Lack of contralateral suppression in transient-evoked otoacoustic emissions in multiple chemical sensitivity: a clinical correlation study.

Multiple chemical sensitivity (MCS) is a chronic disorder characterized by a variety of symptoms associated with the exposure to chemicals at a concentration below the toxic level. Previous studies have demonstrated peculiar responses in brain activity in these patients with respect to sensory stimuli while the association between chemical sensitivity and other environmental intolerances such as noise sensitivity has been questioned by researchers. In this study, a cohort of 18 MCS patients underwent transient-evoked otoacoustic emission (TEOAE) testing with and without contralateral suppression to evaluate the functionality of the medial olivocochlear (MOC) reflex involved in speech-in-noise sensitivity. Results were compared with an age- and gender-matched control group (n = 20) and correlation analysis with disease onset and quick environmental exposure sensitivity inventory (qEESI) symptom severity scale was performed. Subjects affected by MCS showed statistically significant impairment of MOC reflex, and the onset of the disease and several symptom subscales showed to be correlated to such reduction in some of the frequencies tested. These data suggest that alterations of MOC reflex could be part of the complex features of this disease although more studies are needed to further explore auditory perception disorders in environmental intolerances.

Large nasal septal perforation repair by closed endoscopically assisted approach.

Options for the surgical closure of large symptomatic perforations are limited and consist of an open or closed approach using skin or mucosal flaps, with or without different grafts. The aim of this study is to review our experience in treating large nasal perforations using a closed approach with endoscopic assistance, undertaking a 3-layer reconstruction of the septum. We reviewed 14 consecutive patients with large (2-4 cm) nasal septal perforations, who were treated using an endonasal/endoscope-assisted approach. In these cases, the mucosal defect was reconstructed through a horizontal advancement of the bipedicled mucoperichondrial flaps and sutured using absorbable sutures. The cartilagineous defect was consistently reconstructed using autogenous auricular conchal grafts. Pre- and postoperative nasal symptom scores were used for the study; a decline in the number of Nasal Obstruction Symptom Evaluation Scale symptoms were recorded in 12 of 14 patients (85.7%), and visual analogue scale scores for crusting, bleeding, nasal discharge, whistling, headache, nasal pain, snoring, olfactory loss, and overall discomfort levels also decreased. It was concluded that bipedicled mucoperichondrial flaps with the insertion of auricular cartilage for a 3-layer septal reconstruction seem to give reasonably good results. The use of nasal endoscopy is an endonasal approach, which offers superior precision in all surgical steps and provides a way to obtain excellent closure of the perforation without external incisions.

Caudal septal deviation correction by interlocked graft technique.

In this prospective study, we have proposed a new method to straighten the caudal septum using a modified spreader graft interlocked on the convex side. A single-interlocked graft inserted by 2 through-and-through serial sections of the quadrangular cartilage (applied over the misshapen convex side previously scored on the concave side) facilitated adjustment of the distal septum intraoperatively. The strip of cartilage of the desired height and width acted as a spring graft and may be placed at the desired height of the caudal septal area to exactly counteract the eventual tendency of the most deviated area to warp over time. All 15 patients treated had improvement of their nasal airway and in their postoperative appearance of the external and internal nose. Our technique is easy to perform and shows long-term reliability in correcting caudal septal deviation, demanding a wider application to confirm its effectiveness on a larger series of patients.

Benign paroxysmal positional vertigo after intense physical activity: a report of nine cases.

The aim of this study was to report some clinical cases suggesting a possible correlation between benign paroxysmal positional vertigo (BPPV) and intense physical activity. Out of 430 BPPV cases referred to our out-patients clinic, 9 patients, showing symptoms of BPPV arising after an intense period of physical activity, were selected for this study. The posterior semicircular canal was affected in all the nine patients. The canalith repositioning procedure was successful and eliminated vertigo and nystagmus in all patients. During the follow-up period (12 months) all patients continued with the usual physical activity; four of the nine patients showed a recurrence of the BPPV symptoms after a new intense period of exercises: all were successfully treated by a new single Epley repositioning procedure. BPPV due to intense physical activity is a rare condition (9/430) and it may be caused by repeated vibratory vertical accelerations of a minor degree associated with metabolic variations during strenuous exercise.

Cerebral plasticity in acute vestibular deficit.

