Dysmorphism of the middle ear: case report.

Although there are numerous publications in the literature describing the wide range of diagnosis, classifications and treatment of malformations of the hearing apparatus, even more variations can be found in clinical practice. Indeed, each individual case is unique as far as concerns pathogenesis, clinical course and treatment. The case reported herein describes a 12-year-old boy affected by cranio-facial dysmorphism and monolateral conductive hearing loss in the right ear: followed from radiological diagnosis--carried out to study a malformation of the ear pinna--to surgical treatment.

Defective platelet response to arachidonic acid and thromboxane A(2) in subjects with Pl(A2) polymorphism of beta(3) subunit (glycoprotein IIIa).

The membrane complex alpha(IIb)beta(3) is the major receptor for fibrinogen and is involved in platelet adhesion and aggregation. Evidence has been presented that the Pl(A2) allele of the beta(3) Pl(A1/A2) gene polymorphism might be an independent risk factor for coronary thrombosis, but the matter is still controversial. We investigated the relationship between this polymorphism and possible alterations of platelet functions in vitro. The platelet adhesion to fibrinogen-coated microplate wells and the aggregation induced by several different agonists were tested in 63 healthy volunteers, among them, 49 subjects with Pl(A1/A1) polymorphism, 12 subjects with Pl(A1/A2) polymorphism and two subjects with (PlA2/A2) polymorphism. Subjects with PlA1/A2 polymorphism or with Pl(A2/A2) polymorphism showed significantly lower platelet responses as compared with Pl(A1/A1) subjects when either arachidonic acid or the thromboxane A(2) analogue, U46619, were used as agonists. In resting condition and after thrombin or ADP stimulation, platelet function was normal in all the subjects. An increased sensitivity to the anti-aggregatory effect of acetylsalicylic acid was observed in platelets from subjects with the Pl(A2) allele. Finally, using a flow-cytometric evaluation and determining the beta-thromboglobulin plasma levels, we did not find any evidence of a Pl(A2) platelet hyper-reactivity ex vivo. Our findings are not consistent with the hypothesis that the purported increase of cardiovascular risk in these subjects may be as a result of platelet hyperactivation. On the contrary, the Pl(A2) allele is associated with a platelet functional deficiency, specifically linked to the activation of the fibrinogen receptor by thromboxane A(2).

Hemolytic anemia induced by ribavirin therapy in patients with chronic hepatitis C virus infection: role of membrane oxidative damage.

The antiviral drug ribavirin (RBV) is widely used in combination with interferon (IFN) in the treatment of chronic hepatitis C virus (HCV) infection. A major side effect of RBV is a reversible hemolytic anemia. We have evaluated the in vitro effects of RBV on erythrocyte adenosine triphosphate (ATP) content and on hexosemonophosphate shunt (HMS). The ATP levels were significantly decreased in the presence of RBV and the HMS was increased, suggesting the presence of red cell susceptibility to oxidation. In vivo, we have studied the hematologic effects of treatment with RBV alone or in combination with IFN in 11 patients with chronic hepatitis C: 6 were treated with RBV (1,000-1,200 mg/d) and 5 were treated with a combination of RBV and IFN (5 million U thrice weekly). Patients were studied at semi-monthly intervals from 0 to day 60 of therapy. Both treatments were associated with a significant reduction in hemoglobin levels (steady state level at day 45) and a marked increase in absolute reticulocyte counts. Erythrocyte Na-K pump activity was significantly diminished, whereas K-Cl cotransport and its dithiotreitol-sensitive fraction, malondialdehyde and methemoglobin levels were significantly increased. RBV-treated patients showed an increase in aggregated band 3, which was associated with a significantly increased binding of autologous antibodies and complement C3 fragments indicating an erithrophagocytic removal by reticuloendothelial system.

Vestibular function and cochlear implant.

The authors illustrate their personal experience relating to 32 patients, aged between 12 and 74 years, undergoing cochlear implant, in whom vestibular reflexes were evaluated before and after surgery. This series did not include cases of areflexia, but only 1 case of reduced vestibular reflexia consequently to surgery. In this case, owing to the probable intervention of central compensation processes, labyrinthine hyporeflexia never became clinically significant. These personal results enable the authors to affirm that preoperative vestibular reflexes do not offer elements able to influence the choice of the ear in which to perform the cochlear implant. In the series of patients reported by the authors, a cochleostomy by removal of the floor of the round window niche, following the suggestions of O'Leary et al., always headed the electrode implant. This contrivance may reduce or eliminate the negative effects on vestibular receptors indirectly caused by the consequent and inevitable alteration of perilymph pressure produced by the implant.

