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Biomedical subjects

G Paludetti

Publications and source records attributed to G Paludetti.

At least 19 recordsLinked to original sources

Generation of human auditory steady-state responses (SSRs). I: Stimulus rate effects.

Auditory evoked responses were recorded in 16 normally hearing subjects in order to investigate the mechanisms underlying the generation of the 40 Hz steady-state response (SSR). In the first part of our study, auditory potentials were evoked by 0.1 ms clicks presented at 105 dB p.e. SPL with repetition rates of 7.9 (to obtain middle latency response, MLR), 20, 30, 40, 50, 60 Hz. In each subject predictions of the responses recorded at stimulus repetition rates of 30, 40, 50, 60 Hz were synthesized by superimposing MLRs at suitable time intervals. The calculated mean amplitude/rate and phase/rate functions behaved similarly for the recorded and predicted curves, showing the highest amplitude at 40 Hz and a linear increase of phase values when increasing the stimulus rate. Nevertheless the synthetic curves closely predicted amplitude and phase values of the recorded responses only at 40 Hz. At frequencies below 40 Hz, the mean amplitude of the predicted curve was lower than that of the recorded one while at frequencies above 40 Hz the mean amplitude was higher. Predicted phase values were found lagging at 30 Hz, and leading at 50 Hz and 60 Hz in comparison to phase values calculated on the recorded responses. Our findings suggest that a model based on the linear addition of transient MLRs is not able to adequately predict steady-state responses at stimulus rates other than at 40 Hz. Other mechanisms related to the recovery cycle of the activated system come into play in the steady-state response generation causing a decrease in amplitude and an increase in phase lag when increasing the stimulus repetition rate.

Acoustic Stimulation

Generation of human auditory steady-state responses (SSRs). II: Addition of responses to individual stimuli.

In order to investigate the generation of the 40 Hz steady-state response (SSR), auditory potentials evoked by clicks were recorded in 16 healthy subjects in two stimulating conditions. Firstly, repetition rates of 7.9 and 40 Hz were used to obtain individual middle latency responses (MLRs) and 40 Hz-SSRs, respectively. In the second condition, eight click trains were presented at a 40 Hz repetition rate and an inter-train interval of 126 ms. We extracted from the whole train response: (1) the response-segment taking place after the last click of the train (last click response, LCR), (2) a modified LCR (mLCR) obtained by clearing the LCR from the amplitude enhancement due to the overlapping of the responses to the clicks preceding the last within the stimulus train. In comparison to MLRs, the most relevant feature of the evoked activity following the last click of the train (LCRs, mLCRs) was the appearance in the 50-110 ms latency range of one (in 11 subjects) or two (in 2 subjects) additional positive-negative deflections having the same periodicity as that of MLR waves. The grand average (GA) of the 40 Hz-SSRs was compared with three predictions synthesized by superimposing: (1) the GA of MLRs, (2) the GA of LCRs, (3) the GA of mLCRs. Both the MLR and mLCR predictions reproduced the recorded signal in amplitude while the LCR prediction amplitude resulted almost twice that of the 40 Hz-SSR. With regard to the phase, the MLR, LCR and mLCR closely predicted the recorded signal. Our findings confirm the effectiveness of the linear addition mechanism in the generation of the 40 Hz-SSR. However the responses to individual stimuli within the 40 Hz-SSR differ from MLRs because of additional periodic activity. These results suggest that phenomena related to the resonant frequency of the activated system may play a role in the mechanisms which interact to generate the 40 Hz-SSR.

Acoustic Stimulation

[Oncogenes and cancer of the larynx. EGFR, p21 ras and HPV-DNA infections].

