Phase I Study in Healthy Women of a Novel Antimycotic Vaginal Ovule Combining Econazole and Benzydamine.

Purpose: A novel fixed-dose combination of 150 mg of econazole with 6 mg of benzydamine formulated in vaginal ovules was investigated in a randomised, double-blind, four-parallel group, tolerability, and pharmacokinetic Phase I study in healthy women. Methods: The fixed-dose combination was compared to econazole and benzydamine single-drug formulations and with placebo after daily applications for 3 consecutive days. Safety and tolerability were evaluated recording the adverse drug reactions, local and general tolerability scores, clinical laboratory assays, and vital signs. Econazole, benzydamine, and its metabolite benzydamine N-oxide pharmacokinetics were investigated after single and multiple applications. Results: Local reactions were generally absent. Pruritus and pain at the application site were infrequently reported. According to the subjects' evaluations, the overall tolerability of the ovules was rated as excellent or good. No significant effect of any treatment on laboratory parameters, vital signs, body weight, vaginal pH, or ECG was observed. Very low econazole, benzydamine, and benzydamine-N-oxide concentrations were measured in plasma, though quantifiable in almost all samples. Conclusion: The tested fixed-dose combination showed a good safety profile consistently with the known tolerability of both active substances. In addition, the confirmed low bioavailability of the drugs excludes the possibility of any accumulation effects and limits the risk of undesired systemic effects. This trial is registered at ClinicalTrials.gov with the identifier NCT02720783 last updated on 07 February 2017.

Mastoiditis in adults: a 19-year retrospective study.

The objective of our study was to review retrospectively the clinical, radiological and therapeutic findings in 62 adults with acute mastoiditis treated at the ENT Department of Ferrara from 1992 to 2010. 62 adult cases fulfilled the following inclusion criteria: otoscopical evidence of co-existent or recent otitis media; postauricular swelling, erythema or tenderness; protrusion of the auricle; fever and/or significant radiological findings of mastoiditis. Conservative treatment comprehended antibiotic ± ventilation tube. Surgical procedures comprehended mastoidectomy or mastoido-tympanoplasty. The incidence of adult's mastoiditis in our district (0.99 cases/year/100.000 inhabitants) has maintained quite stable during the considered 19-year period. The typical clinical presentation was observed in 48% of cases. Complications were meningitis (15 cases), meningo-encephalitis (1), meningitis associated with lateral sinus thrombosis (1), facial nerve paralysis (11), and labyrinthitis (8). In all cases except one, the facial palsy recovered completely and no mortality was observed due to these complications. Complete cure was obtained with conservative treatment in 69% of uncomplicated cases and in 24% of patients with intracranial complications. Mastoiditis in adults may present as the acute classical form, as well as latent forms which often have prolonged and insidious development followed by a rapid clinical deterioration. Clinical features are frequently atypical, while incidence of meningitis and other complications is still high particularly in the most elderly. Thus, great care is required from clinicians to make an early diagnosis in order to promote adequate treatment.

Prulifloxacin versus levofloxacin in the treatment of severe COPD patients with acute exacerbations of chronic bronchitis.

RATIONALE: Antimicrobial therapy of chronic bronchitis exacerbations in patients with severe chronic obstructive pulmonary disease (COPD) is based on empiric antibiotic treatment. OBJECTIVES: To evaluate the efficacy of prulifloxacin versus levofloxacin therapy in severe COPD patients with exacerbations of chronic bronchitis. METHODS: This study involved a multicenter, parallel, double-blind, randomized clinical trial. Patients aged 40 years or older, smokers, or ex-smokers (>10 pack-years) with spirometrically confirmed severe COPD (FEV1 ≤ 50% predicted and FEV1/FVC ratio < 0.7) and diagnosed with an acute exacerbation of chronic bronchitis were enrolled in the study. Patients were randomized to receive prulifloxacin 600 mg once a day or levofloxacin 500 mg once a day for 7 days. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was clinical assessment at the TOC visit (7-10 days after the end of treatment) of signs and symptoms of exacerbation, namely sputum purulence, sputum volume, dyspnoea, cough and body temperature assessed through semi-quantitative scales. The ITT population included 346 (174 prulifloxacin, 172 levofloxacin) out of 351 treated subjects. A total of 161 patients with prulifloxacin (92.5%) and 166 with levofloxacin (96.5%) were considered cured at TOC (the difference in the percentage of cured patients was -3.98 with 95%CI of -8.76; 0.79). At the 6-month follow-up, the rates of patients with no relapse of AECB were higher than 95% in both the prulifloxacin and levofloxacin groups. CONCLUSIONS: Both prulifloxacin and levofloxacin showed efficacy rates higher than 90% in the treatment of severe COPD patients with exacerbations of chronic bronchitis, with no statistically significant differences between the two antibiotics. The long-term follow-up confirmed a very low incidence of relapse, endorsing the appropriateness of this therapeutic approach. EUDRACT no. 2006-004167-56.

