Evaluation of noise-induced hearing loss by auditory steady-state and auditory brainstem-evoked responses.

OBJECTIVES: Noise-induced hearing loss (NIHL) may result from occupational noise exposures and is considered as an 'Occupational Disease'; therefore, it is compensable. To verify the existence and severity of the work-related hearing loss, there is a need of an objective, reliable auditory measure in cases of arbitration of financial disputes to resolve any medicolegal aspects. The objective of the study was to compare between the ABR and ASSR for predicting the behavioural threshold in subjects with normal hearing or NIHL. DESIGN: The study included 82 subjects regularly exposed to high levels of occupational noise, with normal hearing and NIHL. ABR to clicks and to tone bursts were recorded followed by multiple-frequency ASSR. Physiological and behavioural thresholds were compared for specific frequencies (1000, 2000 Hz) and average of high-frequency range (2000 and 4000 Hz). In addition, Pearson correlations and the specificity and sensitivity of each measure were also calculated using receiver operating characteristic (ROC) curves. RESULTS: In the NIHL group, there was a significantly smaller difference between the behavioural threshold and click-ABR than the ASSR in high-frequency range. Pearson correlations were significantly higher for click-ABR. Analysis of specific frequencies yielded a smaller difference between behavioural and ASSR than tone-burst-ABR thresholds, with a slightly better correlation for ASSR than tone-burst-ABR. Higher sensitivity but lower specificity was suggested for ASSR than ABR. CONCLUSIONS: ASSR is associated with high-frequency specificity, shorter test sessions and good correlations with behavioural thresholds, making it a potentially better measure than ABR for predicting audiograms in subjects with NIHL. These findings have diagnostic implications, especially in cases of workers' compensation when subjects may be uncooperative.

Auditory system dysfunction due to infantile thiamine deficiency: long-term auditory sequelae.

Eleven infants who were fed a thiamine-deficient formula for a mean of 3 months were evaluated for immediate and long-term auditory abnormalities. At presentation, 8 infants had auditory neuropathy spectrum disorder (ANSD), which resolved with supplementary thiamine in 5 children, was permanent in 2 children, and deteriorated in 1 patient who died at the age of 7 years. An additional patient had an auditory pattern corresponding to that of auditory neuropathy of brain stem origin. The 2 remaining patients had unilateral cochlear hearing loss. Six to 8 years later, all patients with transient ANSD had normal audiograms, 2 patients had unilateral cochlear hearing loss, and the rest had neural hearing loss. All survivors had a language developmental delay and impaired speech intelligibility of varying degrees, especially in the presence of background noise. Thiamine is crucial for normal auditory development and function, and its deficiency may be considered an acquired metabolic cause of ANSD in infants.

Transient deafness in young candidates for cochlear implants.

This study describes 5 infants who were diagnosed with auditory neuropathy (AN) associated with severe to profound neural hearing loss shortly after birth. However, on repetition of the tests 7-12 months later, all infants showed full or partial recovery. The follow-up electrophysiological patterns were characterized by the appearance of wave I, followed by wave III and V, reflecting synchronization of auditory pathways and improvement in auditory nerve function. Suspected causative or contributory factors were neonatal hyperbilirubinemia, hypoxia, ischemia, and central nervous system immaturity, alone or in combination. These findings indicate that lack of an auditory brain stem response does not necessarily mean no hearing and that the situation where AN exists can improve. Thus, clinicians should be made aware that although cochlear implants may yield better auditory performance when applied early, they should be considered a therapeutic option only after repeated measures have proved persistent AN, and no child should be considered for an implant until a behavioral measure of hearing has been obtained.

Involvement of the heparanase procoagulant domain in bleeding and wound healing.

