Antibiotic stewardship for reptiles.

This review discusses the general principles underlying responsible antibiotic usage in reptiles. Very little evidence underlies antibiotic usage in reptiles, and there are no published guidelines for responsible antibiotic usage. A literature search was performed to review the evidence for bacterial involvement in the pathology of selected common diseases of reptiles, allowing the development of recommendations for responsible antibiotic treatment of those diseases.

Comparison of veterinary drugs and veterinary homeopathy: part 1.

For many years after its invention around 1796, homeopathy was widely used in people and later in animals. Over the intervening period (1796-2016) pharmacology emerged as a science from Materia Medica (medicinal materials) to become the mainstay of veterinary therapeutics. There remains today a much smaller, but significant, use of homeopathy by veterinary surgeons. Homeopathic products are sometimes administered when conventional drug therapies have not succeeded, but are also used as alternatives to scientifically based therapies and licensed products. The principles underlying the veterinary use of drug-based and homeopathic products are polar opposites; this provides the basis for comparison between them. This two-part review compares and contrasts the two treatment forms in respect of history, constituents, methods of preparation, known or postulated mechanisms underlying responses, the legal basis for use and scientific credibility in the 21st century. Part 1 begins with a consideration of why therapeutic products actually work or appear to do so.

Comparison of veterinary drugs and veterinary homeopathy: part 2.

Part 2 of this narrative review outlines the theoretical and practical bases for assessing the efficacy and effectiveness of conventional medicines and homeopathic products. Known and postulated mechanisms of action are critically reviewed. The evidence for clinical efficacy of products in both categories, in the form of practitioner experience, meta-analysis and systematic reviews of clinical trial results, is discussed. The review also addresses problems and pitfalls in assessing data, and the ethical and negative aspects of pharmacology and homeopathy in veterinary medicine.

Backyard poultry: legislation, zoonoses and disease prevention.

In law, backyard poultry are "food-producing animals" and "farmed animals" and are subject to regulations regarding welfare, prescribing, banned procedures, disposal of carcases, feeding bans, notifiable diseases and disease surveillance in addition to those applying to most other pets. Many owners and some veterinary surgeons are unclear about the requirements of these regulations. Backyard poultry are also associated with some different zoonotic disease risks to mammalian pets. Because a high proportion of poultry morbidity and mortality relates to infectious diseases, the health of backyard poultry is amenable to improvement through basic husbandry, biosecurity, hygiene and preventive medicine measures that can be incorporated into a simple "flock-health plan". This article reviews these topics.

Risk of pyometra in bitches treated for mismating with low doses of oestradiol benzoate.

A review of the literature concerning the effect of oestrogens for treating mismating in bitches on the occurrence of pyometra indicated that low doses of oestradiol benzoate substantially increase the incidence of pyometra. A retrospective study of the clinical records of a UK general practice found that the incidence of pyometra in the four months after administration of low doses of oestradiol benzoate was 8.7 per cent, whereas the incidence in the practice's untreated at-risk population was estimated to be less than 1.32 per cent per interoestrus interval, suggesting that more than 85 per cent of pyometras occurring within four months of treatment are iatrogenic.

Locus of generation for the 2f1-f2 vs 2f2-f1 distortion-product otoacoustic emissions in normal-hearing humans revealed by suppression tuning, onset latencies, and amplitude correlations.

The present study used distortion-product otoacoustic emission (DPOAE) suppression tuning curves (STCs), DPOAE onset latencies (OLs), and DPOAE amplitude correlations to investigate the locus of generation of the 2f1-f2 DPOAE versus the 2f2-f1 DPOAE in humans. The results of the tuning study revealed that, for the 2f1-f2 DPOAE, the tips of the STCs tuned consistently below the geometric-mean (GM) frequency of the primary tones. In contrast, for the 2f2-f1 DPOAE, STCs tuned above the GM of the primaries, with 50% of the tip frequencies at, or above, the 2f2-f1 frequency place. When the average ratio of the 2f2-f1 to the 2f1-f2 tip frequencies was computed, a factor of 1.44 provided an estimate of the frequency shift needed to align the two DPOAE generation sites. Other results showed that OLs for the 2f2-f1 DPOAE were uniformly shorter than those for the 2f1-f2, with differences at the low frequencies amounting to as much as 6-7 ms. Further, for both DPOAEs, curves describing latency decreases as a function of increasing GM frequencies were best fit by power functions. Shifting the GM frequency producing the 2f2-f1 DPOAE by a factor of 1.6 caused the latency distributions for both DPOAEs to overlap thus resulting in a single function that described cochlear delay as a function of GM frequency. Finally, for each GM frequency in the DP-gram, sliding correlations from 108 normal ears were performed on both DPOAEs by holding the primaries producing the 2f1-f2 DPOAE constant, while all 2f2-f1 DPOAE amplitudes were successively correlated with the 2f1-f2 amplitudes. This procedure demonstrated that, for a given GM frequency producing the 2f1-f2, the correlations between the two DPOAEs peaked when the primaries of the 2f2-f1 were at a GM frequency that positioned the 2f2-f1 frequency place near the GM of the primaries that produced the 2f1-f2 DPOAE. As a whole, the above findings strongly suggest that the 2f2-f1 DPOAE in humans is generated basal to the primary-tone place on the basilar membrane.

