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E Mira

Publications and source records attributed to E Mira.

At least 19 recordsLinked to original sources
PubMed2005

[The role of clinical history in the evaluation of balance and spatial orientation disorders in the elderly].

Balance and spatial orientation complaints are very frequent in the elderly. The aetiology of these complaints may be related to specific peripheral or central vestibular disorders or to an extravestibular dizziness resulting from impairment or disease in multiple systems. A preliminary diagnostic orientation, permitting the patient to be referred to the most appropriate specialist (otologist, neurologist, consultant in internal medicine, psychiatrist, physical therapist) would be very useful. We examined 163 patients, referred for balance and spatial orientation complaints to the otoneurological outpatient services of 6 university hospital centres in the northern and central Italy, by a detailed questionnaire about characteristics, frequency, duration of any dizziness symptom and by a bedside vestibular examination. The questions were designed to determine whether the patients suffered from true vertigo, considered to be an expression of a vestibular disorder, or of an aspecific dizziness of multifactorial origin. Comparison of the conclusions of the vestibular examination and the diagnostic hypotheses deduced from the clinical history showed a high degree of concordance (Cohen Index 70.5%). To the patient, vertigo and dizziness are synonymous. By asking appropriate questions, a clearer picture should begin to emerge from the patient complaints so that distinction between psychogenic, nonvestibular and vestibular causes can be made. The importance of obtaining a good history cannot be overemphasized. A correct and rigorous approach by the general practitioner could be of great utility both for the health of the patient and for the efficiency of the national health service. The vestibular examination proved that about half the patients (80/163) suffered from vestibular disorders, mainly of peripheral origin (BPV, Menière's disease, vestibular neuritis).

Aged↗
PubMed2005

[The relationship between cognitive impairment, anxiety-depression symptoms and balance and spatial orientation complaints in the elderly].

Balance and spatial orientation complaints, generically defined as "dizziness", are frequent in the elderly. They can cause a greater or lesser degree of handicap, and be associated with a greater or lesser degree of cognitive impairment and anxiety-depression symptoms. We examined 163 patients, referred for these complaints to the otoneurological outpatient services of 6 university hospital centres of the northern and central Italy, performing a bedside vestibular examination. The test allowed to distinguish between subjects with specific vestibular disorders (mainly BVP, Menière's disease and vestibular neuritis) and subjects in who the vestibular examination was not significant, and whose dizziness probably resulted from impairment or disease in multiple systems. The evaluation of the degree of handicap, using the Dizziness Handicap Inventory, showed that in the former group the physical parameters were significantly impaired with respect of a group of 81 age matched healthy controls, whereas the functional and emotional parameters were not. The evaluation of the degree of anxiety-depression, using the Hospital Anxiety Depression Scale, showed that all elderly people with balance and spatial orientation complaints present a degree of anxiety, but not of depression, greater than the controls, irrespective of the vestibular or extravestibular origin of the symptoms. The evaluation of the cognitive level, using the Mini Mental Test, showed that it is similar to the cognitive level in the controls when, according to the results of the otoneurological examination, the balance and spatial orientation complaints are due to vestibular disorders, but it is impaired when these symptoms are related to a dizziness of multifactorial aetiology. The presence of comorbidities is also higher in these patients. It is likely that in the elderly balance and spatial orientation complaints not caused by specific vestibular disorders are due to a dizziness of multifactorial origin, both organic and psychic, that can be classified as a geriatric syndrome.

Aged↗
PubMed2004

Nicergoline in the treatment of dizziness in elderly patients. A review.

In elderly patients, dizziness occurs very frequently with significant effects on the patient's life. Its frequency increases with age, and may arise from a variety of causes. Chronic dysequilibrium in elderly patients is most probably related to disturbances within the central nervous system, due either to altered neuronal functions or to an underlying vascular disease. Nicergoline, a drug used in the treatment of cognitive disturbances in geriatric patients, improves dizziness in elderly demented and non-demented patients. In a double blind,placebo controlled trial the drug improved (i) the severity of symptoms, measured by the dizziness assessment rating scale (DARS), (ii) the overall clinical conditions revealed by global impression scale, and (iii) the perceived quality of life estimated by the dizziness handicap inventory (DHI). These results indicate a possible positive effect also on posturographic measures. Moreover, the improvement occurred at no expense of the established strategy of postural control suggesting that the effect is mediated by a substitute compensatory mechanism allowing the patient to preserve consolidated postural strategies. The results of previous open clinical studies in about 3000 patients are in agreement with those findings. Overall, severity of symptoms decreased by 68 % (57 % in the control study). Globally, the results indicate a beneficial effect of nicergoline on symptoms related to balance disorders of central origin. Animal studies show that the drug displays a broad spectrum of actions on cellular and molecular mechanisms. Moreover, animal research specifically aimed at vestibular pathophysiology has revealed that nicergoline improves vestibular compensation in models of vestibular lesion. Chronic treatment with nicergoline improved the time-course of behavioral recovery in old rats after hemi-labyrinthectomy and counteracted the regulation of cholinergic receptors observed after lesion in old rats. Nicergoline interacts at several levels by various mechanisms, from the molecular level to cognitive function, probably enhancing spontaneous plasticity phenomena underlying the central vestibular compensation. This effect is not dependent from the interaction with a single-transmitter-identified neural pathway, but from anatomical, functional and neurochemical synergistic adjustments in several brain areas.

