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Larry F Hughes

Publications and source records attributed to Larry F Hughes.

At least 19 recordsLinked to original sources
PubMed2007

Prevention of noise- and drug-induced hearing loss with D-methionine.

A number of otoprotective agents are currently being investigated. Various types of agents have been found in animal studies to protect against hearing loss induced by cisplatin, carboplatin, aminoglycosides, or noise exposure. For over a decade we have been investigating D-methionine (D-met) as an otoprotective agent. Studies in our laboratory and others around the world have documented D-met's otoprotective action, in a variety of species, against a variety of ototoxic insults including cisplatin-, carboplatin-, aminoglycoside- and noise-induced auditory threshold elevations and cochlear hair cell loss. For cisplatin-induced ototoxicity, protection of the stria vascularis has also been documented. Further D-met has an excellent safety profile. D-met may act as both a direct and indirect antioxidant. In this report, we provide the results of three experiments, expanding findings in D-met protection in three of our translational research areas: protection from platinum based chemotherapy-, aminoglycoside- and noise-induced hearing loss. These experiments demonstrate oral D-met protection against cisplatin-induced ototoxicity, D-met protection against amikacin-induced ototoxicity, and D-met rescue from permanent noise-induced hearing loss when D-met is initiated 1h after noise exposure. These studies demonstrate some of the animal experiments needed as steps to translate a protective agent from bench to bedside.

Amikacin↗
PubMed2007

The fundamentals of sound and its measurement.

The purpose of this article is to provide directors of animal care facilities with a basic understanding of some of the principles of acoustics and the measurement of sound. This knowledge likely will enable directors to work effectively with sound and hearing specialists at their institutions to monitor and control the acoustic environments of laboratory animal facilities.

Animals↗
PubMed2006

Age-related changes in the response properties of cartwheel cells in rat dorsal cochlear nucleus.

The fusiform cell and deep layers of the dorsal cochlear nucleus (DCN) show neurotransmitter and functional age-related changes suggestive of a downregulation of inhibitory efficacy onto DCN output neurons. Inhibitory circuits implicated in these changes include vertical and D-multipolar cells. Cartwheel cells comprise a large additional population of DCN inhibitory neurons. Cartwheel cells receive excitatory inputs from granule cell parallel fibers and provide a source of glycinergic inhibitory input onto apical dendrites of DCN fusiform cells. The present study compared the response properties from young and aged units meeting cartwheel-cell criteria in anesthetized rats. Single unit recordings from aged cartwheel cells revealed significantly higher thresholds, increased spontaneous activity and significantly altered rate-level functions characterized by hyperexcitability at higher intensities. Aged cartwheel cells showed a significant reduction in off-set suppression. Collectively, these findings suggest a loss of tonic and perhaps response inhibition onto aged DCN cartwheel neurons. These changes likely reflect a compensatory downregulation of synaptic inhibition in response to a loss of excitatory drive from auditory and non-auditory excitatory inputs via granule cells. The impact of increased excitability of cartwheel cells on DCN output neurons is likely to be complex, influenced by loss of glycinergic release and/or subunit receptor changes which would only partially off-set age-related loss of inhibition onto the somata and basal dendrites of fusiform cells.

Age Factors↗
PubMed2006

Gap detection deficits in rats with tinnitus: a potential novel screening tool.

The study describes a novel method for tinnitus screening in rats by use of gap detection reflex procedures. The authors hypothesized that if a background acoustic signal was qualitatively similar to the rat's tinnitus, poorer detection of a silent gap in the background would be expected. Rats with prior evidence of tinnitus at 10 kHz (n = 14) exhibited significantly worse gap detection than controls (n = 13) when the gap was embedded in a background similar to their tinnitus. No differences between tinnitus and control rats were found with 16 kHz or broadband noise backgrounds, which helped to rule out explanations related to hearing loss or general performance deficits. The results suggest that gap detection reflex procedures might be effective for rapid tinnitus screening in rats.

Animals↗
PubMed2006

Sleep and temperature responses of inbred mice with Candida albicans-induced pyelonephritis.