Visualization of the onset of distortion-product otoacoustic emissions, and measurement of their latency.

This paper describes a method for visualization of the onset of distortion-product otoacoustic emission (DPOAE) waveforms in the time domain. The DPOAE waveforms are obtained using ensemble averaging of samples of microphone output. A rectangular sample window is used, and the primary tones are turned on within the sample window. The phases of the primary tones (f1 and f2) are varied systematically between samples in such a way that the primary tones, and all DPOAEs (e.g., 2f2-f1, 3f1-2f2, 2f1), except the DPOAE of interest (e.g., 2f1-f2), are cancelled in the ensemble average. Visualization of the DPOAE onset allows measurement of the onset latency (OSL) of the DPOAE. These direct measurements of OSL are compared to phase-gradient latencies (PGLs) in the same ears determined by measuring the phase change of the DPOAE as a function of DPOAE frequency. The direct measures of OSL vary from > 10 to < 1 ms, decrease with increasing frequency and increasing stimulus level, and are shorter in rabbits than humans. The direct measures of OSL are, in general, quantitatively similar to PGL estimates, but there are exceptions. Visualization of DPOAE onset also allows quantification of DPOAE rise times, and reveals phase and amplitude changes of the DPOAE that occur several milliseconds after onset in rabbits and humans. It is proposed that the phase and amplitude changes result from vector summation of multiple components of the DPOAE signal, each with a different latency.

Time-windowing of click-evoked otoacoustic emissions to increase signal-to-noise ratio.

OBJECTIVE: To investigate the effects of decreasing the response-window duration on the signal-to-noise ratio (S/N) of click-evoked otoacoustic emissions (CEOAEs). DESIGN: The ILO88 (Otodynamics, Ltd.) was used to measure CEOAEs from 149 normal adult ears, and 75 adult ears with high-frequency sensorineural hearing loss. Data were collected using the default response window of 2.5 to 20.5 msec post-click. Each response was rewindowed, post-hoc, from 2.5 to 7.5 msec, 2.5 to 9 msec, 7.75 to 14.25 msec, and 13 to 19.5 msec post-click. For each window, spectra of the CEOAE and of the background noise were determined. The S/N was estimated by subtracting the noise level from the CEOAE amplitude. RESULTS: The 13- to 19.5-msec window contained little CEOAE energy relative to earlier windows. Relative to the 2.5- to 20.5-msec window, the 2.5- to 7.5- and 2.5- to 9-msec windows reduced noise levels more than CEOAE amplitudes, yielding increased S/N, and greater "reproducibility" values. The increased S/N of the 2.5- to 7.5- and 2.5- to 9-msec windows allowed measurement of greater CEOAE-amplitude reductions in the impaired ears relative to the normal ears. With short-duration windows, click-presentation rate could be increased, allowing more responses to be averaged in a given time, thus further decreasing noise levels. Although click rate was not varied in the present study, the decrease of noise levels is predictable. Accounting for this factor, it is expected that a specified S/N would be obtained about five times faster using the 2.5- to 7.5-msec window with a 7.5-msec interstimulus interval, than when using the default window. CONCLUSIONS: Decreasing the response-window duration substantially increases the measurement efficiency of CEOAEs in adults, and thus may enhance clinical-test performance.

Effects of ear-canal standing waves on measurements of distortion-product otoacoustic emissions.