Aged↗
PubMed2002

[Preliminary results in the use of polydimethylsiloxane textured elastomers (Bioplastique) in the treatment of leakage around tracheoesophageal voice prosthesis].

Leakage around the prosthesis is one of the worst problems afflicting patients fitted with tracheoesophageal (TE) voice prosthesis. Removing the prosthesis for a few days can reduce the size of the fistula, or the leakage may be eliminated simply by replacing the prosthesis. In cases that are refractory to such treatment, the perifistular injection of different types of autologous, heterologous or alloplastic substances has been proposed. A new kind of silicone, previously available abroad, has recently appeared on the Italian market as well; constituted by polydimethylsiloxane textured elastomers (Bioplastique) for soft tissue implants, it appears to guarantee excellent standards of long-term safety and stability. Three patients fitted with Provox2 tracheoesophageal voice protheses who had been experiencing leakage for about 4 months underwent Bioplastique implant procedures. The correction of the fistula size was easy to accomplish and well tolerated by the patients. There was no sign of inflammation, formation of granulomas or other pathological modifications, and the size of the fistula, together with its fluid-tightness, remained stable in time. From our point of view, the Bioplastique implant appears to provide valid and effective treatment of gaping TE fistulas.

Coated Materials, Biocompatible↗
PubMed2001

Segregation of leading-edge and uropod components into specific lipid rafts during T cell polarization.

Redistribution of specialized molecules in migrating cells develops asymmetry between two opposite cell poles, the leading edge and the uropod. We show that acquisition of a motile phenotype in T lymphocytes results in the asymmetric redistribution of ganglioside GM3- and GM1-enriched raft domains to the leading edge and to the uropod, respectively. This segregation to each cell pole parallels the specific redistribution of membrane proteins associated to each raft subfraction. Our data suggest that raft partitioning is a major determinant for protein redistribution in polarized T cells, as ectopic expression of raft-associated proteins results in their asymmetric redistribution, whereas non-raft-partitioned mutants of these proteins are distributed homogeneously in the polarized cell membrane. Both acquisition of a migratory phenotype and SDF-1alpha-induced chemotaxis are cholesterol depletion-sensitive. Finally, GM3 and GM1 raft redistribution requires an intact actin cytoskeleton, but is insensitive to microtubule disruption. We propose that membrane protein segregation not only between raft and nonraft domains but also between distinct raft subdomains may be an organizational principle that mediates redistribution of specialized molecules needed for T cell migration.

Actins↗
PubMed2001

Membrane raft microdomains in chemokine receptor function.

Cell chemotaxis requires the acquisition and maintenance of both spatial and functional asymmetry between initially equivalent cell parts. In leukocytes one becomes the leading edge and the other, the rear edge or uropod. The acquisition of this cell polarity is controlled by an array of chemoattractants, including those of the chemokine family. We propose that chemokine receptor activation in highly organized lipid raft domains is a major determinant for the correct localization of the signaling pathways leading to the cell asymmetries required for migration. The lateral organization imposed by membrane raft microdomains is discussed in the context of other chemokine receptor activities, such as its role as a human immunodeficiency virus (HIV) coreceptor.

Animals↗
PubMed2001

Voice restoration after circumferential pharyngolaryngectomy with free jejunum repair.

Speech restoration after circumferential pharyngolaryngectomy with free jejunal repair for advanced tumors of the hypopharyngo-esophageal tract remains a difficult problem to solve. We report here the results of secondary voice restoration in six patients who received a Provox 2 type prosthesis and intensive speech therapy after circumferential pharyngolaryngectomy with free jejunum repair. No patient had operative or post-operative complications due to insertion of the prosthesis. No patient had to have the prosthesis removed during the follow-up (8 to 14 months). Analysis of some acoustic parameters of voice (fundamental frequency, waveform perturbations) and qualitative characteristics of speech (intelligibility, pleasantness and acceptability) demonstrated that all the patients were able to produce satisfactory speech after tracheojejunum puncture and speech therapy and were satisfied with their own ability to communicate. Our results are reassuring and we therefore advise that in patients undergoing free jejunum flap reconstruction of the hypopharyngo-esophageal tract voice restoration should be attempted by placing a voice prosthesis through a secondary tracheo-esophageal puncture and providing intensive speech training.

