bluuebunny/crossref_metadata_2025 huggingface dataset:
Principles of Cerebral Ultrasound Contrast Imaging
Authors: Powers Jeff , Averkiou Michalakis , Bruce Matthew
Published: April 2009

Ultrasound contrast is gaining acceptance worldwide as an adjunct to conventional ultrasound imaging. It has clinical applications as diverse as liver disease detection and characterization, myocardial perfusion and wall motion studies, and cerebral vascularity and perfusion imaging. This paper will focus on imaging techniques used for transcranial ultrasound contrast imaging. The interaction of ultrasound with the microbubbles in the contrast agent is complex and nonlinear. This has led to the development of a variety of imaging modes to improve contrast detection over noncontrast optimized modes. This article presents several of these imaging methods in such a way as to help clinical and research users of ultrasound contrast understand this rapidly developing field.
Diagnosis of Intracerebral Hemorrhage with Transcranial Ultrasound
Authors: Meyer-Wiethe Karsten , Sallustio Fabrizio , Kern Rolf
Published: April 2009

In acute stroke, different sonographic methods can be used to assess structural and hemodynamic compromise. Structural abnormalities of brain parenchyma such as primary intracerebral hemorrhage (ICH) and epiphenomena such as midline shift can be detected by native transcranial B-mode ultrasound. Moreover, transcranial Doppler provides a functional approach to intracranial hemodynamics and may assist in predicting ICH growth and global intracranial pressure increase. New ultrasound technologies allow the visualization of ultrasound contrast agents in the cerebral microcirculation. According to recent data, ultrasound perfusion imaging provides additional information for the diagnosis of ICH and may differentiate ischemic from hemorrhagic stroke. This review summarizes the impact of these different transcranial ultrasound methods on diagnosis and monitoring of ICH.
Drugs, Biogenic Amine Targets and the Developing Brain
Authors: Frederick Aliya L. , Stanwood Gregg D.
Published: April 2009

Defects in the development of the brain have a profound impact on mature brain functions and underlying psychopathology. Classical neurotransmitters and neuromodulators, such as dopamine, serotonin, norepinephrine, acetylcholine, glutamate and GABA, have pleiotropic effects during brain development. In other words, these molecules produce multiple diverse effects to serve as regulators of distinct cellular functions at different times in neurodevelopment. These systems are impacted upon by abuse of a variety of illicit drugs, neurotherapeutics and environmental contaminants. In this review, we describe the impact of drugs and chemicals on brain formation and function in animal models and in human populations, highlighting sensitive periods and effects that may not emerge until later in life.
Third Pathophysiology of Prenatal Cocaine Exposure
Authors: Lester Barry M. , Padbury James F.
Published: April 2009

The pathophysiology of the effects of cocaine on fetal development has been described along 2 major pathways: neurochemical effects and vasoconstrictive effects. Following a summary of these effects, we suggest a ‘third pathophysiology’ in which altered fetal programming affects the acute and long-term adverse effects of in utero cocaine exposure. We describe how cocaine as a stressor alters the expression of key candidate genes, increasing exposure to catecholamines and fetal cortisol-altering neuroendocrine (hypothalamic-pituitary-adrenal axis) activity, leading to infant behavioral dysregulation, poor behavioral control and emotion regulation during childhood and phenotypes that confer vulnerability to substance use in adolescence. This model is discussed in relation to follow-up studies of the effects of in utero cocaine exposure and maturational changes in brain development.
Towards Conceptualizing a Neural Systems-Based Anatomy of Attention-Deficit/Hyperactivity Disorder
Authors: Makris Nikos , Biederman Joseph , Monuteaux Michael C. , Seidman Larry J.
Published: April 2009

Convergent data from neuroimaging, neuropsychological, genetic and neurochemical studies in attention-deficit/hyperactivity disorder (ADHD) have implicated dysfunction of the dorsolateral prefrontal cortex (DLPFC) and dorsal anterior cingulate cortex (dACC), which form the cortical arm of the frontostriatal network supporting executive functions. Furthermore, besides the DLPFC and dACC, structural and functional imaging studies have shown abnormalities in key brain regions within distributed cortical networks supporting attention. The conceptualization of neural systems biology in ADHD aims at the understanding of what organizing principles have been altered during development within the brain of a person with ADHD.Characterizing these neural systems using neuroimaging could be critical for the description of structural endophenotypes, and may provide the capability of in vivo categorization and correlation with behavior and genes.
Nicotine Exposure in Adolescence Alters the Response of Serotonin Systems to Nicotine Administered Subsequently in Adulthood
Authors: Slotkin Theodore A. , Seidler Frederic J.
Published: April 2009

Developmental nicotine exposure produces lasting changes in serotonin (5-HT) function. We gave nicotine to adolescent rats (postnatal days, PD, 30–47), simulating plasma levels in smokers, and then examined the subsequent effects of nicotine given again in young adulthood (PD 90–107), focusing on 5-HT1A and 5-HT2 receptors and the 5-HT transporter during nicotine treatment (PD 105) and withdrawal (PD 110, 120, 130), and long-term changes (PD 180). Adolescent nicotine exposure by itself evoked long-term elevations in cerebrocortical binding parameters in males that emerged in young adulthood. Nicotine given in adulthood produced transient elevations in 5-HT receptor expression in both males and females during withdrawal, and persistent upregulation in the male cerebral cortex. In contrast, females showed decrements in cerebrocortical 5-HT receptors by PD 180. Adolescent nicotine exposure altered the responses to nicotine given in adulthood, sensitizing the initial effects and changing both the withdrawal response and long-term actions. Our results thus provide mechanistic evidence that nicotine exposure, during the period in which nearly all smokers begin to use tobacco, reprograms the future response of 5-HT systems to nicotine.
Prenatal Cocaine Increases Dendritic Spine Density in Cortical and Subcortical Brain Regions of the Rat
Authors: Frankfurt Maya , Wang Hoau-Yan , Marmolejo Naydu , Bakshi Kalindi , Friedman Eitan
Published: April 2009

