Detection of natural autoimmunity to ghrelin in diabetes mellitus.

Objective: Ghrelin is an orexigenic peptide that becomes post-translationally modified. Natural autoantibodies to ghrelin (ghrelin-aAb) have been described in healthy subjects, in eating disorders and rheumatic diseases, with potential clinical relevance. Despite these important reports, the data base on the prevalence and physiological role is small and technical approaches for assessing ghrelin-aAb are few, encouraging respective research for improving knowledge on the potential endocrine significance. Methods: A novel immunoprecipitation assay was generated based on a fusion protein of human ghrelin with a reporter gene. Assay quality was verified with commercial antibodies. Assay characteristics and matrix effects were determined, including stability of natural ghrelin-aAb to freezing, signal linearity in dilution experiments, and comparison of different matrices. Three groups of serum samples were analyzed for ghrelin-aAb, comprising commercial sera from healthy subjects and patients with type 1 or type 2 diabetes mellitus. Results: The newly generated ghrelin-aAb assay proved sensitive, robust and reliable over a broad concentration range. Results from serum and plasma differed slightly. The signals from serum remained stable towards freezing and thawing, and in dilution experiments. Applying a mathematical criterion for outliers (P75 + 1.5-times IQR), an average prevalence of 11%-12% of positive samples was identified in the different human cohorts, with no significant sex-or disease-related difference. General significance: A novel diagnostic autoantibody assay detected ghrelin-aAb with a similar prevalence in diabetic patients and controls, suggesting that autoimmunity to ghrelin plays little role in diabetes mellitus, but may be of relevance in other diseases where ghrelin signaling is essential.

Re-visiting autoimmunity to sodium-iodide symporter and pendrin in thyroid disease.

OBJECTIVE: Iodide transport across thyrocytes constitutes a critical step for thyroid hormone biosynthesis, mediated mainly by the basolateral sodium-iodide-symporter (NIS (SLC5A5)) and the apical anion exchanger pendrin (PDS (SLC26A4)). Both transmembrane proteins have been described as autoantigens in thyroid disease, yet the reports on autoantibody (aAb) prevalence and diagnostic usefulness are conflicting. Reasons for the inconclusive findings may be small study groups and principle differences in the technologies used. DESIGN: We decided to re-evaluate this important issue by establishing novel non-radioactive tests using full-length antigens and comparable protocols, and analyzing a large cohort of thyroid patients (n = 323) and control samples (n = 400). METHODS: NIS and PDS were recombinantly expressed as fusion protein with firefly luciferase (Luc). Stably transfected HEK293 cells were used as reproducible source of the autoantigens. RESULTS: Recombinant NIS-Luc showed iodide transport activity, indicating successful expression and correct processing. Commercial antibodies yielded dose-dependent responses in the newly established assays. Reproducibility of assay signals from patient sera was verified with respect to linearity, stability and absence of matrix effects. Prevalence of PDS-aAb was similar in thyroid patients and controls (7.7% vs 5.0%). NIS-aAb were more prevalent in patients than controls (7.7% vs 1.8%), especially in Graves' Disease (12.3%). Neither NIS-aAb nor PDS-aAb concentrations were related to TPO-aAb or TSH-receptor-aAb concentrations, or to serum zinc or selenium status. CONCLUSIONS: Our data highlight a potential relevance of autoimmunity against NIS for thyroid disease, whereas an assessment of PDS-aAb in thyroid patients seems not to be of diagnostic value (yet).

Juvenile nasopharyngeal angiofibroma staging: An overview.