The aim of this study was to analyze the effect of acute vestibular deficit on the cerebral cortex and its correlation with clinical signs and symptoms. Eight right-handed patients affected by vestibular neuritis, a purely peripheral vestibular lesion, underwent two brain single photon emission computed tomography (SPECT) in 1 month. The first SPECT analysis revealed reduced blood flow in the temporal frontal area of the right hemisphere in seven of eight patients, independent of the right/left location of the lesion. The alteration was present always in the right, non-dominant hemisphere and was reversible in some patients 1 month after the onset, together with attenuation of signs and symptoms. It may be hypothesized that the transient reduction of cortical blood flow and subsequently of cortical activity in the non-dominant hemisphere, also the expression of cerebral plasticity, may serve as a defense mechanism aimed to attenuate the vertigo symptom.

Taste intensity and hedonic responses to simple beverages in gastrointestinal cancer patients.

Changes in the taste of food have been implicated as a potential cause of reduced dietary intake among cancer patients. However, data on intensity and hedonic responses to the four basic tastes in cancer are scanty and contradictory. The present study aimed at evaluating taste intensity and hedonic responses to simple beverages in 47 anorectic patients affected by gastrointestinal cancer and in 55 healthy subjects. Five suprathreshold concentrations of each of the four test substances (sucrose in black current drinks, citric acid in lemonade, NaCl in unsalted tomato juice, and urea in tonic water) were used. Patients were invited to express a judgment of intensity and pleasantness ranging from 0 to 10. Mean intensity scores directly correlated with concentrations of sour, salty, bitter, and sweet stimuli, in both normals and those with cancer. Intensity judgments were higher in cancer patients with respect to sweet (for median and high concentrations, P<0.05), salty (for all concentrations, P<0.05), and bitter tastes (for median concentration, P<0.01). Hedonic function increased with the increase of the stimuli only for the sweet taste. A negative linear correlation was found between sour, bitter, and salty concentrations and hedonic score. Both in cancer patients and in healthy subjects, hedonic judgments increased with the increase of the stimulus for the sweet taste (r=0.978 and r=0.985, P=0.004 and P=0.002, respectively), and decreased for the salty (r=-0.827 and r=-0.884, P=0.084 and P=0.047, respectively) and bitter tastes (r=-0.990 and r=-0.962, P=0.009 and P=0.001, respectively). For the sour taste, the hedonic scores remained stable with the increase of the stimulus in noncancer controls (r=-0.785, P=0.115) and decreased in cancer patients (r=-0.996, P=0.0001). The hedonic scores for the sweet taste and the bitter taste were similar in cancer patients and healthy subjects, and these scores were significantly higher in cancer patients than in healthy subjects for most of the concentrations of the salty taste and all the concentrations of the sour taste. The present study suggests that cancer patients, compared to healthy individuals, have a normal sensitivity, a normal liking for pleasant stimuli, and a decreased dislike for unpleasant stimuli. Moreover, when compared to controls, they show higher hedonic scores for middle and high concentrations of the salty taste and for all concentrations of the sour taste. Further studies are needed to evaluate whether these changes observed in cancer patients translate into any alteration in dietary behavior and/or food preferences.

Indium111 pentetreotide single photon emission computed tomography (In111 pentetreotide SPECT): a new technique to evaluate somatostatin receptors in chordomas.

Chordomas are rare neoplasms originating along the neuraxis. Although they do not usually show cytological atypia, metastases have been reported in 30 per cent of cases. Survival rates in cases of skull base locations are low, and local recurrence is common after local excision. Radiation therapy is used in post-operative treatment and proton radiation therapy as the primary treatment. In the present paper we present the case of a 50-year-old Caucasian man affected by chordoma of the clivus, with liver and chest metastases, relapsed after several surgical local excisions, to discuss improvements in therapeutic and imaging techniques. Indium111 (In111) pentetreotide single photon emission computed tomography (SPECT) was employed to assess the presence of somatostatin receptors and to treat the tumour with radiolabelled Y90-DOTA-lanreotide. Imaging, performed 2 months afterwards, showed stable disease in the lungs but a local progression in the metastases, in comparison with pre-treatment uptake. These data suggest the usefulness of radiolabelled somatostatin analogues in the diagnosis and therapy of chordomas.

OTX2 regulates the expression of TAp63 leading to macular and cochlear neuroepithelium development.

