Angiogenin expression in head and neck basaloid and conventional squamous cell carcinoma: a site- and stage-matched comparison.

BACKGROUND: Basaloid squamous cell carcinoma is an uncommon variant of squamous cell carcinoma (SCC). Angiogenin (ANG), a member of the ribonuclease super-family, is essential to tumor angiogenesis, but has also been implicated in tumor consolidation and proliferation. METHODS: ANG expression was first investigated in 12 head and neck basaloid squamous cell carcinomas (HNBSCCs) and compared with a control group of 24 site- and stage-matched conventional SCCs to establish whether the supposedly more aggressive biological behavior of HNBSCCs might be ANG-related. RESULTS: No significant differences were found between HNBSCCs, and SCCs in terms of recurrence, disease-free survival (DFS), or overall survival rates. In HNBSCC, we identified a trend toward a significant inverse correlation between endothelial ANG expression and DFS (statistical trend, P = 0.08). Endothelial ANG expression did not differ significantly in HNBSCCs and SCCs. A high ANG expression in carcinoma cells was directly associated with pT in both the HNBSCC (P = 0.04) and the SCC (statistical trend, P = 0.07) groups. ANG expression in carcinoma cells was significantly lower in HNBSCCs than in SCCs (P = 0.005). CONCLUSIONS: All the biological mechanisms investigated to date, including ANG-mediated angiogenesis or cell proliferation, have failed to confirm that HNBSCCs have a more aggressive behavior than matched SCC.

Antioxidant therapy in idiopathic tinnitus: preliminary outcomes.

BACKGROUND: Reactive oxygen species (ROS) play an important role in several pathogenic processes, damaging various structural and functional cellular components. The endothelium is at major risk of radical-induced lesions and this damage is most manifest in microcirculation. It has been recently observed that ROS are implicated in the pathology of the inner ear and the peripheral and central pathways. In a previous study we detected high serum values of ROS in subjects with idiopathic tinnitus. The purpose of the present study was to evaluate the validity of antioxidant treatment in tinnitus sufferers with high ROS values. METHODS: The study considered 31 consecutive patients with unilateral idiopathic tinnitus. The mean pure tone audiometric threshold (PTA), tinnitus loudness, subjective disturbance level [visual analogue scale (VAS) determination], and the indirect ROS dosage 48 h before and after medical treatment were evaluated. Patients underwent an 18-week oral treatment with a mix of phospholipids and vitamins (glycerophosphorylcholine, glycerophosphorylethanolamine, beta-carotene, vitamin C, vitamin E). RESULTS: ROS levels were significantly reduced following antioxidant treatment (malonaldehyde: 2.10 vs. 1.98 mumol/dL, p = 0.003; 4-hydroxynonenal: 2.36 vs. 2.16 mumol/dL, p = 0.002) In addition, great improvement was observed in the reduction of tinnitus (VAS and tinnitus loudness evaluations). No significant changes in audiometric threshold occurred. CONCLUSIONS: Oral antioxidant therapy in patients with idiopathic tinnitus seems to reduce the subjective discomfort and tinnitus intensity and may be considered as an additional treatment modality.

Psychological, neural, endocrine, and immune study of stress in tinnitus patients: any correlation between psychometric and biochemical measures?

