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Biomedical subjects

M Barbara

Publications and source records attributed to M Barbara.

At least 19 recordsLinked to original sources

Resolution of pluripotential intermediates in murine hematopoietic differentiation by global complementary DNA amplification from single cells: confirmation of assignments by expression profiling of cytokine receptor transcripts.

Although hematopoiesis is known to proceed from stem cells through a graded series of multipotent, oligopotent, and unipotent precursor cells, it has been difficult to resolve these cells physically one from another. There is, therefore, corresponding uncertainty about the exact distribution and timing of the expression of genes known to be important in hematopoietic differentiation. In earlier work, the generation of a set of amplified complementary DNAs (cDNAs) from single precursor cells was described, whose biologic potential was determined by the outcome of cultured sibling cells. In this study, the new acquisition of cDNA from multipotent myeloid precursor cells is described, as is the mapping of RNA-level expression of 17 distinct cytokine receptors (c-kit, Flk-1, Flk-2/Flt-3, c-fms, gp130, erythropoietin receptor, GM-CSFRalpha, G-CSFR, TNFR1, IL-1RI, IL-1RII, IL-2Rbeta, IL-3-specific beta receptor, IL-4R, IL-6Ralpha, IL-7Ralpha, and IL-11Ralpha) to the enlarged sample set, spanning stages from pentapotent precursors through oligopotent intermediates to committed and maturing cells in the myeloid and lymphoid lineages. Although the enhanced scope and resolving power of the analysis yielded previously unreported observations, there was overall agreement with known biologic responsiveness at individual stages, and major contradictions did not arise. Moreover, each precursor category displayed a unique overall pattern of hybridization to the matrix of 17 receptor probes, supporting the notion that each sample pool indeed reflected a unique precursor stage. Collectively, the results provide supportive evidence for the validity of the cDNA assignments to particular stages, the depth of the information captured, and the unique capacity of the sample matrix to resolve individual stages in the hematopoietic hierarchy.

Animals↗

Laser Doppler measurement of cochlear blood flow changes during conditioning noise exposure.

Using laser Doppler flowmetry, cochlear blood flow was assessed in Mongolian gerbils exposed to noise. Anesthetized animals were surgically implanted with permanent electrodes and then exposed for 10 consecutive days (6 h on/18 h off) to an octave band noise centered at 4 kHz (85 dB SPL). The auditory brainstem responses and the blood flow in the basal turn of the cochlea were compared with those of gerbils not exposed to noise. The exposed animals developed an initial threshold shift, followed by a progressive reduction in threshold shift up to complete recovery at the end of the test. In the exposed animals, a reduction in the cochlear blood flow during the first 4 days of exposure was observed, which was then followed by a progressive increase up to the end of the test. The results of this study exclude a possible role of the microvasculature of the lateral cochlear wall in determining the resistance to 4 kHz frequency noise exposure.

Acoustic Stimulation↗

Local pressure protocol, including Meniett, in the treatment of Ménière's disease: short-term results during the active stage.

Treatment of Ménière's disease (MD) is still controversial and pressure changes transmitted to the inner ear have been reported to have effects similar to those of other non-surgical therapies. This paper reports on a clinical trial of MD patients which has been carried out using a portable piece of equipment, called Meniett, which delivers a pulsed, controlled, positive pressure to the middle ear, provided that a ventilation tube (VT) has previously been inserted. A comparison was made of the number of vertigo spells during the 2 months before treatment and during the 40-day treatment period. In addition, within this latter period a comparison was made between use of VT and use of VT + Meniett. Use of VT only had a positive effect in 90% of patients, with either absence (n = 10: 50%) or marked reduction (n = 8; 40%) in episodes of vertigo. When Meniett was also applied, stabilization of the positive effect on vertigo was registered, with a concomitant improvement in hearing threshold in 2 patients (10%). Although a longer and more reliable long-term follow-up of this treatment is needed, it is possible to propose the use of this therapeutic approach as it has been proven to induce a dramatic improvement in the symptoms affecting patients with Ménière's disease during reactivation of the disease.

