The chinchilla microdialysis model for the study of antibiotic distribution to middle ear fluid

In cases of slow or limited penetration of an antibiotic to the site of infection such as in acute otitis media (the middle ear), plasma levels of the agent may not reflect the concentrations that are relevant in determining clinical outcome. There is a need for a model that allows prediction of the time-course of unbound, pharmacologically active drug levels in middle ear fluid (MEF). This article introduces microdialysis as a sampling tool to measure unbound antibiotic concentrations in the MEF of the chinchilla, and briefly summarizes the results of studies of MEF penetration of a cephalosporin, a macrolide, and a ketolide antibiotic using this technique. The general concurrence of preliminary results of the chinchilla studies with clinical findings suggests that the chinchilla microdialysis model may be useful in predicting efficacy in patients.     

64层VCT对外中内耳结构的重建成像探讨

目的：探讨64层螺旋容积扫描（简称VCT）对双耳重度感音性耳聋患者外耳、中耳、内耳立体影像的人工耳蜗植入术前重建。方法：利用64层VCT对19例双耳重度感音性耳聋患者进行了容积扫描及外耳、中耳、内耳影像结构的立体重建。结果：容积扫描及重建的速度快,重建出清晰的外耳、中耳、内耳的结构。结论：64层VCT的容积重建技术可以清楚的显示人工耳蜗植入时所要观察到的外耳道后壁,面神经管走行,砧骨短脚,外半规管,面神经隐窝,镫骨肌腱,鼓岬,圆窗龛,鼓阶,骨迷路及膜迷路。     

TGF与中耳胆脂瘤相关性的Meta分析

目的 对转化生长因子 (transforming growth factor,TGF)与中耳胆脂瘤相关性研究的国内文献进行Meta分析,探讨TGF与中耳胆脂瘤发病的相关性.方法 检索中国学术期刊全文数据库、中国生物医学文献数据库、万方及维普数据库,收集 1989～2009年国内公开发表论文,且为TGF在中耳胆脂瘤中表达...     

分泌性中耳炎听力与中耳积液P物质含量的相关性

目的探讨与分泌性中耳炎有关的P物质对患者听力的影响,为临床工作提供依据。方法观察64例(79耳)分泌性中耳炎患者的听力、中耳积液性质和采用放射免疫技术测定其中耳积液中的P物质含量之间的关系。结果浆液组听力下降为传音性的耳聋,而黏液组的听力下降则为混合性和感音性耳聋,且听力损失的程度黏液组明显多于浆液组;浆液性中耳积液中P物质的浓度比黏液性者明显增高(P<0.01);浆液组患者听阈与其中耳积液中P物质含量呈正相关(r=0.985,P<0.01),黏液组听阈与中耳积液中P物质含量不相关(r=-0.2415,P>0.05)。结论①分泌性中耳炎患者的听力损失在黏液期较重,且呈现出感音性听力下降;②P物质在分泌性中耳炎的浆液期起主要作用,是导致浆液期传音性听力下降的主要致病介质。     

中耳变压治疗急性分泌性中耳炎的临床研究

目的：探讨中耳变压疗法治疗成人急性分泌性中耳炎的临床疗效。方法：选择2010年2月～2011年2月来本院耳鼻喉科就诊的成人急性分泌性中耳炎患者56例（72耳）,按年龄将56例患者进行配对,分成治疗组和对照组,治疗组使用中耳变压疗法进行治疗,对照组则使用一般的Valsava吹张法进行治疗,观察并比较两组的治疗效果和并发症情况。结果：对56例（72耳）患者进行相应的治疗后进行3个月的随访,治疗组的PTA和PTA-ABG均明显低于对照组（P〈0.05）。治疗组的痊愈率和总有效率均明显高于对照组（P〈0.05）。结论：中耳变压疗法治疗成人急性分泌性中耳炎的治疗上疗效可靠,值得在临床上进行推广。     

