Toll-like receptors 2, 3 and 4 (TLR-2, TLR-3 and TLR-4) are expressed in the microenvironment of human acquired cholesteatoma

Human toll-like receptors (TLR 1-10) are crucial in the induction and activation of innate immunity in the course of an infection. They are expressed mainly on the cells of the immune system, and also on some epithelia and endothelia. Their ligands so called pathogen associated molecular patterns are abundant on invading microbes. TLR-ligand binding results in cell signal transduction and subsequent production of various proinflammatory cytokines such as IL-1 and TNF-α. Acquired cholesteatoma is formed during chronic otitis media in the proportion of cases. It has adverse effects on ear structures, resulting in osteolysis and bone resorption. Its formation and pathogenesis are not fully understood. The current study attempted to search the possible role of TLRs in this somewhat awkward pathological condition. Surgical specimens of human acquired cholesteatoma (n=15) and normal external auditory canal skin (n=5, control tissues) were tested by immunohistochemistry for the presence of TLRs. Three TLRs were examined: TLR-2, TLR-3 and TLR-4. All TLRs tested were demonstrated in matrix (layer of keratinizing epithelium) and perimatrix (granulation tissue) of this inflammatory tumour. Expression of particular TLRs within the keratinizing epithelium was distinct and uneven. In the perimatrix, numerous T (CD3⁺) cells were seen and relatively few macrophages (CD11c⁺, HLA-DR⁺). There was a weak expression of all TLRs on normal (non-inflammatory) skin. Expression of TLR-3 both on the epithelium and some cells within the perimatrix and the presence of T cells may suggest that apart from innate immune responses, mechanisms of adaptive immunity also operate in cholesteatoma. Weak expression of these receptors on normal skin may also suggest the important role of TLRs in the etiopathogenesis of cholesteatoma.     

隐匿性乳突炎(附4例报告)

目的：探讨隐匿性乳突炎的诊断和治疗方法。方法：总结4例隐匿性乳突炎的诊治经验，其中2例在发生耳源性并发症前明确诊断。结果：4例病人经详细的病史和影像学检查获得确诊，给予相对保守的手术或非手术治疗，均获得令人满意的疗效。结论：对于可疑的隐匿性乳突炎病人，要注意详细收集病史，辅以必要的检查，颞骨薄层CT等影像学检查是主要的诊断方法；多数病人需手术治疗，要注意掌握手术时机，减少并发症。     

诊治颈动脉体瘤4例体会

报告诊治4例颈动脉体瘤的体会。认为彩色Doppler超声（彩超）检查和颈动脉造影，尤其是数字减影血管造影（DSA）对诊断颈动脉体瘤具有较高的价值。本病的唯一治疗方法是手术；术前应行颈总动脉压迫锻炼，为手术创造条件；术式的选择主要根据术前彩超和DSA结果，以及术中所见肿瘤与颈动脉的关系而定。     

The effects of maturation and stimulus parameters on the optimal f(2)/f(1) ratio of the 2f(1)-f(2) distortion product otoacoustic emission in neonates(1)

Distortion product otoacoustic emission (DPOAE) measurements are becoming popular in the clinical realm because they have been shown to reflect cochlear function. The primary tones used to evoke the DPOAE are important in determining the amplitude of the emission recorded in the ear canal. This study examined the ratio of the primaries necessary to determine the maximum amplitude emission as a function of development, stimulus level and frequency. Optimum f(2)/f(1) ratios were measured utilizing the f(1)-sweep technique from 105 neonates between 30-42 weeks conceptional age (CA) and 40 adults. No significant difference for optimum ratio was shown between the neonatal and the adult groups. Primary tone frequency had a significant effect on optimum ratio for both neonates and adults. Low f(2) frequencies (<4 kHz) were associated with higher optimum ratios than high f(2) frequencies (>4 kHz). The adult group was used to investigate the effect of stimulus level on the optimum f(2)/f(1) ratio for f(2) frequencies from 1.7 to 10 kHz. Regression analysis showed significant differences across levels of the primaries at all frequencies except for f(2)=3.4 and 7.0 kHz. These differences in f(2)/f(1) ratio across stimulus frequency and level may be attributed to the change in the shape of the excitation profiles along the basilar membrane.     

良性对称性脂肪瘤病4例

目的 探讨良性对称性脂肪瘤病(BSL)的诊断和治疗.方法 采取手术切除的方法治疗,回顾性分析4例BSL患者的病历资料及诊治过程,结合文献复习讨论BSL诊治特点.结果 术后病理诊断均为无包膜脂肪组织.所有病例术后外形恢复满意,无1例出现并发症.结论 BSL是一种脂肪代谢障碍引起的脂肪组织弥漫性、对称性沉积于颈项部等皮下浅筋膜间隙和(或)深筋膜间隙的良性疾病.以中老年男性居多,与酗酒有关,可伴有高尿酸血症、高胆固醇血症等代谢性疾病,CT检查有助于本病的诊断.对于影响美观及功能的患者手术疗效理想.     