Adult↗

Protective effect of the cochlear efferent system during noise exposure.

The aim of the present study was to confirm the hypothesis that the cochlear efferent system is involved in the mechanisms underlying the "toughening" effect at high frequencies. The toughening effect is defined as a progressive threshold shift reduction when repeated exposures to the same noise are applied. Vestibular neurectomy was performed through a posterior cranial fossa approach in six healthy pigmented guinea pigs, and it assured the interruption of both crossed and uncrossed olivocochlear bundles to one ear only, before their entrance in the internal auditory meatus. The animals were then implanted with permanent electrodes for the electrocochleographic findings. Ten days after the operation the animals were exposed to octave-band toughening noise, centered at 4 kHz, at 85-dB SPL, for 10 consecutive days, 6 hours on/18 hours off. The hearing threshold was registered before and at the end of each exposure session. The behavior of the hearing threshold in the operated ears was then compared to that of the controlateral, nonoperated ears. Complete recovery from TS in the control ear began after four days of exposure, whereas in the operated ear hearing loss increased to day 7 (55 dB), with only a partial reduction (45 dB) beyond ten days of exposure. The results of the present study clearly demonstrated that sectioning of the OCB in guinea pigs causes persistent hearing loss during noise-exposure conditioning, in comparison to the contralateral, nonoperated ear. Thus, one can assume that the lack of decrease of TS during intermittent noise exposure could be due to the loss of the protective effect of the efferent fibers, perhaps mediated by the lateral OC neurons that synapse beneath the IHCs.

Animals↗

Clarion cochlear implants: surgical implications.

The surgical aspects of 34 Clarion cochlear implants, positioned during a five-year period on 31 profoundly-deaf subjects as primary (11 children, 20 adults) and revision surgery (one child, three adults) were taken into consideration. Intra- and post-operative complications related to the specific structure of this device were considered along with the benefits obtained by update of the hardware and surgical approach. A smaller thickness of the internal receiver as well as the shifting from a retro-auricular/sub-temporal (RA-ST) to an endaural-retromastoid (EA-RM) approach have contributed to a dramatic drop in post-operative complications, such as skin defect or device extrusion. Special care should, however, be taken when cochlear implantation is planned in ears with chronic otitis or its surgical sequelae. From the two revised cases (hardware failure, electrode displacement) in whom re-implantation in the same side was performed, it has been demonstrated that the helicoidal shape of the electrode carrier is not inducing any additional trauma to the cochlear structure.

Adolescent↗

Vestibular neurectomy in the guinea-pig: a retrosigmoid approach.

The efferent cochlear system, composed of both ipsi- and contralateral bundles, runs along with the vestibular nerve and may serve as protection for the inner ear. Sectioning of the vestibular nerve could thus create an experimental model for further in-depth study of such a protective role. A personal surgical approach is described, involving a suboccipital (or retrosigmoid) route to the postero-medial aspect of the guinea-pig temporal bone, chosen because of its use for the induction of endolymphatic hydrops in the same species. The crucial step in this approach is the separation of the sigmoid sinus in its entirety, through an intra-dural access with a minimal removal/retraction of cerebellar tissue. This did not affect either the post-operative recovery of the animal or its hearing threshold level as assessed via auditory brainstem responses.

Animals↗

Transforming growth factor-beta1 expression in human acoustic neuroma.