Esophageal Neoplasms↗
PubMed2001

Nasal endoscopy in asthmatic children: assessment of rhinosinusitis and adenoiditis incidence, correlations with cytology and microbiology.

BACKGROUND: Upper respiratory airway diseases may induce a worsening of asthma. Sinusitis represents one of the most common chronic diseases. The association of asthma and sinusitis varies greatly in different studies, depending on diagnostic procedures. OBJECTIVE: The aims were: (i) to demonstrate that nasal endoscopy may be easily feasible in asthma at paediatric age; (ii) to evaluate the incidence of rhinosinusitis and adenoiditis in children with asthma by nasal endoscopy; (iii) to correlate inflammatory parameters such as cytology and microbiological cultures with nasal endoscopy findings. SUBJECTS AND METHODS: One hundred and forty-five asthmatic children were evaluated, 48 males and 97 females, with an average age of 7.27 years. Evaluated parameters were the incidence of rhinosinusal infections in asthmatic children, and the role of: (i) nasal endoscopy, (ii) nasal cytology, and (iii) nasal microbiology in their diagnoses. RESULTS: Nasal endoscopy was successfully performed on 128 patients. Twenty-six children had endoscopic rhinosinusitis alone, 10 had adenoiditis alone, and 35 showed endoscopic rhinosinusitis associated with adenoiditis. There were significant correlations between endoscopic rhinosinusitis and adenoiditis (P < 0.001), between clinical and endoscopic rhinosinusitis (P < 0.001), between endoscopic rhinosinusitis and adenoiditis and microbiology (P < 0.05 and P < 0.0001, respectively), and between microbiology and cytology (P < 0.05). CONCLUSION: This study shows that rhinosinusal infections are common in asthmatic children. Moreover, nasal endoscopy might represent a fruitful tool in the management of asthmatic children.

Adenoids↗
PubMed2001

A role for chemokine receptor transactivation in growth factor signaling.

Complex cell responses require the integration of signals delivered through different pathways. We show that insulin-like growth factor (IGF)-I induces specific transactivation of the Gi-coupled chemokine receptor CCR5, triggering its tyrosine phosphorylation and Galpha recruitment. This transactivation occurs via a mechanism involving transcriptional upregulation and secretion of RANTES, the natural CCR5 ligand. CCR5 transactivation is an essential downstream signal in IGF-I-induced cell chemotaxis, as abrogation of CCR5 function with a transdominant-negative KDELccr5A32 mutant abolishes IGF-I-induced migration. The relevance of this transactivation pathway was shown in vivo, as KDELccr5A32 overexpression prevents invasion by highly metastatic tumor cells; conversely, RANTES overexpression confers built-in invasive capacity on a non-invasive tumor cell line. Our results suggest that this extracellular growth factor-chemokine network represents a general mechanism connecting tumorigenesis and inflammation.

Breast Neoplasms↗
PubMed2001

Antonio Scarpa and the discovery of the membranous inner ear.

OBJECTIVE: To give a historical perspective of Antonio Scarpa's contributions to otology, specifically the discovery of the inner ear organs as the foundation for the experimental work that followed. BACKGROUND/METHOD: Scarpa's original descriptions of the human inner ear were translated from the Latin text, and his illustrations were analyzed and compared with current knowledge. CONCLUSIONS: Antonio Scarpa's anatomic and clinical studies place him among the great scientists of the eighteenth century. His discoveries about the inner ear established the limit of what could be learned without advanced histologic techniques and provided the foundation for the work that eventually led to the modern understanding of ear physiology.

Anatomy↗
PubMed2001

A multicenter study on the clinical efficacy and safety of roxithromycin in the treatment of ear-nose-throat infections: comparison with amoxycillin/clavulanic acid.

