Kartagener's syndrome. A blinded, controlled study of cilia ultrastructure

We investigated respiratory mucosa cilia ultrastructure in patients homozygous for the gene for Kartagener's syndrome (KS) and patients apparently phenotypic for KS who had bronchiectasis and sinusitis but without situs inversus. Parents, as obligate carriers of the recessive KS gene, were also evaluated among other control groups. The four patients with KS had significantly fewer cilia outer dynein arms than normal subjects or parents of patients with KS. Two of five patients apparently phenotypic for KS demonstrated distinctive ultrastructural changes. No other subjects demonstrated explicit ultrastructural abnormalities. Internal control specimens showed that the number of outer dynein arms was consistent within a subject compared with variation between subjects. The outer dynein arm serves as a dependable ultrastructural marker. Carriers of KS do not demonstrate distinctive morphologic cilia abnormalities. Not every patient with chronic bronchiectasis and sinusitis demonstrates abnormal cilia ultrastructure.     

鼻内类固醇激素对变应性鼻炎动物模型鼻腔黏膜的影响

目的:通过变应性鼻炎(AR)动物模型观察鼻内类固醇激素对鼻腔黏膜的影响。方法:36只SD大鼠随机分为3组:鼻内类固醇激素组(A组),AR模型组(B组)和正常对照组(C组)。A、B组以卵清蛋白建立大鼠AR模型,C组用生理盐水代替卵清蛋白。然后A组以鼻内类固醇激素喷鼻,B、C组以生理盐水代替。末次激发后观察动物鼻部症状和体征,并取鼻黏膜行苏木精-伊红染色计数鼻黏膜内嗜酸粒细胞(EOS)数,阿辛蓝-过碘酸-希夫染色观察杯状细胞变化,扫描电镜下观察各组鼻黏膜超微结构的改变。结果:鼻内类固醇激素能明显减轻AR鼻部症状,其评分与B组差异有统计学意义(P<0.01);其鼻腔黏膜内EOS数和杯状细胞数明显降低,与B组相比差异有统计学意义(P<0.01),而与C组差异无统计学意义(P>0.05);扫描电镜检查结果显示A组鼻黏膜纤毛结构与C组相似,而B组纤毛倒伏、排列紊乱、缠绕集结、大量分泌物附着等。结论:鼻内类固醇激素能明显缓解AR症状及鼻黏膜炎性反应状态,并对受损纤毛有明显修复作用。     

Ciliary ultrastructure in a child with Kartagener's syndrome

Summary Kartagener's syndrome has been characterized by a primary ultrastructural abnormality of the cilia which consequently impairs their movements. We used transmission electron microscopy with tannic acid staining to investigate the fine structure of the cilia from the nasal mucosa of a 7-year-old girl with Kartagener's syndrome. The staining technique employed was useful for visualizing the dynein arms and protofilaments of the microtubules of the cilia. Although 15% of the cilia examined demonstrated microtubular disarrangements, these findings were considered to be acquired changes due to chronic sinusitis. No abnormal ciliary ultrastructures specific to Kartagener's syndrome, such as absence of dynein arms, were detected in this study. In such cases without any abnormal ciliary ultrastructures, it is conceivable that some other unknown factor may be involved in the impaired ciliary movement.     

Polypous ethmoiditis

Investigations of etiology, pathogenesis and treatment of polypous ethmoiditis show the role of chronic inflammation, sensitization and autoimmune reactions in mechanisms of nasal polyposis (NP). The development of postoperative recurrences of NP depends on the microflora, defective microcirculation, permeability of the histohematic barriers of the nasal and labyrinthine mucosa and metabolism of glycosaminoglycanes in the above mucosa. Adequate treatment methods are suggested: He-Ne laser radiation, UV blood radiation, cryotherapy, corticosteroids. Promising are also autovaccine, autovaccine with tissue (polypous) antigen, ozone solutions.     

Ultrastructural changes of the nasal mucosa in primary ciliary dyskinesia

Primary ciliary dyskinesia syndrome (PCD) is a rare, autosomal receive disorder. Kartagener's syndrome is a subgroup of the PCD with situs inversus, bronchiectasis, and sinusitis. The symptoms results from an abnormal ultrastructural morphology of the cilia such as absence of dynein arms and other changes. As a consequence ciliary motility is disturbed. A 25-year-old man was examined because he suffered from recurrent severe pneumonia and Aspergillus infections of the lungs. On electron micrographs, ciliary abnormalities including deficiency of inner and outer dynein arms, dysmorphic outer dynein arms, and disorientation of the cilia were demonstrated. The diagnosis of PCD requires electron-microscopic investigations of the ciliated mucosa. Special attention should be given to ultrastructural changes of nasal or bronchial mucosa if a young patient suffers from recurrent severe respiratory infections.     

