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Biomedical subjects

R Santarelli

Publications and source records attributed to R Santarelli.

At least 19 recordsLinked to original sources
PubMed2006

Cochlear microphonic potential recorded by transtympanic electrocochleography in normally-hearing and hearing-impaired ears.

The cochlear microphonic is a receptor potential believed to be generated primarily by outer hair cells. Its detection in surface recordings has been considered a distinctive sign of outer hair cell integrity in patients with auditory neuropathy. This report focuses on the results of an analysis performed on cochlear microphonic recorded by transtympanic electrocochleography in response to clicks in 502 subjects with normal hearing threshold or various degrees of hearing impairment, and in 20 patients with auditory neuropathy. Cochlear microphonics recorded in normally-hearing and hearing-impaired ears showed amplitudes decreasing by the elevation of compound action potential Cochlear microphonic responses were clearly detected in ears with profound hearing loss. After separating recordings according to the presence or absence of central nervous system pathology (CNS+ and CNS-, respectively), cochlear microphonic amplitude was significantly higher in CNS+ than in CNS- subjects with normally-hearing ears and at 70 dB nHL compound action potential threshold. Cochlear microphonic responses were detected in all auditory neuropathy patients, with similar amplitudes and thresholds to those calculated for normally-hearing CNS- subjects. Cochlear microphonic duration was significantly higher in auditory neuropathy and normally-hearing CNS+ patients compared to CNS- subjects. Our results show that: 1. cochlear microphonic detection is not a distinctive feature of auditory neuropathy; 2. CNS+ subjects showed enhancement in cochlear microphonic amplitude and duration, possibly due to efferent system dysfunction; 3. long-lasting, high frequency cochlear microphonics with amplitudes comparable to those obtained from CNS- ears were found in auditory neuropathy patients. This could result from a variable combination of afferent compartment lesion, efferent system dysfacilitation and loss of outer hair cells.

Adolescent↗
PubMed2004

Method for the deconvolution of auditory steady-state responses.

The potential evoked by a 'train' of N equally spaced auditory clicks, with an inter-click period shorter than the duration of the response to an isolated click, is said to be a steady-state response (SSR). Extracting the individual responses evoked by the clicks of the train during steady state can be key to understanding of the neurophysiological mechanisms underlying SSR generation. In the literature, this task has been dealt with only under the (unwarranted) assumption that the response of the system does not vary during the presentation of the clicks, i.e. no neurophysiological adaptation is present. In this work, a new, non-parametric algorithm is proposed that, relaxing the time-invariance hypothesis, allows the extraction from the SSR of the N waveforms individually evoked by the N clicks of the train. The performance of the approach is evaluated on simulated SSRs and on real data recorded from the temporal cortex of awake rats. Results show that the method is able to detect and assess possible adaptation of the neurophysiological system in the generation of SSRs.

Acoustic Stimulation↗
PubMed2001

Direct correlation between human herpesvirus-8 seroprevalence and classic Kaposi's sarcoma incidence in Northern Sardinia.

The human herpesvirus-8 (HHV-8) has been associated with the development of Kaposi's sarcoma. A high incidence of classic Kaposi's sarcoma has been described in Sardinia, an island West of Italy's mainland. Different seroepidemiological analyses have reported that prevalence of HHV-8 infection varies worldwide: a high HHV-8 seroprevalence has been shown in Italy. The present survey was carried out to evaluate the correlation between HHV-8 infection and classic Kaposi's sarcoma incidence in northern Sardinia. Blood samples were collected from 226 healthy donors born and resident in five different areas of North Sardinia. Seroprevalence to HHV-8 was determined searching antibodies to viral lytic proteins by immunofluorescence in sera diluted at 1:10. Classic Kaposi's sarcoma incidence data spanning a period of 23 years were examined in the areas studied. The present screening revealed that seroprevalence was 35%, within a range of 15.3-46.3% in the five areas, although it should be considered that the seroprevalence to HHV-8 can be established more accurately by the combined use of different assays. Age emerged as an important risk factor. Indeed, subjects aged > 50 years showed a higher seroprevalence to HHV-8 as compared with younger individuals. A strong direct correlation between HHV-8 prevalence and classic Kaposi's sarcoma incidence has been also observed. The wide diffusion of HHV-8 in Sardinia appears to represent an important factor in the high incidence of classic Kaposi's sarcoma reported in the island. However, additional co-factors, such as age, sex, genetic traits, or viral strain pathogenicity, are likely to play a role in the development of the disease.

Adult↗
PubMed2000

Utility of postintubation chest radiographs in the intensive care unit.