The modern concept of oncogenesis is based upon the interaction between factors which modulate cellular growth and differentiation, in particular oncogenes and tumor suppressor genes. The molecular events which induce laryngeal carcinogenesis are not yet known. Protoncogenes seem to be the target of the risk factors (cigarette smoking, alcohol abuse, ionizing radiations and, not least HPV-DNA) that are commonly considered related to laryngeal squamous cell carcinoma. New information on the role of alterations of oncogenes and/or their proteic products in laryngeal cancer will be useful in identifying new diagnostic and clinical therapeutical applications. The Authors investigated Epidermal Growth Factor Receptor (EGFR) expression in 103 primary laryngeal squamous cell carcinoma and 42 normal laryngeal tissue specimens in order to assess its clinical significance in primary laryngeal cancer. Significantly higher EGFR levels were found in cancer specimens compared with normal mucosa (p < 0.001). EGFR expression did not correlate with age, tumor localization, T classification, cervicallymphonode involvement or surgery, whereas in G3 tumors it was significantly higher than in G1-G2 (p < 0.05). Follow-up data were available for 74 cases: EGFR levels resulted significantly higher in patients who had a recurrence of the disease than those in recurrence-free patients (p < 0.05). The 24-month disease-free survival (DFS) was 58% for EGFR+ patients and 82% for EGFR-subjects. Multivariate analysis permitted identification of EGFR status and tumor localization as significant independent prognostic factors. Data reported here suggest that EGFR expression probably plays a role not only by regulating the growth of laryngeal cancer, but also by identifying a sub-set of laryngeal cancer patients at a higher degree of relapse risk and with an unfavorable prognosis. Furthermore, in this study p21-ras expression in 43 primary laryngeal cancers and in 7 normal laryngeal mucosa specimens was evaluated. Scattered p21 levels, expressed as optical density (O.D), were found in normal mucosa (median = 1.94) and in primary laryngeal tumours (median = 1.74). Higher p21 levels were found in neoplastic tissue than in normal laryngeal tissue (median = 2.54 vs median = 1.94; p = 0.023). The correlation between p21 ras protein and EGFR levels was also investigated. EGFR+ cases do not show any difference in p21 expression with respect to EGFR- cases (median = 1.52 O.D. vs median = 1.84). Our findings suggest that overexpression of p21 is associated with malignant phenotype in laryngeal cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Cathepsin D in primary squamous laryngeal tumors: correlation with clinico-pathological parameters and receptor status.

Using an immunoradiometric assay, Cathepsin D (Cath D) levels were measured in the cytosol of 23 normal and 39 neoplastic human laryngeal tissues. Scattered Cath D levels (from 2.2 to 17.8 pM/mg protein; median = 7.6) were found in normal mucosa specimens. Cath D concentrations range from 2.0 to 29.3 pM/mg protein (median = 8.5) in laryngeal tumors. When a comparison between Cath D levels in normal and neoplastic tissue specimens from the same patient was done, Cath D levels were significantly higher in laryngeal cancers than in their normal counterparts (P = 0.03). No correlation with clinico-pathological parameters and steroid hormone and epidermal growth factor receptor status was found. Further studies should investigate whether the production of Cath D by laryngeal tumors could have a clinical relevance for this neoplasia.

Adult

EGF receptor expression in primary laryngeal cancer: correlation with clinico-pathological features and prognostic significance.

Epidermal-growth-factor-receptor(EGFR) expression was evaluated in 103 primary laryngeal tumors and in 42 normal laryngeal tissue specimens. Significantly higher EGFR levels were found in cancer specimens than in normal mucosa (p = 0.0053). EGFR expression did not correlate with age, tumor localization, T classification, cervical-lymph-node involvement or type of surgery, whereas it was higher in poorly differentiated tumors (G3) than in well/moderately differentiated (G1-G2) tumors (p < 0.05). Follow-up data were available for 74 patients. When EGFR status and the most important clinico-pathological characteristics were submitted to univariate analysis, tumor localization, type of surgery and EGFR status were found to be significantly correlated with disease-free survival. The 24-month disease-free survival rate was 58% for EGFR+ cancer patients and 82% for EGFR- ones. With multivariate analysis, only EGFR status and tumor localization were identified as significant independent prognostic parameters. Data reported here suggest that high EGFR levels may identify a sub-set of laryngeal-cancer patients with a particularly unfavorable prognosis.

Adult

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.

Adult

Functional study of the eustachian tube with sequential scintigraphy.