Magnitudes and phases of human distortion-product otoacoustic emissions at 2f(1)-f(2) against f(2)/f(1): effects of an audiometric notch

The influence of the frequency ratio f(2)/f(1) of two pure-tone stimuli on the distortion-product otoacoustic emissions (DPOAEs) at 2f(1)-f(2) was assessed in 14 hearing-impaired human ears exhibiting a narrow audiometric notch at 4 kHz, whereas 11 normally hearing ears served as controls. A fixed-f(2) paradigm was used, with f(2) values varying from 2 to 8 kHz in 1-kHz steps. The intensities of the two stimuli were either 60 or 70 dB SPL. The magnitudes and phases of DPOAEs were extracted so that the bandpass filter-like profile of DPOAE magnitude against f(2)/f(1) (f(2)/f(1) magnitude function) could be characterized by the presence and position of its maximum, and DPOAE group delays were derived from the phase gradient of the DPOAE when f(1) varied. The main difference between normal and impaired ears occurred at 4 kHz in that, in contrast with normal ears, nine impaired ears out of 14 did not present any peak in their f(2)/f(1) magnitude function, while the remaining five ears only differed from normal ones by a slightly shifted maximum toward larger f(2)/f(1)s. Group delays were significantly shortened in all impaired ears, with a tendency to be shorter in the subset of ears with flat DPOAE magnitude profiles with f(2)/f(1). No clear effect of notch depth was observed, and with the chosen stimulus characteristics, no abnormal DPOAE result was observed whenever f(2) fell outside the audiometric notch. It is concluded that DPOAE group delays apparently provide useful objective clues of cochlear dysfunction, more sensitive than DPOAE magnitudes inasmuch as many of them remained near the normal range. Although a majority of f(2)/f(1) magnitude functions were clearly flattened when f(2) was impaired, this feature was less systematic.     

Expression of CC-chemokine receptor 7 (CCR7) and CXC-chemokine receptor 4 (CXCR4) in head and neck squamous cell carcinoma

Objectives

We tried to clarify the correlation of the expression of CCR7 and CXCR4 with lymph node and distant metastasis.

Materials and methods

We examined expression of CCR7 and CXCR4 in 9 HNSCC cell lines and 25 HNSCC tissues by semi-quantitative RT-PCR and immunohistochemistry study. We examined the expression levels of CCR7 and CXCR4 in undifferentiated and differentiated human normal keratinocyte.

Results

All cell lines expressed CCR7 mRNA, and three expressed CXCR4 mRNA. CCR7 and CXCR4 mRNAs were significantly higher in HNSCC tissues than in non-neoplastic tissues (p < 0.05, respectively) and correlated with lymph node metastasis (p < 0.05, respectively). The level of CXCR4 mRNA also correlated with distant metastasis (p < 0.05). Immunohistochemistry demonstrated localization of CCR7 and CXCR4 to carcinoma cells and lymphocytes and immunohistochemical staining scores of CCR7 and CXCR4 also showed similar correlation to lymph node and distant metastasis with CCR7 and CXCR4 mRNA levels. The level of CCR7 mRNA was significantly higher in poorly and moderately differentiated than in well-differentiated HNSCC (p < 0.05). The level of CCR7 mRNA in undifferentiated keratinocyte was significantly higher than that in differentiated keratinocyte.

Conclusion

The expression of CCR7 in HNSCC increases by dedifferentiation and plays an important role in lymph node metastasis of HNSCC and CXCR4 plays an important role in lymph node metastasis as well as distant metastasis.     

Components of the 2f(1)-f(2) distortion-product otoacoustic emission in a moth.

The noctuoid moth Empyreuma affinis has a simple tympanal organ with only two receptor cells attached to the eardrum. As in vertebrates, the growth of distortion-product otoacoustic emissions (DPOAE) with increasing stimulus level is characterized by two distinct components. An initial increase of DPOAE level for f(2) levels in the range of 30-65 dB SPL is followed by a second steep growth of the DPOAE at f(2) levels above 65 dB SPL. Both components increase at a slope of about 2 dB/dB and the difference between both components was used to assess a mechanical gain of the tympanal organ of 17 dB (n=23). At around 65 dB SPL, a notch in the level function coincides with an abrupt phase change of up to 180 degrees. The sensitive component induced by f(2) levels below 65 dB SPL is selectively affected by application of ethyl ether and disappears more quickly than the high-level component during ongoing deterioration of the moth preparation.     