OBJECTIVE: To determine the clinical usefulness of immediate (stat) chest radiographs after endotracheal intubation when performed by experienced critical care personnel. PATIENTS AND METHODS: This was a prospective study. Endotracheal intubations in an 11-bed intensive care unit and a nine-bed intermediate intensive care unit were included. After intubations were performed by an experienced critical care operator, that individual recorded demographic and procedural data, and predicted radiographic findings on a data collection sheet. Experience at intubation was stratified into four levels of lifetime experience: fewer than 10 procedures, 10-20 procedures, 20-50 procedures, and more than 50 procedures. Radiographic findings evaluated included endotracheal tube position and procedure-related complications. The postintubation chest radiograph was then reviewed and the actual findings were also recorded. RESULTS: A total of 101 evaluable intubations were recorded, two of which were predicted to show tube malposition. Actual radiographic findings revealed 10 malpositions, three of which were too high and seven were too low (one at the level of the carina). A single witnessed aspiration that occurred during intubation was not radiographically apparent until 24 h later. Only the tube positioned at the carina was felt to be of acute clinical significance or to place the patient at any acute risk. CONCLUSIONS: The incidence of endotracheal tube malposition after intubation was underestimated. However, when performed by experienced critical care personnel, acutely significant malpositions were rare (one out of 101 intubations). We conclude that, in the absence of specific pulmonary complications, endotracheal intubations performed by experienced operators may be followed by routine, rather than 'stat' chest radiographs.

Clinical Competence↗
PubMed2000

Compound action potential and cochlear microphonic extracted from electrocochleographic responses to condensation or rarefaction clicks.

In electrocochleography (ECochG) compound action potential (CAP) and summation potential (SP) are usually separated from the cochlear microphonic (CM) by the CM cancellation technique consisting in averaging the responses evoked by rarefaction and condensation clicks. With the aim of analysing the ECochG responses evoked by monophasic clicks, we developed a numerical method based on the theory of optimal filtering, which makes no assumptions about the unknown potentials. The application of the filtering technique to the ECochG recordings obtained from 6 normally hearing children and 10 children with cochlear hearing loss allowed us to perform CAP extraction in cases where CM was not cancelled by the conventional method. Differences in SP amplitude and polarity were found between rarefaction and condensation click-evoked responses in cochlear hearing losses.

Acoustic Stimulation↗
PubMed2000

The BFRF1 gene of Epstein-Barr virus encodes a novel protein.

Computer analysis of the Epstein-Barr virus (EBV) genome indicates there are approximately 100 open reading frames (ORFs). Thus far about 30 EBV genes divided into the categories latent and lytic have been identified. The BamHI F region of EBV is abundantly transcribed during lytic replication. This region is highly conserved among herpesviruses, thus suggesting that some common function could be retained in the ORFs encompassed within this viral fragment. To identify putative novel proteins and possible new markers for viral replication, we focused our attention on the first rightward ORF in the BamHI F region (BFRF1). Histidine and glutathione S-transferase-tagged BFRF1 fusion proteins were synthesized to produce a mouse monoclonal antibody (MAb). Analysis of human sera revealed a high seroprevalence of antibodies to BFRF1 in patients affected by nasopharyngeal carcinoma or Burkitt's lymphoma, whereas no humoral response to BFRF1 could be detected among healthy donors. An anti-BFRF1 MAb recognizes a doublet migrating at 37 to 38 kDa in cells extracts from EBV-infected cell lines following lytic cycle activation and in an EBV-negative cell line (DG75) transfected with a plasmid expressing the BFRF1 gene. Northern blot analysis allowed the detection of a major transcript of 3.7 kb highly expressed in EBV-positive lytic cycle-induced cell lines. Treatment with inhibitors of viral DNA polymerase, such as phosphonoacetic acid and acyclovir, reduced but did not abolish the transcription of BFRF1, thus indicating that BFRF1 can be classified as an early gene. Cell fractionation experiments, as well as immunolocalization by immunofluorescence microscopy, immunohistochemistry, and immunoelectron microscopy, showed that BFRF1 is localized on the plasma membrane and nuclear compartments of the cells and is a structural component of the viral particle. Identification of BFRF1 provides a new marker with which to monitor EBV infection and might help us better understand the biology of the virus.

Amino Acid Sequence↗
PubMed1999

Global problem of drug-induced hearing loss.

Clinically used drugs and chemical agents may potentially cause adverse effects to the human auditory and vestibular systems. Many of them, such as aminoglycosides and cisplatin, can play a critical role in the treatment of serious or life-threatening diseases; others, like loop diuretics or salycilates, offer such important therapeutical effects compared to the ototoxic side effects that the ototoxicity risk can be considered to be of minor importance. The problem of ototoxic side effects is more acute in developing countries, where highly effective and low-cost drugs are more easily prescribed without adequate monitoring. Medical awareness of doses, forms of administration, populations at risk, and possible synergism is necessary in order to develop appropriate care in the prescription of drugs with ototoxic side effects. Relatively recent issues such as risk-benefit analysis, patient-informed consent, and quality-of-life considerations, particularly when life expectancy can be low, are also to be considered. At present, a uniform method of monitoring for all potentially ototoxic therapeutics does not seem reasonable or practical. It is recommended, however, that individual auditory function be noted for a particular drug being employed. Protocols and exams should be easy, quick, sensitive, reliable, and as objective as possible. Benefits of audiological monitoring include the opportunity to change the patient's treatment course, improvement of patient and family awareness of the impact of hearing impairment, and timely prescription of amplification devices. Finally, particular attention should be paid to high-risk populations such as neonatal intensive care unit patients.