Estimated 6-year event-free survival of 55% in 60 consecutive adult acute lymphoblastic leukemia patients treated with an intensive phase II protocol based on high induction dose of daunorubicin.

On the basis of a previous experience suggesting that daunorubicin dose in induction was an independent prognostic factor in adult ALL, we designed a chemotherapeutic regimen (ALLVR589) characterized by high doses of daunorubicin (270 mg/m2) in induction and by high-dose Ara-C in post-remission. The protocol was otherwise conventional: induction and post-remission therapy were followed by chemo-radio prophylaxis of the central nervous system (CNS) and periodical reinductions over a 3-year maintenance period. Sixty consecutive patients (male 42, female 18, median age 34 years, range 14-71; B-lineage, 35; T-lineage, 25; Ph' and bcr/abl positive, 7) recruited between 1989 and 1996, were evaluated for treatment outcome. Complete remissions were 56 (93%), one patient had refractory disease, early deaths were five (8%); 19/56 (34%) patients relapsed, five of whom were Ph'+. Median time to relapse was 11 months (range 3-47); 68% of relapses occurred within 12 months from CR. No CNS relapses were observed. After a median follow-up of 44 months (1-100), 33/60 (55%) patients remain event-free; 23/60 (38%) are off-therapy in continuous CR (median follow-up from diagnosis: 63 months; range 38-100). These results suggest that increasing DNM dosage in induction is one of the possible approaches to improve the outcome of adult ALL by decreasing the relapse occurrence.

[The usefulness of computer tomography in planning cochlear implant surgery]. / Utilità della Tomografia Computerizzata nella pianificazione dell'intervento di impianto cocleare.

In recent years, technical progress has created new complex acoustic implants which send an electrical stimulus to the eighth cranial nerve through one or more electrodes inserted through the round window into the scala tympani of the cochlea. The abnormal--mostly osteosclerotic--processes which cause deep hearing loss may prevent electrode insertion. Therefore, internal ear anatomy must be detailed, which is essential to assess the feasibility of surgery and, if surgery is indicated, to plan it properly. High resolution CT (HRCT) was performed on 79 patients to study cochlear patency, round window shape and patency, degree of temporal bone pneumatization and the proximity of vascular structures (carotid artery and jugular vein). On the basis of HRCT results, 14 of 79 patients were excluded from surgery. Comparing HRCT with surgical findings, the authors conclude that HRCT is the method of choice to examine the candidates to cochlear implant thanks to its high spatial resolution and excellent depiction of even the smallest structures. Its only limitation is that it fails to assess the lack of patency of the cochlear canal due to fibrosis, which is not associated with demonstrable density changes (3 of 19 surgical patients). This problem may be solved by submitting the potential surgical candidates to MRI.

Blood copper and zinc changes in runners after a marathon.

This study reports plasma and total blood cell (TBC) Cu and Zn levels of 16 runners before and after a marathon race. All the pre-race plasma values were in the normal range, while the TBC Cu level was 29.3% (P < 0.01) lower and the TBC Zn level was 29.5% (P < 0.01) higher than mean values of the control group. The run induced a significant decrease in TBC Cu concentration during the days following the race and a light increase in plasma Cu values. It caused a significant increase in TBC Zn concentration at the end of the race (followed by a decrease 24 hours later) without plasma Zn variations. These data show that intense physical exercise could modify trace-element metabolism.

Cochlear interdependence and micromechanics in man and their relations with the activity of the medial olivocochlear efferent system (MOES).

