鼻内镜手术合并大环内酯类抗生素治疗鼻窦炎43例

目的：评价鼻内镜手术治疗合并术后利用大环内酯类抗生素治疗鼻窦炎的疗效,探讨鼻窦炎患者治疗前后血清中IL-17及其受体的表达及血清中总IgE的变化。方法：鼻窦内窥镜行病侧上颌寞自然口扩大及下鼻道开窗双进路,彻底清除鼻腔、鼻窦病变组织,术后采用大环内酯类抗生素治疗;采用酶联免疫法检测30例患者治疗前后血清中IL-17,IL-17R及IgE的含量。结果：治疗30例,其中术后病理证实鼻寞真菌球20例,治愈20例;曲霉菌感染23例,治愈10例,6个月随访无复发;与只治疗前相比,手术治疗后鼻窦炎患者血清IL-17,IL-17R及IgE的含量均明显降低。结论：鼻内镜手术是治疗真菌性鼻一鼻窦炎的主要方法,IL-17和IL-17R均参与鼻窦炎的发病过程,可作为诊断鼻窦炎的新指标,鼻内镜术后使用大环内酯类抗生素进一步巩固治疗,可降低复发率。     

鼻内镜再手术对复发性鼻窦炎、鼻息肉的疗效探讨

目的:探讨鼻窦炎、鼻息肉复发的相关性因素及鼻内镜再手术的疗效。方法:将我院近年来住院治疗的78例复发性鼻窦炎、鼻息肉患者随机分为两组,对照组根据患者要求予以保守治疗共21例,观察组57例,给予正性鼻内镜手术治疗,术前行鼻窦CT及鼻内镜检查,术后随访1-4年。结果:观察组较对照组患者在疗效、总有效率好,且GM-CSF、IL-5的阳性表达率低,两组之间存在显著性差异(P<0.05),术后出现的相关并发症较对照组无显著性差异(P>0.05)。结论:鼻肉镜再次手术对复发性鼻窦炎、鼻息肉复发的疗效好,结合全面的围手术期处理,掌握熟练的鼻内镜手术操作技巧可以显著改善患者的预后。     

变应性鼻炎患者血清IL-17和IL-17R表达及其与IgE的相关性

目的:探讨变应性鼻炎患者血清中IL-17及其受体的表达,及其与血清中总IgE的关系.方法:采用酶联免疫法检测51例健康志愿者(对照组)和37例变应性鼻炎患者(实验组)血清中IL-17,IL-17R及IgE的含量.结果:与对照组相比,变应性鼻炎患者血清IL-17,IL-17R及IgE的含量均明显升高.IL-17与变应性鼻炎患者血清中IgE成正相关(r=0.9678,P＜0.05),而IL-17R与IgE无明显相关性.结论:IL-17和IL-17R均参与变应性鼻炎的发病过程,可作为诊断变应性鼻炎的新指标,且降低IL-17的含量有助于变应性鼻炎的临床治疗.     

鼻内镜技术用于鼻腔鼻窦良恶性肿瘤的治疗

目的:评估鼻内镜手术对于鼻腔鼻窦良恶性肿瘤的治疗效果及应用价值.方法:收集我科采用鼻内镜或鼻内镜辅助手术治疗的鼻腔鼻窦良恶性肿瘤共109例,并进行回顾性分析.结果:经随访12-60个月,本组109例患者中,应用单纯鼻内镜下治疗的4例鼻腔鼻窦肿瘤患者术后出现复发,1例失访,复发率为5％;鼻内镜联合柯陆氏入路手术的16例患者中未出现术后复发;2例鼻内镜辅助鼻侧切开手术治疗的恶变内翻乳头状瘤患者术后1年出现局部复发及广泛脑膜侵犯死亡;鼻内镜辅助鼻侧切开手术中的2例恶性黑色素瘤其中1例术前已出现颊部及颈部淋巴结转移,于术后8个月-1.5年中出现远处转移后死亡.结论:鼻内镜手术已经逐渐成为多种鼻腔鼻窦良性肿瘤以及部分恶性肿瘤的首选治疗方式.     