OBJECTIVES: The present study was carried out in tinnitus patients in order to study the psychological distress and the biochemical measures of this stressful condition. Psychological features were compared to immune and neuroendocrine parameters in order to verify in these subjects the possible presence of psychological and somatic responses to stress. METHODS: We studied 85 tinnitus patients who underwent hematochemical immune tests: lymphocyte subpopulations (CD3; CD4; CD3+CD4; CD8; CD19; CD16NK; CD3+CD16+CD56; and CD4/CD8), cortisol, adrenocorticotropic hormone, beta-endorphin, prolactin, and urinary catecholamine. RESULTS: Clinically, significant scores were obtained for hysteria, depression, paranoia, hypochondrias, and social introversion; and high scores were obtained for anxiety, depression, care for health, difficulty of treatment, low self-esteem, family and work difficulties, and social discomfort. There was a low to medium level of self-perception of stress. The less a subject felt stressed, the higher was his or her satisfaction level in the areas of psychological and physical functioning. The scores on the tests and the biochemical measures did not show a significant correlation, but there was a tendency to correlation for the lymphocytes CD19 and CD16NK and for adrenocorticotropic hormone. CONCLUSIONS: The comparison between the psychometric and biochemical variables did not reveal any significant correlation among stress perception, daily satisfaction, and the biochemical parameters of stress.

Psychological characteristics of patients with Ménière's disease compared with patients with vertigo, tinnitus, or hearing loss.

An association between Ménière 's disease and psychological distress is frequently reported. Patients who do not have Ménière's disease but who have similar symptoms also experience various kinds of psychological disturbances. We conducted a study to investigate the relationship between Ménière's disease and personality traits, illness behavior, depression, and anxiety. We compared these factors in 77 patients who had Ménière's disease and 133 controls who did not have the disease but had one of its symptoms--either vertigo, tinnitus, or hearing loss. The mental status of study participants was assessed with standard tests. Patients in both groups had higher than normal levels of anxiety and neuroticism. The only significant difference between the two groups was a higher rate of extroversion in the Ménière's disease group. Minor differences emerged when Ménière's patients with tinnitus or vertigo were compared with similar controls. Relationships between psychological observations and otologic symptomatology or an otologic diagnosis were not specific, which illustrates the need to consider the role of illness behavior and personality as targets for psychological support or therapy associated with ENT treatment.

Oxidative stress, nitric oxide, endothelial dysfunction and tinnitus.

To assess whether pathogenic endothelial dysfunction is involved in acute idiopathic tinnitus we enrolled 44 patients and 25 healthy volunteers. In blood from the internal jugular vein and brachial vein we determined malonaldehyde, 4-hydroxynonenal, myeloperoxidase, glutathione peroxidase, nitric oxide, L-arginine and L-ornitine, thrombomodulin (TM) and von Willebrand factor (vWF) activity during tinnitus and asymptomatic period. Higher plasma concentrations of oxidative markers and L-arginine, and lower nitric oxide and L-ornitine levels were observed in jugular blood of patients with tinnitus, there being a significant difference between brachial and jugular veins. TM and vWF activity were significantly higher in patients' jugular blood than in brachial blood. Our results suggest oxidant, TM, vWF activity production are increased and nitric oxide production reduced in brain circulation reflux blood of patients with acute tinnitus. These conditions are able to cause a general cerebro-vascular endothelial dysfunction, which in turn induce a dysfunction of microcirculation in the inner ear.

Expression of the apoptosis inhibitor protein Survivin in primary laryngeal carcinoma and cervical lymph node metastasis.

BACKGROUND: Survivin is the smallest mammalian member of the inhibitor of apoptosis (IAP) proteins family. The aim of the present study was to determine survivin expression in laryngeal squamous cell carcinoma (SCC) and in neck lymph node metastases. The survivin value in predicting prognosis in laryngeal SCC was also investigated. PATIENTS AND METHODS: Survivin expression was investigated in 37 laryngeal SCCs and in 12 cervical lymph node metastases. RESULTS: A nuclear reaction predominated in laryngeal SCCs. Survivin expression was significantly higher in pN+ laryngeal SCCs than in pN0 (p = 0.017). Survivin expression was higher in cervical lymph node metastases than in correspondent primary laryngeal SCCs (p = 0.002). Survivin expression in laryngeal SCCs that developed loco-regional recurrence was significantly higher than in laryngeal SCCs without recurrence of disease (p = 0.039). CONCLUSION: Nuclear expression of survivin should be studied as a hallmark of higher risk laryngeal SCCs to develop loco-regional recurrences. Higher survivin expression in pN+ laryngeal SCC may suggest elective neck dissection in clinically N0 patients with high survivin expression in primary SCC. The extremely high survivin expression in lymph node metastases may support the use of survivin in the diagnosis of lymph node micro-metastases.