Essentials Heparanase forms a complex with tissue factor and enhances the generation of factor Xa. The present study was aimed to identify the procoagulant domain of heparanase. Procoagulant peptides significantly shortened bleeding time and enhanced wound healing. Tissue factor pathway inhibitor (TFPI)-2 derived peptides inhibited the procoagulant peptides. SUMMARY: Background Heparanase, which is known to be involved in angiogenesis and metastasis, was shown to form a complex with tissue factor (TF) and to enhance the generation of activated factor X (FXa). Our study demonstrated that peptides derived from TF pathway inhibitor (TFPI)-2 impeded the procoagulant effect of heparanase, and attenuated inflammation, tumor growth, and vascularization. Aims To identify the procoagulant domain in the heparanase molecule, and to evaluate its effects in a model of wound healing that involves inflammation and angiogenesis. Methods Twenty-four potential peptides derived from heparanase were generated, and their effect was studied in an assay of FXa generation. Peptides 14 and 16, which showed the best procoagulant effect, were studied in a bleeding mouse model and in a wound-healing mouse model. Results Peptides 14 and 16 increased FXa levels by two-fold to three-fold, and, at high levels, caused consumption coagulopathy. The TFPI-2-derived peptides explored in our previous study were found to inhibit the procoagulant effect induced by peptides 14 and 16. In the bleeding model, time to clot formation was shortened by 50% when peptide 14 or peptide 16 was topically applied or injected subcutaneously. In the wound-healing model, the wound became more vascular, and its size was reduced to one-fifth as compared with controls, upon 1 week of exposure to peptide 14 or peptide 16 applied topically or injected subcutaneously. Conclusions The putative heparanase procoagulant domain was identified. Peptides derived from this domain significantly shortened bleeding time and enhanced wound healing.

Dysfunction of the auditory efferent system in patients with traumatic brain injuries with tinnitus and hyperacusis.

OBJECTIVES: Tinnitus, hyperacusis and difficulty listening in background noise are common symptoms reported by patients with traumatic brain injury (TBI). The aim of this study was to explore the function of the auditory system in TBI patients with and without auditory complaints but having normal pure-tone audiograms. METHODS: The study consisted of 24 TBI patients with and 10 TBI patients without auditory complaints. In addition, 15 normal controls were included in the study. The function of the auditory system was tested by recording transient otoacoustic emissions (TEOAE) during the presentation of increasing levels of white noise in the contralateral ear. RESULTS: Most of the TBI patients with auditory complaints (87%) showed absent or significantly reduced effect of the auditory efferent system as compared with the TBI patients without auditory complaints and to normal controls. However, the global amplitude of the TEOAE was significantly higher in TBI patients with auditory complaints compared to those without. CONCLUSIONS: Due to its role in peripheral and central auditory activity, dysfunction of the efferent system may be at least partially responsible for these auditory complaints. This study underscores the importance of testing and evaluating the functional integrity of the medial efferent system by an objective and non-invasive method in patients with TBI.

The angiotensin-converting enzyme inhibitor, fosinopril, and the angiotensin II receptor antagonist, losartan, inhibit LDL oxidation and attenuate atherosclerosis independent of lowering blood pressure in apolipoprotein E deficient mice.

OBJECTIVE: To investigate the possible mechanisms of the antiatherosclerotic effects of the angiotensin-converting enzyme (ACE) inhibitor, fosinopril, in apolipoprotein (apo) E deficient mice. METHODS: Apo E deficient (E0) mice at the age of 8 weeks received either placebo or a high dose (25 mg/kg/d) of fosinopril supplemented in their drinking water. RESULTS: After 12 weeks of treatment, fosinopril reduced the aortic lesion size by 70%, compared with the placebo group. At this dosage, fosinopril significantly reduced blood pressure from 93 +/- 2 mmHg before treatment to 70 +/- 2 mmHg at the end of the treatment period (P < 0.005). Fosinopril also increased the resistance of the mice plasma low density lipoprotein (LDL) to CuSO4-induced oxidation, as shown by a 90% reduction in the LDL content of malondialdehyde (MDA) and also by a prolongation of the lag time required for the initiation of LDL oxidation (from 100 min in the placebo-treated mice to more than 240 min in the fosinopril-treated mice; P < 0.001). In addition, fosinopril inhibited CuSO4-induced oxidation of LDL that was obtained from the aortas of the treated mice, as shown by an 18% and 37% reduction in the LDL content of lipid peroxides and hydroperoxy-cholesterol linoleate, respectively, compared with the placebo-treated mice (P < 0.01). A low dosage of fosinopril (5 mg/kg/d) that was still adequate to reduce their plasma ACE activity and LDL propensity to lipid peroxidation was insufficient to lower their blood pressure. This dosage also reduced the aortic lesion size in the apo E deficient mice by 40% (P < 0.01). CONCLUSIONS: The antiatherogenic effects of fosinopril in apo E deficient mice are due not only to blood pressure reduction but also to the direct inhibition of angiotensin II-dependent effects, which are probably also associated with the inhibition of LDL oxidation.