HYPOTHESIS: The differing clinical behavior of acoustic neuroma (AN) may be explained by the presence of specific biological features involved in tumorigenesis and growth. BACKGROUND: Transforming growth factor (TGF) beta1 is known to participate in the regulation of peripheral nerve tumors, modulating cell proliferation and differentiation with mechanisms different from those of glial growth factors (GGF) and fibroblastic growth factors (FGF), which are responsible for Schwann cells' mitogen activity. METHODS: Surgically removed human AN specimens were fixed in formalin and embedded in paraffin for immunohistochemistry studies. Expression and localization of TGF-beta1 in different tumor regions were assessed after incubation of paraffin sections with a mouse monoclonal anti-TGF beta1 antibody (DBA, Milan, Italy). Clinically, the time elapsed between the beginning of symptomatology and AN size as shown by preoperative computed tomography, magnetic resonance imaging, or both was calculated as rough value of growth rate, which enabled slow-growing and fast-growing ANs to be distinguished. RESULTS: Eighty-four percent of AN specimens expressed TGF-beta1 positivity at the level of the cytoplasm of the Schwann cells. TGF-beta1 reactivity was also shown in the blood vessel walls (96.15%) and the tumor capsule (80.86%). TGF-beta1 reaction appeared higher in Antoni A regions than in Antoni B regions. No significant relationship was found between TGF-beta1 positivity and AN growth rate in the two groups. CONCLUSIONS: TGF-beta1 could participate in the biological behavior of AN, particularly as an important factor of tumor growth prediction by allowing rapidly progressive or potentially recurrent tumors to be differentiated from slow-growing tumors that are unlikely to recur. The clinical course of patients with AN is currently still of little help in predicting the rate of AN growth.

Adult↗

Presence of glycosaminoglycans in the endolymphatic sac.

Earlier morphological investigations have revealed that the endolymph, which is present in the endolymphatic sac (ES) seems to differ from that found elsewhere in the labyrinth, in that it contains a stainable substance. Histochemical investigations indicate that this substance is rich in glycosaminoglycans (GAGs). It has been speculated that the stainable substance might play a role in regulation of fluid and ions and also, possibly, the pressure within the endolymphatic sac compartment. Endolymphatic sac specimens obtained from adult guinea pigs, rats, mice and in vitro cultured fetal inner ears were incubated with monoclonal antibodies against epitopes, and after enzymatic digestion revealed five different GAGs: hyaluronan, chondroitin-4-sulphate+dermatan sulphate, chondroitin-6-sulphate and keratan sulphate. In order to verify the specificity of these antibodies, otocysts from fetal mice were incubated in the same way. These cartilaginous specimens are known to contain GAGs in abundance and served as positive controls. The results indicate that the hyaluronan visualized by the monoclonal antibody is present to a large extent in the lumen of the ES and in the epithelial cells. Keratan sulphate and chondroitin-4-sulphate+dermatan sulphate are present within the epithelial lining, in the subepithelial tissue, and to some minor extent in the lumen, while chondroitin-6-sulphate does not show any specific staining.

Animals↗

Osmotic drugs in the treatment of cochlear disorders: a clinical and experimental study.

On the grounds of positive results obtained with Meniere's patients, agents such as glycerol and mannitol have been included in the therapeutical protocol of other cochlear disorders presenting with hearing loss either of sudden onset, but not observed at an early stage, or accompanied by tinnitus and aural pressure. Intravenous infusions of either 10% glycerol or 18% mannitol were given to selected patients 3 to 6 times with a time interval of 1 to 3 days. Hearing loss, tinnitus and aural pressure were evaluated as improved, unchanged or worsened. In 33% of the glycerol group and 23.8% of the mannitol group we observed hearing threshold improvement, while aural fullness improved in 45% of the glycerol and 56.2% of the mannitol groups, and tinnitus was only relieved in 13.1% of the glycerol and 5.8% of the mannitol group. A parallel experimental study was carried out on guinea-pigs in order to shed light on the effects of mannitol and glycerol on the inner ear. Cochlear blood flow was measured with a laser Doppler flowmeter at the level of the basal turn of the cochlear lateral wall, both in normal and hydropic guinea-pigs, before and after osmotic intraperitoneal infusion. Basal values in the normal cochlea were much higher than in the hydropic one, and both mannitol and glycerol markedly influenced the local blood flow in the normal cochlea, giving few or no changes in the hydropic one.

Animals↗

Natural history of Menière's disease: staging the patients or their symptoms?