Scanning and transmission electron microscopic aspects of the nasal acilia syndrome

A 3-month-old boy was admitted with failure to thrive and persistent fevers. During a 4 month hospitalization for treatment of suspected sepsis, persistent purulent nasal discharge developed. Biopsies of his nasal mucosa on 3 separate occasions disclosed thinned respiratory epithelium and a complete absence of cilia when examined by electron microscopy (EM). Despite an initial granulocytopenia and a wide range in T-cell numbers, he did not show any evidence of lower respiratory tract infection. A tracheal biopsy processed for EM demonstrated normal ciliated epithelium. This patient appears to have an unrecognized syndrome of normal tracheal cilia but absent nasal cilia.     

鼻咽癌放疗后鼻黏膜组织形态学的研究

目的:研究放疗对鼻咽癌患者鼻黏膜组织形态学的影响.方法:按患者纳入条件和剔除条件选择鼻咽癌患者47例,于放疗前后各取中鼻甲黏膜组织1块,采用常规苏木精-伊红染色及PAS染色,光镜下观察鼻咽癌放疗前后中鼻甲黏膜之上皮层的纤毛和细胞、基底层及固有层的腺体和腺细胞的改变;同时随机抽取6例用扫描电镜和透射电镜观察其上皮层的纤毛及纤毛柱状上皮细胞的变化.结果:放疗前,47例患者鼻黏膜组织形态均正常;放疗后,6例无明显变化,41例出现不同层次和不同程度改变.光学显微镜下见:上皮细胞及纤毛脱落,基底膜增厚,固有层的浆液腺减少,黏液腺增多,血管扩张、充血、增生,血管内皮细胞损伤等;扫描电镜下见:纤毛结构异常,出现脱落、粘连成簇状等现象;透射电镜下见:上皮细胞的细胞核形态不规则、固缩,细胞质出现空泡,细胞器明显减少等.结论:鼻咽癌放疗后鼻黏膜组织形态受到不同程度破坏,这可能是鼻咽癌放疗后并发鼻及鼻窦炎的病理学基础.     

常用减充血剂对鼻黏膜纤毛毒性的观察

目的:观察减充血剂对鼻黏膜纤毛的毒性作用,为临床选择合适的鼻腔减充血剂提供参考。方法:①选健康志愿者100例,分别用0.05%、0.025%盐酸羟甲唑啉,1.0%、0.5%麻黄素喷鼻7d,进行糖精试验以检测鼻黏膜纤毛输送率(MTR),并与对照组进行比较。②用药7d后每组各取1例下鼻甲黏膜进行扫描电镜观察。结果:①用药7d后,0.05%盐酸羟甲唑啉组鼻黏膜纤毛MTR为(7.64±1.56)mm/min;0.025%盐酸羟甲唑啉组为(7.46±1.65)mm/min,其差异无统计学意义(P>0.05);1.0%麻黄素组为(4.73±2.03)mm/min;0.5%麻黄素组为(4.38±2.04)mm/min,其差异亦无统计学意义(P>0.05)。0.05%、0.025%盐酸羟甲唑啉组分别与对照组[(7.14±1.76)mm/min]比较,差异无统计学意义(均P>0.05);1.0%、0.5%麻黄素组分别与对照组比较,差异有统计学意义(均P<0.01)。0.05%、0.025%盐酸羟甲唑啉组分别与1.0%、0.5%麻黄素组比较,差异有统计学意义(均P<0.05)。②电镜观察:1.0%、0.5%麻黄素组黏膜上皮纤毛脱落,0.05%、0.025%盐酸羟甲唑啉组纤毛排列整齐。结论:麻黄素对鼻黏膜纤毛有不良影响;盐酸羟甲唑啉对鼻黏膜纤毛无明显影响,没有破坏鼻黏膜纤毛的正常生理功能,是理想的鼻腔减充血剂。     