Alterations in dendritic spine density following prenatal cocaine exposure were examined in the present study. Timed pregnant rats were injected daily with 30 mg/kg cocaine or saline during gestation. At postnatal day 21, male and female animals were separated and spine density was assessed following Golgi impregnation. In prenatal cocaine-exposed rats, significant increases in dendritic spine density were observed on pyramidal cells in the CA1 region of the hippocampus, basal dendrites of layer II/III of the medial prefrontal cortex, medium spiny neurons of the striatum and the core of the nucleus accumbens, as well as in neurons of the ventromedial hypothalamic nucleus. No differences were observed in either apical or basal dendrites of pyramidal cells in layer III of the sensory cortex or layer V of the medial prefrontal cortex, or in apical dendrites of layer II/III pyramidal cells of the medial prefrontal cortex. Moreover, there were no sex differences in any region examined. These results demonstrate that prenatal cocaine exposure increases spine density in many brain regions at postnatal day 21, and this effect is independent of sex.
Augmentation of Cocaine-Sensitized Dopamine Release in the Nucleus Accumbens of Adult Mice following Prenatal Cocaine Exposure
Authors: Malanga C.J. , Ren Jia-Qian , Guerriero Réjean M. , Kosofsky Barry E.
Published: April 2009

Behavioral changes in adult mice after prenatal exposure to cocaine have been identified. Mice exposed to cocaine in utero (40 or 20 mg/kg/day) and controls were given a sensitizing cocaine regimen (15 mg/kg every other day × 7 doses), withdrawn for 21 days, and challenged with 15 mg/kg cocaine. In vivo microdialysis for dopamine (DA), serotonin, and their metabolites in awake behaving mice on the first, seventh and challenge doses showed increased cocaine-stimulated DA release in the nucleus accumbens, which was significantly enhanced after prenatal cocaine exposure. This effect was not due to fetal malnutrition or changes in the total tissue DA content. Early developmental cocaine exposure may alter adaptation of brain reward systems to chronic psychostimulant exposure in adulthood.
Dissociation between Serotonin Neurotoxicity and Brain-Derived Neurotrophic Factor Induction following Neonatal MDMA Exposure in Rats
Authors: Piper Brian J. , Farelli Jeremiah D. , Meyer Jerrold S.
Published: April 2009

Early developmental treatment of rats with 3,4-methylenedioxymethamphetamine (MDMA) was previously found to cause an abnormal pattern of forebrain serotonergic axon density in adulthood consisting of a cortical hypoinnervation and a striatal hyperinnervation. The present study tested the hypothesis that this reorganization was due to regional differences in brain-derived neurotrophic factor (BDNF) expression. Rats received MDMA (10 mg/kg, s.c., b.i.d.) on postnatal days (PD) 1–4, after which brain tissues were collected on PD 11, 30, and 67 for analysis. BDNF protein levels were found to be elevated in the occipital cortex but not in the hippocampus or striatum following MDMA administration. Serotonin transporter binding (an index of serotonergic fiber integrity) was significantly reduced in the hippocampus at PD 11 but returned to normal by PD 30, whereas the cortex exhibited a delayed reduction that was not manifested until PD 30. These results do not support the view that a region-specific enhancement in BDNF expression mediates the abnormal serotonergic reinnervation observed following neonatal MDMA exposure.
(+/–)3,4-Methylenedioxymethamphetamine (MDMA) Dose-Dependently Impairs Spatial Learning in the Morris Water Maze after Exposure of Rats to Different Five-Day Intervals from Birth to Postnatal Day Twenty
Authors: Vorhees Charles V. , Schaefer Tori L. , Skelton Matthew R. , Grace Curtis E. , Herring Nicole R. , Williams Michael T.
Published: April 2009

During postnatal days (PD) 11–20, (+/–)3,4-methylenedioxymethamphetamine (MDMA) treatment impairs egocentric and allocentric learning, and reduces spontaneous locomotor activity; however, it does not have these effects during PD 1–10. How the learning impairments relate to the stress hyporesponsive period (SHRP) is unknown. To test this association, the preweaning period was subdivided into 5-day periods from PD 1–20. Separate pups within each litter were injected subcutaneously with 0, 10, 15, 20, or 25 mg/kg MDMA ×4/day on PD 1–5, 6–10, 11–15, or 16–20, and tested as adults. The 3 highest MDMA dose groups showed reduced locomotor activity during the first 10 min (of 60 min), especially in the PD 1–5 and 6–10 dosing regimens. MDMA groups in all dosing regimens showed impaired allocentric learning in the Morris water maze (on acquisition and reversal, all MDMA groups were affected; on the small platform phase, the 2 high-dose groups were affected). No effects of MDMA were found on anxiety (elevated zero maze), novel object recognition, or egocentric learning (although a nonsignificant trend was observed). The Morris maze results did not support the idea that the SHRP is critical to the effects of MDMA on allocentric learning. However, since no effects on egocentric learning were found, but were apparent after PD 11–20 treatment, the results show that these 2 forms of learning have different exposure-duration sensitivities.
Rhythm in Speech and Language
Authors: Kohler Klaus J.
Published: April 2009

