reactivation and the ideal timing of medical intervention have not been fully evaluated. We report the cases of two female patients dually infected with HBV and HCV. Both patients were inactive HBV carriers. Although the serum HCV RNA levels promptly decreased after the initiation of DAA‐based therapy, the serum HBV DNA levels gradually increased during DAA‐based therapy, with the peak serum HBV DNA levels observed at 16 weeks after the initiation of DAA‐based therapy in both cases. Subsequently, we checked the serum HBV DNA levels closely every week several times. Fortunately, the serum HBV DNA levels gradually decreased without medical intervention. Neither case developed an alanine aminotransferase flare‐up. The HCV genotypes were 2a and 1b, and the DAA‐based therapies of Cases 1 and 2 were 12 weeks of sofosbuvir/ribavirin and ombitasvir/paritaprevir/ritonavir, respectively. The significance of our case reports is the demonstration of the existence of spontaneous remission of HBV reactivation that developed during DAA‐based therapy, the avoidance of intervention of nucleot(s)ide analogs by frequent monitoring of serum HBV DNA levels, and development of HBV reactivation regardless of the viral genotype or class of DAA. In conclusion, the close monitoring of serum HBV DNA levels during and after DAA‐based therapy is essential and medical intervention for HBV reactivation should be carefully considered on an individual basis.     

Glycaemic control and hypoglycaemia with insulin glargine 300 U/mL versus insulin glargine 100 U/mL in insulin-naïve people with type 2 diabetes: 12-month results from the EDITION 3 trial

AimTo explore if efficacy and safety findings for insulin glargine 300 U/mL (Gla-300) versus insulin glargine 100 U/mL (Gla-100), observed over 6 months in insulin-naïve people with type 2 diabetes, are maintained after 12 months.MethodsEDITION 3 was a phase 3a, randomized, multicentre, open-label, parallel-group, treat-to-target study of once-daily Gla-300 versus Gla-100 (target fasting self-monitored plasma glucose, 4.4–5.6 mmol/L [80–100 mg/dL]). Participants completing the initial 6-month treatment phase continued their previously allocated basal insulin.ResultsOf 878 participants randomized, 337/439 (77%) and 314/439 (72%) assigned to Gla-300 and Gla-100, respectively, completed 12 months of treatment. Improved glycaemic control was sustained until 12 months in both treatment groups, with similar reductions in HbA_1c from baseline to month 12 (difference: −0.08 [95% confidence interval (CI): −0.23 to 0.07] % or −0.9 [−2.5 to 0.8] mmol/mol). Relative risk of experiencing ≥ 1 confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycaemic event with Gla-300 versus Gla-100 was 0.86 (95% CI: 0.69 to 1.07) at night and 0.92 (0.82 to 1.03) at any time of day. For events with a glycaemic threshold of < 3.0 mmol/L (< 54 mg/dL) these numbers were 0.76 (0.49 to 1.19) and 0.66 (0.50 to 0.88). A similar pattern was seen for documented symptomatic events. No between-group differences in adverse events were identified.ConclusionOver 12 months, Gla-300 treatment was as effective as Gla-100 in reducing HbA_1c in insulin-naïve people with type 2 diabetes, with lower overall risk of hypoglycaemia at the < 3.0 mmol/L threshold.     

Calcium sensitization with pimobendan: pharmacology, haemodynamic improvement, and sudden death in patients with chronic congestive heart failure

Calcium sensitization increases myocardial contractility byimproving energy utlization of the myocardium, without an increasein intracellular concentrations of cyclic adenosine monophosphate.The calcium sensitizer most extensively studied up to now ispimobendan (UD-CG 115 BS). Vasodilatation results primarilyfrom phosphodiesterase III inhibition Orally administered pimobendan appears rapidly in plasma. Apeak concentration is reached 1.5 h after drug intake; eliminationfrom the plasma compartment has a half-life of 1.5 h. First-passhepatic O-desmethylation of pimobendan produces the active metaboliteUD-CG 212; plasma concentration curves of UD-CG 212 are similarto those of pimobendan, with apeak concentration 1–2 hlater than the peak concentration of the parent compound. In patients with chronic congestive heart failure, pimobendanproduces a dose-dependent and prolonged decrease in pulmonarycapillary wedge pressure and an increase in cardiac output.Maintenance doses ofpimobendan are well tolerated and may leadto lasting symptomatic improvement in patients with heart failure;open and blinded trials show that exercise tolerance increases.No attenuation of these effects is seen during long-term therapywith pimobendan. Patients in chronic congestive heart failure frequently diesuddenly; many inotropic agents increase the incidence of suddendeath in these patients. Although proarrhythmia has never beenobserved with pimobendan, arrhythmia suppression with amiodaroneseems prudent in heart failure patients receiving maintenancedoses of pimobendan.     

纯钛表面激光合成钙磷生物陶瓷涂层的组成与结构

目的 采用廉价的CaCO_3和CaHPO_4·2H_2O作为原料,在激光的作用下通过反应制备HA生物陶瓷涂层。方法 利用X射线衍射仪和电子探针分析仪对涂层进行相分析、组织观察和成分分析。结果CaCO_3和CaHPO_4·2H_2O按20:80的质量比混合时,在功率为600W、扫描速度为3.5mm/s的激光作用下可一步合成钙磷生物陶瓷涂层。结论 在一定实验条件下,CaCO_3和CaHPO_4·2H_2O可合成组织致密、结合状态良好的钙磷生物陶瓷涂层。     

A shear-induced in vitro platelet function test can assess clinically relevant anti-thrombotic effects

Morphological features of haemostatic plugs formed in vitro under high shear forces were investigated. Electron microscopy confirmed the relevance of such haemostatic plug to a platelet-rich arterial thrombus, which is formed in vivo. In rat blood samples, the effects of anticoagulants and various antiplatelet agents on platelet reactivity (rate of haemostatic plug formation) and subsequent coagulation of the flowing blood were investigated. Haemostasis did not occur in citrated blood, and heparin greatly inhibited the shear-induced platelet reaction. Aspirin (1 mM), a thromboxane A₂ receptor antagonist (5 μM), a stable prostacyclin (0.55 nM), a stable prostaglandin E₁ (141 nM) and a phosphodiesterase inhibitor (100 μM) were tested. All these agents exerted significant inhibitory effect on shear-induced platelet reaction, including the inhibition of the very first phase of platelet plug formation, due to aggregation of shear-activated platelets. Except for the phosphodiesterase inhibitor, which prolonged clotting time, none of the above agents affected dynamic coagulation. These results suggest that the employed in vitro shear-induced thrombosis/haemostasis test can reveal in vivo the antithrombotic effect of various agents independently of their mechanism of action.