At frequencies above 3 kHz, standing waves in the ear canal complicate calibration of stimulus sound-pressure levels (SPLs) for measurements of distortion-product otoacoustic emissions (DPOAEs). In the literature, two stimulus-presentation strategies have been used for DPOAE measurements. In the "in-the-ear adjustment" strategy, the voltage command to the speakers is adjusted to maintain a constant stimulus SPL across frequency at the DPOAE-measurement microphone. In the "iso-voltage" strategy, the voltage presented to the speakers is held constant across frequency, on the basis of the assumption that the frequency response of the speakers is approximately flat at the eardrum in the average human ear canal. Because of standing-wave effects, there are large, systematic but idiosyncratic differences of stimulus SPL between the two strategies. DPOAE-versus-frequency functions ("DPOAE audiograms") obtained using both stimulus-presentation strategies in the same ears are presented. The differences of stimulus SPL between the two strategies, and the associated differences of DPOAE amplitude, are described and quantified. Around frequencies of standing-wave minima at the DPOAE probe, the in-the-ear adjustment strategy resulted in smaller DPOAEs at high L1 = L2, but much larger DPOAEs at low L1 = L2, than did the iso-voltage strategy. For any L1, the DPOAE-amplitude differences between the two strategies varied systematically with L1-L2. At the stimulus levels used to construct previously published population norms for clinical applications (i.e., L1 > or = 65 dB SPL), there are only small differences of mean DPOAE amplitudes, and of the standard deviations of these means, between the two strategies.

Dependence of distortion-product otoacoustic emissions on primary levels in normal and impaired ears. I. Effects of decreasing L2 below L1.

The 2f1-f2 distortion-product otoacoustic emission (DPOAE) is evoked by two primary tones of frequencies f1 < f2, and levels L1 and L2. Previous reports indicate that decreasing L2 below L1 = L2 can; (1) increase DPOAE amplitude in normal ears, and (2) increase the degree to which DPOAE amplitudes are reduced by cochlear trauma. Although both of these factors could be advantageous for clinical applications of DPOAEs, neither has been explored in detail. In the present study, 2f1-f2 DPOAE-amplitude frequency functions were collected from normal and impaired ears of rabbits and humans, with L1 = L2, and with L2 < L1, at each of three values of L1. In rabbits, controlled tonal or noise overexposures were used to produce permanent reductions of DPOAE amplitudes. Comparison of pre- and postexposure DPOAE-amplitude frequency functions demonstrated that the frequency-specific reductions of DPOAEs were enhanced by decreasing L2 below L1. In humans, DPOAE-amplitude frequency functions obtained with the various L1 and L2 combinations were collected from 16 normal ears to provide preliminary normative data for each stimulus-level condition. The L1-L2 that produced the maximum DPOAE amplitude in normal ears was systematically dependent on L1. Thus at most frequencies, decreasing L2 below L1 = L2 substantially reduced mean DPOAE amplitude when L1 > or = 75 dB SPL, but increased mean DPOAE amplitudes at L1 = 65 dB SPL. However, the increase of mean DPOAE amplitude obtained by decreasing L2 below L1 = 65 dB SPL was small, being less than 3.5 dB at most frequencies. More importantly, at L1 = 65 dB SPL, L2 could be decreased considerably below L1 = L2 without reducing mean DPOAE amplitude relative to that at L1 = L2. Inspection of DPOAE-amplitude frequency functions obtained from subjects with mild or moderate sensorineural hearing losses indicated that, in frequency regions of hearing impairment, decreasing L2 below L1 can enhance the degree of reduction of DPOAEs below the corresponding normative amplitudes, without reducing the normative amplitude. It is concluded that decreasing L2 below L1 = L2 has the potential to enhance the performance of DPOAEs in clinical applications.

Dependence of distortion-product otoacoustic emissions on primary levels in normal and impaired ears. II. Asymmetry in L1,L2 space.