Like any other aspect of spoken language, rhythm needs to be, and has been, studied from four different perspectives for a comprehensive and insightful account of its nature and functioning in speech communication: symbolic representation, production, perception, communicative function. The paper first gives an overview of the milestones in the analysis of rhythm under the headings of these four approaches over the past 70 years. This survey of the development of scientific ideas in rhythm research prepares the ground for the integration of the four strands in an interrelated framework of linguistic and speech signal analysis. On the basis of a definition of rhythm derived from the theoretical and methodological discussion, a new paradigm is outlined for future research, centred on the listener and on communicative function.
Rhythm, Timing and the Timing of Rhythm
Authors: Arvaniti Amalia
Published: April 2009

This article reviews the evidence for rhythmic categorization that has emerged on the basis of rhythm metrics, and argues that the metrics are unreliable predictors of rhythm which provide no more than a crude measure of timing. It is further argued that timing is distinct from rhythm and that equating them has led to circularity and a psychologically questionable conceptualization of rhythm in speech. It is thus proposed that research on rhythm be based on the same principles for all languages, something that does not apply to the widely accepted division of languages into stress- and syllable-timed. The hypothesis is advanced that these universal principles are grouping and prominence and evidence to support it is provided.
The Pairwise Variability Index and Coexisting Rhythms in Language
Authors: Nolan Francis , Asu Eva Liina
Published: April 2009

The Pairwise Variability Index (PVI) has been widely used as a metric for quan-tifying rhythm in languages, often with a view to placing them on a continuum between notional categories of stress-timing and syllable-timing. We review the history of and rationale for the PVI, and point out three potential anomalies in the way the PVI has been applied. Following up one of these we apply the PVI to the level of the foot, and argue that stress-timing and syllable-timing are not points at either end of a continuum but orthogonal dimensions, so that a language can be (for instance) both syllable-timed and stress-timed. Results from Estonian, English, Mexican Spanish, and Castilian Spanish are presented which give some support for this view.
F₀-Based Rhythm Effects on the Perception of Local Syllable Prominence
Authors: Niebuhr Oliver
Published: April 2009

A perception experiment shows for German that different global, F₀-based speech rhythms in the context section of stimuli influence the local prominence position in the target section. This effect may be conceptualized as a perceptual adjustment of the syllables in the target section to the ones of the global rhythmic context with regard to both the prominence and the F₀ patterns. Two conclusions were drawn on this basis. First, listeners use speech rhythm to predict the perceptual properties of syllables, which is in line with the guide function that speech rhythm is assumed to have in German and other Western Germanic languages. Secondly, speech rhythm is a perceptual phenomenon, generated by a cyclic construction process that involves repetitive patterns in multiple dimensions. Thus, although speech rhythm is initiated by changes in acoustic parameters, it cannot be soaked up by acoustic measurements, especially, if these measurements refer to duration alone.
On the Possible Role of Brain Rhythms in Speech Perception: Intelligibility of Time-Compressed Speech with Periodic and Aperiodic Insertions of Silence
Authors: Ghitza Oded , Greenberg Steven
Published: April 2009

This study was motivated by the prospective role played by brain rhythms in speech perception. The intelligibility – in terms of word error rate – of natural-sounding, synthetically generated sentences was measured using a paradigm that alters speech-energy rhythm over a range of frequencies. The material com-prised 96 semantically unpredictable sentences, each approximately 2 s long (6–8 words per sentence), generated by a high-quality text-to-speech (TTS) synthesis engine. The TTS waveform was time-compressed by a factor of 3, creating a signal with a syllable rhythm three times faster than the original, and whose intel-ligibility is poor (<50% words correct). A waveform with an artificial rhythm was produced by automatically segmenting the time-compressed waveform into consecutive 40-ms fragments, each followed by a silent interval. The parameters varied were the length of the silent interval (0–160 ms) and whether the lengths of silence were equal (‘periodic’) or not (‘aperiodic’). The performance curve (word error rate as a function of mean duration of silence) was U-shaped. The lowest word error rate (i.e., highest intelligibility) occurred when the silence was 80 ms long and inserted periodically. This is also the condition for which word error rate increased when the silence was inserted aperiodically. These data are consistent with a model (TEMPO) in which low-frequency brain rhythms affect the ability to decode the speech signal. In TEMPO, optimum intelligibility is achieved when the syllable rhythm is within the range of the high theta-frequency brain rhythms (6–12 Hz), comparable to the rate at which segments and syllables are articulated in conversational speech.
Botulinum Neurotoxin: The Ugly Duckling
Authors: Koussoulakos Stauros
Published: April 2009

This review presents a brief account of the most significant biological effects and clinical applications of botulinum neurotoxins, in a way comprehensive even for casual readers who are not familiar with the subject. The most toxic known substances in botulinum neurotoxins are polypeptides naturally synthesized by bacteria of the genus Clostridium. These polypeptides inhibit acetylcholine release at neuromuscular junctions, thus causing muscle paralysis involving both somatic and autonomic innervation. There is substantial evidence that this muscle-paralyzing feature of botulinum neurotoxins is useful for their beneficial influence on more than 50 pathological conditions such as spastic paralysis, cerebral palsy, focal dystonia, essential tremor, headache, incontinence and a variety of cosmetic interventions. Injection of adequate quantities of botulinum toxins in spastic muscles is considered as a highly hopeful procedure for the treatment of people who suffer from dystonia, cerebral palsy or have experienced a stroke. So far, numerous and reliable studies have established the safety and efficacy of botulinum neurotoxins and advocate wider clinical therapeutic and cosmetic applications.
Psychiatric Comorbidity in Patients Evaluated for Chronic Epilepsy: A Differential Role of the Right Hemisphere?
Authors: Sperli F. , Rentsch D. , Despland P.A. , Foletti G. , Jallon P. , Picard F. , Landis T. , Seeck M.
Published: April 2009

