Investigation of interleukin 10, 12 and 18 levels in patients with head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy. It is the most common neoplasm arising in the upper aerodigestive tract. Interleukin (IL) 12 and IL-18 are cytokines which have a major anti-tumour activity via stimulation of a T-helper type 1 (Th1) immune response. Interleukin 10, a potent antagonist of IL-12, is a cytokine which possesses immunosuppressive activity mainly produced via T-helper type 2 (Th2) cells. Studies of other types of cancer have shown that the level of IL-12 in serum or tissues is suppressed and/or the IL-10 level is increased, suggesting that there is an impaired cell-mediated anti-tumour response. The aim of this study was to measure pre-operative serum cytokine concentrations in HNSCC patients in order to detect any changes in IL-10, IL-12 and IL-18, compared with non-tumour controls. The relationship between cytokine levels and standard clinicopathological features, including tumour site, tumour stage and presence of nodal metastasis, was also examined. Fifty-seven patients with primary HNSCC were prospectively recruited, together with 40 non-tumour control patients with a similar age and sex distribution. Serum cytokine levels were measured using commercial quantitative enzyme-linked immunosorbent assay. The HNSCC patients had significantly lower IL-12 levels (median; interquartile range) than controls (42.8 pg/ml, 26.2-61.6 vs 52.3 pg/ml, 37.5-113.7; p=0.018). Also, patients were more likely to have detectable IL-10 levels than were controls, as IL-10 was positive in 27/55 patients but in only 9/39 controls (p=0.011). Furthermore, IL-10 detectability varied according to primary site, being more commonly observed in hypopharyngeal and laryngeal tumours, and IL-10 was more likely to be detected with advanced tumour stage (T3 and T4). No differences in IL-18 levels were observed between patients and controls (p=0.169). These results suggest (in agreement with studies on other solid malignancies) that HNSCC causes a significant change in the serum levels of specific Th1 and Th2 cytokines, producing an in vivo environment that is unlikely to promote an effective cell-mediated anti-tumour response.     

新型肿瘤靶向超顺磁氧化铁纳米粒在裸鼠头颈移植瘤MRI诊断中的实验研究

目的探讨叶酸-羧甲基壳聚糖-超顺磁氧化铁纳米粒（folic-acid o-carboxymethyl chitosans superamagnetic nanoparticle,FA-OCMCS-SPIO-NPs）在头颈移植瘤MRI诊断中的价值。方法雌雄各半的20只BACB/C裸鼠为动物模型,皮下种植KB细胞（人口咽癌细胞）4周后,建立KB细胞移植瘤模型,取荷瘤成功的16只裸鼠MRI平扫后,按数字随机法分为FA-OCMCS-SPIO-NPs组（实验组）和羧甲基壳聚糖-超顺磁氧化铁纳米粒OCMCS-SPIO-NPs（对照组）,每组8只。实验组尾静脉注射FA-OCMCSSPIO-NPs,对照组尾静脉注射OCMCS-SPIO-NPs,并进行MRI增强扫描。T2 WI图像比较增强前、后信号强度,结合HE和普鲁士蓝染色结果,评价FA-OCMCS-SPIO-NPs在头颈移植瘤诊断中的价值。结果实验组FA-OCMCS-SPIO-NPs增强前后,T2WI肿瘤区域信号强度较平扫信号降低27.23%,两者比较差异具有统计学意义（P=0.001）;肿瘤组织普鲁士蓝染色阳性,HE染色有大量散在SPIO聚集;对照组OCMCS-SPIO-NPs增强后,T2 WI肿瘤区域SI与平扫比较信号无明显下降（P〉0.05）,普鲁士蓝染色阴性,HE染色亦未见SPIO聚集。结论 FA-OCMCS-SPIO-NPs可以提高头颈肿瘤MRI诊断的准确性和可靠性,能够作为理想的对比剂而用于头颈移植瘤的MRI诊断。     

Gram-negative pathogen Klebsiella oxytoca is associated with spontaneous chronic otitis media in Toll-like receptor 4-deficient C3H/HeJ mice