Western blot immunoassay for HSP-70 antibodies in idiopathic tinnitus: a preliminary report.

OBJECTIVES: Our preliminary study investigated the role of nonspecific immunologic tests and immunoassay for heat shock protein 70 (HSP-70) in supporting the possibility of an autoimmune inner ear process determining idiopathic tinnitus. METHODS: Thirty-six consecutive patients with idiopathic tinnitus without other otologic or autoimmune diseases and 20 healthy blood donor subjects underwent determinations of circulating immune complexes (CICs) and other nonspecific immunologic factors and immunoassay for HSP-70. RESULTS: The mean CIC values were 4.2 microg/mL in the tinnitus patients and 0.9 microg/mL in the control group (p = .012). Thirteen of the 36 tinnitus patients and none of the control group were HSP-70-positive. Ten of the 13 HSP-70-positive patients had CIC values higher than normal. In the tinnitus group, the mean CIC values were 6.9 microg/mL and 2.6 microg/mL in the HSP-70-positive and -negative subgroups, respectively (p = .024). CONCLUSIONS: It may be hypothesized that in a significant number of cases, idiopathic tinnitus could be induced by immune response to inner ear-specific HSP-70.

Tinnitus and bilateral sensorineural hearing loss: ankylosing spondylitis or a side-effect of sulphasalazine treatment?

We report the case of a young male patient with ankylosing spondylitis treated with sulphasalazine who developed bilateral sensorineural hearing loss with tinnitus. Discontinuation of sulphasalazine led to complete resolution of tinnitus and an improvement in hearing loss. We discuss the features of this case and also review the relevant literature.

A protocol of study for tinnitus in childhood.

The presence in childhood of tinnitus is still a neglected problem both in pediatric and otorhinolaryngological literature, even if it is not uncommon in the pediatric population. In fact its incidence ranges from 13 to 29% in children with normal hearing function and is reported in 59% of children with hearing loss. Even if a child does not mention the existence of tinnitus, nevertheless, it may cause difficulties in concentration and bring about behavioral problems such as irritation, nervousness and deterioration in the lingual capacity. It is recommended to perform standardized studies regarding pediatric tinnitus. First of all, an accurate medical history must be performed asking specifically about tinnitus. Then it is necessary to perform an audiological examination that includes the subjective description and the following audiometric tests, pure tone audiometry; tympanometry; and tinnitus measurements.

Wolfram syndrome.

The Wolfram syndrome is a rare dysmorphogenetic disease of autosomic recessive hereditary nature. The pathogenesis of the disease is still not well known. It is characterised by the presence of diabetes insipidus, diabetes mellitus, optic atrophy and deafness. Other anomalies, such as renal outflow tracts and multiple neurological disorders may develop later. In our case report the diabetes mellitus appeared at the age of 4; the hearing loss and renal disturbances at the age of 11; the optic atrophy at the age of 16. No signs of ataxia, diabetes insipidus and neurologic anomalies were found. The diagnosis of Wolfram syndrome is not always easy in the first stages of the disease. The suspect may come from the presence of a juvenile diabetes mellitus asssociated with optic atrophy. For the diagnosis a valid clue can be given from the results of some clinical tests such as the positivity of the visual evoked potentials and the retinogram reliefs and the exclusion of the autoimmune origin of the diabetes mellitus. Other signs such as the progressive sensorineural hearing loss, the presence of nystagmus and of urodynamic disturbances and renal complications makes the diagnosis of this syndrome easier.

Lidocaine intradermal injection--a new approach in tinnitus therapy: preliminary report.