Postoperative complications in cochlear implants: a retrospective analysis of 438 consecutive cases.

Our objective is to determine the complication rate in a population of infants, children, adolescents and adults, from a University Hospital Cochlear Implant program and to discuss their causes and treatments. The methods include a retrospective study of 438 consecutive patients in a tertiary referral centre, the Audiology Department of the University Hospital of Ferrara. All patients receiving cochlear implants, between 1 January 2003 and 31 December 2009, have been included. All complications and treatments were systematically reviewed with an average duration of follow-up of 46 months (range 10-84 months). The results reveal that the overall rate of complications in our group was 9.1% (40 of 438), and most of them were minor. Wound swelling and infections represent the most common complication occurred. There were no cases of transient or permanent facial palsy following surgery, and also we did not register any case of postsurgical meningitis. Thirteen patients (3.0%) underwent explantation followed by reimplantation. In conclusion, we find that Cochlear implantation is a safe low-morbility technique with a relatively low complication rate in the presented population.

Are systemic oral steroids effective for sensorineural hearing loss in bullous myringitis? Considerations from a preliminary study.

BACKGROUND: It is common in clinical practice to administer systemic steroids to treat sensorineural hearing loss due to bullous myringitis (BM). Nonetheless, there is currently no definitive evidence that steroid therapy is effective and appropriate for BM. OBJECTIVE: The aim of this study was to assess the effectiveness of systemic steroid therapy for treating BM. PATIENTS AND METHODS: This prospective study included 23 patients affected by BM with sensorineural hearing loss (median age, 45.8 years). The subjects were divided into two groups: Group A received only systemic antibiotic treatment and Group B received systemic antibiotics plus systemic steroid treatment. RESULTS AND CONCLUSIONS: There were no differences between the groups in terms of the sensorineural hearing loss recovery. Both treatments were effective, suggesting that administration of oral steroids in combination with antibiotics did not confer an advantage in terms of sensorineural hearing loss recovery rate in the tested population.

Hearing threshold estimation by auditory steady state responses (ASSR) in children.

Hearing threshold identification in very young children is always problematic and challenging. Electrophysiological testing such as auditory brainstem responses (ABR) is still considered the most reliable technique for defining the hearing threshold. However, over recent years there has been increasing evidence to support the role of auditory steady-state response (ASSR). Retrospective study. Forty-two children, age range 3-189 months, were evaluated for a total of 83 ears. All patients were affected by sensorineural hearing loss (thresholds ≥ 40 dB HL according to a click-ABR assessment). All patients underwent ABRs, ASSR and pure tone audiometry (PTA), with the latter performed according to the child's mental and physical development. Subjects were divided into two groups: A and B. The latter performed all hearing investigations at the same time as they were older than subjects in group A, and it was then possible to achieve electrophysiological and PTA tests in close temporal sequence. There was no significant difference between the threshold levels identified at the frequencies tested (0.25, 0.5, 1, 2 and 4 kHz), by PTA, ABR and ASSR between the two groups (Mann Whitney U test, p < 0.05). Moreover, for group A, there was no significant difference between the ASSR and ABR thresholds when the children were very young and the PTA thresholds subsequently identified at a later stage. Our results show that ASSR can be considered an effective procedure and a reliable test, particularly when predicting hearing threshold in very young children at lower frequencies (including 0.5 kHz).

Acute mastoiditis in children: the "Ferrara" experience.