Human patients with renal disease frequently develop disturbed sleep and severe fatigue. To develop a model for studying factors that contribute to these symptoms, we characterized the sleep patterns of various strains of mice after acute challenge with the fungal organism Candida albicans. After intravenous administration to mice, C. albicans typically colonizes the kidney, producing acute pyelonephritis. Various strains of inbred mice demonstrate marked variation in the temperature and sleep responses that develop after challenge, with individual strains generally showing increased or reduced somnolence in association with fever or hypothermia, respectively. C. albicans-infected mice may be a useful model for identifying the genes and mechanisms that link sleep, temperature, fatigue, and the immune response.

Animals↗
PubMed2006

Sleep, temperature, activity, and prolactin phenotypes of genetically epilepsy-prone rats.

Sleep-wake disturbances are common in epilepsy, yet the potential adverse effect of seizures on sleep is not well characterized. Genetically epilepsy-prone rats (GEPRs) are a well-studied model of genetic susceptibility to audiogenic seizures. To assess their suitability for investigating relationships between seizures and disordered sleep, we characterized the sleep, activity, and tempera ture patterns of 2 GEPR strains (designated 3 and 9) and Sprague-Dawley (SD) rats in the basal state, after forced wakefulness, and after exposure to sound-induced seizures at light onset and dark onset. Because of observed differences in rapid-eye-movement sleep (REMS), we also assessed serum levels of prolactin, which is implicated in REMS regulation. The data reveal that under basal conditions, the GEPR3 strain shows less SWS and REMS, higher core temperatures, and higher serum prolactin concentrations than do GEPR9 and SD strains. All 3 strains respond similarly to enforced sleep loss. Seizures induced at light onset delay the onset of SWS in both GEPR strains. Seizures induced at dark onset do not significantly alter sleep. Genotype assessment indicates that although both GEPR strains are inbred (that is, homozygous at 107 genetic markers), they differ from each other at 74 of 107 loci. Differences in basal sleep, temperature, and prolactin between GEPR3 and GEPR9 strains suggest different homeostatic regulation of these functions. Our detection of concurrent alterations in sleep, temperature, and prolactin in these 2 GEPR strains implicates the hypothalamus as a likely site for anatomic or physiologic variation in the control of these homeostatic processes.

Acoustic Stimulation↗
PubMed2005

Age-related changes in the inhibitory response properties of dorsal cochlear nucleus output neurons: role of inhibitory inputs.

Age-related hearing loss frequently results in a loss in the ability to discriminate speech signals, especially in noise. This is attributable, in part, to a loss in temporal resolving power and ability to adjust dynamic range. Circuits in the adult dorsal cochlear nucleus (DCN) have been shown to preserve signal in background noise. Fusiform cells, major DCN output neurons, receive focused glycinergic inputs from tonotopically aligned vertical cells that also project to the ventral cochlear nucleus. Glycine-mediated inhibition onto fusiform cells results in decreased tone-evoked activity as intensity is increased at frequencies adjacent to characteristic frequency (CF). DCN output is thus shaped by glycinergic inhibition, which can be readily assessed in recordings from fusiform cells. Previous DCN studies suggest an age-related loss of markers for glycinergic neurotransmission. The present study postulated that response properties of aged fusiform cells would show a loss of inhibition, resembling conditions observed with glycine receptor blockade. The functional impact of aging was examined by comparing response properties from units meeting fusiform-cell criteria in young and aged rats. Fusiform cells in aged animals displayed significantly higher maximum discharge rates to CF tones than those recorded from young-adult animals. Fusiform cells of aged rats displayed significantly fewer nonmonotonic CF rate-level functions and an age-related change in temporal response properties. These findings are consistent with an age-related loss of glycinergic input, likely from vertical cells, and with findings from other sensory aging studies suggesting a selective age-related decrement in inhibitory amino acid neurotransmitter function.

Acoustic Stimulation↗
PubMed2005

Affects of aging on receptive fields in rat primary auditory cortex layer V neurons.