Staging of tumors is very important in treatment and surgical decision making, as well as in predicting disease recurrence and prognosis. This review focuses on the different available classifications of juvenile nasopharyngeal angiofibroma (JNA) and their impact on the evaluation, management, and prognosis of JNA. The literature was reviewed, and publications on JNA staging were examined. Our MEDLINE search of the entire English-language literature found no review article on the current available staging systems for JNA. In this article, we review the common JNA classification systems that have been published, and we discuss some of their advantages and disadvantages. The most commonly used staging systems for JNA are the Radkowski and the Andrews-Fisch staging systems. However, some newer staging systems that are based on advances in technology and surgical approaches-the Onerci, INCan, and UPMC systems-have shown promising utility, and they will probably gain popularity in the future.

Vestibular rehabilitation strategies and factors that affect the outcome.

Ever since the introduction of Cawthorne-Cooksey exercises, vestibular rehabilitation (VR) has been gaining popularity in the treatment of the dizzy patient. Numerous studies support the effectiveness of VR in improving balance/walking skills, eye-head coordination and the quality of life of the patient. Different rehabilitation protocols have been used to treat patients with peripheral and central vestibular disorders. Assessment of the patients' progress is based on the patients' selfperception of dizziness and their functional skills. Factors such as age, medication, time of onset of vertigo and home based VR have been evaluated on their effect on the rehabilitation's outcome. The aim of this review is to evaluate rehabilitation strategies and discuss the factors that affect the outcome.

Role of the recently identified dysadherin in E-cadherin adhesion molecule downregulation in head and neck cancer.

Dysadherin is a cancer-related cell membrane glycoprotein, recently identified, playing an important role in tumor progression and metastasis. In the present minireview article, we are focusing on the role of dysadherin in E-cadherin downregulation, the various expression patterns of the molecule in head and neck cancer as well as its potential role as a molecular target for future applications in diagnosis, clinical routine and prognosis of the disease.

Vestibular-evoked myogenic potentials eliciting: an overview.

Recently, the favoured approach for unilateral testing of saccular function is the recently developed method of vestibular-evoked myogenic potentials (VEMPs). VEMP testing is a reliable technique, since it selectively stimulates and investigates each lateral canal in isolation from the other, providing information for the assessment of otolith function and inferior vestibular nerve integrity. The aim of this study was to provide a current review of the different methods used to record VEMPs. We noticed discrepancies in relation to the ways used to record the VEMPs in relation to the following factors: types of stimuli used (clicks or tone bursts) and body muscles tested, patient position at the time of recording, response, type of phone used and way of stimulus presentation (mono or binaural, ipsi or contralateral) and others. As a conclusion, despite the numerous studies in the field, there is no consensus in the literature as to the best recording method for VEMPs. However, the new ocular VEMPs in response to bone conducted vibration seem to be of clinical importance for the evaluation of utricular function. Further research is needed to support its clinical usefulness.

Noise-induced changes in gene expression in the cochleae of mice differing in their susceptibility to noise damage.

The molecular mechanisms underlying the vast differences between individuals in their susceptibility to noise-induced hearing loss (NIHL) are unknown. The present study demonstrated that the effects of noise over-exposure on the expression of molecules likely to be important in the development of NIHL differ among inbred mouse strains having distinct susceptibilities to NIHL including B6 (B6.CAST) and 129 (129X1/SvJ and 129S1/SvImJ) mice. The noise-exposure protocol produced a loss of 40 dB in hearing sensitivity in susceptible B6 mice, but no loss for the two resistant 129 substrains. Analysis of gene expression in the membranous labyrinth 6 h following noise exposure revealed upregulation of transcription factors in both the susceptible and resistant strains. However, a significant induction of genes involved in cell-survival pathways such as the heat shock proteins HSP70 and HSP40, growth arrest and DNA-damage-inducible protein 45ß (GADD45ß), and CDK-interacting protein 1 (p21(Cip1)) was detected only in the resistant mice. Moreover, in 129 mice significant upregulation of HSP70, GADD45ß, and p21(Cip1) was confirmed at the protein level. Since the functions of these proteins include roles in potent anti-apoptotic cellular pathways, their upregulation may contribute to protection from NIHL in the resistant 129 mice.