OBJECTIVE: This study aims to investigate the clinical features and outcomes of acute mastoiditis in children referred to the ENT/Audiology Department of the University of Ferrara from January 1994 to December 2005. It also aims to discuss risk factors and to find predictors for surgery. METHODS: A retrospective study on case sheets of children with an acute mastoiditis diagnosis was carried out. Fifty-five cases fulfilled the inclusion criteria: they presented otoscopical evidence of acute otitis media and inflammatory findings of the mastoid area such as post-auricular swelling, redness or tenderness, protrusion of the auricle and/or radiological findings. RESULTS: Twenty-six patients were only treated with antibiotic therapy, tympanocentesis alone was performed in 11 cases; in 5, a ventilation tube was positioned. Mastoidectomy was performed in 13 patients. The group who underwent mastoidectomy had a median hospital stay of 15 days (5-54), in this group were found the following complications: 1 meningitis, 1 meningo-encephalitis, 1 lateral and sigmoid sinus thrombosis, 1 facial palsy. CONCLUSION: the incidence of otomastoiditis does not seem to be decreasing, on the contrary, in some countries, it seems to be on the increase. Our experience cannot confirm a real increase of the incidence but we noted periodic variations during the time of observation. It is important, that careful attention is paid to the clinical assessment of children who are 2-years old or under, as they seem to be more exposed to the risk of clinical complications; therefore, it is highly recommended that the otologist and the paediatrician collaborate closely.

Idiopathic sudden sensorineural hearing loss: cardiovascular risk factors do not influence hearing threshold recovery.

Previous studies have suggested that risk factors for ischaemic vascular disease, such as cigarette smoking, hypertension and hyperlipidaemia, can also be considered risk factors for the development of idiopathic sudden sensorineural hearing loss (ISSNHL). In this study, we have evaluated the hypothesis that these factors can influence hearing threshold recovery in patients affected by ISSNHL. A total of 141 subjects who suffered an episode of ISSNHL were included. All subjects were assessed with tonal audiometry, auditory brainstem responses and MRI to exclude retrocochlear pathology. Hearing tests were conducted at ISSNHL onset (t = 0) and after 30 days. Patients were divided into three classes according to the presence/absence of one or more cardiovascular risk factors including: history of smoking, total serum cholesterol/triglycerides, history of hypertension and diabetes mellitus. Values of hearing threshold recovery were estimated and comparisons were conducted across the three risk factor classes. 75% of patients affected by ISSNHL showed a threshold recovery. However, the threshold recovery was found to be class-independent (average recovery value of 18 dB HL per classes) and also independent of age and gender. Even if cardiovascular risk factors have been found to be involved in the pathogenesis of ISSNHL, the present study suggests that these factors do not have any significant influence on the threshold recovery in ISSNHL.

Double-blind randomized study of lonidamine and radiotherapy in head and neck cancer.

PURPOSE: Preclinical studies showed lonidamine to potentiate the effects of x-irradiation by inhibiting the repair of potentially lethal damage. This Phase III double blind, placebo-controlled study was performed to evaluate whether lonidamine can increase the tumor control of radiotherapy in the treatment of advanced head and neck cancer without any synergistic toxic effects on the exposed normal tissues. METHODS AND MATERIALS: Ninety-seven patients with Stages II-IV squamous cell carcinoma of the head and neck were enrolled. Separate analyses were done on the 96 eligible patients and the 90 patients who completed the prescribed treatment regimen. Patients received radiotherapy up to a planned total of 60-66 Gy, in 2 daily fractions of 1.5 Gy each and either lonidamine (450 mg p.o. in three divided daily doses) or placebo, given continuously for 3 months or up to 1 month after the end of radiotherapy. RESULTS: The rate of tumor clearance was 66% (32/48) in the lonidamine group and 65% (31/48) in the placebo group, while the subsequent failure rate was 50% and 77%, respectively (p < 0.05). The 3 and 5 year locoregional control rates in the adequately treated patients achieving complete tumor clearance were 66% and 63% for lonidamine vs. 41% and 37% for placebo. The disease-free survival in adequately treated patients was significantly better in the lonidamine group (p < 0.03), with 3 and 5 year rates of 44% and 40%, respectively, vs. 23% and 19% in the placebo group. The overall survival rate for all eligible patients at both 3 and 5 years was 44% in the lonidamine group and 44% and 31%, respectively, in the placebo group. Both acute and late radiation reactions were similar in the two groups. Myalgia and testicular pain were the most frequent side effects of lonidamine with an incidence of 8.5% and 4.2%, respectively. CONCLUSION: The addition of lonidamine to hyperfractionated radiotherapy was correlated with a statistically and clinically significant proportion of long-term disease-free patients. The toxicity of radiotherapy was not aggravated by the drug and the overall tolerance of the combined regimen was acceptable.