Following stimulation of one ear with white noise (WN) or 0.5, 1 and 2 kHz tone bursts a statistically valid mean reduction in the amplitude of delayed evoked otoacoustic emissions (DEOE), elicited from the contralateral ear by bursts of the same frequencies, was observed in 10 people (19-23-years-old) with normal hearing. This reduction only appeared in response to a contralateral stimulus delivered 7, 8 and 9 ms earlier than that used to produce the DEOE. This inhibitory effect was just referable to the activity of the medial olivocochlear efferent system (MOES). This research has shown that: (i) the cochlear interdependence is linked to activation of the MOES; (ii) in man the activity of MOES is inhibitory and only appears for a stimulus of the same frequency or (for WN) including that used to elicit DEOE; (iii) the cochlear interdependence is frequency selective and the MOES thus establishes a direct functional interdependence between homologous sectors of the organs of Corti on the two sides; (iv) DEOE would appear to be no more than partly generated by outer hair cells (OHC) of the organ of Corti in relation to the frequency of the stimulus employed, thus substantiating the hypothesis that in their production the effects of an 'active' mechanism, represented by the 'slow' contractile activity of the OHC, is overlain by those of a 'passive' mechanism formed by the oscillations induced by the movements of the stapes in the basilar membrane (BM) or in the set of membranes and liquids of cochlear canal.

Recovery time of the temporary threshold shift for delayed evoked otoacoustic emissions and tone bursts.

The recovery time of temporary threshold shift after 1-kHz tone bursts delayed evoked otoacoustic emissions (DEOE) after the same stimulus were studied after auditory fatigue (AF) with a pure tone (0.75 kHz, 10 min, 95 dB HL) in 20 normal-hearing subjects aged 19-23 years. Close similarities were observed in the two experimental conditions. Since DEOE are transmitted to the outer ear via structures independent of the fibers of the afferent acoustic pathway and their synapses, it may be supposed that changes in the motile activity of the outer hair cells caused by AF could be partly responsible for their production and could constitute an active intracochlear mechanism taking part in this phenomenon. It may also be supposed that the effects of this active mechanism could be superimposed on those produced by a passive intracochlear mechanism consisting of the traveling wave induced in the basilar membrane by the perilymph owing to the movements of the stapes.

Are delayed evoked oto-acoustic emissions (DEOE) solely the outcome of an active intracochlear mechanism?

Post-mumps and post-measles hearing losses are a result of the destruction of Corti's organ. Both the basilar and the Reissner membranes are unimpaired. In 11 subjects with post-mumps (8 cases) and post-measles (3 cases) unilateral anacusis, DEOE with a mean amplitude lower than that of the contralateral normal ear with the same sensation level were observed with 0.5, 1 and 2 kHz tone-bursts and air conduction stimulation. These findings lend credit to the view that DEOE could in part be produced by a passive intracochlear mechanism, probably a consequence of the basilar membrane travelling wave induced by the displacement of the perilymph. In a normal ear, this passive mechanism could be superimposed by an active mechanism linked to the contractile activity of the outer hair cells (OHC) which modulates and increases the travelling wave depth.

Evoked otoacoustic emissions (EOAE) and bone conduction stimulation. A preliminary report.

Otoacoustic emissions were evoked (EOAE) in 6 normal-hearing subjects by both bone (BCS) and air conduction stimulation (ACS). Four subjects affected by unilateral otosclerosis were also examined in order to determine the role of the ossicular chain in EOAE transmission to the eardrum. In normal-hearing subjects, EOAE by BCS showed the same characteristics as those evoked by ACS. The morphological features remained unchanged over a period of 4 months and their amplitude increased non-linearly with increasing stimulus intensity. In subjects with unilateral otosclerosis before surgery, no EOAE could be elicited by ACS from the otosclerotic ear, whereas they could be recorded by BCS. After stapedectomy, EOAE could be obtained by ACS too. These results suggest that the ossicular chain is important but not essential in the transfer of the EOAE to the eardrum.

Delayed oto-acoustic emissions evoked by bone-conduction stimulation: experimental data on their origin, characteristics and transfer to the external ear in man.

1) BCEOE have been obtained in subjects with normal hearing by 1 kHz tone-bursts; 2) the morphology of BCEOE varies from one subject to another, and is stable over the course of time. BCEOE do not display a linear relation between their amplitude and the intensity of the stimulus, whose spectral composition is the same as theirs; 3) by contrast with ACEOE, whose mean threshold is the same as that of the subjective tonal threshold for the same stimulus presented by the same stimulation modality, BCEOE threshold, on overage, is about 10 dB HTL higher; 4) this difference in threshold is not due to interference on the part of the controlateral ear, via the efferent fibres, since it is also observed in persons with unilateral anacusis. It is probably the outcome of unilateral competitive inhibition between two stimuli presented to the same ear at the same time. By bone-conduction stimulation in fact, when the meatus is occluded by the probe, as in our experimental situations, Corti's organ is reached by a supplementary contingent of mechanical energy generated by the vibration of the bony part of the meatus and transmitted by air conduction; 5) ACEOE cannot be obtained in otosclerotic subjects whereas they appear after surgery. BCEOE are obtained before surgery and increase in amplitude post-operatively; 6) the findings mentioned in point 5) clearly demonstrate that the ossicular chain plays an important, but not an essential role in the transfer of EOE from the inner to the external ear.