慢性鼻-鼻窦炎鼻息肉内镜鼻窦术后上颌窦口黏膜恢复过程观察

目的 试图通过对内镜鼻窦手术(endoscopic sinus surgery,ESS)后患者鼻腔鼻窦黏膜的内镜、光镜、透射电镜和扫描电镜下连续动态观察,揭示病变黏膜转归的过程。方法 选取2001年1-12月行ESS的慢性鼻-鼻窦炎伴鼻息肉患者31例(53侧)作为研究对象,其中Ⅱ型2期11例(20侧)、3期12例(20侧),Ⅲ型8例(13侧)。分别于ESS术前、术后2-3周、8-11周、13-16周钳取上颌窦口后囟相同部位的黏膜组织进行观察。结果 术前均可见上皮剥蚀、鳞状上皮化生、腺体及纤维组织增生(53侧);微管结构异常、线粒体减少(53侧)。术后2-3周,形态学观察与术前比较没有明显的改变。术后8-11周,纤毛柱状细胞增多,并可见许多带有微绒毛的柱状细胞和大量短纤毛,所有病例均可见病理性腺体及纤维组织增生。术后13-16周,Ⅱ型2、3期和Ⅲ型患者术腔光滑干净,上皮化较好(50侧),窦口通畅(53侧)。纤毛覆盖面积增加,方向一致(50侧)。微管结构清晰,线粒体狭长致密(49侧)。3侧无纤毛柱状细胞排列整齐,形成病理性修复。结论 ESS术后,黏膜形态的基本恢复一般需要3个月左右;有些病理改变是不可逆的;病变程度与黏膜修复情况有关;术中尽可能多地保留黏膜组织、术后局部及时清理换药,有利于黏膜纤毛的形态和功能的恢复。     

麻黄碱滴鼻5天对家兔鼻腔黏膜的影响

目的 通过麻黄碱对家兔鼻腔黏膜纤毛影响的动态观察,为临床选择合适的鼻腔减充血剂滴用时间提供参考.方法 以27只新西兰白兔为实验对象,2只为对照,其余25只均以1%麻黄碱鼻腔点鼻5 d,分别于点药后当天、10 d、20 d、30 d、50 d处死,取鼻中隔黏膜,进行电镜扫描观察.结果 滴用麻黄碱后家免鼻腔黏膜纤毛排列紊乱...     

Investigation of the nasal mucosa in perennial allergic rhinitis with SEM and TEM

The ultrastructure of 20 PAR nasal mucosa specimens was investigated with both transmission and scanning electron microscopes. The cilia were found to be defective or desquamated in advanced cases. Cilia in PAR may be divided into three types: normal, adherent and exfoliative types. It had been found that changes in cilia morphology and its function varied with the duration of the disease. The nasal mucosa showed inflammatory cell infiltration and increase in number of glands. Plasma cells full of secretory granules were found both in the epithelial layer and lamina propria. Capillaries, arterioles and venules showed various degrees of pathological changes. The cholinergic nerve endings had increased in number at the expense of the adrenergic nerve endings.     

慢性鼻-鼻窦炎鼻息肉内镜鼻窦术后上颌窦口黏膜恢复过程观察

目的 试图通过对内镜鼻窦手术(endoscopic sinus surgery，ESS)后患者鼻腔鼻窦黏膜的内镜、光镜、透射电镜和扫描电镜下连续动态观察，揭示病变黏膜转归的过程。方法 选取2001年1～12月行ESS的慢性鼻一鼻窦炎伴鼻息肉患者31例(53侧)作为研究对象，其中Ⅱ型2期11例(20侧)、3期12例(20侧)，Ⅲ型8例(13侧)。分别于ESS术前、术后2～3周、8～11周、13～16周钳取上颌窦口后囟相同部位的黏膜组织进行观察。结果 术前均可见上皮剥蚀、鳞状上皮化生、腺体及纤维组织增生(53侧)；微管结构异常、线粒体减少(53侧)。术后2～3周，形态学观察与术前比较没有明显的改变。术后8～11周，纤毛柱状细胞增多，并可见许多带有微绒毛的柱状细胞和大量短纤毛，所有病例均可见病理性腺体及纤维组织增生。术后13～16周，Ⅱ型2、3期和Ⅲ型患者术腔光滑干净，上皮化较好(50侧)，窦口通畅(53侧)。纤毛覆盖面积增加，方向一致(50侧)。微管结构清晰，线粒体狭长致密(49侧)。3侧无纤毛柱状细胞排列整齐，形成病理性修复。结论 ESS术后，黏膜形态的基本恢复一般需要3个月左右；有些病理改变是不可逆的；病变程度与黏膜修复情况有关；术中尽可能多地保留黏膜组织、术后局部及时清理换药，有利于黏膜纤毛的形态和功能的恢复。     

Histological comparison of nasal polyposis in black African,Chinese and Caucasian patients