迷路骨化：附2例报告

报告手术中发现的迷路骨化病例2例.1例系由于颞骨骨折引起伤侧全聋和面瘫,术中见伤侧颞骨内迷路和面神经管等结构消失并由骨化组织所代替.另一例系由不明原因引起双侧重度感音神经性聋,人工耳蜗植入术前CT扫描示双侧迷路骨质正常但术中发现仅一侧迷路正常而另一侧完全骨化.对迷路骨化的病因、病理特点、影像学诊断和临床意义进行了讨论.     

Evaluation of the polymorphism in the Toll-like receptor 4 (TLR4) genes of tympanosclerosis patients

Objective

Although eardrum perforations which endure etiopathogenesis for a long-time and middle ear infections are proposed for causing the tympanosclerosis (TS), tympanosclerosis emerges in some chronic otitis media (COM), some of them do not appear although a continuing COM and enduring perforation last. In this study, the effect of the molecular reasons which display genetic differences in TS formation is evaluated; our aim is to determine the Asp299Gly polymorphism frequencies in the TLR4 gene of patients with TS who have COM, and patients who do not.

Materials and methods

Patients who have undergone COM surgery, were divided into two groups of 50 persons who were selected in accordance with the fact, whether they had TS in their middle ear cavity or not during operation. 100 healthy persons who had similar demographic data, were evaluated as the control group. The DNA isolation was executed by using standard methods with peripheric blood specimen of the diseased group and control group. The Restriction Fragment Length Polymorphism method was used in determining the Asp299Gly allel in the TLR4 gene. Items of 249 bc for the wild tip (Asp) post-restriction enzyme segment wild tip (Asp) allel, and 23 bc and 196 bc post-restriction enzyme segment polymorphic allel (Gly) were obtained.

Results

TLR4 Asp299Gly polymorphism (10%) was asserted in a total of five specimens in the diseased group with TS. TLR4 Asp299Gly polymorphism was found positive in only one (2%) of the 50 phenomenons in the group without TS. TLR4 Asp299Gly polymorphism was found positive in six (6%) of the 100 phenomenons in the control group. The positive polymorphism in phenomenons with TS was significant in accordance with statistics, when compared with the group without TS (p < 0.05). However, although the polymorphism rates were higher than the rates of the control group, it was not statistically significant (p > 0.05).

Conclusion

TS may not appear in many patients who had undergone middle ear infection, and had perforation for many years. The polymorphism in arteriosclerosis in the TLR4 gene which caused the inflammatory cytokines oscillation recognize the bacterial LPS, was also accused. It is engrossing to find out from the results of our study on a restricted number of patients, and on only one gene, that molecular reasons which display genetic differences can also be effective in forming TS. Serial researches of greater dimensions are required.     

Acquired total (grade 4) subglottic stenosis in children

Pediatric acquired total subglottic stenosis (SGS) is a challenging problem. The management of these patients has evolved at our institution over the past 25 years. We conducted a retrospective study to evaluate the surgical management and outcomes of children with grade 4 SGS. Fifty-six patients have presented with acquired grade 4 SGS since 1981. The causes included previous surgery (34), prolonged intubation (15), bums (1), and unknown causes (6). Of the 56 patients, 44 (79%) were decannulated; 120 total procedures were performed, and 39 patients (70%) required more than 1 procedure for decannulation. The decannulation rate has risen from 67% in the 1980s to 86% in the 1990s. Patients who underwent cricotracheal resection (CTR) had a higher decannulation rate than patients who underwent laryngotracheal reconstruction (LTR) with anterior and posterior costal cartilage grafting (CCG) (92% versus 81%), and were less likely to need additional open procedures to achieve decannulation (18% versus 46%). The decannulation rate for children with grade 4 SGS has improved because of advances in surgical technique. Currently, the principal operations used at our institution are 1) CTR and 2) LTR with anterior and posterior CCG. There was a trend toward a higher decannulation rate in patients who underwent CTR, and they were less likely to require further reconstructive surgery before decannulation.     

Localization of histamine (H1, H2, H3 and H4) receptors in mouse inner ear

Conclusion The present findings show that all four types of histamine receptors (H1R, H2R, H3R, and H4R) are present in the inner ear, thus supporting the hypothesis that histamine plays a physiological role in the inner ear. Objective To analyse the presence of histamine receptors in the normal mouse inner ear. Methods CBA/J mice were used in this study. The localization of H1R, H2R, H3R, and H4R in the inner ear, i.e. cochlea, vestibular end organs, vestibular ganglion, and endolymphatic sac, was studied by real-time PCR and immunohistochemistry. Results The mRNA for each receptor sub-type was detected in the inner ear. In the immunohistochemical study, the organ of Corti, spiral ganglion, vestibular ganglion, vestibular sensory epithelium, and endolymphatic sac cells showed an immunofluorescent reaction to all histamine receptors.