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Biomedical subjects

D T Kemp

Publications and source records attributed to D T Kemp.

At least 37 records · Page 2Linked to original sources

Pharmacokinetics of clindamycin phosphate in dogs after single intravenous and intramuscular administrations.

Clindamycin phosphate was administered to dogs at dosage of 11 mg/kg of body weight via IV and IM routes. The disposition curve for IV administration was best represented as a 2-compartment open model. Mean elimination half life was 194.6 +/- 24.5 minutes for IV administration and 234.8 +/- 27.3 minutes for IM administration. Bioavailability after IM administration was 87%. Dosage of 11 mg/kg, IV, given every 8 hours, provided serum concentration of clindamycin that exceeded the minimal inhibitory concentration for all Staphylococcus spp, as well as most pathogenic anaerobes, throughout the dosing interval. Intramuscular administration induced signs of pain and cannot be recommended.

Animals↗

Time-domain observation of otoacoustic emissions during constant tone stimulation.

Observation of the otoacoustic emissions (OAEs) evoked during a continuous single stimulus tone have been made on humans using a nonlinear residual time domain technique. The technique, described in this paper, involved the digital summation of responses to contiguous stimulation intervals, some of which included short bursts of a suppressor, or probe, tone. Stimulus intervals are constructed so that both the stimulus and probe tones summed to zero cyclically, leaving a residual response. This residual is attributable to the nonlinearity of the whole acoustic response, as measured in the ear canal, to the stimulus and probe tone complex. A theoretical treatment of this paradigm is presented examining the relation of this residual to the OAE evoked by the stimulus tone. It is shown experimentally that the residual, found at the stimulus tone frequency, has a latency and saturating input-output growth functions indicative of an OAE. The detailed OAE amplitude-versus-frequency variations, and the general latencies of the OAEs in two human ears were measured using both the constant tone evoked residual method described and the click evoked delayed emission method. The results from both methods are in agreement. The frequency-dependent properties of the suppression of the OAE were investigated using various stimuli to probe frequency ratios. The continuous tone time domain residual method has advantages for the observation of stimulus frequency OAEs and for relating these to any distortion product simultaneously generated.

Acoustic Stimulation↗

Otoacoustic emission tests in neonatal screening programmes.

Otoacoustic emission (OAE) testing has many characteristics which suit it for use as an objective neonatal auditory screener. The most important of these is the speed with which it can be performed. This feature alone opens up the possibility of much more general neonatal screening programmes. We here review the important considerations in applying otoacoustic testing to neonatal screening applications, and discuss the future role of OAE testing. Practical considerations in applying the technique are illustrated by examples and experiences drawn from a pilot whole-population neonatal screening project. Unselected screening takes us into unexplored territory. Test failure rate will inevitably far exceed the real incidence of hearing impairment. The concept of rapid whole-population neonatal OAE screening techniques as an additional risk factor detector rather than a definitive hearing test seems more appropriate to the low incidence of hearing impairment in the population and to the ethical problems surrounding early and erroneous diagnosis of hearing impairment.

Cochlea↗

The influence of contralateral acoustic stimulation on click-evoked otoacoustic emissions in humans.

Contralateral acoustic stimulation has the effect of reducing the amplitude and shifting the phase of click-evoked OAEs. This effect is thought to be mediated via the medial efferent system and, therefore, the presence of this effect could be used to test the integrity of the neural pathway from one cochlea to the other. With a clinical application in mind, a technique for demonstrating the influence of contralateral acoustic stimulation on click-evoked OAEs was designed to overcome fluctuations in patient and environmental noise. The results of this test on three normal subjects and a patient with a posterior fossa lesion are described.

Acoustic Stimulation↗

Effect of contralateral auditory stimuli on active cochlear micro-mechanical properties in human subjects.