We have compared the histological aspects of nasal mucosa biopsies (n = 130) obtained during bilateral polypectomy and ethmoidectomy performed in black African (n = 50), Chinese (n = 30) and Caucasian patients (n = 50) suffering from bilateral nasal polyposis (NP). The three groups of patients were matched for age and sex. The African and Chinese patients did not receive any medical treatment before endoscopic nasal surgery (ENS). All Caucasian patients were treated with corticosteroid nasal spray (400 mg/day) for 6 months. In the absence of subjective and objective clinical improvement, ENS was performed after antibiotic treatment for 10 days and prednisolone 1 mg/kg/day for 5 days. Clinical staging of the NP was graded from I to III (I = polyps limited to the middle meatus, II = polyps extending beyond the middle meatus, and III = polyps occupying the entire nasal cavity). Stage I NP was present in 22% of the Caucasians and 30% of the Chinese. Stage II was found in 58% of the Caucasians, 56% of the Chinese and 8% of the Africans. Stage III was found in 92% of the Africans, while only 20% of the Caucasians and 14% of the Chinese patients had stage III. The extent of submucosal oedema and number of mast cells were similar for the three groups of patients. A significantly greater number of eosinophils were observed in African polyps. Lymphocytes as well as plasmocytes were rare in African but abundant in polyps from both Chinese and Caucasian. Ulceration of the overlying epithelium of the polyps was observed in 20% of the African and 10% of both Chinese and Caucasians patients. We did not find any significant thickening of the basal membrane. We cannot exclude the possibility that the histological difference observed between African and Chinese polyps is related to the very common use among the Chinese population of topical intranasal treatment according to their traditional medicine practices. Since no major histological difference was found in the nasal mucosa and polyps obtained from the three groups of patients, NP in African, Chinese and Caucasian patients is very probably a similar inflammatory disease in all three ethnic groups.     

Primary Kaposi’s sarcoma of the nasal cavity not associated with AIDS

Kaposi’s sarcoma (KS) is an unusual vascular tumor characterized by multiple reddish blue nodules, which usually present on the skin of the lower and upper extremities. KS may also involve mucosal sites, lymph nodes and visceral organs. During the last two decades, with the large increase in the incidence of this tumor associated with the acquired immune deficiency syndrome (AIDS), there have been increasing number of cases with KS presenting on the skin or mucosa of the head and neck. A review of the literature revealed that only six cases of primary KS of the nasal cavity have previously been published and only one of them presented in a patient not associated with AIDS. We report the case of a 59-year-old woman who presented 4 years ago with nasal obstruction and intermittent minor epistaxes. Physical examination revealed the presence of a fleshy tumor arising from the left nasal septum, which was excised. Histological examination of the tumor showed morphological and immunohistochemical features of KS. A complete physical and laboratory examination revealed no other pathological findings. The patient received no further treatment and 4 years later, she is in excellent condition. In the present study, we report the second case where the primary manifestation of the KS was in the nasal cavity in a patient with an adequate immune system.     

Development and validation of a method of cilia motility analysis for the early diagnosis of primary ciliary dyskinesia

BackgroundPrimary ciliary dyskinesia (PCD) is a clinically uniform entity, but cilia motility and structure can vary between patients, making the diagnostic difficult. The aim of this study was to evaluate the sensitivity and specificity in diagnosing PCD of a system of high-resolution digital high-speed video analysis with proprietary software that we developed for analysis of ciliary motility (Desinsoft-Bio 200). The secondary aim was to correlate nasal ciliary activity with clinical and structural abnormalities in PCD.Material and methodsWe analysed nasal mucociliary transport, cilia ultrastructure, nasal ciliary beat frequency and beat pattern studied by high-resolution digital high-speed video in 25 cases of PCD (11 Kartagener syndrome), 27 secondary ciliary dyskinesia and 34 healthy volunteers.ResultsNasal mucociliary transport was defective in both primary and secondary ciliary dyskinesia. Ciliary immotility was observed only in 6 patients with Kartagener syndrome and correlated with the absence of dynein. We observed a correlation between partial dynein deficiencies and ciliary dyskinesia. Cilia activity and structure was normal in secondary ciliary dyskinesia.ConclusionNasal mucociliary transport showed high sensitivity for PCD diagnosis with a low specificity. High-resolution digital high-speed video has a high sensitivity and specificity for diagnosing PCD. This system of video analysis is more useful than ultrastructural study and mucociliary transport for PCD screening. Dynein absence is correlated with cilia immotility and is more common in patients with Kartagener syndrome.     