Introduction: Psychiatric disorders are known to occur frequently in chronic epilepsy. The aim of this study is to investigate the prevalence of psychiatric comorbidity and its relationship to regional cerebral dysfunction in patients admitted to a tertiary epilepsy center for epilepsy surgery. Methods: 217 patients were investigated. A presurgical workup was performed and allowed precise localization of the epileptogenic focus in 156 patients. Sixty-one patients had multifocal or generalized discharges. After 1–3 psychiatric interviews, a psychiatric diagnosis was made (DSM-IV classification). Results: Psychiatric comorbidity was found in 85 patients (39%), more often in those with right or bilateral hemispheric dysfunction (74%, p = 0.04) with no difference between temporal or extratemporal foci location frequency. Additionally, patients with psychiatric disorders were less likely to undergo epilepsy surgery compared to ‘epilepsy-only’ patients (p = 0.003), despite similar good outcome in patients with and without psychiatric comorbidity. Conclusions: Right-sided or bilateral foci seem to represent a risk factor for psychiatric comorbidity in epilepsy, although we did not find any particular association between a psychiatric syndrome and focus localization. Recognition and treatment of psychiatric comorbidity is of major importance since its presence may interfere with patient’s decision making for epilepsy surgery treatment.
In vivo Morphometry of Corneal Endothelial Cells in Pseudoexfoliation Keratopathy with Glaucoma and Cataract
Authors: Wali Upender K. , Bialasiewicz Alexander A. , Rizvi Syed G. , Al-Belushi Habiba
Published: April 2009

Background: This study was designed to define correlations between in vivo morphometric and demographic data of pseudoexfoliation (PEX) keratopathy patients from Omani Arab origin with cataract and glaucoma. Methods: In a non-randomized controlled comparative case series, 69 adult patients (43 males and 26 females) with 78 cataract and 48 glaucoma eyes with corneal PEX material were assessed by confocal biomicroscopy (Confoscan 2, Nidek) and values compared to normative US and Omani Arab population values. Descriptive statistics. Results: The mean age of glaucoma patients was 60.81 ± 8.33 years, of cataract patients 64.65 ± 6.67 years; 109/126 eyes (74%) were from patients >60 years old (14 glaucoma and 95 cataract eyes). Age-adjusted endothelial cell counts were similar to normative values in 108/126 eyes (85.7%). Polymegathism and pleomorphism were abnormal in 124/126 (98.4%) and 122/126 eyes (96.8%), respectively. The correlation of pleomorphism and polymegathism with males (R2 = 0.6378, p = 0.05) was stronger than with females (R2 = 0.6024, p = 0.06), and stronger for patients <60 years (R2 = 0.7268, p = 0.01) than >60 years old (R2 = 0.5805, p = 0.01). Cataracts: Endothelial cell counts were normal (mean 2,483 ± 511.2). Pleomorphism was 33.12 ± 11.44% and different from Omani Arab controls (p < 0.01), polymegathism 58.14 ± 16.58% (p <0.01). Glaucomas: Endothelial cell counts were normal (mean: 2,438 ± 503). Pleomorphism and polymegathism were 37.09 ± 12.43% (p < 0.01) and 59.69 ± 16.79% (p < 0.01), respectively. Pleomorphism and polymegathism were more associated with glaucomas (R2 = 0.7652, p = 0.02) than with cataracts (R2 = 0.6041, p = 0.06). Conclusions: Endothelial cell polymegathism and pleomorphism in PEX keratopathy with glaucoma is more frequently associated with age <60 years and male gender than with cataract.
Impact of Vitamin D Dose on Biochemical Parameters in Patients with Secondary Hyperparathyroidism Receiving Cinacalcet
Authors: Wilkie Martin , Pontoriero Giuseppe , Macário Fernando , Yaqoob Magdi , Bouman Koen , Braun Johann , von Albertini Beat , Brink Hans , Maduell Francisco , Graf Helmut , Frazão João M. , Bos Willem Jan , Torregrosa Vicente , Saha Heikki , Reichel Helmut , Zani Valter J. , Carter Dave , Messa Piergiorgio
Published: April 2009

Background/Aims: The calcimimetic cinacalcet (Mimpara®/Sensipar®) simultaneously lowers parathyroid hormone (PTH), phosphorus (P) and calcium (Ca) levels in patients with secondary hyperparathyroidism. The OPTIMA study demonstrated that cinacalcet and adjusted doses of vitamin D maximized control of these parameters. This post-hoc analysis of OPTIMA data assessed the impact of reducing or increasing the dose of concomitant vitamin D on PTH, P and Ca in patients receiving cinacalcet. Methods: Dialysis patients with mean baseline intact PTH (iPTH) 300–800 pg/ml (31.8–84.8 pM) received doses of cinacalcet titrated to achieve an iPTH of 150–300 pg/ml (15.9–31.8 pM). The dose of vitamin D could then be decreased to further reduce serum P or Ca, or increased/initiated to further decrease PTH levels if iPTH >300 pg/ml or to increase Ca if Ca <8.0 mg/dl (2.0 mM). Results: Vitamin D dose was assessed for 345 patients during a 23-week period. A total of 91 and 129 patients had an increase or decrease in vitamin D dose, respectively. By study end, mean iPTH, P, and Ca were similar in both vitamin D groups, although there were differences in biochemical parameters between groups at the start of the study. There were statistically significant reductions from baseline to study end in iPTH and Ca in both groups (p < 0.001). Although P was significantly reduced by week 23 in the group in which vitamin D dose was decreased (p = 0.007), the reduction in P was less and did not achieve significance in the group in which vitamin D dose was increased (p = 0.71). Conclusions: After initiating cinacalcet, the dose of vitamin D can be adjusted to maximize reductions in PTH, P and Ca; however, vitamin D-induced decreases in PTH need to be balanced with the diminished response in P and Ca.
Predictive Role of Audiological and Clinical Features for Functional Results after Stapedotomy
Authors: Marchese M.R. , Conti G. , Cianfrone F. , Scorpecci A. , Fetoni A.R. , Paludetti G.
Published: April 2009