曲安奈德注射液联合左氧氟沙星滴耳液治疗急性化脓性中耳炎的临床研究

目的观察鼓室内注射曲安奈德联合左氧氟沙星滴耳液治疗急性化脓性中耳炎的临床疗效及安全性。方法将46例急性化脓性中耳炎患者随机分为对照组及试验组,每组23例。对照组给予盐酸左氧氟沙星滴耳液,每次7滴,每天2次,滴耳;试验组在对照组的基础上加用曲安奈德注射液,每次40 mg,每周2次,鼓室内注射。比较2组患者治疗前后的症状积分、气导听阈水平、治疗有效率及药物不良反应发生情况。结果治疗后,试验组的总有效率为95.65%(22例/23例),对照组为73.91%(17例/23例),差异有统计学意义(P<0.05)。治疗后,对照组与试验组症状积分分别为(2.93±0.41),(1.15±0.16)分,气导听阈水平分别为(22.86±3.26),(16.29±2.32)d B,差异均有统计学意义(均P<0.05)。对照组的不良反应有耳道内灼热、头晕,药物不良反应发生率为8.69%(2例/23例);试验组的不良反应有注射部位疼痛、耳内胀闷,药物不良反应发生率为13.04%(3例/23例),2组患者的药物不良反应发生率比较,差异无统计学意义(P>0.05)。结论鼓室内注射曲安奈德联合左氧氟沙星滴耳液能够显著改善急性化脓性中耳炎患者的临床症状和听力,提高临床疗效,且安全性较高。     

分泌性中耳炎患者血清及耳积液HA及白介素的变化观察

目的：观察分泌性中耳炎患者血清及耳积液HA及白介素的变化情况。方法选取2011年12月～2013年7月于本院进行诊治的42例分泌性中耳炎患者为观察组,并以42名健康人员为对照组,然后将观察组血清及耳积液HA、白介素和对照组的血清HA、白介素进行比较。结果观察组的血清HA、白介素水平均高于对照组,且慢性分泌性中耳炎患者的血清及耳积液检测结果均高于急性分泌性中耳炎患者,耳积液检测结果高于血清检测结果,P均＜0.05,差异均有统计学意义。结论分泌性中耳炎患者血清及耳积液HA及白介素呈现异常的状态,且慢性期患者更为明显,耳积液的检测水平均高于血清含量,因此可用于疾病的诊断与治疗监测的指标。     

中耳变压疗法治疗成人急性分泌性中耳炎的疗效分析

目的探讨中耳变压疗法治疗成人急性分泌性中耳炎的疗效。方法选择48例（56耳）成人急性分泌性中耳炎患者,按年龄配对分为中耳变压疗法治疗组（24例,28耳）和Valsava法吹张对照组（24例,28耳）,治疗后随访3个月,比较其疗效。结果治疗组治疗后纯音听阈均值、气骨导差均值明显低于对照组（P〈0．05）。治疗组痊愈24耳,显效1耳,有效2耳,总有效率为96．42％（27／28耳）,对照组痊愈17耳,显效3耳,有效4耳,总有效率为85．71％（24／28耳）,两组间痊愈率差异有统计学意义（χ2=4．462,P=0．035）,两组间总有效率差异无统计学意义（χ2=0．878,P=0．349）。两组均无化脓性中耳炎、鼓膜穿孔等并发症发生。结论应用中耳变压疗法治疗成人急性分泌性中耳炎疗效优于传统Valsava法吹张治疗,值得在临床上推广应用。     

Effectiveness of amoxicillin, azithromycin, cefprozil and clarithromycin in the treatment of acute otitis media in children: a population-based study

Population-based studies may give results different from randomized clinical trials assessing the efficacy of antibiotics.OBJECTIVE: To determine the effectiveness of amoxicillin, azithromycin, cefprozil and clarithromycin in the treatment of acute otitis media (AOM) in children. METHODS: Using Quebec Health Insurance databases (RAMQ), we selected a cohort of children aged < or = 6 years, with a first episode of AOM between 1999 and 2002. The index AOM was defined as a medical service claim with a diagnosis of AOM and an antibiotic dispensation in the following 72 hours. Failures were defined as a new antibiotic dispensation, a hospitalization or outpatient visit for complications related to AOM in the 30 days after the index AOM. Data were analyzed using logistic regression. RESULTS: Overall, 12,693 failures occurred among 60,513 first episodes of AOM. Azithromycin was the only antibiotic that was associated with a decreased risk of failure overall, when compared to amoxicillin (OR 0.88, 95% CI: 0.82, 0.94). However in the first 3 days of treatment (n = 680), azithromycin was more associated with treatment failure (OR 1.6, 95% CI: 1.3, 2.0). Compared to amoxicillin, post-therapy failures (n = 9387) were more likely to occur with cefprozil (OR 1.2, 95%CI: 1.2, 1.3) but were less with azithromycin (OR 0.8 95% CI: 0.8, 0.9). CONCLUSIONS: Azithromycin had the lowest risk of failure 30 days after the onset of treatment but an increased risk of failure during the first few days of treatment. Amoxicillin remains an effective first-line drug for treating first AOM episodes.     

