The effect of daily repeated sedation using ketamine or ketamine combined with medetomidine on physiology and anesthetic characteristics in Rhesus Macaques

Background  Non-human primates are frequently sedated to permit handling that can alter physiological values. The purpose of this study was to identify the effects of daily serial sedation using ketamine (K) or ketamine combined with medetomidine (KM). We hypothesized KM would reduce observed effects of repeated sedation.
Methods  Eight rhesus macaques were anesthetized for three consecutive days. Physiological data were recorded daily at 5-minute intervals. Time intervals from injection to ataxia, recumbency, first movement and recovery were recorded. Depth of anesthesia was evaluated.
Results  Data showed an 11.7% increased heart rate at 5 minutes between the first and third day of injection with K and 17.9% with KM. Time from injection to ataxia increased 13.7% with K and 14.3% with KM. Time to recumbency increased 34.7% with K and 37.1% with KM.
Conclusion  These findings demonstrate repeated anesthesia with ketamine can initiate changes suggesting a tolerance effect.     

The effect of repeated testing on judgement biases in sheep

Testing judgement biases of animals may provide insight into their affective states; however important questions about methodologies need to be answered. This experiment investigated the effect of repeated testing using unreinforced, ambiguous cues on the response of sheep to a go/no-go judgement bias test. Fifteen sheep were trained to differentiate between two locations, reinforced respectively with feed (positive) or with the presentation of a dog (negative). The responses to nine ambiguous locations, positioned between the positively and negatively reinforced locations, were tested repeatedly over 3 weeks. Sheep exhibited a symmetrical gradation in response to ambiguous locations between the positive and negative reinforcers. There was a significant decline (P = 0.001) in the total number of approaches to the ambiguous positions over time (weeks). This effect of time suggests that sheep learnt that the ambiguous locations were unrewarded. This result supplies evidence of a limitation identified in current judgement bias methodology, due to repeated testing, which has the potential to provide misleading results.     

Estimating a treatment effect with repeated measurements accounting for varying effectiveness duration

To assess treatment efficacy in clinical trials, certain clinicaloutcomes are repeatedly measured over time for the same subject.The difference in their means may characterize a treatment effect.Since treatment effectiveness lag and saturation times may exist,erosion of treatment effect often occurs during the observationperiod. Instead of using models based on ad hoc parametric orpurely nonparametric time-varying coefficients, we model thetreatment effectiveness durations, which are the time intervalsbetween the lag and saturation times. Then we use some meanresponse models to include such treatment effectiveness durations.Our methodology is demonstrated by simulations and analysisof a landmark HIV/AIDS clinical trial of short-course nevirapineagainst mother-to-child HIV vertical transmission during labourand delivery.     

The effect of repeated temperature shock on baker's yeast

Summary In a recycle system in which evaporation is used for ethanol recovery during fermentation, temperature changes of the broth in the loop will occur. These repeated temperature shocks may have an effect on the microbial ethanol production rate. In this study such repeated temperature changes were simulated in a recycle system with ethanol production by baker's yeast. The magnitude of the temperature change, as well as the time of exposure to this change were found to have an effect on the ethanol production rate. A temperature increase from 30°C in the fermentor to 35°C or more in the recycle loop led to a significantly lower ethanol concentration in the broth. This effect became negligible at a short exposure time of 18 s of the yeast to the higher temperature. Correspondence to: R. G. J. M. van der Lans     

The dual effect of enflurane on gill withdrawal reflex ofAplysia

Superfusion of clinical concentrations of enflurane (0.5% or 1.0%), an inhalation anaesthetic, over the abdominal ganglion ofAplysia significantly affected the amplitude of the gill withdrawal reflex evoked by tactile stimulation of the siphon. Enflurane superfusion (0.5%) suppressed the gill withdrawal reflex amplitude (to 46.1% of control; P<0.001 vs control) in eight of ten experiments. In the remaining two experiments, enflurane superfusion of the abdominal ganglion significantly facilitated the gill withdrawal reflex amplitude (174.5% of control;P<0.01). In addition, enflurane superfusion significantly reduced the number of action potentials evoked in central gill motor neurons by the siphon stimulation (to 47.1% of control;P<0.01) in six out of nine experiments. In one of the remaining three experiments, enflurane increased the number of action potentials evoked by the stimulus (to 200.0% of control). In two of the three, enflurane did not alter the numbet of action potentials. Behavioural responses were ‘uncoupled’ from the neuronal responses as a result of enflurane superfusion.     