The issue of what can be considered "natural" in the evolution of Menière's disease is reassessed in terms of basic assumptions regarding the definition of this inner ear disorder. Strict principles for the identification of Menière's patients are recommended; i.e. episodic vertigo, fluctuating-ascending hearing loss and tinnitus, accompanied by a positive electrocochleographic pattern (summating/action potential ratio > 0.51). When considering the evolution of Menière's disease, it is worth stressing that almost all patients receive several different kinds of treatment which affect the natural course of the disease to different degrees. When staging the patients, a prodromic stage (Stage 0), with intermittent, isolated symptoms of variable duration, precedes the disabling stage (Stage I) with its full array of symptoms. Stage la can be distinguished from Stage Ib depending on the fluctuation in hearing and different therapeutic strategies can be proposed in order to reach the stabilised stage (Stage II). A limited number of patients are susceptible to either reverting into a disabling stage or progressing to Stage III, with possible involvement of the contralateral ear. We conclude that the full expression of the disease is a self-running course which can be only slightly modified by medical or surgical therapy but, instead, can be controlled by psychological counselling and dietary-hygienic principles.

Hearing Disorders↗

Electrocochleographic findings: Menière's disease versus sudden sensorineural hearing loss.

Electrocochleography was conducted in 185 patients with Menière's disease and 117 with sudden deafness. Electrophysiological findings from the two groups were compared in order to identify pathogenic similarities between the two conditions. Parameters investigated were the summating potential (SP)/action potential (AP) ratio, audiometric profiles and audiometric changes after medical therapy. A high SP/AP ratio was found in the patients with sudden deafness, thus supporting a possible hydropic aetiology in this group. In conclusion, electrocochleography can be considered a useful technique as it permits identification of an hydropic condition in certain cases of sudden deafness.

Audiometry↗

Clarion cochlear implant: short-term effects on voice parameters.

OBJECTIVE: This study aimed to evaluate the moment-to-moment auditory control of voice at an early stage after implantation with Clarion cochlear implants. STUDY DESIGN: A perceptive and electroacoustic evaluation of the voice was carried out through a digital analysis immediately after the activation of the implant, before the fitting procedure has begun. SETTING: The study was performed at the Department of Otolaryngology, University "La Sapienza" of Rome. PATIENTS: Nine profoundly deaf subjects (five post-linguistic deaf adults, two pre-linguistic deaf children and two peri-linguistic deaf subjects, one adult and one child). INTERVENTION: Surgical insertion of a Clarion cochlear device. MAIN OUTCOME MEASURES: Qualitative (short-term pitch and energy perturbation, intonation, vocal attack, quality, and intensity) and quantitative (F0, F1, F2 and F3 frequency values), under non activated (NAI) and activated (AI) condition, have been obtained. RESULTS: In the majority of patients, the perceptive evaluation under AI showed a lowering of voice intonation, a better control of voice intensity, and a reduction of nasal quality. These findings were confirmed by a significant lowering of F0 (Wicoxon non parametric test) in all cases and lowering of F1 and F2 in five cases. Additionally, a better definition of all formats in the majority of cases as well as by a parallelism of pitch and energy profile was observed. CONCLUSIONS: The Clarion cochlear implant device provided a recognizable moment-to-moment auditory control on voice and articulatory patterns. By monitoring the articulated voice during adjustment of the electrical stimulation at the first fitting session, one may be able to include these data and assist in the selection of the best rehabilitative strategy.

Adolescent↗

Role of transient-evoked otoacoustic emissions for hearing preservation in acoustic neuroma surgery.