Event-related potentials in post-traumatic stress disorder of combat origin.

Visual event-related potentials (ERPs) of primary interest in this study of post-traumatic stress disorder (PTSD) were N1, N2, P2, and P3. Forty Israeli combat veterans consisting of 20 PTSD sufferers and 20 normal controls were evaluated. ERPs were recorded in response to three sets of computer-generated visual stimuli, presented in the form of a modified oddball paradigm. These stimuli included: domestic animal pictures (targets), emotionally neutral pictures of furnishings (nontargets), and combat-related pictures (nontarget probes). Subjects were required to discriminate between target and nontarget stimuli by pressing a button in response to target stimuli only. Subjects were instructed to ignore all nontarget stimuli. As expected, target stimuli evoked accentuated P3 amplitudes in both controls and PTSD patients. The nontarget combat-related pictures elicited enhanced P3 and N1 amplitudes in the PTSD patients only. N2 amplitudes were accentuated in PTSD patients for both targets and combat-related pictures. P3 latencies and reaction times to target stimuli were prolonged in PTSD patients. The same tendency was observed for N1 latencies. These results may indicate that an altered state of early and late cognitive selective attention processing exists in PTSD patients in addition to a vulnerability to traumatic reminiscences.

Sleep disturbance associated with chronic tinnitus.

Sleep disturbance is a common and frequent complaint reported by tinnitus sufferers. Recent studies have shown that when insomnia and depression are associated with tinnitus there is decreased tolerance and increased discomfort with the tinnitus. The purpose of this study was to assess the reported prevalence and severity of sleep disturbance in chronic tinnitus patients. Patients (n = 80) were military personnel without major psychiatric disturbance and their tinnitus was associated with noise-induced permanent hearing loss (NIHL). Mini Sleep Questionnaire (MSQ) scores for sleep disturbance were found to be higher than those of normal controls in 77% of the patients. Highest MSQ scores in tinnitus patients with a sleep complaint were for delayed sleep, morning awakenings, mid-sleep awakenings, morning fatigue, and chronic fatigue. In contrast, a complaint of excessive daytime sleep (EDS) was not common. The self-rated severity of the tinnitus was greater in subjects with higher sleep disturbance scores. Self-rated depressive symptomatology was also highly correlated with sleep disturbance. Retrospective examination of sleep records and polysomnographic data for 10 patients with a complaint of chronic tinnitus revealed a combined effect for the tinnitus condition when associated with another conventional sleep disorder. In spite of the common complaint of sleep disturbance in tinnitus, only a minority seek a sleep examination.

Audiological evaluation of nonalcoholic, drug-free posttraumatic stress disorder patients.

Auditory functions of 32 Israeli soldiers with posttraumatic stress disorder (PTSD) were evaluated and compared with those of 32 matched controls without PTSD. The evaluation included peripheral auditory functions, tolerance to noise, and central auditory informational functions. Tolerance of intense auditory stimuli by PTSD patients was similar to that of controls. Significant differences were found between left and right ear central auditory functions in a subgroup of 13 PTSD subjects, but neither in other PTSD patients nor in controls. These findings are discussed in the light of previous research concerning abnormal responses to auditory stimulus in PTSD, hemispheric disconnection, alexithymia, and psychosomatic disorders.

[Purification of two beta-D-glycosidases from the digestive juice of Achatina balteata]. / Purification de deux bêta-D-glycosidases du suc digestif d'Achatina balteata.