The efficacy of lidocaine in controlling tinnitus is well documented. It can be administered intravenously or by transtympanic injection. The first method of delivery can produce cardiovascular and central nervous system adverse reactions. The transtympanic injection can bring about slight sensorineural hearing loss, vertigo, vomiting, and taste disturbances. To improve on results obtained in persons with tinnitus, the vasoactive drug lidocaine was delivered by a novel intradermal route in 68 patients. The control group, which received intradermal saline injection, included 20 patients with tinnitus. As parameters of evaluation, the self-evaluation scale of subjective disturbance and tinnitus loudness were considered. Significant improvement in level of disturbance and tinnitus loudness was observed both in patients with tinnitus intensity less than 10 dB and in those with tinnitus intensity greater than 10 dB. No significant results were observed in the control group. Of particular interest was the complete absence of unpleasant complications with intradermal lidocaine.

Rieger syndrome: case report.

Rieger syndrome is a dysembryogenetic disease in which labyrinthic damage can be associated with other genetic anomalies. The case presented here is of a patient who has bilateral dysgenesis of the iris, with bulbar atrophy and dyscoria. The patient does not present any malformation of the craniofacial structures, of the periumbilical skin, or of the skeletal bones. The case is, therefore, a variant of the Rieger syndrome labeled Axenfeld-Rieger syndrome. The patient reported a progressive sensation of auricular fullness, and liminal audiometry revealed a sensorineural hearing loss. Computed tomography scanning of the temporal bone revealed a bilateral dysmorphism of the acoustic channels. The presence of a bilateral cochlcopathy in a patient suffering from the Axenfeld-Rieger syndrome could be the expression of a genetic "disorder." We cannot exclude the possibility also that this genetic anomaly is responsible for the bony dysmorphism of the inner ear channels shown by the computed tomography scan of the temporal bone.

Troublesome tinnitus in childhood and adolescence: data from expert centres.

OBJECTIVE: Whilst there are several published studies of the prevalence of troublesome tinnitus in childhood and adolescence (indicating that up to a sixth may experience bothersome tinnitus), there is sparse information regarding incidence. METHODS: In this study a retrospective case review of patients aged under 18 with a primary complaint of tinnitus seen in 2009 was undertaken in four European clinics known to accept such referrals. RESULTS: A total of 88 young persons with a primary complaint of tinnitus were seen in 2009 by these services, and this represents 3.8% of the paediatric clinical workload of these services and 0.3% of the total clinical workload in that year. The overwhelming majority (93%) of cases were aged 10 years or over at presentation. In only 16 cases (18%) was the tinnitus classified as severe by the reviewing clinician. Tinnitus was accompanied by hyperacusis in 34 cases (39%). CONCLUSIONS: Whilst tinnitus in childhood or adolescence can be severe, this is rarely seen in the clinic. Epidemiological data for childhood tinnitus reported previously should be interpreted with caution, as it is dissonant with the data presented in the current study. This may represent an unmet need in the population, but it may also be the case that the incidence of tinnitus in childhood and adolescence is low.

Perichondritis with or without external otitis and intradermal injection: a new therapeutic approach.

Auricular perichondritis and fiogosis of the external auditory canal are not uncommon pathology of the ear. These inflammatory processes are often accompanied by reactive locoregional lymphadenopathy. An inadequate or insufficient systemic therapy may lead to the persistence of otalgia and of signs of flogosis. The administration of local intradermaltherapy allows a strengthening of the pharmacological effect and a reduction in the quantity of drug used. It provides a rapid improvement in the locoregional signs of infection.Intradermal injection is performed on two pretragral points, two retroauricular points and one in the posterior surface of the pinna. The drugs injected are corticosteroids and antibiotics.The administration of intradermal therapy in the cases presented gave excellent results: control of pain, rapid improvement in the signs of infection, complete recovery from the flogosis, no side-effects.The intradermal lijection of small quantities of drugs allows a rapid and complete recovery from external otitis while the systemic approach leads often to the persistence of the flogosis.