Objective: To analyze and compare the preoperative factors that potentially influence the outcome of stapedotomy in our study group. Materials and Methods: 161 cases were enrolled. Clinical variables considered to influence functional results – air conduction (AC) and bone conduction (BC) pure-tone average (PTA), air-bone gaps (ABG), sensorineural hearing loss (SNHL), ABG gain and ΔSNHL – were gender, age, case type (unilateral vs. bilateral), ear side (right vs. left), pregnancy, vascular disease and family history of otosclerosis. The audiometric variables were preoperative AC- and BC-PTA, SNHL and ABG. Results: Univariate logistic regression analysis showed that the probability of obtaining a ≥10 dB gain is significantly affected by the following factors: age <50 years, AC-PTA ≥50 dB and preoperative ABG ≥30 dB. All the other factors included into the registration (gender, familiarity, side, bilateral vs. unilateral, pregnancy, vascular diseases and preoperative BC-PTA) were not found to significantly affect postoperative gain (p > 0.05). Nevertheless, multivariate logistic regression analysis maintained a statistically significant correlation only between gain ≥10 dB and both preoperative ABG ≥30 dB and age <50 years. Conclusions: The accurate knowledge of predictive factors is a valuable tool that permits the surgeon to plan surgery with a better case selection as well as assisting in counseling the patient with regard to the likelihood of success of the procedure.
Are Results of Tinnitus Retraining Therapy Maintained over Time?
Authors: Forti S. , Costanzo S. , Crocetti A. , Pignataro L. , Del Bo L. , Ambrosetti U.
Published: April 2009

Tinnitus retraining therapy (TRT) is a useful treatment for tinnitus. The aim of this study was to evaluate the resultsobtained after 18 months of TRT as well as 18 months after completion of therapy, i.e. 36 months after initiation of TRT. Forty-five subjects suffering from an idiopathic tinnitus with or without hyperacusis for at least 6 months were recruited. There were significant improvements during therapy (p < 0.001) and the mean Tinnitus Handicap Inventory (THI) was lowered by more than 20 points. These improvements persisted 18 months after treatment completion. Furthermore, the percentage of patients reporting the disappearance of their difficulties in various activities (relaxation, concentration, sleep, social relations and work) increased continuously after treatment completion. TRT improved self-perceived disability induced by chronic tinnitus for a long time after the end of therapy.
Multiple Viral Genome Search in Endolabyrinthic Fluids of Profoundly Deaf Patients: Possible Cytomegalovirus Intracochlear Reactivation
Authors: Di Nardo W. , Cattani P. , Lopizzo T. , Cantore I. , Marchese M.R. , Marchetti S. , Scorpecci A. , Giannantonio S. , Parrilla C. , Cianfrone F. , Fadda G. , Paludetti G.
Published: April 2009

Background:The cause of about 30% of bilateral sensorineural hearing loss (SNHL) is still unknown. A viral etiology is among the most frequently proposed ones and the supposed diagnosis is only based upon few clinical and laboratory data. The detection of viral presence within a damaged compartment may represent a way to supply interesting data for confirmation of viral etiology and to explain pathogenic mechanisms. Objectives:The aim of our study was to identify the possible presence of pathogenic viruses in the inner ear extracellular compartment in patients with bilateral severe sensorineural deafness of unknown etiology who underwent cochlear implant surgery. Methods: 4 patients, aged from 2 to 7 years and affected by SNHL underwent cochlear implantation surgery and, at the same time, endolabyrinthine fluid sampling. The samples were subsequently sent for viral nucleic acid extraction and polymerase chain reaction (PCR) treatment: multiplex PCR and realtime-PCR were used. In each endolabyrinthine fluid sample, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella-zoster virus (VZV), herpes simplex virus type 1 and 2 (HSV-1, HSV-2) and enterovirus genomes were searched for. Results: One patient was positive for intracochlear CMV, as confirmed by another base-pair segment PCR. EBV, VZV, HSV and enterovirus were detected in none of the 4 patients. Conclusions: Our finding of CMV genome within the cochlea of a deaf patient without any evidence of acute and prenatal CMV infection suggests its possible role in postnatal inner ear injury through reactivation of latent virus within the cochlea. This hypothesis could also be considered valid for some patients with anti-CMV-IgG-positive serology and absence of endolabyrinthine viral genome since viruses can be in an inactive state at the time of fluid collection. PCR has proved to be a very useful tool in order to investigate infectious causes of deafness even for more than one virus type at a time and in a limited quantity of sample, such as the small volume of endolabyrinthine liquid collected from children during cochlear implant surgery.
Temporal Processing Disorder Associated with Styrene Exposure
Authors: Zamyslowska-Szmytke Ewa , Fuente Adrian , Niebudek-Bogusz Ewa , Sliwinska-Kowalska Mariola
Published: April 2009