OBJECTIVE: This study aimed to assess whether transient-evoked otoacoustic emissions (TEOAEs), which are known to be expressions of an intact cochlear function, could be useful for the rationale of hearing preservation in acoustic neuroma (AN) surgery. STUDY DESIGN: The TEOAEs were measured before, during, and after surgery in a consecutive series of patients affected by cerebellopontine angle tumors. SETTING: The study was performed at the Department of Otolaryngology, University "La Sapienza" of Rome. PATIENTS: Five patients with AN and one with a meningioma totally involving the Cochlear (VIII) nerve. INTERVENTION: Retrosigmoid approach on the ground of the limited AN size (within 20 mm) and the 30/70 rule, as proposed by the American Academy of Otolaryngology-Head and Neck Surgery nomogram. Two patients also were selected despite a poor hearing level and the absence of TEOAEs. MAIN OUTCOME MEASURES: Preoperative and postoperative pure tone audiometry compared with TEOAEs. Intraoperative TEOAEs were compared with electrocochleographic findings. RESULTS: The TEOAEs were found to be present also in patients with AN with poor pure-tone average (PTA) threshold (i.e., > 75 dB). Intraoperatively, TEOAEs recording showed to be markedly affected by the environmental noise as well as by specific intraoperative maneuvers, such as drilling of the internal auditory canal or tumor removal or both. In the three patients in whom hearing successfully was preserved. TEOAEs were present in the first postoperative days, despite a temporary deterioration of the PTA threshold. CONCLUSIONS: The intraoperative use of TEOAEs showed to be scarcely reliable, whereas their presence in the preoperative assessment of patients with AN could lead to an extended number of patients to be selected for hearing-preservation surgery. Finally, an early postoperative identification of TEOAEs may be considered a favorable prognostic sign for foreseeing a delayed pure-tone hearing threshold recovery.

Acoustic Stimulation↗

Nerve fibres of the endolymphatic sac: electronmicroscopic findings in the Mongolian gerbil.

The presence of separate bundles of nerve fibres in the gerbilline endolymphatic sac (ES) is described, paying particular attention to their ultrastructure and localization. One bundle, localized in the area of the subepithelium which separates the sigmoid sinus from the ES, is composed only of myelinated fascicles which, moreover, seem to have an isolated contact with the ES area. Other two single nerve fibres, much smaller in caliber, are localized in the ES subepithelium and laterally to the ES area, still close to the sigmoid sinus. These fibres, composed of myelinated and unmyelinated fascicles, seem to have a rather longitudinal orientation and, moreover, contract close relationships with the rich vascular network of the ES subepithelial tissue. As far as the course is concerned, the serial sectioning technique would suggest that the nerve fibres get very close to the ES epithelial cell layer, going proximal to distal. Speculations on the origin of this nerve contingent in the ES are proposed and discussed in view of possible new theories for pathogenesis and therapy of some inner ear diseases.

Animals↗

Expression of steroid receptors in acoustic neuroma.

The expression of steroid receptors has been investigated in an attempt to clarify the role of steroid hormones in the proliferation and progression of acoustic neuromas. Specimens of tumours taken during translabyrinthine surgery were tested for cytosolic (c) and nuclear (n) steroid receptors. Oestrogen and progesterone receptor levels were evaluated by enzymatic immuno-assay, while androgen receptor binding levels were detected by dextran-coated charcoal method in a single-step determination. In some cases, the six point Scatchard analysis of cytosolic and nuclear androgen receptor was also performed. Threshold values were: 3 fmol/mg of proteins for cytosolic steroid receptors and 20 fmol/mg DNA for nuclear steroids, which corresponded to approximate median values of cytosolic and nuclear oestrogen and progesterone, respectively. Oestrogen and progesterone appeared to be localized more frequently in the nuclei rather than in the cytosol (70% oestrogen and progesterone positivity in the nuclei; 30% oestrogen, 40% progesterone positivity in the cytosol), while androgen receptors were preferentially localized in the cytosol (80% positivity in the cytosol; 40% positivity in the nuclei). A negative non-linear correlation between cytosolic oestrogen and cytosolic androgen receptors was found. There was a direct linear correlation between cytosolic oestrogen and nuclear oestrogen levels. A strict correlation between nuclear oestrogen and nuclear progesterone incidence was shown. Preliminary analysis of clinical data and biochemical parameters showed that cytosolic progesterone levels inversely correlated with tumour size.

Aged↗