Bindarit prolongs survival and reduces renal damage in NZB/W lupus mice.

OBJECTIVE: The present study was designed to investigate the effects of bindarit on animal survival and renal damage in murine lupus autoimmune disease. METHODS: Female NZB/W mice were used. Bindarit was administered, as a 0.5% medicated diet, starting either before the onset of the pathology or early in the course of the disease, in order to assess the effects of age upon the response. Furthermore, the effects of combined administration of bindarit with low dose i.p. cyclophosphamide bolus were also studied. Proteinuria and anti-dsDNA antibody levels were determined during the course of the study. Renal damage was evaluated by light microscopy. RESULTS: Bindarit markedly prolonged the NZB/W mouse life span (p < 0.001 vs. controls), showing a significant difference even against high dose cyclophosphamide (90 mg/kg ip bolus) chosen as the reference (p < 0.01). Bindarit significantly reduced the degree of renal damage, delayed proteinuria and did not prevent autoantibody development, thus confirming the lack of immunosuppressive activity. CONCLUSION: The present results and other experimental data demonstrating the capacity of the drug to interfere with the inflammatory and immune response cross-talking, indicate that bindarit exerts its action in murine lupus through a novel and original mechanism. These findings, coupled with the evidence that the drug possesses a very safe toxicological profile, suggest that further investigations to assess the potential value of bindarit in the treatment of SLE are warranted.

Microbial flora of surface versus core tonsillar cultures in recurrent tonsillitis in children.

Surface and 'core' tonsillar specimens were collected from 60 children, between 2 and 14 years of age, suffering from recurrent tonsillitis, in order to establish the reliability of surface tonsillar swabbing technique and to define the most frequently involved aerobic and anaerobic microorganisms. From the qualitative point of view, the same mixed aerobic and anaerobic flora were obtained in both samples thus demonstrating the reliability of the surface swabbing technique. From the quantitative point of view, 187 microorganisms, 129 (69.2%) aerobes and 58 (30.8%) anaerobes were isolated from surface cultures while 184, 109 (59.2%) aerobes and 75 (40.8%) anaerobes from the core cultures, thus demonstrating a greater number of anaerobes in the core of the tonsil. The most common isolated aerobic microorganisms were the alpha- and beta-hemolytic Streptococci, the Neisseriae and the Staphylococcus aureus; the predominant anaerobic ones were the Fusobacterium nucleatum, the Bacteroides sp. and the Veillonella parvula. The isolated staphylococcus aureus and the bacteroides sp. were all beta-lactamase producers.

Effects of ibopamine eye drops on intraocular pressure and aqueous humor flow in healthy volunteers and patients with open-angle glaucoma.

PURPOSE: On the basis of intraocular pressure measurements and fluorophotometry we assessed the effects of 2% ibopamine eye drops on aqueous humor production in normal and glaucomatous eyes. METHODS: Thirty subjects (15 healthy volunteers and 15 open-angle glaucoma patients with ocular hypertension) were included in a placebo-controlled study with random assignment of treatment from masked containers. All subjects underwent ophthalmologic examinations and intraocular pressure (IOP) measurements. Fluorophotometry was done in both eyes at baseline (without treatment) and during treatment. Each subject was treated with 1 drop of 2% ibopamine in one eye and 1 drop of placebo in the fellow eye 30 minutes before fluorophotometric scans and every hour after the first instillation (for a total of 4 times). Safety was evaluated by recording adverse events and ocular symptoms and signs. Aqueous humor flow data were analyzed using the paired t-test, comparing ibopamine and placebo-treated eyes. RESULTS: No changes in IOP were detected in normal eyes, whereas glaucomatous eyes showed a mean increase of 4 mmHg (95% CI 3.46-4.51) from baseline. The difference in IOP between healthy eyes and those with glaucoma was significant (p < 0.0001). In normal eyes and patients with glaucoma ibopamine led to a significant increase in aqueous humor flow compared with placebo-treated eyes (p < 0.01). The safety profile of ibopamine was very good. CONCLUSIONS: The results seem to confirm that ibopamine increases aqueous humor production in normal and glaucomatous eyes, raising IOP only in eyes with glaucoma.