This multicenter, randomized open-label study compared the efficacy and safety of roxithromycin tablets 300 mg once a day (Rx) and amoxicillin/clavulanic acid tablets 875+125 mg twice a day (Acx), administered for a mean of 7 days. The study was carried out in five centers on 100 in- or out-patients of both sexes, aged between 18 and 91 years (mean 38+/-14). All patients suffered from ENT diseases, 85% with acute otitis media, 31% pharyngotonsillitis and 11% rhinosinusitis. The patients were divided into two randomized groups of 50 patients each. Clinical evaluations (signs and symptoms) were performed before, during and at the end of therapy. At the end of therapy, for intent-to-treat and per-protocol populations, a satisfactory overall clinical response was achieved by 82% of patients in the Rx group and 78% in the Acx group with similar reductions in signs and symptoms of disease in both groups. Safety was good, with only 2 patients of the Rx group and 4 patients of the Acx group presenting side effects, involving mainly the gastrointestinal system. Rx appears to be active and safe in the therapy of ENT diseases exhibiting similar effects on the reduction of signs and symptoms as Amx but with better compliance because of once-a-day administration.

Acute Disease↗
PubMed2001

Betahistine in the treatment of vertigo. History and clinical implications of recent pharmacological researches.

A short profile of betahistine and its activity in treatment of Menière's disease and other forms of peripheral vertigo is presented. The clinical efficacy of betahistine is documented by a series of more than twenty controlled clinical studies, performed in the years 1966-2000. Basic researches initially proved that bethaistine acts trough a vasodilating action on inner ear and cerebral blood flow (Suga and Snow, 1969; Martinez, 1972). In the following years this activity was confirmed using the modern laser doppler flowmetry technique (Laurikainen et al, 1998). Further recent studies proved that betahistine acts on the central vestibular histaminergic system as a weak H1 agonist and a strong H3 antagonist (Arrang et al., 1985), improving the process of vestibular compensation (Tighilet et al., 1995) as well as on peripheral labyrinthine receptors, reducing the spontaneous firing rate but not the activity induced by thermal or mechanical stimulation (Botta et al., 1998). More than forty years after its discovery, this series of studies carried out in the second half of the 90s leads to the conclusion that betahistine is a drug which maintains its scientific interest and its pharmacological potential in the treatment of vertigo.

Betahistine↗
PubMed2001

Effects of betahistine and of its metabolites on vestibular sensory organs.

Betahistine is widely used in the treatment of peripheral and central vestibular disorders. Till now the anti-vertigo effect of the drug was though to be mainly due to an action of betahistine on inner ear or cerebral microcirculation or on some structures of the CNS, chiefly the vestibular nuclei. Vertigo, however is, in most cases, of peripheral origin but it remains unknown whether betahistine, or some of its metabolities, may directly affect the vestibular system at peripheral level. Pharmacokinetic studies have in fact demonstrated that betahistine is transformed, mainly at the hepatic level, in aminoethylpyridine (M1), hydroxyethylpyridine (M2) and, finally, in pyridylacetic acid (M3) which is excreted with the urine. All these substances are therefore present in the body fluids of subjects treated with betahistine, and thus might have pharmacological effects. The goal of the present study was to investigate whether betahistine or some of its metabolites could exert any effect on vestibular receptors. To this end, the effects of the drugs (10(-7)-10(-2) M) have been examined on frog semicircular canals, an animal model well suited for this purpose. The effects of betahistine and of its metabolites have been evaluated by recording ampullar receptor activity both at rest and during mechanical stimulation of the sensory organ. The results demonstrated that both betahistine and one of its metabolites, the aminoethylpyridine (M1), exert effects quite similar on ampullar receptors; both these substances in fact could reduce greatly ampullar receptor resting discharge but had scanty effects on mechanically-evoked responses. This observation might justify betahistine and possibly M1 anti-vertigo effects. In fact vertigo is normally due to uncontrolled changes in vestibular receptor resting discharge. It is therefore probable that any factor able to reduce vestibular receptor resting firing rate and, in consequence, its variations, may have, as final effect, an anti-vertigo action. The observation that betahistine and M1 have similar effects might be of some clinical interest. In fact, on the basis of our data, the hypothesis may be put forward that the anti-vertigo action of betahistine is at first achieved by betahistine itself and then sustained and prolonged in time by M1.

Animals↗
PubMed2001

Action mechanism of betahistine in the vestibular end organs.