Analysis of experimental data with repeated measurements

Summary. Experimental data often consist of serial measurements on subjects after a treatment. Typical questions concerning such data are: (A) Do subjects really react to treatment or are the fluctuations just random? (B) What are the numerical characteristics of the response? (C) Is the response identical in all groups? Differences between the individuals in the dynamics of the reaction make it difficult to apply standard statistical procedures. This paper proposes to answer questions (A) and (B) at the individual level, then to give an answer to (C) on the basis of this information. This kind of analysis may be useful since it can separate subjects giving response from those that do not and can identify individual response patterns and compare treatments with respect to each numerical characteristic separately. To answer question (A), a permutation test is proposed and its power is evaluated by simulation.     

The effect of repeated intermittent hypoxia on pulmonary vasoconstriction in the newborn

The effect of repeated intermittent hypoxia upon the basal pulmonary vascular tone in the newborn period is unknown. We therefore studied the central hemodynamic response to seven repeated intermittent hypoxic challenges in acutely prepared piglets under 2 weeks of age. Catheters were placed in the aorta, pulmonary artery, and atria, and an electromagnetic flow probe was positioned around the main pulmonary artery. Each hypoxic challenge (Fio2 = 0.14) lasted 5 min, and was separated by an equal duration of ventilation with air. Nine control animals were ventilated with air for 90 min, a period of time equivalent to the seven challenges in the experimental group, and subjected to one hypoxic challenge at the end. Hypoxia uniformly induced pulmonary vasoconstriction. Repeated intermittent hypoxic challenges produced a progressive increase in pulmonary artery pressure and vascular resistance, both during air ventilation and hypoxia. For each challenge, the vascular resistance value achieved during hypoxia was directly related to the immediately preceding air ventilation one, and the magnitude of hypoxic pulmonary vasoconstriction, defined as the incremental change in resistance from air to hypoxia, was not different from the first to the last challenge in the experimental group. In the control group the pulmonary vascular tone did not change during the 90 min of air ventilation, and the single hypoxic challenge induced an increase in pulmonary vascular pressure and resistance similar in magnitude to the first challenge in the experimental group. Indomethacin administration to five experimental animals, after the last challenge, reversed the increase in air ventilation pulmonary artery pressure and vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sample sizes in the multivariate analysis of repeated measurements

Determination of sample sizes for comparing two or more treatments in repeated measurements experiments is considered. Multivariate normality of the individual's vector of repeated measures is assumed. Particular emphasis is placed on applications wherein the error variance-covariance matrix is arbitrary positive-definite. Sample size determination is based on power considerations associated with Hotelling's T2 test and the desire to detect a specified difference between any pair of treatment means. Tabulated sample sizes are given in the case of an equal variance-unequal covariance structure. The utility of these sample sizes is also demonstrated for a more general variance-covariance structure. Applications of these sample sizes are illustrated with two examples.     

The effect of delta-9-tetrahydrocannabinol on barbiturate withdrawal convulsions in the rat

Rats were given increasing oral doses of sodium barbital over a four-week period until a daily dose of 400 mg/Kg was attained and continued for one week. Upon withdrawal from the barbital, the animals were found to be susceptible to sound-induced convulsive seizures. Dose-dependent seizure protection was provided by administration of delta-9-tetrahydrocannabinol (THC).     

Effect of repeated daily electrical stimulation on seizure activity in the rabbit limbic system

The order of appearance, the functional relations, and changes in the epileptiform effects of electrical stimulation of the limbic system (septum, amygdala, hippocampus) were studied. During repeated electrical stimulation regular changes took place in the seizure activity: the duration, frequency, and amplitude of the after-discharges were increased, their polarity was changed, seizures and unsynchronized high-amplitude activity appeared, and the after-discharges were reactivated. The most common variants of the seizure patterns are described. Close correlation was found between the greatest intensity of the after-discharges and the appearance of seizures. Besides a critical number of after-discharges, their parameters and their degree of irradiation also play an important role in the onset of the seizures. It is postulated that the limbic structures may play the role of an organized epileptogenic focus. Facts indicating that the seizure activity in response to direct electrical stimulation of the limbic structures may have a reflex mechanism are presented.     