鼻内镜下手术结合术后鼻窦冲洗治疗变应性真菌性鼻窦炎的临床研究

目的:研究鼻内镜下手术结合术后鼻窦冲洗治疗变应性真菌性鼻窦炎的临床疗效。方法:选取2010年3月到2013年3月我院收治的变应性真菌性鼻窦炎患者67例为研究对象,对其临床资料进行回顾分析,所有患者均给予鼻内镜下手术结合术后鼻窦冲洗治疗,术后随访患者1年。另选取健康者50例为对照组,应用视觉模拟量表(VAS)评价患者术前术后主观感受,应用鼻内镜和鼻腔纤毛功能评价患者术前术后客观感受,并应用生活质量量表(SF-36)评价患者的生活质量。结果:患者术后VAS评分为(18.5±1.3)分显著优于术前的(29.3±0.2)分,与术前比较差异具有统计学意义(t=11.026,P=0.018);术后鼻内镜总分为(4.1±0.2)分显著优于手术前,与手术前比较差异具有统计学意义(t=9.037,P=0.027);术后1年鼻纤毛传输速度(6.9±0.3)mm/min,与对照组比较差异无统计学意义(t=3.984,P=0.092);术后1年SF-36评分为(649.6±23.2)分,与对照组比较差异无统计学意义(t=4.018,P=0.096)。结论:鼻内镜下手术结合术后鼻窦冲洗治疗变应性真菌性鼻窦炎具有较好的临床疗效,能显著改善患者的症状,提高患者的生活质量。     

鼻内镜手术联合咪康唑鼻窦内灌注治疗非侵袭性真菌性鼻窦炎的疗效观察

目的探讨鼻内镜手术联合咪康唑鼻窦内灌注治疗非侵袭性真菌性鼻窦炎的疗效。方法选取住院治疗的非侵袭性真菌性鼻窦炎患者68例,随机将其分为观察组和对照组,每组34例。对照组患者采用鼻内镜手术治疗非侵袭性真菌性鼻窦炎,观察组患者在对照组治疗基础上予以咪康唑鼻窦内灌注。观察并记录两组患者治疗1个月后的临床疗效及药物不良反应,并比较治疗后随访半年与1年复发率。结果治疗1个月后,观察组患者临床总有效率明显高于对照组(χ2=4.22,P0.05)。观察组治疗中有2例患者出现不良反应,症状较轻。治疗后随访半年与1年,观察组患者的复发率分别为3.13%和9.38%,均明显低于对照组的26.92%和34.62%(χ2=4.98或5.57,P0.05)。结论鼻内镜手术联合咪康唑鼻窦内灌注治疗非侵袭性真菌性鼻窦炎的疗效明显优于单纯的鼻内镜手术治疗,安全性较好,且其中远期疗效较好,能减少其术后复发,具有预防其病情复发作用。     

鼻内镜动力切削术对鼻前庭囊肿患者CRP、TNF-α、IL-6及IL-8的影响

目的:探讨鼻内镜下动力切削系统治疗对鼻前庭囊肿患者CRP、TNF-α、IL-6和IL-8的影响。方法:选取2012年6月至2013年1月我院收治的鼻前庭囊肿患者163例,随机分为两组。实验组(80例)行鼻内镜下动力切削系统行囊肿切除术,对照组(83例)给予微波治疗。观察并比较两组患者手术前后血清CRP、TNF-α、IL-6和IL-8水平的变化情况,并比较两组患者手术情况、术后并发症及远期疗效。结果:与对照组比较,实验组手术时间较长,术中出血量较多,差异具有统计学意义(P0.05),实验组术后感染率较低,术后复发率较低;术后CRP、TNF-α、IL-6和IL-8水平升高,与对照组相比,实验组各项指标较高(P0.05)。结论:鼻内镜下动力切削系统治疗鼻前庭囊肿具有较好的临床治疗效果,且复发率低,值得临床推广。     

鼻内镜手术治疗慢性鼻窦炎54 例临床疗效分析

目的:研究鼻内镜手术治疗慢性鼻窦炎的疗效。方法:选取在2008年10月至2010年1月之间来本院进行手术治疗的慢性鼻窦炎患者54例,使用鼻内镜手术进行治疗,作为此次研究的治疗组;而同时选取在同一时期来到本院的38例患者,作为此次研究的对照组采用一般的鼻外径手术治疗。在手术结束以后每位患者均需随访1年,根据患者的恢复情况比较两种手术方法对鼻窦炎的疗效,以上手术方式均根据患者意愿。结果:使用鼻内镜手术进行治疗的患者中治愈的有31例,有效的有18例,而无效的则有5例,总的有效率为90.7%;而采用一般手术的患者中治愈的患者为17例,有效的患者为12例,无效的则有9例,其总的有效率为76.3%;且应用鼻内镜手术的治疗组的并发症发生率小于使用一般手术的对照组,两组患者疗效比较差异有统计学意义(P<0.05)。结论:鼻内镜手术治疗慢性鼻赛炎的疗效确切,安全可靠,值得广大医务工作者在临床上大力推广。     