Two beta-D-glycosidases have been purified from the digestive juice of Achatina balteata by acetone fractionation, ion exchange chromatography through DEAE-Sephadex A-50, ammonium sulphate fractionation and gel chromatography through Sephadex G-200. The preparations are homogeneous by p/lyacrylamide gel electrophoresis. Both enzymes are highly specific for the beta-D-anomeric configuration of the glycosidic linkage. They hydrolyse lactose, cellobiose and synthetic beta-D-galactosides, -glucosides and -fucosides at a pH optimum of 5,2 to 5,6 and are inactive on alpha-glycosides. The hydrolyzed substrates are recognized by the same catalytic site as shown by mutual competition studies between substrates and competitive inhibition observed with aldonolactones and glycopyranoses such as D-galactose, D-glucose and D-fucose. The different substrates are not hydrolyzed at the same rate by the two enzymes. They also differ by their electrophoretic mobility, their behaviour in gel chromatography and their stability towards pH and heat. The most salient property is the important beta-D-fucosidase activity of the two purified enzymes.

[Characterization of some hydrolase activities in digestive juice of Achatina balteata]. / Caractérisation de quelques activités hydrolasiques du suc digestif d'Achatina balteata

The digestive juice of Achatina balteata, a giant snail of the West African Coast catalyses the hydrolysis of several natural and synthetic compounds. Enzymatic activities on lactose, o- and p-nitrophenyl-beta-D-galactoside, p-nitrophenyl-beta-D-glucoside, p-nitrophenyl-beta-D (and alpha-L-) fucoside, o-nitrophenyl-beta-D-xyloside, p-nitrophenyl-N-acetyl-beta-D-glucosaminide and phenolphthalein-glucuronide have been shown to be present. The effect of pH and substrate concentration on these activities were studied. The galactosidase, glucosidase and fucosidase activities were studied with respect to temperature, heat inactivation, pH stability and incubation with trypsin. Kinetic experiments suggest the presence of several galactosidase activities. This hypothesis is confirmed by specific staining after polyacrylamide gel electrophoresis. These activities showed a broad specificity towards galactosides and glucosides. The digestive juice showed no action on acetyl-L-tyrosine and benzoyl-L-arginine ethyl esters. However a small protease activity was observed on hemoglobine. No lipase activity was found. Sulfatase content was low compared to that of Helix pomatia.

Angiotensin II atherogenicity in apolipoprotein E deficient mice is associated with increased cellular cholesterol biosynthesis.

Angiotensin II (Ang II) was shown to be an important risk factor for accelerated atherosclerosis. Inhibition of Ang II action on the arterial wall by blocking its production with angiotensin converting enzyme (ACE) inhibitors, or by blocking binding to its receptors on cells with antagonists was shown to attenuate atherogenesis in animal model of atherosclerosis. We questioned whether Ang II atherogenicity is related to a stimulatory effect of Ang II on macrophage cholesterol biosynthesis. Angiotensin II injected intraperitoneally once a day (0.1 ml of 10(-7) M per mouse) for a period of 30 days, to the apolipoprotein E deficient mice increased the atherosclerotic lesion area by 95% (P < 0.01 vs. control), compared to placebo-injected mice, with no significant effect on blood pressure or on plasma cholesterol levels. On using mouse peritoneal macrophages (MPMs) that were harvested after intraperitoneally injection of Ang II, an increased rate of cellular cholesterol biosynthesis (measured as incorporation of [3H]acetate into cholesterol) by up to 90% (P < 0.01 vs. control) was observed. In mice treated with the ACE inhibitor, Fosinopril (25 mg/kg per day) a reduction in their MPM's cholesterol synthesis by up to 70% (P < 0.01 vs. control) was obtained. In vitro studies in human monocyte-derived macrophages (HMDM), in MPMs from control BALB/c mice, and in J-774 A.1 macrophage-like cell line demonstrated up to 44, 34 and 30% stimulation of macrophage cholesterol biosynthesis, respectively, following cell incubation with 10(-7) M Ang II for 18 h at 37 degrees C. The stimulatory effect of Ang II on macrophage cholesterol biosynthesis could be related to its interaction with the macrophage AT1 receptor, as Losartan (10(-5) M), an AT1 blocker, but not PD 123319 (10(-5) M), an AT2 blocker, prevented the stimulatory effect on macrophage cholesterol synthesis. Furthermore, in cells that lack the AT1 receptor (RAW macrophages), Ang II did not increase cellular cholesterol synthesis. Ang II increased macrophage 3-hydroxy-3-methyl glutaryl CoA (HMG CoA) reductase mRNA levels in a dose dependent manner in J-774 A.1 macrophages and in MPM. Losartan, the AT1 receptor antagonist clearly attenuated this mRNA induction. We thus conclude that Ang II stimulation of macrophage cholesterol biosynthesis is related to its interaction with the AT1 receptor, followed by stimulation of macrophage HMG CoA reductase gene expression, which leads to increased cellular cholesterol biosynthesis, and can possibly result in macrophage cholesterol accumulation and foam cell formation.