The effect of repeated bouts of backward walking on physiologic efficiency

Previous studies have demonstrated an increased energy expenditure with novel tasks. With practice, the energy cost decreases as the body more efficiently recruits motor units. This study examined whether one becomes more efficient after repeated bouts of backward walking. The subjects were 7 healthy subjects between the ages of 23 and 49 years. A backward walking speed was calculated to elicit a VO(2) equal to 60% of the VO(2)max. There were 18 training sessions at the prescribed walking speed 3 d x wk(-1) for 20 min x d(-1). The backward walking speed required to elicit a fixed VO(2) increased between weeks 4 and 6 of the training period. This finding suggests that backward walking is indeed a novel task and that motor learning occurs as a result of practice, leading to a more efficient recruitment of motor units.     

The effect of daily disturbance on the breeding performance of mice

The United Kingdom Home Office Code of Practice for the housing and care of breeding animals requires that, 'the general well-being of all animals must be checked at least once daily'. However, excessive daily disturbance of rodent breeding colonies could be counter-productive to animal welfare if it increases pre-weaning mortality. An experiment involving 100 breeding cages of BALB/c mice compared daily inspection of the mouse cages, but without disturbing the mice within the nest, with daily inspection in which every individual was studied even if this involved removing the cage lid and disturbing the nest. No statistically significant differences were found between the two groups in breeding performance or pre-weaning mortality, though the disturbed group produced marginally fewer offspring and had slightly higher mortality. Average weaning weight did not differ between the groups, but sexual dimorphism at weaning was significantly increased in the disturbed group. It is concluded that there are unlikely to be any welfare benefits in an inspection regimen that involves disturbance of breeding mice, provided the cage is inspected daily.     

An approach to the analysis of repeated measurements

A linear model for repeated measurements is proposed in which the correlation structure within each time sequence of measurements includes parameters for measurement error, variation between experimental units, and serial correlation within units. An approach to data analysis is presented which involves preliminary analysis by ordinary least squares, use of the empirical semi-variogram of residuals to suggest a suitable correlation structure, and formal inference using likelihood-based methods. Applications to two biological data sets are described.     

The effect of repeated boar exposure on cortisol secretion and reproduction in gilts

It has been proposed that short-term activation of the hypothalamo-pituitary adrenal axis, with a consequent increase in the secretion of cortisol, may disrupt the endocrine events prior to ovulation and thereby impair reproduction in females. We investigated this concept in gilts in which oestrus was detected by introduction to boars, where intense physical contact is possible, or by applying pressure to the back of gilts (back-pressure test) during fence-line exposure to boars, where intense physical contact is prohibited. We expected that there would be a greater release of cortisol and that reproduction would be inhibited in gilts introduced to boars compared to gilts in which the back-pressure test was used. As expected, introduction of gilts to boars resulted in a significant transient increase in plasma concentrations of cortisol while there was no significant effect of using the back-pressure test on plasma cortisol. Nevertheless, introduction of gilts to boars did not impair reproduction and there was no effect of method of detecting oestrus on duration of oestrus, sexual receptivity, fertility or fecundity. The length of the oestrous cycle was decreased and ovulation rate increased in gilts that were introduced to boars compared to gilts that underwent the back-pressure test, indicating that introduction of gilts to boars may have stimulated these aspects of reproduction. These stimulatory effects may have been due to an increased exposure of gilts to sexual behaviour and stimuli from boars when introduced to boars and/or to stimulatory effects of the hypothalamo-pituitary adrenal axis on some aspects of reproduction.     

The effect of repeated reproduction on the incidence of pituitary tumours in Wistar rats

Weanling female litter mates were equally proportioned at the start of the study between a breeding and a non-breeding group. At 10 weeks of age, each rat of the breeding group was housed individually with a male until 5 litters were produced (or exceptionally for a maximum of 42 weeks) before the male was removed. Females of the non-breeding group were kept singly in similar cages. 2 years after the start of the study all the surviving rats of both groups were killed. Comprehensive necropsies were performed on the decedents and survivors and the pituitary gland of each rat was examined histologically. The 48% survival of the female rats which were allowed to breed was better, but not significantly so, than the 38% of those not allowed to breed. Overall fewer, 70% (35 of 50) of the mated female rats had pituitary tumours compared with 80% (40 of 50) of the non-mated group. Fewer of the decedents, 69% (18 of 26), of the mated females had pituitary tumours compared with 94% (29 of 31) in the decedents of the non-mated group. More survivors, 71% (17 of 24), of the mated females had pituitary tumours compared with 58% (11 of 19) of the surviving non-mated rats. A tumour was first observed at day 328 in the non-mated group, whilst in the mated group the first tumour was identified at day 450. It is suggested that breeding delays the appearance of pituitary tumours in the female rat.