等离子低温射频消融术联合鼻内镜对慢性鼻窦炎患者嗅觉功能及血清炎症介质的影响

目的:探讨等离子低温射频消融术联合鼻内镜对慢性鼻窦炎(CRS)患者嗅觉功能及血清炎症介质的影响。方法:选取2016年3月～2018年7月期间我院收治的CRS患者127例,根据手术方式的不同将患者分为A组(n=62,鼻内镜手术)和B组(n=65,等离子低温射频消融术联合鼻内镜手术),术后随访1年,比较两组患者临床疗效、症状评分、嗅觉功能、血清炎症介质及并发症情况。结果:B组术后1年的临床总有效率为87.69%(57/65),高于A组的72.58%(45/62)(P0.05);术后3个月B组的嗅觉功能分布优于A组(P0.05);两组患者术后3个月鼻塞、头面部胀痛、流脓涕、鼻涕倒流、头痛等症状评分均降低,且B组低于A组(P0.05)。两组患者术后1周血清白介素-5(IL-5)、白介素-17(IL-17)以及肿瘤坏死因子-α(TNF-α)均降低,且B组低于A组(P0.05)。两组术后并发症发生率比较无差异(P0.05)。结论:CRS在鼻内镜的基础上联合等离子低温射频消融术治疗的疗效显著,能够有效改善患者嗅觉功能和临床症状,抑制机体炎性反应的同时不增加并发症发生率。     

功能性内窥镜鼻窦术对慢性鼻窦炎患者TIgE、Eos及鼻纤毛传输功能的影响

目的:探讨功能性内窥镜鼻窦术对慢性鼻窦炎患者总免疫球蛋白(TIg E)、嗜酸性粒细胞(Eos)及鼻纤毛传输功能的影响。方法:选择2015年12月-2019年12月在我院接受治疗的120例慢性鼻窦炎患者,采用抽签法将其分为观察组(n=61)和对照组(n=59)。对照组给予传统腺样体刮除术治疗,观察组给予功能性内窥镜鼻窦术治疗。比较两组患者的临床疗效、治疗前后血清TIg E、Eos、白细胞介素4(IL-4)、白细胞介素8(IL-8)、肿瘤坏死因子(TNF-α)水平、鼻黏液纤毛清除率、清除速度、传输速度的变化及并发症的发生情况。结果:治疗后,观察组的总有效率分别为95.08%,明显高于对照组(77.97%,P0.05)。治疗前,两组血清TIg E、Eos水平比较无明显差异;治疗后,两组血清TIg E、Eos水平均较治疗前显著降低,且观察组血清TIg E、Eos水平均低于对照组(P0.05)。治疗前,两组鼻黏液纤毛清除率、清除速度、传输速度水平比较均无明显差异;治疗后,两组以上指标均显著升高,且观察组上述指标均高于对照组(P0.05)。治疗前,两组血清IL-4、IL-8、TNF-α水平无明显差异;治疗后,两组血清IL-4、IL-8、TNF-α水平均较治疗前显著降低,且观察组上述指标均显著低于对照组(P0.05)。两组并发症总发生率分别为4.92%、20.34%,观察组显著低于对照组(P0.05)。结论:功能性内窥镜鼻窦术用于慢性鼻窦炎患者的临床效果显著优于传统腺样体刮除术治疗,且安全性更高,其可有效改善患者鼻纤毛传输功能,可能与其降低血清TIg E、Eos水平有关。     

Effect of Macrolide Antibiotics on Macrophage Functions

Macrolide antibiotics have a variety of actions other than antimicrobial activities. Recently, it has been suggested that macrolide antibiotics act as immunomodulators. In this study, we evaluated the effects of macrolide antibiotics on macrophage functions. For the macrophage, we used the mouse macrophage cell line J774.1. The following effects of macrolide antibiotics on macrophage functions were evaluated: the effect of macrolide antibiotics on macrophage growth; the phagocytosis of beads; cytocidal activity against Candida albicans; and chemotaxis to lipopolysaccharide (LPS). Macrolide antibiotics except for azithromycin significantly stimulated the growth of the macrophage. In addition, pretreatment with macrolide antibiotics except for roxithromycin significantly stimulated the macrophage phagocytosis of beads, macrophage chemotaxis to LPS, and macrophage cytocidal activity against Candida albicans. These results suggest that macrolide antibiotics stimulate macrophage functions.     