Ectodermal dysplasia, ectrodactyly and macular dystrophy (EEM syndrome) in siblings.

We report a brother and sister with ectodermal dysplasia, ectrodactyly, and macular dystrophy (the EEM syndrome). Both children had abnormalities of the hands and the hair, and bilateral macular degeneration. The clinical picture in both is similar to, but less severe than, that described in the previously reported cases of this rare syndrome. Even though the parents are not related, they are both of Jewish Yemenite origin, and the possibility of a common ancestor cannot be ruled out. This would suggest autosomal recessive inheritance. The clinical picture in these patients suggests either variable expression or genetic heterogeneity in the EEM syndrome and further delineates the clinical and genetic spectrum of this condition.

Effect of transdermal scopolamine on salivation.

The effect of transdermal scopolamine on salivary flow and composition was analyzed in 21 healthy volunteers. The flow rate of whole saliva was significantly lowered by transdermal scopolamine. Significant positive correlations were found between the placebo rate of flow and both the quantity and percentage decreases in response to transdermal scopolamine. The magnesium concentration was significantly increased during transdermal scopolamine administration, whereas the sodium, potassium, and calcium concentrations were not consistently altered. Accordingly, the magnesium secretion rate was unaltered, whereas sodium, potassium, and calcium secretion rates were significantly lowered by transdermal scopolamine administration.

Effect of hypoxemia and ethacrynic acid on ABR and distortion product emission thresholds.

Various studies have shown that induction of hypoxemia in animals such that arterial blood oxygen tensions reach 20-30 mm Hg is accompanied by reversible threshold elevations of the auditory nerve-brain-stem evoked response (ABR). In this state, the endocochlear potential (EP) is depressed, causing a smaller potential difference across the hair cells and/or reduced activity of the cochlear amplifier of the outer hair cells. In order to test these possibilities, ABR threshold (an expression of the overall sensitivity of the cochlea) and changes in threshold of the cubic (2f1-f2) distortion product emissions (DPE) (an expression of activity of the cochlear amplifier) were measured in the same cats while the EP was depressed by hypoxemia or by ethacrynic acid. During the episodes of hypoxemia, DPE thresholds were elevated by 10 dB while ABR thresholds were elevated by 22.8 dB. Therefore, it seems that a normal EP is necessary both for normal cochlear transduction (inner hair cells) and for normal cochlear amplification (outer hair cells). The human fetus in utero is relatively hypoxic and there is evidence that its auditory threshold is also similarly elevated. Therefore the threshold elevation in the fetus in utero, estimated to be about 20 dB, is a consequence of both reduced transduction current through the inner hair cells (about 10 dB) and an additional 10 dB reduction in the activity of the cochlear amplifier of the outer hair cells.

Auditory event related potentials in chronic tinnitus patients with noise induced hearing loss.

In order to explore a possible deficit in auditory central neural activity in tinnitus with noise induced hearing loss (NIHL), auditory event related potentials (ERP) and reaction time (RT) were recorded (measures of central processing) from tinnitus patients (N = 12) and hearing and age matched controls (N = 12). Testing procedure included oddball paradigms and 1 KHz repetitive stimulus, as well as click-induced brainstem auditory evoked potentials (BAEP). ERP amplitudes (waves N1, P2 and P3) in tinnitus patients were significantly lower than in controls in all testing paradigms. No differences were found in ERP peak latencies, BAEP, RT, or response scoring. The lower ERP amplitudes may indicate attenuated or 'abnormal' auditory central processing in NIHL tinnitus patients. It is suggested that this dysfunction reflects an adaptive brain process response to the tinnitus and points to auditory central involvement in tinnitus sensation.