Advanced age is commonly associated with progressive cochlear pathology and central auditory deficits, collectively known as presbycusis. The present study examined central correlates of presbycusis by measuring response properties of primary auditory cortex (AI) layer V neurons in the Fischer Brown Norway rat model. Layer V neurons represent the major output of AI to other cortical and subcortical regions (primarily the inferior colliculus). In vivo single-unit extracellular recordings were obtained from 114 neurons in aged animals (29-33 mo) and compared with 105 layer V neurons in young-adult rats (4-6 mo). Three consecutive repetitions of a pure-tone receptive field map were run for each neuron. Age was associated with fewer neurons exhibiting classic V/U-shaped receptive fields and a greater percentage of neurons with more Complex receptive fields. Receptive fields from neurons in aged rats were also less reliable on successive repetitions of the same stimulus set. Aging was also associated with less firing during the stimulus in V/U-shaped receptive field neurons and more firing during the stimulus in Complex neurons, which were generally associated with inhibited firing in young controls. Finally, neurons in aged rats with Complex receptive fields were more easily driven by current pulses delivered to the soma. Collectively, these findings provide support for the notion that age is associated with diminished signal-to-noise coding by AI layer V neurons and are consistent with other research suggesting that GABAergic neurotransmission in AI may be compromised by aging.

Acoustic Stimulation↗
PubMed2005

Disruption of lateral olivocochlear neurons via a dopaminergic neurotoxin depresses sound-evoked auditory nerve activity.

We applied the dopaminergic (DA) neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the guinea pig cochlear perilymph. Immunolabeling of lateral olivocochlear (LOC) neurons using antibodies against synaptophysin was reduced after the MPTP treatment. In contrast, labeling of the medial olivocochlear innervation remained intact. As after brainstem lesions of the lateral superior olive (LSO), the site of origin of the LOC neurons, the main effect of disrupting LOC innervation of the cochlea via MPTP was a depression of the amplitude of the compound action potential (CAP). CAP amplitude depression was similar to that produced by LSO lesions. Latency of the N1 component of the CAP, and distortion product otoacoustic emission amplitude and adaptation were unchanged by the MPTP treatment. This technique for selectively lesioning descending LOC efferents provides a new opportunity for examining LOC modulation of afferent activity and behavioral measures of perception.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2005

Divergent response properties of layer-V neurons in rat primary auditory cortex.

Layer-V pyramidal cells comprise a major output of primary auditory cortex (A1). At least two cell types displaying different morphology, projections and in vitro physiology have been previously identified in layer-V. The focus of the present study was to characterize extracellular receptive field properties of layer-V neurons to determine whether a similar breakdown of responses can be found in vivo. Recordings from 105 layer-V neurons revealed two predominant receptive field types. Thirty-two percent displayed strong excitatory V/U-shaped receptive field maps and spiking patterns with shorter stimulus-driven interspike intervals (ISIs), reminiscent of the bursting cells discussed in the in vitro literature. V/U-shaped maps remained relatively unchanged across the three sequential repetitions of the map run on each neuron. Neurons with V/U-shaped maps were also easily depolarized with extracellular current pulse stimulation. In contrast, 47% of the neurons displayed Complex receptive field maps characterized by weak and/or inconsistent excitatory regions and were difficult to depolarize with current pulses. These findings suggest that V/U-shaped receptive fields could correspond to previously described intrinsic bursting (IB) cells with corticotectal projections, and that neurons with Complex receptive fields might represent the regular spiking (RS) cells with their greater inhibitory input and corticocortical/corticostriatal projection pattern.

Acoustic Stimulation↗
PubMed2005

Sleep during concanavalin-A-induced hepatitis and peritonitis in inbred mice.

STUDY OBJECTIVES: To assess the suitability of concanavalin-A-induced hepatitis as a model for investigating the relationships between hepatic disease and alterations in somnolence. DESIGN: We characterized the sleep patterns of various strains of inbred mice undergoing ConA-induced inflammation. SETTING: Southern Illinois University School of Medicine, Springfield, IL. INTERVENTION: Intravenous or intraperitoneal administration of concanavalin-A. PARTICIPANTS: Inbred mice. MEASUREMENTS AND RESULTS: Intravenous and intraperitoneal administration of concanavalin-A both elicited strain-dependent changes in slow-wave sleep. ConA treatment also reduced spontaneous locomotor activity. ConA-induced changes in slow-wave sleep varied with dose, route of administration, and circadian period of administration. As compared with the other strains, C57BL/6J mice had lower serum concentrations of interferon-gamma at 8 hours after ConA administration. CONCLUSIONS: These data provide the first demonstration that sleep enhancement and reduced locomotor activity accompany hepatic inflammation in mice.

Animals↗
PubMed2005

Hearing in laboratory animals: strain differences and nonauditory effects of noise.