中耳胆脂瘤患者手术方式选择与术后疗效分析

目的：通过对比不同手术方式的中耳胆脂瘤患者术后疗效,总结中耳胆脂瘤的手术方式及经验。方法回顾性分析手术并随访的中耳胆脂瘤患者的资料,按照不同手术方式分成三组,即A组（乳突根治术）、B组（开放式乳突切开＋鼓室成形术）、C组（完壁式乳突切开＋鼓室成形术）,分析比较各组患者术后干耳时间、手术前后患者听力变化及手术前后耳鸣、眩晕等情况。结果 B组干耳时间较A组短,C组较A组干耳时间短,C组较B组干耳时间短,每组间两两比较差异有统计学意义。术后半年听力结果提示A组患者听力与术前比较差异无统计学意义,B组、C组较术前均有提高,差异有统计学意义。将三组患者术后气骨导差值两两比较,B组与A组的差异有统计学意义,C组与A组的差异有统计学意义,B组与C组的差异无统计学意义。三组手术前均有部分患者伴随耳鸣症状,手术后耳鸣残疾量表（ THI）评分均较术前下降,A组手术前后THI值差异无统计学意义,B组、C组差异有统计学意义。 A组、B组术前有部分患者伴随眩晕症状,两组手术后眩晕致残量表评分较术前均有下降,差异有统计学意义。结论中耳胆脂瘤患者各种手术治疗后均可有效去除病灶,实现干耳,改善眩晕。与乳突根治术相比,开放式乳突切开术＋鼓室成形术和完壁式乳突切开术＋鼓室成形术可以缩短术后干耳时间、提高患者术后听力,减轻耳鸣症状。     

氧氟沙星滴耳液配合泼尼松龙鼓室注射治疗分泌性中耳炎疗效观察

目的探讨鼓室内注入0.3%氧氟沙星滴耳液配合泼尼松龙治疗分泌性中耳炎（SOM）的效果。方法对140例（160耳）SOM患者（治疗组）行鼓膜穿刺,并向鼓室内注射0.3%氧氟沙星滴耳液和泼尼松龙;对照组144例（160耳）鼓室内注射泼尼松龙。随访2个月,对两组的总有效率和治疗次数进行比较。结果治疗组总有效率为97.5%,对照组总有效率为90.0%,两组比较,χ2=7.68,P〈0.01;两组治疗次数比较,χ2=104.532,P〈0.01。结论 0.3%氧氟沙星滴耳液配合泼尼松龙鼓室内注射对SOM患者有明显疗效。     

MMP-2和CD147在中耳胆脂瘤中的表达

目的:研究基质金属蛋白酶-2(MMP-2)和细胞粘附因子CD147在中耳胆脂瘤上皮中的表达,探讨其表达对中耳胆脂瘤侵袭能力的影响。方法:应用免疫组化方法检测MMP-2和CD147在30例中耳胆脂瘤上皮和10例正常外耳道上皮中的表达,应用计算机图像分析系统对其表达进行定量分析。结果:MMP-2和CD147在胆脂瘤上皮中表达的阳性率分别为87.3%和84.5%,均显著高于正常外耳道上皮(P<0.05)。胆脂瘤上皮中MMP-2和CD147表达呈正相关(r=0.682,P<0.01);胆脂瘤侵袭能力与MMP-2表达有显著相关性(r=-0.591,P<0.01),与CD147表达也有显著相关性(r=-0.627,P<0.01)。结论:MMP-2和CD147的表达与胆脂瘤的侵袭能力有显著相关性,提示MMP-2和CD147高表达是胆脂瘤引起骨质破坏吸收的主要因素之一。     