Tinnitus in children without hearing impairment.

OBJECTIVE: Tinnitus is not an uncommon symptom in the pediatric population and, despite its incidence, is still an unrecognized problem, particularly in normal hearing children. As tinnitus is frequently described by adults without evidence of ear disease, reports of tinnitus can be obtained also from a group of children without otological pathology. The present review has been performed in order to emphasize the great importance to try to identify children suffering from tinnitus and to recognize the difference between the tinnitus characteristics in children with ear pathology and those one without otological problems. METHODS: A review of the literature regarding the nature of pediatric tinnitus and the practical diagnostic approach to this symptom has been carried out. RESULTS: Children rarely complain spontaneously of tinnitus but are able to describe it when questioned. In our experience the total percentage of children with tinnitus rises from 6.5% (tinnitus reported spontaneously), to 34% when children are specifically questioned. Most children, more than 50%, have normal hearing; in those with hearing impairment, no particular type or severity of hearing loss has been found. An important point that must be considered much more seriously is tinnitus sequela following head injuries to which children are particularly exposed during their daily activities. Due to the serious consequences that may be caused by tinnitus, it is of great importance to identify and analyze it, so as to minimize its damage, utilizing a protocol of study of pediatric tinnitus which allows to collect interesting informations about tinnitus characteristics. CONCLUSIONS: In considering that tinnitus in children exists and may provoke serious consequences, even in absence of ear pathology, it is necessary to investigate and understand more about this symptom in children. From this viewpoint, it is very important to recognize the value of a global evaluation of a child suffering from tinnitus. There is no reason why such an important symptom well reported in adults should not be investigated in the pediatric population in which it seems to be as frequent as in the adult one. It is reasonable to believe that also in children tinnitus may have significant implications for medical and rehabilitative management.

Tinnitus with or without hearing loss: are its characteristics different?

The present study was carried out in order to analyze the clinical characteristics of tinnitus both in normal hearing subjects and in patients with hearing loss. The study considered 520 consecutive tinnitus sufferers. The following parameters were considered: age, sex, subjective disturbance caused by tinnitus, subjective judgment of tinnitus intensity, tinnitus laterality, tinnitus duration, tinnitus measurements, normal hearing or associated hearing loss. Among the patients considered, 223 have normal hearing while 297 have a hearing deficit. The hearing impairment was found to be in most cases of sensorineural type. The subjective discomfort is higher in presence of hearing loss. Subjects with hearing loss needed significantly higher masking levels. No evident differences in the residual inhibition (RI) result between the two groups were found. The present study confirms that tinnitus is most frequently associated with hearing loss. The characteristics of tinnitus in normal hearing subjects, except for the subjective judgment of tinnitus intensity, the pitch and the RI, are significantly different for those observed in subjects with hearing loss. The association of tinnitus and hearing deficit seems to increase the perceived severity of the symptom.

Non-specific immunological determinations in Meniere's disease: any role in clinical practice?

Several studies supported the hypothesis that an autoimmune response may be a pathogenetic factor in Meniere's disease occurrence. It has been demonstrated that the endo-lymphatic sac has an important role in the immuno-mediated reaction and it has also become evident that an immunological mechanism may be involved in the development of endo-lymphatic hydrops. The present study was carried out in order to analyse the validity of serological non-specific immune tests in determining the possible role of immune pathology in 200 Meniere's suffering patients. The immune activity was investigated determining the erythrocyte sedimentation rate (ESR), the C-reactive protein levels, the rheumatoid factor, the serum immunoglobulin levels by group, the complement levels, the lymphocyte sub-populations, the cryoglobulines, the circulating immune complexes (CIC), organ and non-organ auto-antibodies. Levels of Ig, ESR, C-reactive protein, rheumatoid factor, complement fractions and cryoglobulines were either negative or non-significant in the considered cohort of Meniere's disease suffering patients. On the other hand, in more than half of the sample group high values of CIC were found. Data concerning T-lymphocyte sub-population indicates a clear increase in T-helper compared to T-cytotoxic cells, with an increase in the CD4/CD8 ratio. The datum of particular interest concerns analysis of T-cells activation complexes. Our present findings show that early activated T-lymphocytes change and in particular changes occur in the expression of the interleukin-2 receptor. Moreover, it seems to be possible to correlate the alteration of the immunological tests and the phase of the disease. Present data showed that the immunological factor should be considered a relevant element in most of the cases of Menière's disease.