Hearing in laboratory animals is a topic that traditionally has been the domain of the auditory researcher. However, hearing loss and exposure to various environmental sounds can lead to changes in multiple organ systems, making what laboratory animals hear of consequence for researchers beyond those solely interested in hearing. For example, several inbred mouse strains commonly used in biomedical research (e.g., C57BL/6, DBA/2, and BALB/c) experience a genetically determined, progressive hearing loss that can lead to secondary changes in systems ranging from brain neurochemistry to social behavior. Both researchers and laboratory animal facility personnel should be aware of both strain and species differences in hearing in order to minimize potentially confounding variables in their research and to aid in the interpretation of data. Independent of genetic differences, acoustic noise levels in laboratory animal facilities can have considerable effects on the inhabitants. A large body of literature describes the nonauditory impact of noise on the biology and behavior of various strains and species of laboratory animals. The broad systemic effects of noise exposure include changes in endocrine and cardiovascular function, sleep-wake cycle disturbances, seizure susceptibility, and an array of behavioral changes. These changes are determined partly by species and strain; partly by noise intensity level, duration, predictability, and other characteristics of the sound; and partly by animal history and exposure context. This article reviews some of the basic strain and species differences in hearing and outlines how the acoustic environment affects different mammals.

Animals↗
PubMed2004

Macrophage participation in influenza-induced sleep enhancement in C57BL/6J mice.

Mice develop changes in sleep during the nonspecific immune response that occurs during the initial few days after inoculation with influenza virus. T lymphocytes, neutrophils, macrophages, and natural killer (NK) cells all participate in the early host response to influenza infection. All of these cell types are potential sources of endogenous substances that modulate sleep, but the contributory role of each cell type to the alteration of somnolence during infection has not been determined. To investigate which cell types contribute to the sleep enhancement that develops during influenza infection in mice, the sleep patterns of C57BL/6J mice with perturbations of particular facets of host immune response capabilities were assessed before and after influenza infection. Targeted mutation of the gene Ccl3 (macrophage inflammatory protein 1 alpha) prevented development of the dark phase sleep enhancement that is characteristic of C57BL/6J mice after influenza infection. Other experimental treatments that impair macrophage or monocyte function also produced significant (administration of pentoxifylline or CNI-1493) or marginally significant (deletion of the interferon-gamma gene or intranasal administration of carrageenan) changes in influenza-induced sleep enhancement in C57BL/6J mice. In contrast, functional impairments of NK cells, neutrophils, and T lymphocytes did not significantly influence sleep responses. These data therefore support a contributory role for macrophages, but not for NK cells, neutrophils, and T lymphocytes, in eliciting the sleep response typical of influenza-infected C57BL/6J mice.

Analysis of Variance↗
PubMed2004

Current practice patterns in tonsillectomy and perioperative care.

OBJECTIVES: Tonsillectomy is one of the most commonly performed otolaryngologic procedures in the United States. Many options and controversies exist regarding techniques and peri-operative management. The purpose of the study was to examine current practice patterns among otolaryngologists regarding tonsillectomy. METHODS: A 13 question survey regarding tonsillectomy techniques and peri-operative management was mailed to 10% of randomly selected board certified otolaryngologists of the AAO-HNS in the spring of 2002. Four hundred and eighteen anonymously completed questionnaires were returned, for a response rate of 58.5%. Statistical analysis of survey data was performed by means of cross tabulation and Pearson Chi-Square Calculation. RESULTS: Monopolar electrocautery was the most common technique used among those surveyed (53.5%). There was a significant correlation between choice of monopolar electrocautery and the cited reason for choice of technique being decreased blood loss (P < 0.001). There was no relationship between pediatric fellowship training and choice of technique. 97.7% routinely admitted sleep apnea patients for post-operative observation. There was no significant correlation between practice setting (tertiary versus community) and type of post-operative monitoring for sleep apnea patients, with patients most commonly admitted to an intermediate care setting. CONCLUSION: In our survey, the most common surgical technique for tonsillectomy was monopolar electrocautery, chosen for the reason of decreased blood loss.

Anesthesia, Local↗
PubMed2004

Noise induces A1 adenosine receptor expression in the chinchilla cochlea.