OTX proteins, homologs of the Drosophila orthodenticle (Otd), are important for the morphogenesis of the neuroectoderm, and for the central nervous system formation. OTX1 and OTX2 are important for the cochlea and macula development, indeed when OTX1 is knocked down, these organs undergo developmental failure. Moreover OTX2 transfection revert this effect in OTX1(-/-) mice. The TA isoform of TP63, involved in Notch regulation pathway, has a critical function in the cochlear neuroepithelium differentiation. TAp63 positively regulates Hes5 and Atoh1 transcription. This pathway has been also demonstrated in p63(-/-) mice, and in patients p63 mutated, affected by Ectodermal Dysplasia (ED, OMIM 129810). These patients are affected by mild sensorineural deafness, most likely related to the mutation in p63 gene impairing the Notch pathway. We demonstrated the role of OTX2 on TAp63 regulation necessary for the correct formation of macular neuroepithelium and we confirmed the impairment of vestibular function caused by p63 mutations. Although the abnormalities found in our patient were still at a subclinical extent, aging could exacerbate this impairment and cause a decrease in quality of life.

Clinical associations of serum antiendothelial cell antibodies in patients with sudden sensorineural hearing loss.

OBJECTIVES/HYPOTHESIS: The role of antiendothelial cell antibodies in systemic vasculitis has been reported. The aim of the study was to define the clinical associations of serum antiendothelial cell antibodies in patients with sudden sensorineural hearing loss. STUDY DESIGN: A prospective study in patients with sudden sensorineural hearing loss. METHODS: Serum samples were taken from 59 consecutive patients with sudden sensorineural hearing loss at time of presentation and from 28 normal control subjects. Indirect immunofluorescence assay was used to detect antiendothelial cell antibodies. RESULTS: The prevalence of antiendothelial cell antibody detection was 54% (32 of 59 patients), with a statistically significant difference between patients and control subjects (P =.0004). Antiendothelial cell antibody positivity was significantly associated with absent recovery of hearing loss (P =.0020). CONCLUSIONS: The cytotoxicity to endothelial cells of the inner ear by antiendothelial cell antibody-positive sera might play a role in causing the stria vascularis damage in immune-mediated sudden sensorineural deafness. The appearance of antiendothelial cell antibody is related to the poor outcome of hearing loss, and its detection could be helpful in the selection of particular patients with sensorineural hearing loss for specific immunosuppressive treatments.

Inactivation of human salivary glutathione transferase P1-1 by hypothiocyanite: a post-translational control system in search of a role.

Glutathione transferases (GSTs) are a superfamily of detoxifying enzymes over-expressed in tumor tissues and tentatively proposed as biomarkers for localizing and monitoring injury of specific tissues. Only scarce and contradictory reports exist about the presence and the level of these enzymes in human saliva. This study shows that GSTP1-1 is the most abundant salivary GST isoenzyme, mainly coming from salivary glands. Surprisingly, its activity is completely obscured by the presence of a strong oxidizing agent in saliva that causes a fast and complete, but reversible, inactivation. Although salivary α-defensins are also able to inhibit the enzyme causing a peculiar half-site inactivation, a number of approaches (mass spectrometry, site directed mutagenesis, chromatographic and spectrophotometric data) indicated that hypothiocyanite is the main salivary inhibitor of GSTP1-1. Cys47 and Cys101, the most reactive sulfhydryls of GSTP1-1, are mainly involved in a redox interaction which leads to the formation of an intra-chain disulfide bridge. A reactivation procedure has been optimized and used to quantify GSTP1-1 in saliva of 30 healthy subjects with results of 42±4 mU/mg-protein. The present study represents a first indication that salivary GSTP1-1 may have a different and hitherto unknown function. In addition it fulfills the basis for future investigations finalized to check the salivary GSTP1-1 as a diagnostic biomarker for diseases.

Recurrence of a t(8;21)-Positive Acute Myeloid Leukemia in the Form of a Granulocytic Sarcoma Involving Cranial Bones: A Diagnostic and Therapeutic Challenge.

Granulocytic sarcoma (GS) is a rare extramedullary solid tumor defined as an accumulation of myeloblasts or immature myeloid cells. It can cooccur with or precede the acute myeloid leukemia (AML) as well as following treated AML. The incidence of GS in AML patients is 3-8% but it significantly rises in M2 FAB subtype AML. This variety of AML harbors t(8;21) in up to 20-25% of cases (especially in children and black ones of African origin) and, at a molecular level, it is characterized by the generation of a fusion gene known as RUNX1-RUNX1T1. Approximately 10% of M2 AML patients will develop GS, as a consequence, the t(8;21) and the relative transcript represent the most common cytogenetic and molecular abnormalities in GS. FLT3-ITD mutation was rarely described in AML patients presenting with GS. FLT3 ITD is generally strongly associated with poor prognosis in AML, and is rarely reported in patients with t(8;21). GS presentation is extremely variable depending on organs involved; in general, cranial bones and sinus are very rarely affected sites. We report a rare case of GS occurring as a recurrence of a previously treated t(8;21), FLT3-ITD positive AML, involving mastoid bones and paravertebral tissues.