Previous studies indicate that the amplitude of 2f1-f2 distortion-product otoacoustic emissions (DPOAEs), evoked by two tones of frequencies f1 < f2, demonstrates a complex dependence on the levels (L1 and L2) of the primary tones. In the present study, 2f1-f2 DPOAE amplitudes were measured over a wide range of L1 and L2 in normal human ears, allowing a systematic, level-dependent asymmetry of DPOAE amplitude in L1,L2 space to be characterized. The L1,L2 at which DPOAEs were largest was close to L1 = L2 at high stimulus levels, but moved monotonically toward L1 > L2 as stimulus levels decreased. A related observation was that DPOAE amplitude had a greater dependence on L1 and on L2. These asymmetries were quantified in normal human ears, and compared to the corresponding asymmetries apparent in data from animal models. Recent studies have demonstrated that the reduction of DPOAE amplitude by cochlear trauma is greater when L1 > L2 than when L1 = L2, suggesting that the reduction of DPOAEs by trauma demonstrates an asymmetry in L1,L2 space that is qualitatively similar to that of normative DPOAE amplitude. To investigate this issue, 2f1-f2 DPOAE amplitudes were measured over a wide range of L1 and L2 in rabbit ears pre- and postinjection of the ototoxic loop-diuretic ethacrynic acid. The results indicate that the asymmetry in L1,L2 space of the reduction of DPOAEs by trauma is both qualitatively and quantitatively similar to the asymmetry in L1,L2 space of normative DPOAE amplitude. Specifically, the L1 values that maximized normative DPOAE amplitudes for any specified L2 (or, equivalently, the L1 values that allowed L2 to be minimized for any specified normative DPOAE amplitude) also yielded the greatest reduction of DPOAEs by the diuretic. In humans, the L1 values that maximize normative DPOAE amplitudes for any specified L2 are well approximated by a simple equation, with parameters that vary with frequency and f2/f1. It is suggested that the L1,L2 values defined by this equation may be optimum for use in clinical applications.

New approaches to the evaluation of the auditory system and a current analysis of otoacoustic emissions.

Healthy ears generate low-level sounds known as otoacoustic emissions that are produced by the normal workings of the inner ear. By placing a specially constructed probe containing an assembly of miniature microphones in the ear canal, hearing investigators can listen to these sounds. Before emissions were discovered, the only methods available to explore the ordinarily inaccessible structures of the cochlea involved invasive and, thus damaging, experiments, which could only be performed on animals. With the discovery of otoacoustic emissions, noninvasive research on the inner ear became possible, thus allowing study of the fundamental processes that determine the excellent sensitivity and fine frequency tuning that are uniquely associated with human hearing. The results of these basic experiments have made it possible to develop a number of useful clinical applications based on emissions testing. One noteworthy benefit is the use of emissions as a screening test that objectively assesses the functional integrity of peripheral processing in patients who are difficult to examine, such as infants and young children. Other applications take advantage of the test's diagnostic strength as an indicator of the sensory component of a sensorineural hearing loss. Finally, because emissions testing can be conducted rapidly and accurately under computer control, it has proved useful in the serial monitoring of ear performance in instances where a progressive hearing impairment is suspected.

Sensitivity of distortion-product otoacoustic emissions in humans to tonal over-exposure: time course of recovery and effects of lowering L2.

An important concern of industrial hearing-conservation programs is detecting the onset of noise-induced hearing loss. If it can be shown that otoacoustic emissions are sufficiently sensitive to reliably detect auditory fatigue and the permanent hearing loss that eventually develops, they could become an important part of the hearing-conservation test battery. The present study in humans was designed to examine the influence of overall primary-tone level and the effects of lowering the f2 primary on the sensitivity of distortion-product otoacoustic emissions (DPOAEs) to acoustic overstimulation. One ear from each of 14 subjects with normal hearing was exposed to a 105-dB SPL pure tone at 2.8 kHz for 3 min using a protocol consisting of distinct pre-exposure, exposure, and post-exposure periods. As a quantitative index of the functional status of the outer hair cells, 2f1-f2 DPOAEs were monitored systematically over time using four stimulus-test conditions consisting of either one of two levels of equilevel primary tones, or one of two levels of offset primaries, with L2 set 25 dB lower than L1. The overall finding was that the DPOAE protocol incorporating both the lowest level of stimulation and an f2-primary tone that was 25 dB below the level of the f1 stimulus [i.e., L1 (55 dB SPL) - L2 (30 dB SPL) = 25 dB] was most sensitive to the exposure effects. The results establish that DPOAEs elicited with unequal, in contrast to equal-level primaries, have comparable signal-to-noise ratios, but are considerably more sensitive to reductions in emission levels induced by exposure to short-lasting, moderately intense tones. The recovery of DPOAE amplitudes over the first 15 min post-exposure appeared to be roughly linear in log time and, in many cases, could be closely approximated by fitting a logarithmic curve to the post-exposure data. From these functions, the initial amount of loss (y-intercept) and the slope of recovery were identified as potential measures of vulnerability to acoustic exposure in that these variables appeared to be related to the susceptibility of some of the subjects, who also participated in a subsequent experiment on the behavioral effects of the exposure stimulus. Finally, compared to behaviorally measured temporary threshold shift (TTS), the time course of the recovery for DPOAEs was very similar, suggesting that, with the appropriate parameters, DPOAEs can be as sensitive to TTS as routine pure-tone audiometry.