Effect of perioperative immuno-enhanced enteral nutrition on inflammatory response, nutritional status, and outcomes in head and neck cancer patients undergoing major surgery.

Administration of immuno-enhanced nutritional support may decrease postoperative morbidity, mortality, and infectious complications in cancer patients. The aim of this study was to verify that perioperative enteral diet, enriched with the nutrients arginine, ribonucleic acid (RNA), and ω-3 fatty acids improves outcomes of head and neck cancer patients undergoing major surgery. Forty patients with squamous cell carcinoma of the head and neck were studied. Group 1 received no preoperative nutritional support, whereas Group 2 received an oral formula with nutrients arginine, RNA, and ω-3 fatty acids. After surgery, Group 1 received a standard enteral formula, whereas Group 2 received an enriched enteral formula. Albumin (g/dl), prealbumin, fibrinogen, CRP, Il-6, and TNFa were measured 5 days before and 8 days after surgery. No statistically significant difference was observed for all the evaluated markers between postoperative and preoperative levels for both groups. The rate of complications was significantly reduced in the total number of patients receiving immunonutrition and in the particular subgroup of well-nourished patients receiving an immuno-enhanced diet. Perioperative enteral immuno-enhanced feeding in head and neck cancer patients undergoing major surgery may influence the postoperative outcomes by reducing the frequency rate of infections and wound complications.

The efficacy of imiquimod on dysplastic lesions of the oral mucosa: an experimental model.

AIM: To study the potent efficacy of the immunomodulatory agent imiquimod when applied on dysplastic lesions of the oral mucosa. MATERIALS AND METHODS: Carcinogen (DMBA) was applied to the mucosa of the left buccal pouch of 26 male Wistar rats for 8 weeks, until dysplastic lesions were observed and histologically diagnosed. At the second phase of the experiment, 5% imiquimod cream was applied to these dysplastic lesions for 16 weeks. Biopsies were taken before and after treatment. RESULTS: The histological effect of imiquimod was the regression of mild dysplasia to hyperplasia for all the samples. In one case, a well-differentiated squamous cell carcinoma was converted to a papilloma-like squamous neoplasm with a benign morphology. CONCLUSION: Our results indicate that imiquimod may be effective in treatment of precancerous lesions of the oral mucosa and thus inhibit the progress of carcinogenesis.

Influence of intranasal sterile isotonic sea water applications on xylometazoline administration: an experimental study in pigs.

OBJECTIVE: The aim of this study was to investigate how isotonic sea water solution (Physiomer) affects the structure of porcine nasal mucosa when it is applied simultaneously with vasoconstrictors (xylometazoline) for a prolonged period of time. METHODS: Twenty pigs of the PMR-Landraze breed formed the study group. A solution of xylometazoline 0, 1% (Otrivin spray, Novartis) was sprayed every 8h in both nasal cavities of the pigs, with two applications into each nostril for 28 days. Between the applications (4h later), the right nasal cavity was washed with sterile isotonic sea water (Physiomer Normal, Geomar). Biopsies were taken under endoscopic guidance from the nasal mucosa of each nasal cavity separately at specific times. Five histological parameters were microscopically examined for each biopsy section: (1) inflammation, (2) fibrosis, (3) metaplasia of the epithelium, (4) reactive atypia of the epithelium and (5) necrosis. RESULTS: Statistically significant differences regarding grade of inflammation on days 7 (p=0.0009), 12 (p=0.01), 20 (p=0.02) and 28 (p=0.0005), regarding grade of fibrosis on day 28 (p=0.026) and regarding epithelial metaplasia on day 5 (p=0.052) were found between the nasal mucosa treated only with vasoconstrictors and the nasal mucosa treated with vasoconstrictors and sea water washing. In all cases, samples from the nasal cavities that had been washed with Physiomer appeared with a lower grade of inflammation, fibrosis and metaplasia compared to the samples from nasal mucosa where no nasal washing was performed. CONCLUSION: Nasal irrigations with isotonic sea water, when are applied 4h after vasoconstrictors for a long period of time, prevent nasal mucosa from histological damage.