Little evidence exists on the possible adverse effects of styrene on the central part of the auditory system. The present investigation aimed to study the possible association between styrene exposure and temporal processing abilities. Fifty-nine styrene-exposed subjects and 50 nonexposed control subjects were tested. Pure-tone audiometry (125–8000 Hz) and 3 temporal processing tests (gaps-in-noise, frequency pattern test and duration pattern test) were carried out. Significant differences between groups were found for most of the audiometric thresholds for both ears. ANCOVA analysis showed that styrene-exposed subjects had significantly poorer performances on the frequency and duration pattern tests than nonexposed subjects, when including hearing level and age as covariates. The results of the present research study suggest an association between styrene exposure and central auditory dysfunction characterized by a temporal processing disorder.
Vestibular Impairment in a Dutch DFNA15 Family with an L289F Mutation in POU4F3
Authors: van Drunen F.J. Wendy , Pauw Robert J. , Collin Rob W.J. , Kremer Hannie , Huygen Patrick L.M. , Cremers Cor W.R.J.
Published: April 2009

Vestibular examination (electronystagmography with rotatory chair and caloric tests) was performed on 18 carriers and 1 phenocopy carrier in a Dutch family with autosomal dominant nonsyndromic DFNA15. This is the second DFNA15 family worldwide to have a novel L289F mutation in POU4F3. Vestibular involvement appeared to be present in 2 affected individuals according to their medical history. Vestibular examination results in an extended subset of L289F POU4F3 mutation carriers varied from normal to areflexia. DFNA15 is the third cochleovestibular disorder, after DFNA9 and DFNA11, in the autosomal dominant nonsyndromic hearing impairment.
Comparison of Music Perception in Bilateral and Unilateral Cochlear Implant Users and Normal-Hearing Subjects
Authors: Veekmans K. , Ressel L. , Mueller J. , Vischer M. , Brockmeier S.J.
Published: April 2009

Music plays an important role in the daily life of cochlear implant (CI) users, but electrical hearing and speech processing pose challenges for enjoying music. Studies of unilateral CI (UCI) users’ music perception have found that these subjects have little difficulty recognizing tempo and rhythm but great difficulty with pitch, interval and melody. The present study is an initial step towards understanding music perception in bilateral CI (BCI) users. The Munich Music Questionnaire was used to investigate music listening habits and enjoyment in 23 BCI users compared to 2 control groups: 23 UCI users and 23 normal-hearing (NH) listeners. Bilateral users appeared to have a number of advantages over unilateral users, though their enjoyment of music did not reach the level of NH listeners.
Effects of Cooperating and Conflicting Cues on Speech Intonation Recognition by Cochlear Implant Users and Normal Hearing Listeners
Authors: Peng Shu-Chen , Lu Nelson , Chatterjee Monita
Published: April 2009

Cochlear implant (CI) recipients have only limited access to fundamental frequency (F0) information, and thus exhibit deficits in speech intonation recognition. For speech intonation, F0 serves as the primary cue, and other potential acoustic cues (e.g. intensity properties) may also contribute. This study examined the effects of cooperating or conflicting acoustic cues on speech intonation recognition by adult CI and normal hearing (NH) listeners with full-spectrum and spectrally degraded speech stimuli. Identification of speech intonation that signifies question and statement contrasts was measured in 13 CI recipients and 4 NH listeners, using resynthesized bi-syllabic words, where F0 and intensity properties were systematically manipulated. The stimulus set was comprised of tokens whose acoustic cues (i.e. F0 contour and intensity patterns) were either cooperating or conflicting. Subjects identified if each stimulus is a ‘statement’ or a ‘question’ in a single-interval, 2-alternative forced-choice (2AFC) paradigm. Logistic models were fitted to the data, and estimated coefficients were compared under cooperating and conflicting conditions, between the subject groups (CI vs. NH), and under full-spectrum and spectrally degraded conditions for NH listeners. The results indicated that CI listeners’ intonation recognition was enhanced by cooperating F0 contour and intensity cues, but was adversely affected by these cues being conflicting. On the other hand, with full-spectrum stimuli, NH listeners’ intonation recognition was not affected by cues being cooperating or conflicting. The effects of cues being cooperating or conflicting were comparable between the CI group and NH listeners with spectrally degraded stimuli. These findings suggest the importance of taking multiple acoustic sources for speech recognition into consideration in aural rehabilitation for CI recipients.
Quality of Life Improvement after Robotically Assisted Coronary Artery Bypass Grafting
Authors: Bonaros Nikolaos , Schachner Thomas , Wiedemann Dominik , Oehlinger Armin , Ruetzler Elisabeth , Feuchtner Gudrun , Kolbitsch Christian , Velik-Salchner Corinna , Friedrich Guy , Pachinger Othmar , Laufer Guenther , Bonatti Johannes
Published: April 2009

Objectives: Coronary artery bypass grafting (CABG) is associated with long rehabilitation periods and slow quality of life (QOL) improvement. Totally endoscopic coronary artery bypass grafting (TECAB) can be performed using robotic technology and remote access perfusion. The aim of this study was to evaluate whether TECAB leads to accelerated QOL improvement as compared to standard CABG. Methods: We included 120 patients who had received robotically assisted CABG, 56 of whom were operated on using standard sternotomy. These patients were compared to 55 patients who underwent the TECAB procedure and to 9 TECAB patients who required conversion to conventional sternotomy. QOL evaluation was performed before the operation and 1, 3 and 6 months after the procedure using the SF-36 health survey and a standardized questionnaire. Results: All quality of life aspects improved significantly in all study patients. At 3 months, TECAB patients showed significantly better QOL scores related to bodily pain and physical health. Hospital stay and time to restoration of daily activities were significantly shorter. Converted patients experienced similar courses to sternotomy patients in terms of QOL. Conclusions: TECAB using robotic technology leads to improved physical health, shorter hospital stay and a more rapid restoration of daily activities. Conversion from TECAB to sternotomy does not lead to QOL impairment as compared to primary sternotomy.
Double-Blind, Placebo-Controlled, Multiple-Ascending-Dose Study on the Pharmacodynamics of ABIO-08/01, a New CNS Drug with Potential Anxiolytic Activity
Authors: Saletu-Zyhlarz Gerda M. , Anderer Peter , Wolzt Michael , Semlitsch Heribert V. , Assandri Alessandro , Nessi Paola , Nannipieri Fabrizio , Rosini Sergio , Saletu Bernd
Published: April 2009