Distribution characteristics of clarithromycin and azithromycin, macrolide antimicrobial agents used for treatment of respiratory infections, in lung epithelial lining fluid and alveolar macrophages

The distribution characteristics of clarithromycin (CAM) and azithromycin (AZM), macrolide antimicrobial agents, in lung epithelial lining fluid (ELF) and alveolar macrophages (AMs) were evaluated. In the in vivo animal experiments, the time‐courses of the concentrations of CAM and AZM in ELF and AMs following oral administration (50 mg/kg) to rats were markedly higher than those in plasma, and the area under the drug concentration–time curve (AUC) ratios of ELF/plasma of CAM and AZM were 12 and 2.2, and the AUC ratios of AMs/ELF were 37 and 291, respectively. In the in vitro transport experiments, the basolateral‐to‐apical transport of CAM and AZM through model lung epithelial cell (Calu‐3) monolayers were greater than the apical‐to‐basolateral transport. MDR1 substrates reduced the basolateral‐to‐apical transport of CAM and AZM. In the in vitro uptake experiments, the intracellular concentrations of CAM and AZM in cultured AMs (NR8383) were greater than the extracellular concentrations. The uptake of CAM and AZM by NR8383 was inhibited by ATP depletors. These data suggest that the high distribution of CAM and AZM to AMs is due to the sustained distribution to ELF via MDR1 as well as the high uptake by the AMs themselves via active transport mechanisms. Copyright © 2011 John Wiley & Sons, Ltd.     

Survivin及Livin在中耳胆脂瘤组织中的表达及相关性研究

目的 探讨Survivin及Livin在中耳胆脂瘤组织中的表达及相关性。方法采用PV-9000二步法免疫组化法检测60例胆脂瘤中耳炎患者(实验组)和20例正常人(对照组)外耳道骨部皮肤组织中凋亡抑制蛋白Survivin和Livin的表达。结果实验组组织中Survivin和Livin蛋白表达的阳性率分别为26.7%和16.7%,明显低于对照组的65.0%和55.0%,差异有统计学意义,P<0.01(χ2=9.538,11.386)。胆脂瘤组织中survivin与livin蛋白(γ=0.614,P<0.01)的表达呈显著正相关。结论胆脂瘤组织中Survivin与livin蛋白的表达明显下调,可能在胆脂瘤的发生、发展中起协同作用。     

NO 、NOS、SOD及氧自由基在分泌性中耳炎中耳积液和血清中的表达及意义

目的：探讨一氧化氮(nitric oxide，NO)、一氧化氮合酶(nitric oxide synthase，NOS)、超氧化物歧化酶(superoxide dismutase，SOD)及氧自由基在分泌性中耳炎(secretory otitis media，SOM)发病机制中的作用。方法：对实验性SOM和SOM患者中耳积液和血清中NO、NOS、SOD及氧自由基进行检测，并比较单纯应用抗生素与NO合成抑制荆 抗氧化荆 抗生素治疗SOM后血清中各指标的变化情况。结果：实验性SOM和SOM患者血清中NO、NOS、SOD、MDA含量均明显高于正常对照组。鼓室积液中NO、NOS、SOD、MDA含量均明显高于血清中含量。NO合成抑制荆 抗氧化荆 抗生素治疗SOM后血清NO、NOS、SOD、MDA含量明显低于单纯应用抗生素组，差别有统计学意义。结论：NO、NOS、SOD及氧自由基在分泌性中耳炎发病和转归中起重要作用，N-硝基-L-精氨酸甲酯(L-NAME)、维生素C、维生素E及SOD对SOM的治疗有效。     