The authors investigated the tubal function by means of sequential scintigraphy in 16 patients affected by chronic otitis media and in 3 patients with posttraumatic perforation of the tympanic membrane. Evaluated parameters were: appearance time (AT), radioactivity peak time, rise time in the tympanic cavity, eustachian tube and rhinopharynx, and radioactivity percent values passed in the rhinopharynx. The tubal pressure-equilibrating function was determined by means of the manometer pump section of the impedance meter. A significant relationship between the pressure-equilibrating function and the tubal scintigraphy parameters has been detected. The variability of the AT in the tube and the almost constant time needed by the radioactive tracer to go through the tube and reach the rhinopharynx could indicate that a major role in the tympanic cavity drainage is played by the tympanic ostium and the surrounding mucosa.

Chronic Disease

Receptors for epidermal growth factor and steroid hormones in primary laryngeal tumors.

The authors investigated the presence of epidermal growth factor (EGF-R), estrogen (ER), progesterone (PR), and androgen (AR) receptors in 42 laryngeal squamous cell carcinomas and 20 normal laryngeal mucosa specimens. EGF-R were expressed in all tumor specimens analyzed, with significantly higher levels in tumor samples compared with normal mucosa (P less than 0.05). The immunohistochemical study demonstrated the presence of EGF-R in basal and parabasal cells of normal mucosa and in most of the cancer cells. There was no correlation between EGF-R and tumor localization or T classification. On the other hand, the authors did find an interesting correlation between EGF-R levels and grading, EGF-R levels being significantly higher in G3 than in G1-G2 tumors. Moreover, the three patients whose tumors expressed the highest EGF-R levels had disease recur within 8 months. Among tumor specimens, 9.5%, 35.7%, and 9.5% expressed very low but detectable ER, PR, and AR levels, respectively. No statistically significant difference was found between the levels of steroid receptors in the tumor and normal mucosa specimens, and neither was there any correlation of ER, PR, and AR with the pathologic findings. The authors' results suggest that the EGF-R system may play a role in regulating the growth of laryngeal cancer. Additional studies should demonstrate whether, as in other tumor types, EGF-R expression may have prognostic significance in human laryngeal cancer.

Adult

Characterization of the cytoskeleton in human normal and otosclerotic osteoblast-like cells.

The localization and distribution of some cytoskeletal protein components were studied by immunostaining methods in normal and ostosclerotic osteoblast-like cells. The protein components investigated were microtubules (beta-tubulin), intermediate filaments (vimentin), microfilaments (actin and myosin) and structural proteins (alpha-actinin and fibronectin). Although the mechanism is not yet clear, the alterations observed in the pathological cells could well play a role in the expression of otosclerosis.

Actinin

Effects of steroids on human normal and otosclerotic osteoblastic cells: influence on thymidine and leucine uptake and incorporation.

Steroid hormones are able to influence the metabolism of bone tissue in vivo, but reports regarding their direct action on bone cells fail to agree. In this study, in vitro administration of 17 beta-estradiol, testosterone and corticosterone to normal and otosclerotic osteoblastic cells induced a drop in DNA synthesis in both populations, an increase in the neosynthesis of endocellular proteins in normal cells and a rise, mainly in proteins secreted into the medium, in otosclerotic cells. The fact that 3H-thymidine and 3H-leucine uptake were lower in otosclerotic than in normal cells suggests that the membrane permeability differs in the two populations and that steroids exert an influence on both isotope uptake and directly modulate DNA and protein synthesis.

Corticosterone

Marijuana smoking as a possible cause of tongue carcinoma in young patients.

A case of T1N0M0 carcinoma of the tongue in a male 23-year-old 'regular' marijuana smoker is described. Hemiglossectomy and complete bilateral neck dissection were carried out. No post-operative radiotherapy was given as the resection margins were histologically negative. The tumour recurred one year later in the left cervical region involving the mandible and surgery was again performed, but after three months, neck disease was still evident. The case described case implies the introduction of marijuana as a possible new risk factor in the development of oral cavity tumours. Resection of the primary lesion has to be as wide as possible even in T1 cases, due to the aggressive biological behaviour of such tumours in young subjects.

Adult

Relationships between middle latency auditory responses (MLR) and speech discrimination tests in the elderly.