An observation of the effect of sulfur dioxide on rat nasal mucosa

This paper reports the effect of SO2 on rat nasal mucosa. The rats were forced to inhale SO2 and the effect on the nasal mucosa observed. The rats were divided into four groups. The first group inhaled 10ppm SO2; the second group 20ppm; the third group 40 ppm and the fourth group served as control. The observation lasted for 6 months. It was found that the nasal mucosa in the control group remained columnar ciliated. In the experimental groups, during the early stage (groups I, II) of exposure, there was no significant morphological change in epithelium. Then (groups I, II) the epithelium changed into cuboidal with complete disappearance of cilia, only some short and slender microvilli remained. While in the late stage (group III), the epithelium had transformed into squamous stratified and the amount of mucosal glands reduced.     

Determination of reactive oxygen species in nasal polyps

A strong relationship between tissue damage and reactive oxygen species (ROS) has been established by previous studies. The aim of the current study was to evaluate the presence of ROS in nasal polyps (NP) by measuring luminol and lucigenin amplified chemiluminescence (CL). Three groups of specimens were studied. Group 1 composed of NPs of 15 patients, and group 2 constituted of healthy appearing nonpolypoid nasal mucosa of the same patients. Group 3 specimens (control group) were obtained from 15 patients who underwent septoplasty and/or inferior turbinectomy operations, and detected to be free of rhinosinusitis. None of the patients had a history of allergy, asthma, or aspirin sensitivity, and all patients showed negative results to a skin prick test. The ROS levels were measured directly with luminol and lucigenin amplified CL. CL measurements revealed significant differences between ROS constituents of NP (group 1) and control (group 3) tissue samples. CL measurements of healthy appearing nonpolypoid nasal mucosa (group 2) of the NP patients revealed values that were scattered between the values of the other two groups. Although insignificant, ROS levels of the nonpolypoid nasal mucosa (group 2) were found to be higher than normal controls (group 3). In this study, ROS levels of NP tissue samples were directly measured. In our study, by measuring high ROS levels in NP samples, a strong relationship between tissue damage in NPs and ROS has been demonstrated, and the contribution of ROS in the pathophysiology of nasal polyposis has been emphasized.     

iTRAQ技术检测鼻息肉和正常鼻黏膜组织间差异表达蛋白质

目的 通过分析鼻息肉蛋白质表达谱的变化探索鼻息肉的发病机制。 方法 采集正常成年人中鼻道鼻腔黏膜以及鼻息肉患者的息肉组织(各4例),用同位素标记相对和绝对定量(iTRAQ)技术分析标本中的蛋白表达谱,筛选差异表达蛋白质。 结果 共筛选出差异表达蛋白311个。上调蛋白88个,主要包括CLC、PLEKHA7等,其中上调2倍以上的蛋白18个;下调蛋白223个,主要包括S100A1等,其中下调50%以上的蛋白65个。 结论 鼻息肉组织蛋白表达谱与正常中鼻道鼻腔黏膜相比有较大差异,差异蛋白可能在鼻息肉的发生发展过程中发挥重要作用,其中CLC可能参与鼻黏膜的炎症及免疫反应,PLEKHA7与鼻腔黏膜损伤修复有关。     

p-ERK2及ERK2在鼻息肉组织的表达及其意义

目的 检测磷酸化细胞外信号调节激酶2(p-ERK2)及细胞外信号调节激酶2(ERK2)在鼻息肉(NP)组织的定位及表达情况;初步探讨p-ERK2/ERK2在NP发病中的临床意义。 方法 应用间接免疫荧光技术(IIF)及蛋白免疫印记技术(WB)检测p-ERK2/ERK2在NP及正常鼻黏膜组织的定位及表达水平,并探讨其临床意义。 结果 NP:p-ERK2主要表达在增生的上皮细胞、炎症细胞以及腺上皮细胞,主要位于胞核;ERK2主要表达在腺上皮细胞、炎症细胞,主要位于胞质。正常鼻黏膜组织:p-ERK2主要表达在炎症细胞、腺上皮细胞,主要位于胞核;ERK2主要位于炎症细胞,主要位于胞质。荧光强度值:p-ERK2在NP和正常鼻黏膜组织的表达有统计学差异(P<0.05);ERK2在NP和正常鼻黏膜组织的表达无统计学差异(P>0.05)。WB灰度值:p-ERK2在NP和正常鼻黏膜组织的表达有统计学差异(P<0.05);ERK2在NP和正常鼻黏膜组织的表达无统计学差异(P>0.05)。 结论 p-ERK2在NP的发病机制中可能具有重要作用,而ERK2与NP的发生可能无关。ERK2在NP组及正常鼻黏膜组织均表达,提示ERK2可能参与鼻黏膜正常生理功能的维持。