Adenosine plays a major cytoprotective role during ischemia and conditions of oxidative stress. Previous studies in our laboratory indicate that oxidative stress induces expression of the A1 adenosine receptor (A1AR) via activation of nuclear factor (NF)-kappaB. In this study, we tested whether noise exposure could induce oxidative stress and determine whether this induces expression of the A1AR in the chinchilla cochlea. Chinchillas were exposed to a 96 dB 4 kHz octave band of noise for 6 h of daily exposure, followed by an 18 h noise-free period. This noise paradigm resulted in threshold shifts of 10-60 dB over the frequency range (1-16 kHz) tested. Radioligand binding studies for the A1AR indicate a significant increase in receptor ( approximately 2-fold) expression soon after the first noise exposure period (usually within approximately 8 h of the initiation of noise), which gradually returned to basal levels by day 7. The rise in A1AR levels was followed by a significant increase in malondialdehyde levels by day 3, which also recovered by day 7. Assessment of the activity of NADPH oxidase in the cochlea indicates a significant increase in enzyme activity which was evident by approximately 8 h following initiation of noise exposure, and which persisted for at least up to day 3. Electrophoretic mobility shift assays indicate that the increase in A1AR was associated with a significant increase in NF-kappaB activity following noise exposure. We conclude that noise exposure induces A1AR expression, which might be mediated, in part, through generation of reactive oxygen species and activation of NF-kappaB.

Adenosine↗
PubMed2003

Postoperative hemorrhage with nonsteroidal anti-inflammatory drug use after tonsillectomy: a meta-analysis.

OBJECTIVE: To use standard meta-analysis techniques to determine the risk of postoperative hemorrhage associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) after tonsillectomy. DATA SOURCES: The MEDLINE database (1966-2001) restricted to the English language was searched using the keywords tonsillectomy, hemorrhage, analgesics, and NSAID in various combinations. Additionally, published articles were cross-referenced. To ensure completeness, the search was rerun using the Science Citation Index database. STUDY SELECTION: Of the 110 articles identified, 7 were selected. Selected studies were prospective trials comparing the effects of an NSAID and a control drug on posttonsillectomy pain and hemorrhage in pediatric and/or adult patients. In all cases, the NSAID or control was administered through an enteric route in the postoperative period. Patients were monitored for early and delayed hemorrhage. DATA EXTRACTION: Data were extracted independently by 2 investigators. DATA SYNTHESIS: A random effects model was used to compute a pooled odds ratio. For the 1368 patients included in analysis, the pooled odds ratio of posttonsillectomy hemorrhage with NSAIDs compared with controls was 1.29 and was not statistically significant (95% confidence interval, 0.85-1.73; P>/=.05). A subgroup analysis revealed an odds ratio of 0.93 (95% confidence interval, 0.44 -1.95; P>/=.05) for the nonaspirin NSAID group, while the aspirin group had a statistically significant odds ratio of 1.94 (95% confidence interval, 1.09-3.42; P =.02). CONCLUSIONS: There is an increased risk of posttonsillectomy hemorrhage with the use of aspirin after tonsillectomy; however, there appears to be no significant increased risk of bleeding for nonaspirin NSAIDs in this meta-analysis.

Adolescent↗
PubMed2003

Disruption of lateral efferent pathways: functional changes in auditory evoked responses.

The functional consequences of selectively lesioning the lateral olivocochlear efferent system in guinea pigs were studied. The lateral superior olive (LSO) contains the cell bodies of lateral olivocochlear neurons. Melittin, a cytotoxic chemical, was injected into the brain stem using stereotaxic coordinates and near-field evoked potentials to target the LSO. Brain stem histology revealed discrete damage to the LSO following the injections. Functional consequences of this damage were reflected in depressed amplitude of the compound action potential of the eighth nerve (CAP) following the lesion. Threshold sensitivity and N1 latencies were relatively unchanged. Onset adaptation of the cubic distortion product otoacoustic emission (DPOAE) was evident, suggesting a reasonably intact medial efferent system. The present results provide the first report of functional changes induced by isolated manipulation of the lateral efferent pathway. They also confirm the suggestion that changes in single-unit auditory nerve activity after cutting the olivocochlear bundle are probably a consequence of disrupting the more lateral of the two olivocochlear efferent pathways.

Action Potentials↗