The present study investigates the possibility that contralateral auditory stimulation along medial efferent system pathways may alter active cochlear micromechanics and hence affect evoked oto-acoustic emissions in humans. A first experiment, involving 21 healthy subjects showed reduction of oto-acoustic emission amplitude under low intensity contralateral white noise (from 30 dB SPL, 10 dB SL, upwards). The effect is found for intensities below the acoustic reflex threshold (85.2 dB HL). A second experiment, involving 10 of the above 21 subjects, sought to rule out any technical artefact. Recording was again carried out, but after sealing of the contralateral ear with a silicon putty plug. No contralateral intensity effect on oto-acoustic emission amplitude was found for contralateral intensities below 65 dB SPL. In subjective perception terms (dB SL) an effect was found under sealing when the sound reached or passed above the 10 dB SL level. These two findings confirm the preceding experiment. The third experiment investigated the role of transcranial transmission of the contralateral auditory stimulus. 16 subjects having total unilateral deafness and one healthy ear were tested by the same procedure as above. No fall-off in oto-acoustic emission amplitude was found for contralateral stimuli equal to or less than 80 dB SPL. There is thus a contralateral auditory stimulus effect on active cochlear micromechanics. The most appropriate explanation involves the medial cochlear efferent system, excited at brainstem level via the afferent auditory pathways. Alteration of active cochlear micromechanics seems promising at a basic level, pointing, as it does, to an interactive cochlear functioning which can be investigated by simple, non-intrusive, objective techniques which can be used with human subjects. We have here a model for functional exploration of the medial olivocochlear efferent system.

Acoustic Stimulation↗

A guide to the effective use of otoacoustic emissions.

Otoacoustic emission test instruments are now entering routine audiological practice. Two general classes of technique are in use in laboratory work--those employing spectrum analysers to observe the continuous generation of OAEs, both stimulated or unstimulated, and those using transient stimulation and waveform averaging to extract a delayed OAE or "cochlear echo" waveform from ear canal sound. Both methods have particular advantages in clinical applications. The transient OAE type of method has proved very effective in screening applications, particularly in neonates. It is possible to perform noninvasive screening acoustic cochleography in about a minute. The technique is also useful for characterizing cochlear mechanical status prior to long term monitoring. Achieving routinely reliable OAE test performance in clinical and screening applications under nonideal conditions makes special demands on the instrumental design and the response evaluation procedures. The essential requirements are reviewed and discussed in a general and specific context. We have tried to meet these requirements in a transient evoked otoacoustic emission system (the ILO88) which we designed to operate with a personal computer. We report on our design of probe, and our use of evaluation procedures for probe fit, and response quality. Signal processing methods have been developed to reject noncochlear acoustic responses, and to optimise the rejection of patient noise. Examples of its clinical use, and the practical problems typically encountered are given here.

Adult↗

Two-year comparative trial on the immunogenicity and adverse effects of purified chick embryo cell rabies vaccine for pre-exposure immunization.

The human diploid cell rabies vaccine (HDCV) has been shown to be highly immunogenic when used for pre-exposure immunization. However, the high cost of the product and the adverse reactions seen following booster doses of HDCV have limited its use. A purified chick embryo cell (PCEC) rabies vaccine was compared with the HDCV by two routes of administration for reactogenicity, antibody response, duration of antibody, and anamestic response to boosters over a 2 year period. The study showed that the two vaccines were comparable in their immunogenicity and reactogenicity after initial three dose series. No adverse reactions were noted following the 2 year booster with PCEC. The PCEC can be produced at less than one-half the cost of the HDCV.

Adult↗

A new rapid component in the cochlear response to brief electrical efferent stimulation: CM and otoacoustic observations.

The onset and time course of cochlear response changes induced by brief electrical stimulation of medial fibres of the OCB have been studied in detail in guinea pig. Changes in both cochlear microphonic and otoacoustic responses begin within 10 ms of electrical excitation. The sensitive differential technique employed has allowed the use of very short and weak electrical stimulations. The effects of induced levels of activity close to those normally present are reported. After transient electrical excitation (a single 100 microseconds, 20 mu amp shock), changes in the cochlear microphonic response reached a maximum around 20 ms. Thereafter the perturbation decayed initially with a time constant between 30 and 45 ms, then more slowly with a time constant greater than 100 ms. For more intense but still brief excitation the initial response decay was even more rapid often resulting in a bimodal decay pattern - a discrete 'burst' and a 'slow tail'. Otoacoustic data was similar. Only the slow tail component corresponds to previously reported effects and we suggest that it may be associated with overstimulation of the efferent system.

Acoustic Stimulation↗

Total parenteral nutrition in four healthy adult horses.