CONCLUSION: This report confirms the presence of gram-negative Klebsiella bacteria in the middle ear of the C3H/HeJ mouse by culture, polymerase chain reaction (PCR), and electron microscopy. Identification of the bacterial pathogen supports the C3H/HeJ mouse as an excellent model for spontaneous chronic otitis media and its effects on the middle and inner ear. OBJECTIVES: The C3H/HeJ mouse has a single amino acid substitution in its Toll-like receptor 4, making it insensitive to endotoxin and suppressing initiation of the innate immune system. This study explored the bacteriology of the resultant middle ear infection by culture, PCR, histology, and electron microscopy. MATERIALS AND METHODS: Twelve-month-old C3H/ HeJ mice were screened positive for spontaneous otitis media. Tympanocentesis and blood cultures of mice were carried out under sedation. Middle ear aspirate material and blood samples were then sent for culture and PCR. Mice were then sacrificed for bright-field and electron microscopy analysis. RESULTS: All tympanocentesis and blood specimens grew gram-negative Klebsiella oxytoca, which was confirmed by PCR. Histopathology confirmed an intense inflammatory reaction and gram-negative bacteria in the middle and inner ears. Electron microscopy of the middle ears revealed abundant rod-shaped Klebsiella bacteria, both free and being engulfed by neutrophils.     

Degeneration of speech, language, and hearing in a patient with mucopolysaccharidosis VII

Mucopolysaccharidosis VII (MPS-VII) is probably the rarest of the mucopolysaccharidoses; literature reveals only 20 cases. We have had the opportunity to study and treat such a child in our clinic, and this paper documents his speech, language, and hearing. Results demonstrated a delay with respect to his chronological age in all cognitive, linguistic, and social domains. He had a mixed hearing loss which could have contributed to his diminishing speech and language abilities; he had chronic otitis media. After 59 h of speech and language intervention (over a period of 19 months), primarily for language treatment, standardized tests revealed that his scores had decreased over time. During this period, both his speech production and his hearing got poorer. At about the time of his 8th birthday, he underwent a permanent tracheostomy, altering further therapy. Although MPS-VII is a very rare disorder, what has been learned here may apply to other MPSs and even to other multiply handicapped patients. We hope that the presentation of our findings may assist others when confronted with complex, degenerative disorders.     

A novel mitochondrial mutation, 1556C --> T, in a Japanese patient with streptomycin-induced tinnitus

OBJECTIVE: Aminoglycoside antibiotics are associated with ototoxicity. The 1555A --> G mutation in the 12S ribosomal RNA gene of mitochondrial DNA has been considered to be associated with susceptibility to aminoglycoside antibiotics. In this study we examined a 79-year-old Japanese patient with a 45-year history of streptomycin-induced tinnitus in an attempt to find a mitochondrial mutation. MATERIALS AND METHODS: DNA was extracted from the patient's leukocytes. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) screening for the 1555A --> G mutation was done in order to detect a mitochondrial mutation and then nucleotide sequencing analysis was performed to identify the mutation. RESULTS: PCR-RFLP screening detected the presence of a mitochondrial mutation in the patient. However, the nucleotide sequencing analysis showed that the mutation was not the 1555A --> G mutation but a novel mutation, 1556C --> T. The mutation was not found in 112 unrelated Japanese control subjects, suggesting that the mutation was specific to our patient. CONCLUSIONS: The 1556C --> T mutation may be a genetic risk factor for aminoglycoside-induced hearing impairment. Our result also suggests that patients with the 1556C --> T mutation exist among those expected to have the 1555A --> G mutation as a result of PCR-RFLP analysis.     

Identification of D179H,a novel missense GJB2 mutation in a Western Sicily family

The main purpose of this study was to describe a novel missense mutation (p.D179H) found in a Western Sicily family and to examine the genetic and audiologic profiles of all family members by performing a GJB2 and GJB6 mutations analysis and a complete audiologic assessment. The proband was a 3-month-old infant with a congenital profound sensorineural hearing loss; direct sequencing of the GJB2 revealed the presence of a c.35delG mutation in the heterozygous state and a heterozygous G>C transition at nucleotide 535 in trans; this novel mutation, called p.D179H, resulted in an aspartic acid to histidine change at codon 179. It was also evidenced in the heterozygous state in two members of this family, both with normal hearing. No GJB6 mutations were evidenced in all subjects studied. Considering the genotypic and phenotypic analysis of all family members, we suggest, differently from the p.D179 N mutation previously reported, a recessive mode of inheritance. Functional studies on p.D179H have to be performed to confirm our hypothesis.     

