同种异体大鼠小肠移植中监测CD4+ T细胞和CD8+ T细胞数比值的意义

目的 探讨CD4+T细胞数/CD8+T细胞数作为大鼠同种异体小肠移植急性免疫排斥反应指标的可行性.方法 选取健康雄性成年SD、Wistar大鼠建立同种异体小肠移植模型,于大鼠术前和术后1、3、5、7、9d共6个时间段静脉取血,应用免疫荧光染色技术及流式细胞仪检测CD4+T细胞和CD8+T细胞百分率,并计算其比值.同期取移植小肠标本做组织学检测.结果 术后CD4+T细胞数和CD8+T细胞数比值前期增高后期降低.组织病理学检测发现术后小肠移植物的排斥反应由轻到重,术后第5天始CD4+T细胞数和CD8+T细胞数比值与急性免疫排斥反应程度呈正相关.结论 CD4+T细胞和CD8+T细胞数比值作为大鼠同种异体小肠移植术后急性免疫排斥反应的监测指标的可行性较大.     

兰索拉唑与莫沙必利联合治疗反流性食管炎的临床观察

目的 观察兰索拉唑与莫沙必利联合治疗反流性食管炎的临床效果.方法 89例反流性食管炎患者随机分为两组,治疗组50例用兰索拉唑和莫沙必利,对照组39例用盐酸雷尼替丁胶囊,观察治疗前及治疗后4、8周的临床症状改善情况和内镜变化.结果 用药4周时,治疗组反酸、恶心及胸骨后疼痛治疗有效率分别为78%、84%、82%,与对照组比较差异有统计学意义(P＜0.05).用药8周结束时,治疗组反酸、恶心及胸骨后疼痛全部改善,总有效率分别是98%、98%和93%,明显优于对照组的64%、81%和73%(均P＜0.05);内镜4周、8周复查治疗组与对照组食管黏膜病损愈合率分别为84%和62%,96%和77%,差异有统计学意义(P＜0.05).结论 兰索拉唑、莫沙必利联合用药是治疗反流性食管炎安全、有效的方法.     

Acute otomastoiditis and its complications: role of CT

Acute bacterial (suppurative) otomastoiditis responds to antibiotic treatment; radiologic study is required only when there is clinical suggestion of coalescent mastoiditis, intracranial complications, or an underlying chronic disease. Computed tomography (CT) is the method of choice for evaluating otogenic intra- or extra-cranial complications. CT scans can show stages of disease progression when infection has spread by way of soft tissue, blood, and bone pathways into the dural venous sinuses, meninges, labyrinth, facial nerves, epidural and other intracranial spaces. When there is clinical suggestion of acute coalescent mastoiditis, a CT scan of the temporal bone can confirm the presence of rarefying osteitis, coalescence of the air cells, and subperiosteal abscess.     

Comparative efficacy of first-line ceritinib and crizotinib in advanced or metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer: an adjusted indirect comparison with external controls

Objective: In the absence of head-to-head trials, this study indirectly compared progression free survival (PFS) and overall survival (OS) between ceritinib and crizotinib among patients with previously untreated advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).

Methods: A matching-adjusted indirect comparison method was implemented to adjust for cross-trial differences in patient characteristics between ASCEND-4 and PROFILE 1014 trials. Patient-level data from ASCEND-4 and published summary data from PROFILE 1014 were used. Patients in ASCEND-4 were reweighted to match average baseline characteristics (i.e. age, sex, race, tumor histology, ECOG score, smoking status, extent of disease, and presence of brain metastases) reported for PROFILE 1014 patients using propensity score weighting. PFS and OS were then compared between balanced populations.

Results: ASCEND-4 included more current smokers (8.0% vs 4.4%) and fewer patients under the age of 65 years (78.5% vs 84.0%) compared to PROFILE 1014. After matching, these and all other patient characteristics were balanced between the two trial populations. Compared to crizotinib, ceritinib was associated with a significantly longer PFS (hazard ratio [95% confidence interval] (HR [CI])?=?0.64 [0.47–0.87]; median PFS: 25.2 vs 10.8 months, log-rank p-value?=?0.003). OS did not differ significantly, with a HR of 0.82 [0.54–1.27] for ceritinib compared to crizotinib.

Conclusions: In the adjusted indirect comparison with external controls, the second generation ALK inhibitor, ceritinib, was associated with a significantly prolonged PFS compared to crizotinib as first-line treatment for ALK-positive NSCLC.     