The influence of noise on the measured amplitudes of distortion-product otoacoustic emissions.

This paper describes the influence of noise on the measured amplitudes of tonal signals, as determined using narrowband spectral analysis, that is, the technique typically used to measure distortion-product otoacoustic emissions (DPOAEs). At small signal-to-noise ratios, background noise results in overestimation of DPOAE amplitude and, thus, substantially influences the measured properties of the low-level portions of DPOAE-growth functions, in particular the apparent slope of the functions in this region. It is shown that, because of the influence of noise, the algorithm for the objective estimation of detection thresholds of DPOAEs, and of the slopes of DPOAE-growth functions, described by Nelson and Kimberley (1992), will tend to underestimate these values. This systematic underestimation is presumably the reason why many of the DPOAE-detection thresholds and growth slopes presented in that study were considerably lower than those reported in previous studies using similar measuring equipment and paradigms but different detection-threshold and growth-slope estimation techniques. In the present paper, a simple equation allowing an estimated correction for the effects of noise on measured DPOAE amplitudes is presented. Finally, an alternative strategy for the estimation of DPOAE thresholds, one that is less prone to the influence of noise, is suggested.

Distortion-product emissions in rabbit: I. Altered susceptibility to repeated pure-tone exposures.

An important issue in understanding the development of noise-induced hearing loss is whether prior acoustic overstimulation alters the susceptibility of the cochlea to further damage. The present work was designed to establish a model of activity-dependent changes in the susceptibility of the cochlea to acoustic overstimulation by regularly exposing the ear to a low-frequency pure tone. As a quantitative index of cochlear function, 2f1-f2 distortion-product otoacoustic emissions (DPOAEs) were monitored systematically over time in three groups of rabbits, with each group experiencing a unique paradigm that incorporated repeated exposure to the low-frequency tone. Common to each rabbit's exposure protocol was that a given experimental session consisted of two exposure episodes, separated by a 40-min period. Experimental sessions were repeated three times, with 2- to 3-day recovery periods interposed between sessions. The rate of decrement in DPOAE amplitude over a prescribed time period was utilized as a measure of susceptibility to the acoustic trauma. The overall results indicated that ears were more susceptible to exposure 40 mins after the first exposure of a session than they were initially. A series of control experiments indicated that the robustness of the acoustic middle-ear reflex (AMR) did not change between the exposure episodes. Consequently, changes in the AMR could not account for the increased susceptibility seen following the first exposure. However, in awake rabbits with stronger AMRs, higher pure-tone exposure levels were needed to produce increased susceptibility to the second exposure. After 2-3 days of intersession recovery, susceptibility to the effects of excessive sound returned close to its original baseline level. The outcome of these studies demonstrated a reduced capacity for the ear to resist the harmful effects of exposure to a moderately intense tone, which was repeated twice over a brief 40-min period, but little change in susceptibility when identical exposures were repeated over longer intersession intervals of several days.

Clinical testing of distortion-product otoacoustic emissions.

Otoacoustic emissions have great promise for use in clinical tests of the functional status of outer hair cells, which represent cochlear structures that make a major contribution to the hearing process. A substantial literature is available concerning the evaluation of outer hair cell function by transiently evoked otoacoustic emissions. However, relatively little attention has been focused on the benefits of testing with distortion-product otoacoustic emissions. The purpose of this presentation is to provide knowledge of the principal advantages offered by distortion-product emissions testing.

Spontaneous otoacoustic emissions in different racial groups.

To determine if there are racial differences in the prevalence of spontaneous otoacoustic emissions (SOAEs), both ears of 20 Negro, 20 Asian and 20 Caucasian subjects were examined for the presence of SOAEs. Within each racial group, equal numbers of normally hearing males and females were tested. Significant differences in the occurrence of SOAEs were found between the three racial groups, with Negroes expressing more SOAEs than Caucasians, and Asians demonstrating an intermediate number of these emissions. In support of previous observations, more emissions were recorded from female than from male ears, and a significant correlation of the number of emissions in the two ears of an individual was also noted.