Suppressive activity of macrolide antibiotics on nitric oxide production by lipopolysaccharide stimulation in mice

BACKGROUND: Low-dose and long-term administration of macrolide antibiotics into patients with chronic airway inflammatory diseases could favorably modify their clinical conditions. However, the therapeutic mode of action of macrolides is not well understood. Free oxygen radicals, including nitric oxide (NO), are well recognized as the important final effector molecules in the development and the maintenance of inflammatory diseases. PURPOSE: The influence of macrolide antibiotics on NO generation was examined in vivo. METHODS: Male ICR mice, 5 weeks of age, were orally administered with either roxithromycin, clarithromycin, azithromycin or josamycin once a day for 2-4 weeks. The mice were then injected intraperitoneally with 5.0 mg/kg lipopolysaccharide (LPS) and the plasma NO level was examined 6 h later. RESULTS: Although pre-treatment of mice with macrolide antibiotics for 2 weeks scarcely affected NO generation by LPS injection, the administration of macrolide antibiotics, except for josamycin, for 4 weeks significantly inhibited LPS-induced NO generation. The data in the present study also showed that pre-treatment of mice with macrolide antibiotics for 4 weeks significantly suppresses not only production of pro-inflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha, but also inducible nitric oxide synthase mRNA expressions, which are enhanced by LPS injection. CONCLUSION: These results strongly suggest that suppressive activity of macrolide antibiotics on NO generation in response to LPS stimulation in vivo may, in part, account for the clinical efficacy of macrolides on chronic inflammatory diseases.     

大环内酯类抗生素微生物降解的研究进展

大环内酯类抗生素是一类以大环内酯为母核的广谱抗生素。近些年,由于人们对其不规范的生产和使用,抗生素污染成为了重要的环境问题。大量研究表明,微生物降解是现阶段处理抗生素污染的最理想方法。为进一步推动大环内酯类抗生素生物降解的研究,文中概述了大环内酯类抗生素的环境污染现状、微生物降解菌株、降解酶、降解途径和降解大环内酯类抗生素的微生物处理方法,并对大环内酯类抗生素生物降解亟待解决的瓶颈问题进行了讨论,以期为微生物降解后续研究提供参考。     

酵母中甾醇定向存储转运及理性强化技术研究进展

大环内酯类抗生素是一类以大环内酯为母核的广谱抗生素。近些年,由于人们对其不规范的生产和使用,抗生素污染成为了重要的环境问题。大量研究表明微生物降解是现阶段处理抗生素污染的最理想方法。为进一步推动大环内酯类抗生素生物降解的研究,文中概述了大环内酯类抗生素的环境污染现状、微生物降解菌株、降解酶、降解途径和降解大环内酯类抗生素的微生物处理方法,并对大环内酯类抗生素生物降解亟待解决的瓶颈问题进行了讨论,以期为微生物降解后续研究提供参考。     

Bioassay-guided evolution of glycosylated macrolide antibiotics in Escherichia coli

Macrolide antibiotics such as erythromycin are clinically important polyketide natural products. We have engineered a recombinant strain of Escherichia coli that produces small but measurable quantities of the bioactive macrolide 6-deoxyerythromycin D. Bioassay-guided evolution of this strain led to the identification of an antibiotic-overproducing mutation in the mycarose biosynthesis and transfer pathway that was detectable via a colony-based screening assay. This high-throughput assay was then used to evolve second-generation mutants capable of enhanced precursor-directed biosynthesis of macrolide antibiotics. The availability of a screen for macrolide biosynthesis in E. coli offers a fundamentally new approach in dissecting modular megasynthase mechanisms as well as engineering antibiotics with novel pharmacological properties.     

Lung inflammatory pattern and antibiotic treatment in pneumonia

Background

In community-acquired pneumonia host inflammatory response against the causative microorganism is necessary for infection resolution. However an excessive response can have deleterious effects. In addition to antimicrobial effects, macrolide antibiotics are known to possess immunomodulatory properties.We aimed to evaluate inflammatory cytokine profiles – both locally (bronchoalveolar lavage) and systemically (blood) – in community-acquired pneumonia admitted patients after at least 72 hours of antibiotic treatment (with and without macrolide containing regimens) and requiring bronchoscopic examination for inadequate response due to infection progression and/or lack of clinical stability.

Methods

A prospective study was performed on 52 admitted patients who developed an inadequate response after 72 hours of antibiotic treatment - non-responders community-acquired pneumonia - (blood and bronchoalveolar lavage), and two control groups: 1) community-acquired pneumonia control (blood) and 2) non-infection control (blood and bronchoalveolar lavage). Cytokine profiles (interleukin (IL)-6, IL-8, IL-10), tumour necrosis factor α and clinical outcomes were assessed.