Comparison of drug concentrations between whole blood and oral fluid

The relationship of drug concentrations between oral fluid and whole blood was evaluated by studying the linear correlation of concentrations and calculating the oral fluid to blood concentration ratios (OF/B) for different substances. Paired oral fluid and whole blood samples were collected from volunteers and persons suspected of drug use in four European countries. Oral fluid samples were collected with the Saliva?Sampler? device. All samples were analyzed for drugs of abuse and psychoactive medicines with validated gas and liquid chromatography‐mass spectrometric methods. The median OF/B ratios were, for amphetamines 19–22, for opioids 1.8–11, for cocaine and metabolites 1.7–17, for tetrahydrocannabinol (THC) 14, for benzodiazepines 0.035–0.33, and for other psychoactive medicines 0.24–3.7. Most of the these results were close to theoretical values based on the physicochemical properties of the drugs and to values presented earlier, but there was a lot of inter‐individual variation in the OF/B ratios. For all substances, except for lorazepam (R² = 0.031) and THC (R² = 0.030), a correlation between the oral fluid and whole blood concentrations was observed. Due to large variation seen here, drug findings in oral fluid should not be used to estimate the corresponding concentrations in whole blood (or vice versa). However, detection of drugs in oral fluid is a sign of recent drug use and oral fluid can be used for qualitative detection of several drugs, e.g. in epidemiological prevalence studies. By optimizing the sampling and the analytical cut‐offs, the potential of oral fluid as a confirmation matrix could be enhanced. Copyright © 2013 John Wiley & Sons, Ltd.     

Antibacterial activity of human pleural fluid: alone and in combination with antibiotics.

This study investigated the antibacterial activity of human pleural fluid (HPF) and its interaction with gentamicin (GM), meropenem (MRPM), ciprofloxacin (CPFX) and clarithromycin (CLTM) against Escherichia coli K-12, Proteus rettgeri (Sanelli) and Staphylococcus aureus. Minimal inhibitory concentrations or volumes, expressed as MIC or volume percentage (MIV, V/V%), were measured using a micro-dilution technique in microtiter plates. The antimicrobial activity of HPF combinations with antimicrobial drugs was evaluated by the chequerboard method calculating the fractional inhibitory concentration index (FIC) values. HPF MIVs (%) were: 37.54; 19.85; 1.74 for E. coli, P. rettgeri and S. aureus, respectively. FIC values indicated a synergistic effect with GM, MRPM and CPFX against E. coli and P. rettgeri and an additive effect for the combination HPF plus CLTM or indifference with HPF plus GM and CPFX against S. aureus. The presence of antibodies, complement factors, lysozyme, -defensins and enzymes could explain the antimicrobial activity of HPF and its synergistic effect with certain antibiotics.     

Effects of tramadol on synovial fluid concentrations of substance P and interleukin-6 in patients with knee osteoarthritis: comparison with paracetamol

Both the analgesic drugs tramadol and paracetamol are widely used for the symptomatic therapy of osteoarthritis (OA). The aim of this double-blind, randomised study in patients with knee OA was to compare their effects on synovial fluid concentrations of interleukin (IL)-6 and substance P (SP). Moreover, we evaluated plasma and synovial fluid concentrations of tramadol and its active metabolite (O-desmethyl-tramadol, M1) after oral treatment with this drug. Twenty patients were enrolled. A group of 10 patients received tramadol (50 mg three times a day), and another group of 10 patients were treated with paracetamol (500 mg three times a day) for 7 days. Both drugs significantly reduced the intensity of joint pain. The synovial fluid concentrations of SP were significantly reduced only by the treatment with tramadol. In this group of patients, IL-6 synovial fluid concentrations were slightly, but not significantly, decreased. Paracetamol did not significantly change the synovial fluid concentrations of SP and IL-6. After oral administration, a considerable amount of tramadol was measurable in synovial fluid. Both in plasma and synovial fluid the concentrations of M1 were markedly lower than those of tramadol, with a T/M1 ratio of 14.7+/-4.6 and 9.3+/-3.9, respectively. These data demonstrate that the activity of tramadol may involve the modulation of inflammatory mediators. Moreover, they indicate that after oral treatment with tramadol, both the parent drug and its active metabolite can penetrate into synovial fluid.     

Correlations between theophylline concentrations in plasma,erythrocytes and cantharides-induced blister fluid and peak expiratory flow in asthma patients

Summary Theophylline levels in plasma, erythrocytes and cantharides-induced blister fluid (BF) have been correlated with peak expiratory flow (PEF) in asthmatic patients. Nine asthmatic men received an IV infusion of 240 mg theophylline at a constant rate for 30 min.The theophylline concentrations in erythrocytes and blister fluid were 37 % and 78 % of those in plasma. There was not a strong correlation between erythrocyte or blister fluid penetration and the clinical effect of theophylline.