In a double-blind, placebo-controlled, multiple-ascending-dose study, the encephalotropic and psychotropic properties of ABIO-08/01, a new potentially anxiolytic and nootropic isoxazoline, were studied in 16 young healthy males. In a randomized nonbalanced phase 1 study, they received 3 oral drug doses (10, 20, 40 mg) and placebo for 7 days (washout period 8 days). EEG mapping and psychometry were carried out at hours 0, 1, 6 of day 1 (acute effect) and day 5 (subacute and superimposed effects). MANOVA/ Hotelling T2 test demonstrated significant central effects of ABIO-08/01 versus placebo after acute, subacute and superimposed administration of all doses in the resting, vigilance-controlled and eyes-open EEG. Univariate analysis revealed activating patterns in the resting EEG (40 mg > 20 mg > 10 mg), and sedative patterns in the eyes-open EEG (10 mg > 20 mg > 40 mg). In the vigilance-controlled EEG, 40 mg of ABIO-08/01 induced activating patterns, whereas 10 mg induced sedative patterns. Concerning psychometry, ABIO-08/01 improved concentration (40 mg > 20 mg > 10 mg; activating effect) and deteriorated well-being (10 mg > 20 mg > 40 mg; sedative effect). Ten milligrams also improved reaction time performance and psychomotor activity. ABIO-08/01 is well-tolerated and is of interest in anxiety disorders.
Double-Blind, Placebo-Controlled, Multiple-Ascending-Dose Study on the Pharmacodynamics of ABIO-08/01, a New CNS Drug with Potential Anxiolytic Activity
Authors: Saletu Bernd , Anderer Peter , Wolzt Michael , Nosiska Dorothea , Assandri Alessandro , Noseda Emanuele , Nannipieri Fabrizio , Saletu-Zyhlarz Gerda M.
Published: April 2009

Effects of ABIO-08/01, a new potentially anxiolytic isoxazoline, on regional electrical brain generators were investigated by 3-dimensional EEG tomography. In a double- blind, placebo-controlled, multiple-ascending-dose study, 16 healthy males (30.2 ± 5.7 years) received 3 oral drug doses (10, 20, 40 mg) and placebo for 7 days (8-day wash-out) in a randomized non-balanced design for phase-1 studies. A 3-min vigilance-controlled (V) EEG, a 4-min resting (R) EEG with eyes closed, a 1-min eyes-open (EO) EEG and psychometric tests were performed 0, 1 and 6 h after taking the drug on days 1 and 5. Low-resolution brain electromagnetic tomography (LORETA) was computed from the spectrally analyzed EEG data, and differences between drug and placebo were displayed as statistical parametric maps. Data were registered to the Talairach-Tournoux Human Brain Atlas available as a digitized MRI. An overall omnibus significance test followed by a voxel-by-voxel t test demonstrated significant regional EEG changes after ABIO-08/01 versus placebo, dependent on recording condition, dose and time. While in the EO-EEG specifically the lowest dose of ABIO-08/01 induced pronounced sedative effects (delta/theta and beta increase) 1 h after acute and slightly less so after superimposed administration, in the 6th hour a decrease in alpha and beta activity signaled less sedative and more relaxant action. In the V-EEG these changes were less pronounced, in the R-EEG partly opposite. Hemisphere-specific changes were observed, suggesting increases in LORETA power over the left temporal, parietal, superior frontal regions and decreases over the right prefrontal, temporal pole and occipital regions. These LORETA changes are discussed in the light of neuroimaging findings on anxiety and anxiolytics.
Perinatal Malnutrition Programs Sustained Alterations in Nitric Oxide Released by Activated Macrophages in Response to Fluoxetine in Adult Rats
Authors: Ferreira-e-Silva Wylla T. , Galvão Bruno A. , Ferraz-Pereira Kelli N. , de-Castro Célia B. , Manhães-de-Castro Raul
Published: April 2009

Objective: Nutritional restriction during lactation has long-term consequences on the functioning of neuroimmune systems. Receptors and transporter serotonin (5-HT) are present in macrophages and may influence their role. This study evaluated nitric oxide release by alveolar macrophages (AMs) in adult control rats and rats malnourished during lactation in response to different fluoxetine (FLX) concentrations and 5-HT1A and 5-HT1B agonists at different times. Methods: Male Wistar rats were distributed into two groups according to maternal diet during lactation: a control group of 12 rats whose dams had received a 23% protein diet and a malnourished group of 12 rats whose dams had received an 8% protein diet. After weaning, all rats received a 23% protein diet. On the 90th day after birth, nitric oxide (NO) release kinetics was measured in supernatants of AMs cultured with FLX. The NO release following the adjunction of serotoninergic agonists was also quantified. Results: The malnourished rats weighed less at weaning (control rats = 15.3 ± 0.4 g, malnourished rats = 11.8 ± 0.4 g); this difference persisted until 90 days of life (control rats = 355.4 ± 8.6 g; malnourished rats = 267.8 ± 7.9 g). In the presence of 10–6M FLX, NO release by AMs in control rats was lower. The addition of agonists did not interfere with NO release by AMs in control rats. NO release by AMs from malnourished rats was modified neither by FLX nor by agonists. As a consequence of malnutrition, there were lower numbers of cells and AMs in the bronchoalveolar lavage fluid, and cell viability and NO release by AMs were impaired. Conclusions: Nutritional manipulation in the perinatal period seems to interfere with the functional programming of macrophages; it also seems to affect their serotoninergic regulation through adulthood.
mCD14 Expression in Human Monocytes Is Downregulated by Ouabain via Transactivation of Epithelial Growth Factor Receptor and Activation of p38 Mitogen-Activated Protein Kinase
Authors: Valente R.C. , Nascimento C.R. , Araujo E.G. , Rumjanek V.M.
Published: April 2009