Noise and hypoxia induced temporary threshold shifts in rats studied by ABR.

Rats were exposed for 2 h either to 115 dB SPL noise, to 5% oxygen in nitrogen (hypoxia) or to both hypoxia and noise. Auditory nerve-brainstem evoked responses (ABR) to 80 dB HL clicks and threshold were recorded prior to exposure, immediately (5-10 min) after the exposure, 2 h after and 2 weeks after the exposure. The findings in each experimental animal were compared to those in the control (non-exposed) group and to those in the other groups. Thresholds were elevated in each of the experimental groups, but these were temporary threshold shifts, since 2 weeks following the exposure, threshold had returned to normal. Latencies (wave I and the IV-I interpeak latency difference- (IPLD] were prolonged in the groups exposed to hypoxia (hypoxia alone and hypoxia + noise). These results are discussed in view of possible mechanisms of these noise and hypoxia induced temporary threshold shifts.

Monitoring of the sciatic nerve during hamstring lengthening by evoked EMG.

Traction injury to the sciatic nerve can occur during hamstring lengthening. The aim of this study was to monitor the influence of hamstring lengthening on conduction in the sciatic nerve using evoked electromyography (EMG). Ten children with spastic cerebral palsy underwent bilateral distal hamstring lengthening. Before lengthening, the evoked potential was recorded with the patient prone. During lengthening, it was recorded with the knee flexed to 90 degrees, 60 degrees and 30 degrees, and at the end of lengthening with the hip and knee extended. In all patients, the amplitude of the evoked EMG gradually decreased with increasing lengthening. The mean decrease with the knee flexed to 60 degrees was 34% (10 to 77), and to 30 degrees, 86% (52 to 98) compared with the pre-lengthening amplitude. On hip extension at the end of the lengthening procedure, the EMG returned to the pre-lengthening level. Monitoring of the evoked EMG potential of the sciatic nerve during and after hamstring lengthening, may be helpful in preventing traction injury.

Anxiety reaction in children during removal of their plaster cast with a saw.

We have had experience of an 18-month-old boy with a cardiomyopathy who died a few minutes after removal of his cast with a saw, apparently from a malignant cardiac arrhythmia triggered by anxiety. We therefore examined the anxiety reaction to this method of removal of a plaster cast in 20 healthy children; ten were provided with hearing protectors and ten were not. The level of anxiety was assessed by measuring the heart rate, a known physiological indicator of anxiety, before, during and five minutes after removal of the cast. The noise level was also measured. The results showed a mean increase in heart rate during the procedure of 27.9 beats per minute (bpm) (26.9%) in the children with no hearing protectors and 10.4 bpm (11.1%) in children who used hearing protectors (p < 0.001). Five minutes after the procedure the heart rate had returned to the baseline rate in all patients. We recommend that hearing protectors should be used in children undergoing removal of a plaster cast to decrease the anxiety reaction. If possible, clinicians should avoid the use of a saw for this purpose in children with a cardiomyopathy.

Auditory event related potentials during lexical categorization in the oddball paradigm.

Event related potentials (ERPs) and reaction times (RTs) were recorded from 18 subjects, performing lexical categorization of words and nonwords. Three sets of monosyllable utterances, differentiated in semantic and rhyming attributes, were presented using the "oddball paradigm." ERPs included a sustained negativity which began approximately 100 msec after stimulus onset and peaked at approximately 400 mses (SN4) poststimulus, in response to target as well as to nontarget word stimuli. Semantic effects on SN4 latency were observed only for target utterances. Nonmeaningful word targets were associated with longer SN4 peak latencies as well as slower RTs compared to meaningful word targets. It is suggested that these longer latencies are due to a longer time required for an exhaustive search in permanent memory before categorizing a stimulus as a nonmeaningful word.