天麻素对前庭功能障碍大鼠前庭内侧核组胺受体表达的影响

目的 观察天麻素对单侧迷路破坏(Unilateral labyrinthectomy,UL)后大鼠前庭内侧核(Medial vestibular nucleus,MVN)组胺受体H1、H2、H3亚型表达的影响,探讨天麻素对前庭功能损伤大鼠的干预作用及机制.方法 将99只健康SD大鼠随机分为空白对照组(n=9)、假手术组...     

Prospective, randomized, controlled clinical trial of a novel matrix hemostatic sealant in patients with acute anterior epistaxis

OBJECTIVES: Floseal, a novel hemostatic sealant composed of collagen-derived particles and topical bovine-derived thrombin, is applied as a high-viscosity gel for hemostasis. This study is a prospective, randomized, controlled clinical trial of Floseal compared with nasal packing in patients with acute anterior epistaxis. STUDY DESIGN: Institutional review board-approved, prospective, randomized, controlled, nonblinded, crossover clinical trial. METHODS: Seventy consecutive patients presenting with acute anterior epistaxis were randomized to receive Floseal or nasal packing for control. Patients were crossed over to the other technique after two unsuccessful attempts of the first technique. Patients were seen in the clinic within 7 days for follow-up. Ten-point visual analogue scales were used to rank effectiveness (1 = ineffective, 10 = effective), physician technical ease (1 = difficult, 10 = easy), physician satisfaction (1 = unsatisfied, 10 = satisfied), patient discomfort during hemostasis (0 = none, 9 = unbearable), patient discomfort at follow-up office visit, and patient satisfaction. Additional data included need for subspecialist consultation to control bleeding, rebleeding rates within 7 days, and rebleeding at follow-up visit. RESULTS: Floseal (n = 35) was judged by physicians to be more effective than nasal packing (n = 35) at initial control of anterior epistaxis (9.9 vs. 7.7, P < .001). Physicians found Floseal to be easier to use (9.4 vs. 3.2, P < .001) and were more satisfied with Floseal (9.6 vs. 3.5, P < .001). Patients experienced less discomfort with Floseal than with nasal packing both at initial control (1.4 vs. 8.9, P < .001) and at follow-up visit (0.0 vs. 8.5, P < .001), and Floseal patients were more satisfied overall (9.1 vs. 2.9, P < .001). Fewer in-person otolaryngology consultations were requested for Floseal patients (8.6% vs. 31.0%, P < .05). Floseal patients experienced fewer rebleeding rates within 7 days (14% vs. 40%, P < .05). Rebleeding rates at follow-up visit were higher in the nasal packing than the Floseal group at time of packing removal (63% vs. 0%, P < .001). Eight (23%) patients were crossed over from the nasal packing group to the Floseal group when nasal packing was ineffective. One Floseal patient (3%, P < .05) was crossed over into the nasal packing group. There were no complications in either group. CONCLUSIONS: Floseal hemostatic sealant is a better tolerated, more effective, safe, and easy alternative to nasal packing in patients presenting with acute anterior epistaxis. Future studies may wish to evaluate Floseal's use in posterior epistaxis.     

Galectin-3, an endogenous lectin,as a tool for monitoring cell differentiation in head and neck carcinomas with implications for lectin-glycan functionality

OBJECTIVE: Galectin-3 is an endogenous lectin that reacts with glycan epitopes of membrane and extracellular glycoproteins, including integrins, fibronectin, laminin and tetraspanins. Its expression, and also the presentation of its glycoligands, is controlled in a differentiation-dependent manner in squamous epithelia. The aim of this study was to monitor the carbohydrate-dependent binding of labeled galectin-3 to primary head and neck squamous cell carcinomas (from the tonsil, base of the tongue and larynx) and lymph node metastases. MATERIAL AND METHODS: Double labeling (using antibodies against desmoplakin-1, Ki-67 and cytokeratins) at the single-cell level was employed to cytologically characterize cells reacting with galectin-3. RESULTS: Galectin-3 binds a non-proliferating pool of tumor cells. Colocalization of galectin-3 binding sites with desmosomal proteins may indicate a role for this endogenous lectin in the formation of intercellular contacts of the desmosomal type. Cytokeratin-10-positive tumor cells also presented galectin-3-reactive binding sites on the surface; however, cytokeratin-10-free cells were also recognized by this lectin. CONCLUSION: These findings intimate that galectin-3 may represent a new tool for monitoring the degree of cell differentiation in carcinomas originating from the transformation of squamous cell epithelia.     