Background and Aims: The steroid ouabain is found in plasma and in many mammalian tissues, and is now considered as a hormone. In the immune system, ouabain regulates a number of lymphocyte functions, but little is known about its effects on monocyte function. Monocytes are important for adequate immune responses. The aim of this work was to analyze the effect of ouabain on mCD14 expression, a surface molecule involved in the response against Gram-negative bacteria and phagocytosis. Methods: Human peripheral blood mononuclear cells obtained from healthy donors were separated by density gradient centrifugation. Monocytes were separated by adherence and treated for 24 h with 100 nM ouabain. mCD14, CD1a and P-p38 expression was analyzed by flow cytometry. Inhibitors of cell-signaling pathways, i.e. SB202190, reduced glutathione, rottlerin, tyrphostin A23, genistein, chelerythrine chloride, PD98059, PP1 and Ly 294002, were used concomitantly with ouabain to observe their effect on mCD14 expression. Results: Ouabain induced a significant decrease in mCD14 expression. This feature was not related to receptor endocytosis or cell death. Furthermore, mCD14 downregulation did not reflect a shift in differentiation into dendritic cells because this hormone failed to induce CD1a expression. Amongst several inhibitors of cell-signaling pathways triggered by ouabain, only epidermal growth factor receptor (EGFR) and p38 mitogen-activated protein kinase (MAPK) inhibitors (tyrphostin A23 and SB202109) significantly reverted the effect of ouabain on mCD14 expression. Accordingly, the levels of P-p38 were increased on monocytes after ouabain treatment. However, incubation with epidermal growth factor did not alter mCD14 expression. Conclusion: These findings suggest that ouabain downregulates mCD14 expression on monocytes through EGFR transactivation and p38 MAPK activation.
Cytokine Inhibition after Glucocorticoid Exposure in Healthy Men with Low versus High Basal Cortisol Levels
Authors: Lekander Mats , Axén Jennie , Knutsson Urban , Olgart Höglund Caroline , Werner Sigbritt , Wikström Ann-Charlotte , Stierna Pontus
Published: April 2009

Objective: The balance between glucocorticoid (GC) release and GC sensitivity in target cells is believed to be important to maintain homeostasis in the neuroendocrine control of inflammation. We investigated the impact of in vivo exposure to adrenocorticotropic hormone (ACTH) and dexamethasone (DEX) on GC sensitivity measured in vitro in healthy individuals with high versus low baseline cortisol levels. Methods:136 healthy male volunteers were screened twice and sorted according to their 24-hour urinary free cortisol (UFC) excretion. The 10 individuals with the highest UFC (290 ± 87 nmol/24 h) and the 10 with the lowest UFC (168 ± 34 nmol/24 h) were further tested. Measurements were performed at baseline, after a low dose (0.5 μg/1.73 m2) of ACTH challenge and after 2 weeks’ exposure to DEX (0.1 mg twice daily). GC sensitivity was assessed in vitro as the ability of DEX to inhibit lipopolysaccharide-stimulated production of the cytokines interleukin 1-β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in a whole-blood assay. Results:After exposure to DEX in vivo, inhibition of IL-6 and TNF-α decreased. Also, after DEX in vivo, low-cortisol men showed lower inhibition of IL-1β and IL-6, both compared to the high-cortisol group and their own baseline levels. Conclusion: A downregulation of GC sensitivity in leukocytes after exposure to an exogenous GC seems to occur most strongly in men with low cortisol levels.
Impaired Immune Function in a Homeless Population with Stress-Related Disorders
Authors: Arranz Lorena , de Vicente Aída , Muñoz Manuel , De la Fuente Mónica
Published: April 2009

Objective: Homeless people suffer high levels of psychological distress. The aim of the present work was to study the immune function in a group of homeless people with stress-related disorders and compare it with that of healthy non-homeless controls. Methods: We included in the study 40 homeless persons and 40 housed controls recruited from the population of Madrid and matched for age and gender. Samples from peripheral blood were collected and we studied several leukocyte functions previously described as good health and survival markers [adherence, chemotaxis, phagocytosis, superoxide anion levels, lymphocyte proliferation in response to phytohemagglutinin, NK activity and cytokine (IL-2, TNF-α) levels], as well as other related parameters, such as plasma cortisol levels and total antioxidant capacity. Results: There was a strongly suppressed immune response in the homeless group, with decreased adherence, chemotaxis, phagocytosis, superoxide levels, lymphoproliferation and NK activity. IL-2 and plasma antioxidant levels were also impaired. Conclusions: These findings suggest an altered immune function in the homeless population that might be responsible for the higher morbidity and mortality of homeless people. In addition, the present work points out directions for future research attempting to increase the quality of life and health status of homeless individuals, since it shows that oxidative stress seems to play a key role in this immune function impairment.