Relationships between acoustic reflex patterns elicited by unfiltered white noise and narrow band white noise stimuli of different duration but of the same intensity.

For the purpose of this study, acoustic signals were generated by an Amplaid MK VI. An Amplaid 702 impedence meter was connected to its averaging section and to its computer. The stimuli were bursts of unfiltered white noise (UWN) and of narrow band white noise (NBWN; 30 db./oct/slope; central frequencies 1,000, 2,000, 4,000 Hz.) lasting 3-1,000 msec., at intensity of 105 db. SPL p.e. The following parameters were evaluated: stapedius contraction latency, amplitude, duration and recruitment time. It was found that latency was independent of the spectrum of the stimulus and its duration. Amplitude and recruitment time, on the other hand, were related to spectrum and duration, while duration of contraction was directly related to the duration of the stimulus only.

Influence of stimulus duration and intensity on acoustic reflex parameters.

Four acoustic reflex parameters (latency, duration, amplitude, recruitment time) in response to stimuli lasting 1 000 to 50 msec with an initial intensity of 95 dB SPL p.e. were studied in four sets of experiments. In each set of experiments, each halving of the stimulus duration was accompanied by a 3, 4, 5 and 6 dB SPL p.e. increase respectively (exchange rates: 3, 4, 5 and 6 dB SPL p.e.). It was found that latency was dependent on the threshold only and unaffected by either duration and intensity. Amplitude and recruitment time were mainly determined by energy content of the stimulus, whereas duration of contraction was solely dependent on the stimulus duration. These experiments also demonstrate that, with reference to stimuli employed, an increase of 3 dB SPL p.e. each halving of the stimulus duration is unable to maintain unchanged the environmental acoustic energy reaching the inner ear.

Dynamic parameters of the stapedius muscle reflex in response to stimuli of varying duration but with the same energy content.

An evaluation was made of the behaviour of the dynamic parameters of the stapedius contraction reflex (latency, amplitude, recruitment time, duration, and efficiency) in response to stimuli with the same energy content but of different duration. A comparison was made with the results of a similar experiment in which stimuli with different energy contents were used. As adumbrated in earlier studies, it was found that these parameters are more subject to the influence of the temporal characteristics of the stimulus than to its energy content.

Acoustic reflex patterns according to different intensity and different duration of white noise (WN) stimuli.

The data were gathered by connecting the output from a middle ear impedance meter (Amplaid 702) to the computer and averaging section of the Amplaid MK VI which was also used as an acoustic stimuli generator. The stimuli consisted of white noise bursts having different peak equivalent sound pressures (115, 105, 95, 85 dB SPL) and different durations (from 1000 to 3 msec). The parameters examined were: stapedius muscle contraction latency time; muscle fibre recruitment time, i.e. the interval between the onset of contraction and its maximum; duration of contraction; amplitude of maximum contraction. An evaluation was also made as to the "efficiency" of contraction, expressed as the function of duration and amplitude. The authors discuss the different patterns of "efficiency" curve achieved at various intensity levels by stimuli of different duration.

Electroneuronography in the diagnosis and prognosis of diseases of the facial nerve.

Electroneuronography (ENoG) involves the recording of a summation potential of motor units provoked by an appropriate electrical stimulus. Degeneration (and obviously interruption) of a nerve fibre always means the denervation of all muscular fibres related to them. So the diminution in summation potential amplitude will be proportional to the number of denervated motor units. The test is based on a comparison of responses to stimuli of equal intensity between healthy and diseased side. Comparison with the unimpaired side, makes it possible to establish the percentage number of nerve fibres on the damaged side capable of provoking a contraction in the muscular fibres to which they are distributed. The results obtained in 60 personal cases are illustrated and the undeniable advantages offered by this straightforward diagnostic method discussed with respect to evaluating the development of facial nerve paralysis and the precise, early establishment of therapeutic indications, particularly where surgery is necessary.