The behaviour of wave V latency in cochlear hearing loss.

The audiological approach to the early diagnosis of cerebellopontine angle tumours (APC) is based mainly on ABR. In present work, wave V latency has been studied in two groups of patients: 308 cochlear cases and 74 retrocochlear cases (APC surgically confirmed tumours), in order to increase the sensitivity and specificity of the diagnostic indexes I-V, IT5 and Delta V. Wave V latencies have been evaluated in relation to hearing loss at 2-4 kHz and audiometric profile. Both these factors show a highly significant positive correlation with the latency, which consequently increases proportionally to hearing loss and high-frequency audiometric loss. A multiple regression analysis was therefore used to analyse the effects from the two variables, and a correction factor was calculated to compensate the latency values for hearing loss and threshold configuration. The effects of such a correction on the clinical results consist mainly of a reduction in the rate of cochlear false-negative results, which corresponds to improving the ABR specificity.

Radioisotopic method for nasal mucociliary function evaluation.

In 13 healthy young adults, nasal mucociliary transport velocity was measured by means of albumine microsphere labeled with Tc99m as a tracer. M + ISD of clearance velocity values and of the half time radioactivity (T1/2) resulted to be respectively 1.02 + 0.22 cm/min and 1.07 + 0.24 min. A significant correlation (P less than 0.05) between half time clearance (T1/2) values of the radioactive particles and the mucociliary velocity ones could be detected, making T1/2 a reliable and rapidly obtainable parameter for determining nasal mucociliary function. Advantages and disadvantages of the different techniques are discussed.

Plexiform neurofibroma of the cervical portion of the vagus nerve.

The authors describe a rare case of plexiform neurofibroma of the cervical portion of the vagus nerve, and discuss its aetiopathogenesis, clinical, histological and therapeutic features, emphasizing the difference from other benign tumours of the vagus nerve. The clinical characteristics of the mass, ultrasound tomography, CT scanning and digital subtraction angiography were useful in defining its extension and relationships with the surrounding structures. Surgery is the treatment of choice. After mentioning the most commonly employed surgical approaches, they emphasize the advantages of the lateral-cervical approach which allows a wide exposure of the possible sites of origin of the tumour and its complete removal. Finally they stress the need of an accurate histological and immunohistochemical examination in order to differentiate neurofibromas from neurilemmomas.

[Relations and variability of the stapedial reflex threshold and psychoacoustic discomfort threshold]. / Relazioni e variabilità della soglia del riflesso stapediale e della soglia psicoacustica del disconforto.

Ten normal hearing subjects were subjected to repeated measurement of the stapedial reflex threshold (RT) and loudness discomfort threshold (DT) during five separate sessions. On the average DT was 4.8 dB higher than the RT. The sessions did not affect the intra-individual variance of either threshold. A regression analysis demonstrated that a significant linear relationship exists between RT and DT. However, DT may be lower than RT when the latter is shifted towards its upper variance boundary. Hence, RT and DT are not equivalent as indicators of the upper limit of loudness tolerance; since DT revealed a low intra-subject variance, such a psychoacoustic measurement may be reliably used for clinical purposes.

[Loudness scaling for narrow band noise and speech signal]. / Stime categoriche di loudness per rumore a banda stretta e per segnale vocale.