Skin prick test reactivity to common aeroallergens and ARIA classification of allergic rhinitis in patients of Central Greece.

Allergic rhinitis (AR) is prevalent in Mediterranean countries, but there are no epidemiological studies in the Hellenic milieu in accordance with the recent ARIA guidelines. We investigated aetiological aeroallergens in AR patients of Central Greece using the ARIA classification. Between 2002 and 2006, 911 patients with rhinitis symptomatology were interviewed and underwent Skin prick testing and 623 completed the study. Seasonal rhinitis (SAR) represented 37.6%, Perennial rhinitis (PAR) 46.4% and SAR + PAR 16%. Intermittent mild and moderate/severe AR was evident in 9.3 and 24.5%, persistent mild and moderate/severe in 23.2 and 43.0%. Persistent AR appeared in overall 66.2% of patients and was prevalent in PAR and SAR + PAR (p < 0.0001). Severity of AR symptoms did not correlate more with ARIA than with the traditional subgroups. Marked statistical (p < 0.05) differences were evident for seven aeroallergens between the four geographic areas of the study. Pollen allergy was found in 77.8% but all pollens were significantly lower in coastal areas (p < 0.001), besides Parietaria (p < 0.003). Mite sensitivity manifested in 43.2%. Alternaria affected mostly the paediatric population (p < 0.0001). 12.4% (N = 77) was monosensitive, 58.7% (N = 366) oligosensitive, and 28.9% (N = 180) polysensitive. Rhinitis and asthma comorbidity was high (45.3%) and occurrence of asthma was related with PAR (p < 0.007) and SAR + PAR (p < 0.023) but not with the ARIA classification subgroups. This study provides compelling evidence of a typical Mediterranean allergic profile of patients of Central Greece with significant regional variability. Both classifications had approximately equal diagnostic value in our study besides the fact that ARIA subdivision is considered superior in determining treatment.

Myoepithelial carcinoma of the retromolar area in a young female. A rare case report.

We present a case of a 34-year-old woman with myoepithelial carcinoma of the retromolar area. Myoepithilial carcinoma is a rare tumor of small salivary glands most usually located in the parotid gland. The major differential diagnosis of myoepithelioma is from pleomorphic adenoma. Little is known about the clinical and biological behavior and the prognosis of myoepithelial carcinoma and there is no consensus for its treatment. It is considered a low-grade malignancy; it sometimes shows aggressive behavior and may locally recur. Our patient was treated successfully with wide-local resection and remained free of disease for 6 months.

Differential rates of proliferation and apoptosis in nasal polyps correspond to alterations in DNA spatial distribution and nuclear polarization as observed by confocal microscopy.

The study aimed to investigate the expression of p53, Bcl-2 and Ki-67 in relation to the histologic and nuclear qualitative and spatial characteristics of chronic rhinosinusitis with polyposis (CRP). Imprint smears obtained from surgically removed nasal polyps of 20 patients were studied. The polyps were classified according to their histological characteristics as: hyperplasia (simple and pronounced) and squamous metaplasia. The expression of p53, Bcl-2 and Ki-67 was assessed by immunocytochemistry. DNA spatial distribution and nuclear orientation were studied by staining with propidium iodide and examined by confocal microscopy. Positive immunoreaction for p53, Ki-67 and Bcl-2 was observed in 50, 65, and 50% of polyp's smears, respectively. For each diagnosis, the rates were simple hyperplasia 60, 80 and 30%, pronounced hyperplasia 80, 100 and 40%, metaplasia 0, 0 and 100%, respectively. Abnormal chromatin distribution and nuclear disorientation was observed in three cases of pronounced hyperplasia combined with positive immunoreaction for Ki-67 and p53 and negative immunoreaction for Bcl-2. CRP demonstrated different proliferation and apoptotic rates, according to their histology. Nuclear characteristics observed by confocal microscopy are associated with the immunocytochemical markers of proliferation and apoptosis.