Aminoglycosides↗
PubMed1999

Auditory steady-state responses to click trains from the rat temporal cortex.

In order to investigate the mechanisms underlying the generation of steady-state responses (SSRs), auditory evoked potentials elicited by click trains presented at several stimulation rates (30, 40, 50, 60 Hz) were recorded in 7 awake rats by means of epidural electrodes placed over the temporal cortex. Mean amplitude-rate function calculated on the recorded responses appeared almost flat and showed the maximum value at 50 Hz, while mean phases showed a linear increase when increasing the stimulation rate. In each rat, predictions of the recorded responses at 30, 40, 50 and 60 Hz were synthesized by superimposing middle-latency auditory evoked potentials (MAEPs) at suitable time intervals at each rate. Mean amplitudes calculated on the predicted curves decreased linearly when increasing the stimulation rate and appeared higher in comparison to those obtained from the recorded SSRs. Predicted phases showed a linear increase when increasing the stimulation rate and were leading with respect to corresponding phase values calculated for recorded SSRs. Our findings indicate that the MAEP superimposition mechanism does not adequately predict the generation of temporal recorded SSRs in rats. This was explained by admitting that phenomena related to the recovery cycle and, to a lesser extent, to rate-dependent facilitating effects come into play.

Acoustic Stimulation↗
PubMed1999

Generation of auditory steady-state responses: linearity assessment.

Auditory steady-state responses (SSRs) are believed to result from the superimposition of the middle latency responses (MLRs) evoked by individual stimuli. Our recent studies challenge this hypothesis in several regards. Surface-electrical recordings performed in 16 normal subjects showed that the prediction curves obtained by MLR linear addition failed to predict SSRs at rates other than 40 Hz. Amplitude and phase differences between actual and predicted responses point to the intervention of phenomena related to the recovery cycle of the neural networks underlying the SSR generation. A click train paradigm at a 40 Hz rate was utilized and an approximation to the response evoked by the last stimulus was obtained by an analytical handling. The most relevant feature of this response in comparison to the MLR was the appearance of an additional activity which could be related to the fast oscillations of auditory cortical neurons. Our findings suggest that the responses evoked by individual stimuli during steady-state stimulation change by increasing the repetition rate, thus contradicting the most widely accepted hypothesis of the MLR linear addition in the SSR generation.

Animals↗
PubMed1998

Postural control in benign paroxysmal positional vertigo before and after recovery.

Thirty-two patients affected by idiopathic benign paroxysmal positional vertigo (BPPV) of the posterior semicircular canal were studied before, 3 days and I month after a resolutive Semont manoeuvre by means of dynamic posturography. The overall postural control in BPPV patients was shown to be impaired, as demonstrated by the pathological equilibrium scores. Data obtained before treatment showed a specific pattern of vestibular involvement and a pathological composite score. After the liberatory manoeuvre the Sensory Organization Test indicated a significant improvement in the pathological composite and vestibular scores. However, significant differences from controls were still detected 3 days and 1 month after clinical recovery from BPPV. The results clearly show that, in BPPV patients, there is an impairment of the vestibular system, which seems unable to maintain a normal postural balance. This deficit can be particularly detected when dynamic posturography evaluates the vestibular cues. After the liberatory manoeuvre a consistent improvement in the overall postural control has been observed but the residual differences from controls seem to suggest that damage to the otoconial maculae influences postural control, even when there is significant improvement in the clinical signs.

Analysis of Variance↗
PubMed1997

Transcription of latent and replicative Epstein-Barr-virus genes in bone-marrow and peripheral-blood mononuclear cells of healthy donors.

Reverse-transcriptase polymerase chain reaction has been used to analyze the expression of 2 latent genes (EBNA-1 and LMP-1) and one replicative gene (BZLF-1) of Epstein-Barr virus in mononuclear cells from bone marrow and peripheral blood of healthy donors. EBV-gene transcription was detected in 8 out of 15 bone-marrow samples. Among these, 5 allowed the detection of latency-associated transcripts in the absence of BZLF-1 expression. Only one sample showed positivity for expression of both latent and lytic genes. In 2 cases, BZLF-1 was the only transcript detected. In peripheral blood, 4 out of 7 samples showed evidence of EBNA-1 transcription; LMP-1 was expressed in 5 samples, and in 2 cases concomitant expression of EBNA-1 and BZLF-1 was detected. These results provide a direct demonstration by RT-PCR of EBV-gene transcription in bone-marrow-resident viral infected cells and suggest, in contrast to previous studies on peripheral blood, that LMP-1 and BZLF-1 are frequently transcribed also in absence of EBV-related disease. The heterogeneous viral gene expression found makes it difficult to define a pattern of viral latency in vivo which coincides with that described for lymphoblastoid or Burkitt's-lymphoma cell lines at different stages of differentiation.