Total parenteral nutrition was accomplished in 4 healthy adult horses. During the 10-day study, the horses were not permitted to ingest food or water. Body weight was maintained at 94% of initial values without clinical evidence of dehydration. Serum urea nitrogen and triacylglycerol concentrations decreased during the study, without other significant hematologic or biochemical changes. Horses adapted without problems to the routine of IV feeding and confinement. All horses were healthy at the conclusion of the study. It was concluded that intravenous feeding with a lipid-glucose-amino acid-electrolyte solution was an acceptable method of maintaining nutrition in the healthy adult horse.

Animals↗

Pharmacokinetics of doxycycline in dogs.

Six adult dogs were given doxycycline hyclate at a dosage of 5 mg/kg of body weight intravenously so that pharmacokinetic parameters could be evaluated. Serum doxycycline concentrations were determined over a 48 h period using a modified agar well bioassay. Compartmental pharmacokinetic evaluation of the serum concentration time data indicated that doxycycline has a half-life of 10.36 h, a body clearance of 1.68 +/- 0.44 mL/min/kg, and a volume of distribution at steady state of 1.468 +/- 0.237 L/kg. Doxycycline pharmacokinetics are favorable for therapeutic use in the dog.

Animals↗

Pharmacokinetics of gentamicin after intravenous, intramuscular, and subcutaneous administration in cats.

Six adult mixed breed cats were given 5 mg of gentamicin sulfate/kg of body weight by rapid IV, IM, or SC injection. The serum concentration vs time data were analyzed, using a noncompartmental model based on statistical moment theory. The mean +/- SD for the effective half-life after IV administration was 1.25 +/- 0.30 hours. Mean residence time was 1.80 +/- 0.43 hours. The apparent volume of distribution at steady state was 0.14 +/- 0.02 L/kg. Total body clearance was 1.38 +/- 0.35 ml/min/kg. Bioavailability was 67.8% after IM and 76.2% after SC administration. A recommended dosage of 3 mg of gentamicin/kg every 8 hours was calculated; this dosage would induce an average steady state serum gentamicin concentration of 4 micrograms/ml. The SC route of administration was preferred because of rapid absorption, good bioavailability, and ease of administration.

Animals↗

Otoacoustic emissions, travelling waves and cochlear mechanisms.

The phenomenon of otoacoustic emissions is discussed in relation to the question--is the cochlear travelling wave actively enhanced? Distinctions are made between active loss reduction and true amplification, and between different types of emission source. The dynamic control exercised by the cochlea over the level of mechanical activity is analysed. An adaptive mechanism, capable of oscillatory transient behaviour is found both acoustically and psychophysically in response to strong low frequency stimulation. A feedback model is presented and used to predict aspects of emission behaviour.

Adaptation, Physiological↗

Acoustic emission cochleography--practical aspects.

Otoacoustic emissions are discussed as a means of objectively examining cochlear status. Practical uses of otoacoustic emission recording are reviewed, and the technical requirements of a clinical test are discussed. Details are given of an advanced cochlear echo test procedure, and results from normal and hearing impaired ears are discussed. Finally the alternative technique of distortion product analysis is discussed and results are given.

Biomechanical Phenomena↗

Antidotal effect of vitamin K1 against warfarin-induced anticoagulation in horses.

Warfarin-induced anticoagulation and reversal of the induced anticoagulation by vitamin K1 were evaluated in 4 mature horses. Each horse was given warfarin IV until the prothrombin (PT) time was prolonged by approximately 1.5 times the predosing base-line value. In experiment 1, we evaluated the time required for PT to return to the predosing value (PT reversal time) after warfarin administration was discontinued. Between each experiment, a 1-week rest period was allowed. In experiment 2, two doses of vitamin K1 (100 mg/dose) were administered IM 6 hours apart, and the PT was monitored hourly for 24 hours. In experiments 3 and 4, the horses were dosed with warfarin as in experiment 1, and the PT reversal time was evaluated after administration of 300- and 500-mg doses of vitamin K1 IM, respectively. In experiment 5, one horse was eliminated from the study, 1 horse was given 300 mg of vitamin K1 IV, and 2 horses were given 300 mg of vitamin K1 subcutaneously (SC); the reversal times were evaluated in the 3 horses given vitamin K1. Therapeutic response time was designated as the time required for the mean PT time of treated horses to reach the midpoint between the longest mean PT time achieved during anticoagulation and the mean base-line PT time. The therapeutic response time, without supportive therapy, after discontinuation of warfarin administration was 30 hours, and there was a PT reversal time of approximately 5 days from the last dose of warfarin. The 100-mg dose of vitamin K1 shortened the therapeutic response time to 12 hours and the PT reversal time to 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intermodulation distortion in the cochlea: could basal vibration be the major cause of round window CM distortion?