Analysis of local recurrence in patients with selected T1-3N0M0 squamous cell carcinoma of the true vocal cord managed with a platinum-based chemotherapy-alone regimen for cure

Based on an inception cohort of 35 patients with T1-3N0M0 squamous cell carcinoma of the true vocal cord who had a complete clinical response after a platinum-based induction chemotherapy regimen and a minimum of 3 years of follow-up, the current retrospective study documented the long-term results and consequences of local recurrence following the use of a platinum-based chemotherapy-alone regimen for cure. During the years 1985 to 1996, 231 patients with invasive squamous cell carcinoma of the true vocal cord classified as T1-3N0M0 were managed at our department with a platinum-based induction chemotherapy regimen. A complete clinical response was achieved in 77 patients. Thirty-five of the 77 patients with complete clinical response were managed at our institution with a platinum-based chemotherapy-alone regimen. The statistical analysis of data on survival, local control, nodal control, distant metastasis, and metachronous second primary tumor incidence was based on the Kaplan-Meier product limit method. Univariate analysis was performed for potential statistical relation between local recurrence and various variables. The 3- and 5-year actuarial survival estimates were 91.4% and 88.6%, respectively. Overall, the causes of death were intercurrent disease in 6 patients and metachronous second primary tumor in 4 patients. The 3- and 5-year actuarial local control estimate was 64.8%. No significant statistical relation could be demonstrated between the incidence for local recurrence and the variables under analysis. Salvage treatment in patients with local recurrence yielded a 100% local control rate and laryngeal preservation rate. The 3- and 5-year actuarial lymph node control estimate was 97.1%. The 3- and 5-year actuarial estimate for patients with distant metastasis was 0%. The 5- and 10-year actuarial estimates for patients with metachronous second primary tumor were 9.7% and 28.1%, respectively. Although local recurrence was noted in almost a third of patients with complete clinical response who were managed with a platinum-based chemotherapy-alone regimen, it did not appear to be detrimental, as none of the patients who had local recurrence ultimately died from their disease or lost their larynx.     

变应性鼻炎患者外周血IL-35及EBI3 mRNA和IL-12A mRNA表达的研究

目的：探讨变应性鼻炎（AR）患者外周血IL-35及其亚基病毒诱导基因3（EBI3）mRNA、IL-12A mRNA的表达及意义。方法：分别采集AR组（46例）及对照组（30例）外周血,采用ELISA法检测血清IL-35的表达水平,同时用SYBR Green实时定量PCR检测外周血单个核细胞中EBI3mRNA及IL-12AmRNA的表达水平。结果：AR组和对照组II,35水平分别为（251．22±46．27）、（382．17±25．41）ng／L,2组比较差异有统计学意义（P〈0．01）。外周血单个核细胞EBI3 mRNA的表达水平AR组明显低于对照组,约为对照组的50％,2组差异有统计学意义（P〈0．01）;IL-12AmRNA的表达水平AR组与对照组比较差异无统计学意义（P〉0．05）。结论：IL-35、EBI3 mRNA水平降低可能与AR的发生密切相关。     

Identification of a novel mutation in the SLC26A4 gene in an Italian with fluctuating sensorineural hearing loss

Pendred syndrome is an autosomal recessive disorder characterized by congenital sensorineural deafness, goitre and defective iodide organification. Congenital and profound hearing loss is the hallmark of the syndrome, while goitre and thyroid dysfunction are highly variable even within the same family. Clinical features are due to altered formation of pendrin, a chloride/iodide transporter protein expressed in the inner ear, thyroid gland and kidney. A novel substitution was found in exon 7 of the pendrin encoding gene (SLC26A4) that leads to a stop codon, S314X. The new variation was found in compound heterozygosity with L445W mutation in a hearing impaired patient with bilateral Mondini's dysplasia and goitre.     

Identification of two novel mutations, c.232T>C and c.2006A>T, in SLC26A4 in a Chinese family associated with enlarged vestibular aqueduct

It is known that enlarged vestibular aqueduct syndrome is closely related to the SLC26A4 mutation. Up to date, more than 200 of SLC26A4 mutations have been described, and novel mutations are being continually identified in different countries and ethnic groups. In this study, two novel variations were identified in a Chinese family associated with enlarged vestibular aqueduct. The two novel substitutions, c.232T>C and c.2006A>T, were detected in exon 3 and exon 17 of the pendrin encoding gene, respectively. The T/C transversion at 232 nucleotide caused p.Y78H mutation while the A/T transversion at 2006 nucleotide caused p.D669V mutation.     