A group of normal-hearing subjects underwent an experimental procedure to obtain estimates of loudness for two narrow band noises, centered at 0.25 and 3 kHz respectively, and meaningful unfiltered speech signals (sentences). Stimuli consisted of 12 intensity levels, spaced equally over the dynamic auditory range. The subjects were asked to associate each level of intensity to one 7 loudness categories. The loudness growth for a noise bands is defined by an exponential function. The loudness growth for the speech signal is better approximated by a linear function. However the mean intensity/loudness function shows two steep portions at the low and high intensities and these are separated by a shallow tract between 55 and 75 dB SPL. The loudness growth for meaningful speech signals--differing from the typical exponential function shown by noise stimuli--seems to confirm the contribution of factors that depend on central auditory organization, most likely operated by the perceptive auditory continuity attributes and the semantic content of the speech signals.

[Influence of a CNS pathology on the electrocochleography response]. / Alterazioni dei potenziali elettrococleografici in presenza di patologie del sistema nervoso centrale.

This study analyzed 73 electrocochleographic recordings made in children with a normal hearing threshold, selected retrospectively from 1563 recordings made between 1973 and 1990. The aim of the study was to check the original findings for any correlation between the various response parameters which might be indicative of a pathological condition. Compound action potential (AP) latency and amplitude, presynaptic summation potential (SP) and cochlear microphonic (CM) amplitudes and AP rapid adaptation behavior were calculated and recordings were associated with clinical information on aetiologic diagnosis, otoscopic examination, impedance measurement data and the finding of any central nervous system (CNS) pathology. The trend of the amplitudes as a function of the intensity of all three potentials (input-output functions), CM and SP in particular, demonstrated unexpected scattered values especially towards the high intensities. This was found correlated to the presence of CNS pathology. The comparison between the two groups (with vs without CNS pathology) with the aid of the Student's t-test proved statically significant, especially for CM and SP amplitudes while rather less so for AP amplitude. In particular, all CM and SP amplitude values outside the confidence intervals (calculated as 95% of normal cases) revealed CNS pathology. It has been suggested that the influence of the CNS on cochlear function is due to a disturbed function of the olicocochlear bundle, which is known to have an inhibitory effect on cochlear dynamics; furthermore, there is also proof that it can be activated regardless of any ipso-and/or contra-lateral acoustic stimulation. The effects observed on the electrocochleography in cases with CNS disorders would thus be explained by an interruption of the olivocochlear bundle at the CNS level or a disruption of the CNS mechanism capable of controlling its activation.

[Hemangiopericytoma of parapharyngeal space]. / Emangiopericitoma dello spazio parafaringeo.

The parapharyngeal space is a rare site of parapharyngeal neoplasms: their diagnosis and therapeutic treatment offer peculiar challenges. Parapharyngeal tumours may be primary, metastatic or diffused with regaed continuity. They are mostly benign (mixed, neurogenic, vascular tumours, etc.) rather than malignant neoplasms (adenocystic carcinoma, adenocarcinoma, lymphoma, etc.). In order to diagnosis parapharyngeal tumours differentially it is important to consider very rare type of neoplasms such as hemangiopericytomas. In this paper the Authors describe a case of hemangiopericytoma of the parapharyngeal space indicating the main diagnosis procedures, especially CT scan, Magnetic resonance and angiography. They discuss pathological aspects with particular regard to the differential diagnosis between benign and malignant tumour of this kind as well as prognoses. The Authors also describe surgical treatment in relation to particular parapharyngeal localization.

[Quantitative abnormalities in nystagmus induced by caloric stimulation in multiple sclerosis]. / Anormalità quantitative del nistagmo indotto da stimolazioni termiche nella sclerosi multipla.

Vestibular nystagmus induced by caloric stimulation (20 degrees and 44 degrees C) was evaluated in terms of duration, frequency and slow phase velocity in 80 patients suffering from clinically defined multiple sclerosis. Criteria of abnormality were established with reference to 3 confidence levels from normative data of a 15-subject control group. Abnormal data representative of vestibular hypo- and hyperreflexia were found ranging between 27 and 53% depending on different parameters and diagnostic criteria. Significant differences in occurrence of nystagmus abnormalities became evident by analyzing 6 different windows of the vestibular response. Different distributions of hypo- and hyperreflexia were observed in relation to the time-course of the normal cumulative response curve, as well as to different stimulus temperatures. For each subject the abnormal data of the 2 stimulated ears X 2 caloric stimulations X 6 analysis windows were cumulated, yielding an overall outcome of pathological results in 66% to 90% of the patients, depending on the different diagnostic criteria.