Acoustic and cochlear microphonic (CM) distortion products (DPs) have been measured at the meatus and round window, respectively, in the gerbil. It was hoped to deduce the relationship between round window CM distortion and vibrational energy of cochlear origin recorded as acoustic DP emissions in the meatus. Five different distortion components have been studied. For moderate intensities of stimulation, correlation between ear canal acoustic and CM distortion signals in respect of level and delay provides evidence of a common transmission path. One explanation of this is that the CM is being generated as a direct result of cochlea-generated vibration which reaches the base of the cochlea. The basalward propagation of these signals is discussed.

Acoustic Stimulation↗

Compartmental and noncompartmental pharmacokinetic analyses of minocycline hydrochloride in the dog.

Six adult dogs were given 5 mg of minocycline hydrochloride/kg of body weight IV. Pharmacokinetic evaluation of the serum drug concentration versus time data was performed, using the 2-compartment open model, the 3-compartment open model, and a noncompartmental model involving use of the statistical moment theory. All pharmacokinetic values except clearance were model independent. Minocycline half-life ranged between 6.48 and 7.24 hours; volume of distribution at steady state, between 1.859 +/- 0.368 and 2.001 +/- 0.468 L/kg; and clearance, between 3.195 +/- 0.618 and 3.424 +/- 0.684 ml/min/kg. These data are similar to those reported for oxytetracycline and indicate that the frequency of administration of the 2 tetracyclines should be the same. Three of the 6 dogs developed an adverse response to the IV injection of minocycline. Dog 1 developed urticaria and had initial serum drug concentrations of approximately 2 times the mean concentrations for the other dogs; values were not included in the pharmacokinetic analysis. Two other dogs had transient signs indicating cardiovascular depression or hypotension; their data were included. Due to the frequency of the unexpected reactions found in this study, it was concluded that dogs should not be given minocycline rapidly IV.

Animals↗

Pre-exposure rabies prophylaxis: efficacy of a new packaging and delivery system for intradermal administration of human diploid cell vaccine.

The efficacy of a newly designed syringe prepacked with human diploid cell vaccine in a sufficient quantity to deliver individual 0.1 ml doses intradermally was tested by injecting 40 veterinary students with a single dose on each of days 0, 7 and 28. A second group of 20 students received the ordinary series of three 1.0 ml intramuscular vaccine doses by needle and syringe. All participants in both groups developed neutralizing antibodies to rabies above the suggested minimum of 0.5 international units per ml by day 49. The geometric mean titres were somewhat lower in the group receiving the 0.1 ml doses compared to the group given 1.0 ml doses; however, this was considered of no clinical significance since everyone achieved a titre above the suggested minimum. There was little difficulty in reconstituting the vaccine prepacked in the lumen of the syringe and the syringe was easy to manipulate.

Adult↗

Suppressibility of the 2f1-f2 stimulated acoustic emissions in gerbil and man.

The suppression tuning properties of the oto-acoustic distortion product emission, 2f1-f2 have been measured in the ear canal of gerbil and man. The results show the acoustic response to be suppressible in a similar, frequency-dependent manner in both species. Frequencies near to those of the stimulating tones are most effective in suppressing the response. Derived iso-suppression tuning curves have Q10dB values of between 1 and 6. Suppressor tones having frequencies near to f2 (the higher frequency stimulus) make a contribution to the tuning curve which is largely independent of the stimulus intensity and the frequency ratio between the two primary tones. Suppressors having f1-associated frequencies produce a variable amount of suppression depending on the stimulus parameters chosen. No specific suppression feature could be associated with suppressors near to 2f1-f2. The frequency selectivity of the acoustic DP generation mechanism shown by this study indicates a close association with the transduction mechanism. The demonstration of comparable signals in gerbil and man facilitates the direct transfer of laboratory results to the study of human ears.

Acoustic Stimulation↗