Animals↗
PubMed1997

Inhibition of nitric oxide synthase prevents magnesium-free-induced epileptiform activity in guinea-pig piriform cortex neurones in vitro.

The effects of N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, were examined on Mg2+-free-induced epileptiform activity, in guinea-pig piriform cortex slices in vitro. L-NAME (0.1-1 mM) had no effect on neuronal membrane properties or electrically-evoked postsynaptic potentials (PSPs). In contrast, during superfusion of the slices with Mg2+-free solution neurones exhibited spontaneous and stimulus-evoked epileptiform potentials that were suppressed in the presence of L-NAME (100 microM) or the selective NMDA receptor antagonist DL-APV (100 microM). The inhibitory effects induced by L-NAME were reversibly reduced by L-arginine (1 mM), but not D-arginine (1 mM), the latter drug not being a substrate for NO formation. It was concluded that L-NAME can suppress epileptiform activity induced by Mg2+-free exposure primarily through a decrease in presynaptic transmitter release, although additional actions on the NMDA-receptor complex were also considered.

Animals↗
PubMed1996

Sympathetic control of skeletal muscle function: possible co-operation between noradrenaline and neuropeptide Y in rabbit jaw muscles.

Stimulation of the cervical sympathetic nerve at 10/s increases by 12.9 +/- 0.7% peak tension of maximal twitches in the directly stimulated jaw muscles and markedly depresses (41.6 +/- 1.3%) the tonic vibration reflex (TVR) elicited in the same muscles by vibration of the mandible. Both effects are not significantly influenced by administration of beta-adrenoceptor antagonists. When both alpha- and beta-adrenergic receptors are blocked, sympathetic stimulation induces a very small increase in twitch tension (3.8 +/- 0.7%), while no detectable change in the TVR is observed. Close arterial injection of alpha 1-adrenoceptor agonist phenylephrine mimics the effects induced by sympathetic stimulation on twitch tension and TVR, dose-dependently. The noradrenaline co-transmitter neuropeptide Y also produces a long-lasting, dose-dependent increase in the twitch tension which is unaffected by blockade of adrenergic receptors as well as of the neuromuscular junctions. Contribution of neuropeptide Y to the sympathetically-induced reduction of the stretch reflex is not clearly demonstrated. These data suggest that co-operation between noradrenaline and neuropeptide Y may be effective in determining sympathetic modulation of skeletal muscle function.

Animals↗
PubMed1996

The SV40 T-antigen induces premature apoptotic mammary gland involution during late pregnancy in transgenic mice.

Transgenic animals of the line 8 contain the WAP-SV-T transgene. Females of this line synthesise the SV40 T-antigen in mammary gland epithelial cells during pregnancy and the lactation period. All females are 'milk-less' and the offspring have to be nursed by foster mothers. The reason for this phenomenon is a premature apoptosis during late pregnancy. Nontheless a significant number of mammary epithelial cells escape apoptosis and all transgenic females devlop breast cancer after the first lactation period.

Animals↗
PubMed1996

SV40 T-antigen induces breast cancer formation with a high efficiency in lactating and virgin WAP-SV-T transgenic animals but with a low efficiency in ovariectomized animals.

The whey acid protein (WAP) is a major mouse milk protein and its gene expression is induced by various lactotrophic hormones (eg, estrogen, progesterone). Transgenic animals harboring the early SV40 coding region (T/t-antigen) under the transcriptional control of the WAP promoter develop breast cancer after the first lactation period. The tumor cells synthesize the SV40 T-antigen with a high efficiency indicating that WAP-SV-T expression escapes down-regulation after the lactation period. However about 5-10% of the tumors became T-antigen negative during tumor progression and WAP-SV-T expression was only demonstrable by PCR analysis. Both T-antigen positive and negative tumor cells expressed the estrogen and progesterone receptor at a comparable rate, indicating that hormone receptor levels do not determine expression of the WAP-SV-T transgene. Furthermore, WAP and WAP-SV-T gene expression are not restricted to the pregnancy-lactation period. Virgin animals also express both genes with a low efficiency and about 70% of these animals also developed T-antigen positive breast tumors. The tumor rate however was strongly reduced in ovariectomized animals, indicating that the ovary hormones play a critical role in breast cancer formation.

Animals↗