Test-retest reliability of p13n23 and n34p44 components of vestibular evoked myogenic potentials in a large healthy population.

OBJECTIVE: The aim of this study is to evaluate the reliability of the VEMP characteristics recorded in a large number of healthy subjects. METHODS: VEMP response was obtained on 75 healthy volunteers. Thirty-nine (39) of them were males and 36 were females. Their age varied between 25 and 63 years (mean value 43). Recording was achieved using monaural acoustic stimulation and ipsilateral muscle contraction. Latencies of p13, n23, n34, p44 peaks, p13n23 and n34p44 amplitudes and the interaural amplitude differences (IAD) were assessed. RESULTS: The stability of latencies, amplitudes of the first p12-n23 and second n34-p44 waveforms was verified. The second complex was present in 76%. No factor indicates statistically significant side difference for both runs. IAD variable was not statistically different from zero in all cases. Results show very good reliability for amplitudes, good for some latencies, poor for some other latencies and IAD34-44 and very poor for IAD13-23. No strong and significant correlations were also found between IAD34-44 and IAD13-23 and between p13n23 and n34p44 amplitudes. CONCLUSION: It is the first time that optimal latencies and amplitudes for early and late components of VEMP are described in a large sample of healthy subjects. The p13, n23, n34 and p44 latencies and p13-n23, and n34-p44 amplitudes were reliable, verifying that the method is reproducible and feasible. The IAD13-23 has the disadvantage of low reliability.

Resection of giant ethmoid osteoma with orbital and skull base extension followed by duraplasty.

BACKGROUND: Osteomas of ethmoid sinus are rare, especially when they involve anterior skull base and orbit, and lead to ophthalmologic and neurological symptoms. CASE PRESENTATION: The present case describes a giant ethmoid osteoma. Patient symptoms and signs were exophthalmos and proptosis of the left eye, with progressive visual acuity impairment and visual fields defects. CT/MRI scanning demonstrated a huge osseous lesion of the left ethmoid sinus (6.5 cm x 5 cm x 2.2 cm), extending laterally in to the orbit and cranially up to the anterior skull base. Bilateral extensive polyposis was also found. Endoscopic and external techniques were combined to remove the lesion. Bilateral endoscopic polypectomy, anterior and posterior ethmoidectomy and middle meatus antrostomy were performed. Finally, the remaining part of the tumor was reached and dissected from the surrounding tissue via a minimally invasive Lynch incision around the left middle canthus. During surgery, CSF rhinorrhea was observed and leakage was grafted with fascia lata and coated with bio-glu. Postoperatively, symptoms disappeared. Eighteen months after surgery, the patient is still free of symptoms. CONCLUSION: Before management of ethmoid osteomas with intraorbital and skull base extension, a thorough neurological, ophthalmological and imaging evaluation is required, in order to define the bounders of the tumor, carefully survey the severity of symptoms and signs, and precisely plan the optimal treatment. The endoscopic procedure can constitute an important part of surgery undertaken for giant ethmoidal osteomas. In addition, surgeons always have to take into account a possible CSF leak and they have to be prepared to resolve it.

Acoustic stapedial reflex in normal adults: biological behavior and determination of threshold levels.