A case of PANDAS treated with tetrabenazine and tonsillectomy.

PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) is a rare clinical syndrome characterized by the presence of tics, Tourette syndrome, obsessive-compulsive disorder, or chorea in the context of an immediately precedent streptococcal infection. In this report, we describe the case of an 11-year-old boy who developed PANDAS with severe choreic movements. The criteria for PANDAS diagnosis were met. Moreover, serum antibrain antibodies were present. The patient was initially treated with tetrabenazine 12.5 mg twice daily with remission of the neurological symptoms. Subsequently, the patient underwent tonsillectomy and has been asymptomatic since, with antistreptolysin O titer levels in range.

Voice disorders and posturography: variables to define the success of rehabilitative treatment.

Previous studies have investigated the relationship between muscular tension, body posture, and voice quality. The aim of this paper is to study the postural pattern during voice production in healthy subjects compared with patients affected by voice disorders and in the same patients before and after vocal treatment by means of static posturography. Classic posturographic variables and spectral frequency analysis of body sway have been measured. Posturographic values in patients before vocal treatment and controls were within normal ranges but not homogeneous. Body sway significantly decreased during voice production in patients after voice training. Spectral frequency analysis of body sway showed a significantly decreased body sway at middle frequencies on the anteroposterior (y) plane during voice production after voice training. Our results would suggest that in patients affected by voice disorders rehabilitative treatment may cause an improvement of the body proprioceptive scheme and this improvement might be useful to evaluate the proper (ongoing) treatment.

Evaluation of telomerase activity in nasal polyps.

BACKGROUND: The objective of this study was to assess if nasal polyps express telomerase activity and whether a difference could be found between the polyp and the surrounding mucosa of the middle meatus and between different portions of the polyp itself METHODS: Nine patients affected by nasal polyposis were included in this study; four of these patients had recurring polyposis. Telomerase activity was measured by telomeric repeat amplification protocol assay. In six patients, the telomeric repeat amplification protocol assay was performed on the polyp and on the mucosa from the ipsilateral middle meatus. In a polyp, we were able to investigate telomerase activity of its different portions, corresponding to pedicle and fundus. RESULTS: Telomerase activity observed in nasal polyps was higher than that observed in samples from the ipsilateral middle meatus mucosa. High or intermediate telomerase activity was found to be related to predominant recurring polyposis. CONCLUSIONS: Therefore, it could be postulated that telomerase activity could be related with the tendency of polyps to recur.

Autoimmunity in sudden sensorineural hearing loss: possible role of anti-endothelial cell autoantibodies.

In order to verify whether anti-endothelial cell autoantibodies (AECAs) can be used as serological markers of inner ear vasculitis in sudden sensorineural hearing loss (SSHL), 32 patients affected by idiopathic SSHL were investigated. All patients underwent a routine general physical examination and extensive audiovestibular, microbiological and immunological investigations. Fourteen normal subjects without a history of HL, autoimmune or metabolic disease served as controls. Detection of AECAs was performed using an indirect immunofluorescence technique. AECA-positive patients were treated with methylprednisone, while AECA-negative patients were treated with a combined regimen of steroids, plasma expander and aspirin. The average hearing recovery for 5 frequencies (0.25-4 kHz) was analyzed in each subject 1 month after treatment and every 3 months thereafter; median follow-up was 12 months (range 9-18 months). A total of 15/32 patients (46.8%; 11/19 females, 4/13 males) were AECA-positive and thus differed significantly from the normal population in whom only 2/14 tested cases were positive (p = 0.03). Severe hearing loss was associated with being AECA-positive in 8/11 cases. During follow-up, 25/32 patients improved their hearing and 17 of these patients were AECA-negative. The seven cases without hearing improvement were all AECA-positive. In patients with SSHL, immune-mediated vascular damage may have a pathogenetic role and AECAs may represent a serological marker of vasculitis even if they are not inner ear-specific and even if they represent an epi-phenomenon rather than the only cause of SSHL.