Betahistine has been used to treat several vestibular disorders of both central and peripheral origin. The objective of this work was to study the betahistine action mechanism at the vestibular end organs. Experiments were carried out in wild larval axolotl (Ambystoma tigrinum). Multiunit extracellular recordings were obtained from the semicircular canal nerve using a suction electrode. Betahistine (10 microM to 10 mM, n = 32) inhibited the basal spike discharge of the vestibular afferent neurons with an IC50 of 600 microM. To define the site of action of betahistine, its interactions with antagonists of nitric oxide sintethizing enzyme, cholinergic drugs, and excitatory amino acids were studied. Betahistine 1 mM (n = 5) was coadministered with NG-nitro-L-arginine 3 microM. The action of betahistine remained as in control experiments. Betahistine 1 mM reduced the excitatory action of carbachol (200 microM, n = 5) in a 30 +/- 3.4%. Cholinergic antagonists atropine (10 microM, n = 3) and d-tubocurarine (10 microM, n = 3) did not modify betahistine actions. Betahistine 1 mM also reduced kainic acid (10 microM, n = 4) excitatory action in 45.5 +/- 9.8%. These results corroborate that betahistine has a peripheral inhibitory action in the spike discharge of the afferent neurons in the vestibule. This action seems to involve neither NO production nor modifications in the release of acetylcholine from the efferent fibers. The inhibitory action of betahistine seems to be due to a postsynaptic binding site on the afferent neurons.

Ambystoma↗
PubMed2000

Induction chemotherapy by superselective intra-arterial high-dose carboplatin infusion for head and neck cancer.

To evaluate the feasibility, maximum dose of drug tolerated, technical problems, systemic and local toxicity, response rate, overall and disease-free survival, we studied superselective intra-arterial infusion of high-dose carboplatin as part of a multimodality treatment for head and neck cancer. Forty patients with untreated stage II-IV head and neck squamous cell carcinomas received induction chemotherapy with high-dose carboplatin (three cycles at 2-week intervals using 300-350 mg/m2 per cycle), delivered via superselective transfemoral angiography followed by radiotherapy or surgery plus radiotherapy. No technical complications occurred during or after the infusion. Systemic toxicity was minimal, and local toxicity was moderate. At the end of chemotherapy the overall complete and partial response rate was 90% (36/40) at the primary site and 64% (16/25) at the neck nodes. The median follow-up was 24.4 months (range 3-52). To date 21 patients are alive without disease, 2 are alive with disease, 13 have died of disease, and 4 have developed a metachronous lung tumor. There was a good correlation between the response to chemotherapy and disease-free survival. No statistically significant benefit in survival was observed with respect to other series of head and neck tumors treated with different protocols. However, discriminating between responding and nonresponding patients, this procedure can have a prognostic significance in planning integrated treatments for these types of tumors.

Adult↗
PubMed2000

Effects of betahistine metabolites on frog ampullar receptors.

Previous studies have demonstrated that betahistine, an histamine-like substance used widely as an anti-vertigo drug, can decrease ampullar receptor resting discharge without affecting their mechanically evoked responses. Pharmacokinetic studies have shown that this drug is transformed, mainly at the hepatic level, into aminoethylpyridine (M1), hydroxyethylpyridine (M2), then excreted with the urine as pyridylacetic acid (M3). The goal of the present study was to investigate whether betahistine metabolites are also able to affect vestibular receptor activity. Results demonstrated that, in the range tested (10(-7)-10(-2) M), M2 and M3 exerted no effect, whereas M1, at concentrations higher than 10(-6) M, was able to reduce the resting discharge of ampullar receptors without affecting the evoked responses. M1 therefore exerts effects similar to those of betahistine on ampullar receptors. This might be of some clinical interest. On the basis of our data, the hypothesis may be put forward that the anti-vertigo action of betahistine is at first achieved by betahistine itself and then sustained by M1.

Animals↗
PubMed2000

Cells on the move: a dialogue between polarization and motility.

Throughout evolution, both prokaryotic and eukaryotic cells have developed a variety of biochemical mechanisms to define the direction and proximity of extracellular stimuli. This process is essential for the cell to reply properly to the environmental cues that determine cell migration, proliferation, and differentiation. Chemotaxis is the cellular response to chemical attractants that direct cell migration, a process that plays a central role in many physiological situations, such as host immune responses, angiogenesis, wound healing, embryogenesis, and neuronal patterning, among others. In addition, cell migration takes part in pathological states, including inflammation and tumor metastasis. Indeed, tumor progression to invasion and metastasis depends on the active motility of the invading cancer cells and the endothelial cell bed during tumor neovascularization. Cell migration switches "off" and "on," based on quantitative differences in molecular components such as adhesion receptors, cytoskeletal linking proteins, and extracellular matrix ligands, and by regulating the affinity of membrane-bound chemoattractant receptors. A clear understanding of how cells sense chemoattractants is, therefore, of pivotal importance in the biology of the normal cell as well as in prevention of malignant cell invasion. Here we offer a perspective on cell migration that emphasizes the relationship between cell polarization and cell movement and the importance of the equilibrium between the signals that drive each process for the control of tumor cell invasion.

Animals↗