OBJECTIVE: To record acoustic reflex thresholds for admittance (Y) and its components, susceptance (B) and conductance (G) in healthy subjects and to establish normative data. STUDY DESIGN: Acoustic reflex threshold was determined in 100 healthy persons, divided into 5 age groups of 20 persons each (20-29, 30-39, 40-49, 50-59 and 60-69 years old). Detection was performed for Y, B, and G at 226-, 678- and 1,000-Hz probe tones, using 500-, 1,000-, 2,000- and 4,000-Hz stimuli. RESULTS: Statistically significant differences in acoustic reflex thresholds were revealed between different components, stimuli and tones. The lowest threshold level was recorded for Y at 226 Hz using stimulus 1,000 Hz. Four percent missing values were observed at 226 Hz. Subjects belonging to different age groups had different reflex thresholds. CONCLUSION: Inclusion of acoustic reflex detection for B and G offers more detailed information about the middle ear status compared with Y alone, and appears to be sensitive in detecting subtle diseases.

Juvenile nasopharyngeal angiofibroma stages I and II: a comparative study of surgical approaches.

OBJECTIVE: The aim of this study was to compare different surgical options used for removal of stages I and II juvenile nasopharyngeal angiofibromas (JNAs). Treatment morbidity was evaluated through blood loss, surgery duration, postoperative hospitalization and outcome. Moreover, an effort was made to explore the role and limits of endoscopic surgery. MATERIALS AND METHODS: 20 male patients (mean age 14.9 years) were treated for JNA using three different surgical approaches in the Department of Otolaryngology of the University of Athens between May 1998 and January 2007. 9 patients were managed using endoscopic approach, while 5 were treated through midfacial degloving. A transpalatal approach was performed in remaining 6 patients. Preoperative angiography with embolization was performed in all 9 patients who underwent endoscopic removal and in 3 patients treated by midfacial degloving technique. RESULTS: Findings demonstrated that endoscopic approach, assisted by preoperative embolization, lead to less intraoperative blood loss, shorter duration of surgical procedure, shorter length of hospital stay and no complications, compared with the conventional techniques. CONCLUSIONS: Our data suggest that with proper patient selection, endoscopic resection of stages I and II JNA, when it is performed after embolization of the feeding vessels, is remarkably bloodless and precise and may be preferable to traditional open approaches.

Vestibular evoked myogenic potential eliciting in normal subjects: comparison of four different methods.

OBJECTIVE: Vestibular evoked myogenic potential (VEMP) recording is a new method for testing the otolith receptors and vestibulospinal pathways. The aim of this study was to evaluate the characteristics of VEMP using four different techniques to find reasons to prefer one type of recording over the others. MATERIAL AND METHODS: Twenty healthy persons, 10 males and 10 females with ages ranging from 20 to 57 years (mean age 41 years), were enrolled in this study. Eliciting of VEMPs by using monaural or binaural acoustic stimulation and unilateral or bilateral SCM contraction was evaluated; 105 dB NHL acoustic stimulation consisting of 145 dB rarefaction clicks was applied. Latencies of p13, n23, n34, p44 peaks; amplitudes p13-n23 and n34-p44; and interaural amplitude differences (IADs) were assessed. RESULTS: All four methods elicited constant and evident waveforms. The reliability coefficients of amplitudes were high for all four methods and for both waves. However, the higher scores of reliability appeared for the monaural-ipsilateral recording. The results indicated no statistically significant difference between the right and left sides for all four types of VEMP eliciting. No correlation was found between IAD13-23 and IAD34-44 for all four methods. Statistically significant differences were found only for n23 latency among the four methods. CONCLUSIONS: Although no evidence to reject or strongly favour a specific method was found, the monaural-ipsilateral recording was associated with some advantages.

Metallic foreign body in middle ear: an unusual cause of hearing loss.

This is a rare case report of a foreign metallic body found in the middle ear. During the use of an electric welding by a metalworker, a glowing drop of dissolved metal overrun, burning the skin of his external auditory meatus, perforated the tympanic membrane and finally was implanted around the ossicles as a foreign body. Due to difficulty of the physical examination and the moderate symptoms (hearing loss and sense of fullness), the foreign body was detected six months after the incident, by CT scanning and it was removed by a transcanal approach under general anesthesia. A successful ossiculoplasty-tympanoplasty was followed four weeks later.