Macrolides: A Canadian Infectious Disease Society position paper

Since the introduction of erythromycin in 1965, no new compounds from the macrolide antimicrobial class were licensed in Canada until the 1990s. Clarithromycin and azithromycin, since their introduction, have become important agents for treating a number of common and uncommon infectious diseases. They have become prime agents in the treatment of respiratory tract infections, and have revolutionized the management of both genital chlamydial infections, by the use of single-dose therapy with azithromycin, and nontuberculous mycobacterial infections, by the use of clarithromycin. The improvement of clarithromycin and azithromycin over the gastrointestinal intolerability of erythromycin has led to supplanting the use of the latter for many primary care physicians. Unfortunately, the use of these agents has also increased the likelihood for misuse and has raised concerns about a resultant increase in the rates of macrolide resistance in many important pathogens, such as Streptococcus pneumoniae. This paper reviews the pharmacology and evidence for the current indications for use of these newer agents, and provides recommendations for appropriate use.Key Words: Azithromycin, Clarithromycin, Erythromycin, Macrolides, Review, Therapeutic useErythromycin A is a naturally occurring, microbiologically active compound of the macrolide class of antibiotics. Chemical modification of erythromycin A''s 14-membered lactone ring has led to the formation of semisynthetic derivatives with not only improved bioavailability and tolerability, but also expanded spectrums of microbiological activity and improved pharmacokinetic profiles. Such modifications produced clarithromycin, classified as a macrolide because it retains the central 14-membered lactone ring (1,2), and azithromycin, classified as an azalide due to its 15-membered aglycone ring (1). The latter two compounds are the newest agents in the macrolide class licensed for use in Canada. Roxithromycin and dirithromycin are available in other countries.These compounds are clinically active against Gram-positive and Gram-negative cocci, and Gram-negative bacilli (primarily Haemophilus influenzae, Legionella species, Moraxella catarrhalis, Campylobacter jejuni, Bordatella pertussis and Helicobacter pylori). Azalides such as azithromycin have exhibited superior activity against Gram-negative pathogens and are generally less active against Gram-positive pathogens. Intracellular pathogens such as Chlamydia species, Mycoplasma species, Ureaplasma species, Borrelia species and nontuberculous mycobacteria species show varying susceptibilities. On the basis of their microbial activity, both the macrolides and azalides have been shown to be clinically useful in the treatment of uncomplicated skin and soft tissue infections, upper and lower respiratory tract infections, sexually transmitted Chlamydia trachomatis infection and peptic ulcer disease. Additionally, the improved pharmacokinetic profiles and acid stability exhibited by the newer agents may lead to enhanced patient adherence through less frequent dosing and improved bioavailability in the presence of food.     

Innominate artery aneurysm with thrombus: detection by two-dimensional echocardiography

A 51 year old man with an innominate artery aneurysm presented with claudication and ischemia of the right forearm and hand. Two-dimensional echocardiography visualized the saccular aneurysm and a pedunculated mobile thrombus within it that were not seen during aortic arch angiography. Two-dimensional echocardiography, shown to be useful in identifying intracardiac masses and aortic aneurysms, may be important in selecting patients with increased risk of embolization.     

Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4

Heparin-induced thrombocytopenia (HIT) is an important complication of heparin therapy. Although there is general agreement that platelet activation in vitro by the HIT IgG is mediated by the platelet Fc receptor, the interaction among the antibody, heparin, and platelet membrane components is uncertain and debated. In this report, we describe studies designed to address these interactions. We found, as others have noted, that a variety of other sulfated polysaccharides could substitute for heparin in the reaction. Using polysaccharides selected for both size and charge, we found that reactivity depended on two independent factors: a certain minimum degree of sulfation per saccharide unit and a certain minimum size. Hence, highly sulfated but small (< 1,000 daltons) polysaccharides were not reactive nor were large but poorly sulfated polysaccharides. The ability of HIT IgG to recognize heparin by itself was tested by Ouchterlony gel diffusion, ammonium sulfate and polyethylene glycol precipitation, and equilibrium dialysis. No technique demonstrated reactivity. However, when platelet releasate was added to heparin and HIT IgG, a 50-fold increase in binding of radio-labeled heparin to HIT IgG was observed. The releasate was then depleted of proteins capable of binding to heparin by immunoaffinity chromatography. Only platelet factor 4-immunodepleted releasate lost its reactivity with HIT IgG and heparin. Finally, to determine whether the reaction occurred on the surface of platelets or in the fluid phase, washed platelets were incubated with HIT IgG or heparin and after a wash step, heparin or HIT IgG was added, respectively. Reactivity was only noted when platelets were preincubated with heparin. Consistent with these observations was the demonstration of the presence of PF4 on platelets using flow cytometry. These studies indicate that heparin and other large, highly sulfated polysaccharides bind to PF4 to form a reactive antigen on the platelet surface. HIT IgG then binds to this complex with activation of platelets through the platelet Fc receptors.