Audiometric characteristics of a Dutch family linked to DFNA15 with a novel mutation (p.L289F) in POU4F3

OBJECTIVE: To report on the audiometric characteristics of a large Dutch family linked to DFNA15 with a novel mutation (p.L289F) in POU4F3 (OMIM 602460). DESIGN: Clinical investigation. SETTING: Tertiary referral center. PATIENTS: Family members from a large 5-generation pedigree with sensorineural hearing impairment segregating as an autosomal dominant trait. MAIN OUTCOME MEASURES: Cross-sectional and longitudinal analyses of pure-tone audiometric data, and cross-sectional analyses of speech audiometry data. RESULTS: Overall, a flat to gently downsloping audiometric configuration was observed with a progression rate of approximately 0.8 dB/y across most frequencies. Speech recognition scores remained fairly good in relation to age and hearing level compared with a group of patients with presbycusis. Interindividual variability was observed in terms of subjective onset age and audiometric configuration. Two mutation carriers, who reported vestibular symptoms, underwent vestibular examination and showed hypofunction of the vestibular labyrinth. CONCLUSIONS: The audiometric phenotype of the Dutch family linked to DFNA15 with a novel mutation in POU4F3 is comparable to that observed in the original Israeli family linked to DFNA15. Relatively good speech recognition scores suggest outer hair cell involvement. DFNA15 may represent a cochleovestibular disorder.     

Efficacy of an oral antihistamine,loratadine, as compared with a nasal steroid spray,beclomethasone dipropionate,in seasonal allergic rhinitis

The aim of the study was to compare the efficacy and side-effects of oral antihistamine and nasal glucocorticoid therapy in seasonal allergic rhinitis. In a double-blind, double-dummy, group-comparative study, 60 birch and grass pollen allergic patients were treated with either loratadine (10 mg daily) or beclomethasone dipropionate (BDP) (100 μg in each nostril twice daily) during a 3 weeks' study period. Grading of 4 nasal and 3 non-nasal symptoms was performed at 4 weekly visits, and patients recorded daily symptoms and possible adverse experiences in a diary. Patients treated with BDP showed significantly less nasal blockage than those receiving loratadine (P < 0.05), but there was no difference (P < 0.05) in other nasal symptoms (sneezing, itching and discharge). Patients treated with loratadine showed a statistically significantly greater relief in eye symptoms as compared with BDP (P < 0.05). The side-effects caused by the 2 treatments were few and insignificant. We conclude that loratadine and intranasal BDP were effective in the treatment of seasonal allergic rhinitis, but the spectrum of individual symptoms controlled was different for the 2 drugs.     

A prospective,feasibility study to evaluate the efficacy and usability of a novel drivable endoscope in patients with chronic rhinosinusitis

European Archives of Oto-Rhino-Laryngology - To carry out a pilot study to evaluate the efficacy of a novel, drivable endoscope (the Peregrine™ Drivable ENT Scope), compared to standard rigid...     

Efficacy of an oral antihistamine, loratadine, as compared with a nasal steroid spray, beclomethasone dipropionate, in seasonal allergic rhinitis.

The aim of the study was to compare the efficacy and side-effects of oral antihistamine and nasal glucocorticoid therapy in seasonal allergic rhinitis. In a double-blind, double-dummy, group-comparative study, 60 birch and grass pollen allergic patients were treated with either loratadine (10 mg daily) or beclomethasone dipropionate (BDP) (100 micrograms in each nostril twice daily) during a 3 weeks' study period. Grading of 4 nasal and 3 non-nasal symptoms was performed at 4 weekly visits, and patients recorded daily symptoms and possible adverse experiences in a diary. Patients treated with BDP showed significantly less nasal blockage than those receiving loratadine (P less than 0.05), but there was no difference (P greater than 0.05) in other nasal symptoms (sneezing, itching and discharge). Patients treated with loratadine showed a statistically significantly greater relief in eye symptoms as compared with BDP (P less than 0.05). The side-effects caused by the 2 treatments were few and insignificant. We conclude that loratadine and intranasal BDP were effective in the treatment of seasonal allergic rhinitis, but the spectrum of individual symptoms controlled was different for the 2 drugs.