Results

Non–responders patients treated with macrolide containing regimens showed significantly lower levels of IL-6 and TNF-α in bronchoalveolar lavage fluid and lower IL-8 and IL-10 in blood than those patients treated with non-macrolide regimens. Clinical outcomes showed that patients treated with macrolide regimens required fewer days to reach clinical stability (p < 0.01) and shorter hospitalization periods (p < 0.01).

Conclusions

After 72 hours of antibiotic effect, patients who received macrolide containing regimens exhibited lower inflammatory cytokine levels in pulmonary and systemic compartments along with faster stabilization of infectious parameters.     

Macrolide and aminoglycoside antibiotic resistance mutations in the Bacillus subtilis ribosome resulting in temperature-sensitive sporulation

Summary Mutants of Bacillus subtilis resistant to various macrolide antibiotics have been isolated and characterized with respect to their sporulation phenotype and the electrophoretic mobility of their ribosomal proteins (r-proteins). Two types of major alterations of r-protein L17, one probably due to a small deletion, are found among mutants exhibiting high-level macrolide resistance. These mutants are all temperature-sensitive for sporulation (Spo^ts). Low-level resistance to some macrolides is found to be associated with minor alterations in r-protein L17. These mutations do not cause a defective sporulation phenotype. All of the macrolide resistance mutations map at the same locus within the Str-Spc region of the B. subtilis chromosome. Hence, changes in a single ribosomal protein can result in different sporulation phenotypes.Mutants resistant to the aminoglycoside antibiotics neomycin and kanamycin have been isolated. Approximately 5% of these are Spo^ts. Representative mutations, neo 162 and kan25, cause concomitant drug resistance and sporulation temperature-sensitivity and map as single-site lesions in the Str-Spc region of the chromosome. Strains bearing neo162 or kan25 are equally cross-resistant to several aminoglycoside antibiotics but show no resistance to streptomycin or spectinomycin. These mutations define a new B. subtilis drug resistance locus at which mutation can cause defective sporulation.     

Influence of macrolide maintenance therapy and bacterial colonisation on exacerbation frequency and progression of COPD (COLUMBUS): Study protocol for a randomised controlled trial

ABSTRACT: BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive development of airflow limitation that is poorly reversible. Because of a poor understanding of COPD pathogenesis, treatment is mostly symptomatic and new therapeutic strategies are limited. There is a direct relationship between the severity of the disease and the intensity of the inflammatory response. Besides smoking, one of the hypotheses for the persistent airway inflammation is the presence of recurrent infections. Macrolide antibiotics have bacteriostatic as well as anti-inflammatory properties in patients with cystic fibrosis and other inflammatory pulmonary diseases. There is consistent evidence that macrolide therapy reduces infectious exacerbations, decreases the requirement for additional antibiotics and improves nutritional measures. Because of these positive effects we hypothesised that maintenance macrolide therapy may also have beneficial effects in patients with COPD who have recurrent exacerbations. The effects on development of bacterial resistance to macrolides due to this long-term treatment are unknown. Until now, studies investigating macrolide therapy in COPD are limited. The objective of this study is to assess whether maintenance treatment with macrolide antibiotics in COPD patients with three or more exacerbations in the previous year decreases the exacerbation rate in the year of treatment and to establish microbial resistance due to the long-term treatment. Methods/design The study is set up as a prospective randomised double-blind placebo-controlled single-centre trial. A total of 92 patients with COPD who have had at least three exacerbations of COPD in the previous year will be included. Subjects will be randomised to receive either azithromycin 500 mg three times a week or placebo. Our primary endpoint is the reduction in the number of exacerbations of COPD in the year of treatment. DISCUSSION: We investigate whether long-term therapy with macrolide antibiotics can prevent exacerbations in patients with COPD. Additionally, our study aims to assess the effect of long-term use of macrolide on the development of antimicrobial resistance and on inflammatory parameters related to COPD. We believe this study will provide more data on the effects of macrolide treatment in patients in COPD and will add more knowledge on its working mechanisms. Trial registration www.clinicaltrials.gov NCT00985244.     

Short peptides conferring resistance to macrolide antibiotics

Translation of specific short peptides can render the ribosome resistant to macrolide antibiotics such as erythromycin. Peptides act in cis upon the ribosome on which they have been translated. Amino acid sequence and size are critical for peptide activity. Pentapeptides with different consensus sequences confer resistance to structurally different macrolide antibiotics, suggesting direct interaction between the peptide and the drug on the ribosome. Translation of resistance peptides may result in expulsion of the macrolide antibiotics from the ribosome. The consensus sequence of peptides conferring erythromycin resistance is similar to the sequence of the leader peptide involved in translational attenuation of erythromycin resistance genes, indicating that a similar type of interaction between the nascent peptide and antibiotics can occur in both cases.