Tongue base metastasis from neuroendocrine endometrial small cell carcinoma.

The endometrial small cell carcinoma (ESCC) is a rare and aggressive malignancy with an estimated prevalence of less than 1% of endometrial carcinomas. Endometrial small cell carcinoma is frequently diagnosed at an advanced stage and has a poor prognosis. Although the most common presenting sign of ESCC is definitely a peri- or postmenopausal vaginal bleeding, we report for the first time the occurrence of tongue base bleeding as first manifestation of disseminated neuroendocrine ESCC. From a clinical viewpoint, tongue metastasis from primary endometrial carcinoma is a manifestation of widespread disease. Albeit, our patient underwent complete hysterectomy and postoperative chemotherapy, she died of disseminated disease 3 months after ESCC diagnosis.

Evolution of audiometric pattern in Meniere's disease: long-term survey of 380 cases evaluated according to the 1995 guidelines of the American Academy of Otolaryngology-Head and Neck Surgery.

OBJECTIVES: Hearing loss in the early stages of Meniere's disease is characterized by a fluctuation in the audiometric pattern limited to the low frequencies, and then, during the disease's evolution, the hearing loss involves the medium and high frequencies. As far as the prevalence of different types of audiometric curves is concerned, there is no agreement among the various studies. The study of audiometric evolution in the course of the disease has been limited owing to the difficulties in following a relevant number of patients for a long period of time. The aim of the present study was to compare the auditory level and audiometric pattern evolution in a significant number of patients suffering from Meniere's disease who had undergone long-term follow-up (at least 10 years). METHODS: The study considered 380 patients with a confirmed diagnosis of Meniere's disease. The audiometric data were collected at the onset of the disease and after 5 and 10 years. Four patterns were considered: peak, rising, falling, and flat. Audiometric evolution analysis in four stages, defined by the guidelines of the American Academy of Otolaryngology-Head and Neck Surgery, was evaluated. RESULTS: At the onset, in 190 cases, the audiometric pattern was a peak curve, with fluctuation of the threshold in 68% of cases. The mean threshold shift for the 500 to 3000 Hz range was between 26 and 40 dB. After 5 years, a peak type (41.9%) or a flat type (42.9%) was observed; the pure-tone average (PTA) ranged between 26 and 40 dB in 47.9% and between 41 and 70 dB in 51.8% of cases. After 10 years, in most cases (57.9%), a flat curve was observed, and the PTA in 100% ranged between 41 and 70 dB. CONCLUSION: The most common audiometric pattern at the onset of the disease is the peak type; long-term transformation of the initial audiometric pattern into a flat curve has been confirmed. High-frequency involvement seemed to be related more to Meniere's disease duration than to the influence of aging on hearing loss.

Cervical necrotizing fasciitis: a novel clinical presentation of Burkholderia cepacia infection.

Necrotizing fasciitis is a soft-tissue infection characterized by progressive destruction of fascia and adipose tissue which may not involve the skin. Cervical necrotizing fascitis (CNF) is an uncommon clinical entity. The development of CNF is frequently related to synergistic infections of aerobic and anaerobic organisms of the upper aerodigestive tract. We describe the first case of CNF due to multi-drug resistant Burkholderia cepacia and Peptostreptococcus infection in an immuno-competent patient without cystic fibrosis.