74 subjects aged between 60 and 80 years underwent tonal audiometry, speech discrimination tests (phonetically balanced words, normal sentences and compressed sentences) and middle latency responses (MLRs) in order to evaluate possible correlations between behavioural and electrophysiological tests. The results showed that in elderly patients normal sentences are better understood than phonetically balanced words, that performances decrease dramatically when listening conditions became difficult, that auditory threshold seems to influence speech discrimination scores more than does age per se. MLRs seem to be unaffected both by age and by auditory threshold and Pa occurrence is a more reliable parameter than its latency. No correlation between speech discrimination tests and MLRs could be observed; on the contrary in the presence of abnormal speech discrimination tests the MLRs were almost normal and vice versa.

Aged

Auditory steady-state responses in the rabbit.

The authors have studied auditory brainstem (ABRs), middle latency (MLRs) and steady-state potentials (SSRs) in 15 adult male rabbits weighing between 2.5 and 3 kg in order to verify if SSRs are due to a mere superimposition of ABRs and MLRs or to a resonance phenomenon. Ten of them were awake while 5 were studied under urethane anesthesia. Acoustic stimuli consisted in 0.1-ms square-wave pulses delivered at presentation rates ranging between 1 and 80/s at a stimulus intensity of 80 dB p.e. SPL. Our data show that reliable auditory SSRs can be obtained in the rabbit at a presentation rate of 30 stimuli/s, probably due to the superimposition of ABRs and MLR Pb waves which show an interwave interval of about 35 ms. The nonlinear aspects which can be detected are probably due to the effect of decreasing interstimulus intervals on the duration and amplitude of the Pb wave. It can then be concluded that SSRs in the rabbit are due more to a superimposition of ABR and MLR waves than to a resonance phenomenon.

Acoustic Stimulation

40-Hz steady-state responses in newborns and in children.

The authors investigated the 40-Hz steady-state responses (SSR) in 32 full-term newborns and in 10 normal children (5-8 years old), using 500-Hz tone bursts. The 40-Hz SSR threshold is located at about 50 and 30 dB nHL in newborns and older children, respectively. The latencies of both P1 and N1 waves decreased significantly with age, while the amplitudes increased. No significant latency and amplitude intersex differences have been observed. Moreover, with age, the 40-Hz SSR became more stable, their test-retest replicability improved, and P1-N1 wave occurrence increased. The authors finally discuss the possible underlying mechanisms of these findings and conclude that the 40-Hz SSR are difficult to obtain and are scarcely reliable in defining the low-frequency threshold in newborns. The stability and reliability of the responses increase with age, and the electrophysiological and behavioral thresholds to low-frequency stimuli tend to overlap.

Audiometry, Evoked Response

Altered adenylate cyclase activity in human otosclerotic bone cell cultures.

Adenylate cyclase (AC) activity was studied in whole homogenates of normal and otosclerotic bone cell cultures. When Mn2+ or Ca2+ was added to the medium there was a similar increase in AC activity in both cell types. F- provoked a greater rise in normal than in pathological cells, whereas 0.01 mM guanosine triphosphate (GTP) significantly raised cAMP synthesis in otosclerotic cells only. Mn2+ + calcitonin (Ct) increased AC activity in both cell preparations. With Ca2+ as cofactor there was no significant rise in either normal or pathological cells. However, while the combination Ca2+ + Ct + GTP had little effect on normal cells, it markedly increased cAMP synthesis in the pathological cells. 1 microgram/ml of the beta-blocker propranolol inhibited the effect Ct exerts on AC in normal cells, but enhanced it in otosclerotic cells. It would, therefore, seem that the pathogenesis of otosclerosis could be associated with an alteration in the AC system associated with Ct receptors.

Adenylyl Cyclases

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.

Adolescent

Auditory brainstem responses in noise-induced permanent hearing loss.

Fifty-four patients (108 ears) with presumed noise-induced hearing loss, were subjected to tonal and speech audiometry, impedance tests and measurements of auditory brainstem responses (ABR), in order to check for possible retrocochlear involvement. ABR data indicated that latency values of waves I, III and V, as well as III-I, V-III and V-I intervals fell within the normal range in all cases (M +/- 2 SD), even for fast repetition rates (51 stim/s). Poor waveform resolution of early components, particularly of wave I, was found in 12 ears (11.1%) and a total absence of evoked potentials not always related to the hearing loss, occurred in 5 ears (4.6%).

Acoustic Impedance Tests