Lameness in the dairy cow: pain and welfare.
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Biomedical subjects
Publications and source records attributed to A M Nolan.
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The anti-inflammatory effects of the non-steroidal anti-inflammatory drugs phenylbutazone (PBZ) and flunixin meglumine (FM) and the relationship between the effects and drug concentration in vivo were studied using a subcutaneous tissue-cage model in sheep. Intracaveal injection of carrageenan induced prostaglandin (PG) E2 production in tissue-cage exudate (maximal concentration, 101 nM) with significant increases in white blood cell (WBC) numbers, skin temperature over the inflamed cage and exudate leukotriene B4 (LTB4) concentration (P < 0.05). Intravenous PBZ, 4.4 mg kg-1 produced mild inhibition of exudate PGE2 generation (10%), but greater inhibition of serum TXB2 (75.3%). The IC50 for TXB2 was 36.0 microM. Phenylbutazone did not alter effects on skin temperature, WBC numbers or exudate LTB4 concentrations. Intravenous FM, 1.1 mg kg-1, significantly inhibited carrageenan-induced exudate PGE2 formation (Emax, 100%, IC50, < 0.4 nM) and serum TXB2 generation (Emax, 100%, IC50, 17 nM) for up to 32 h. Flunixin meglumine significantly inhibited the rise in skin temperature but had a limited effect on exudate WBC. Phenylbutazone and FM have distinct effects on carrageenan-induced cyclooxygenase (COX-2) and platelet COX (COX-1). Flunixin meglumine was a more potent COX inhibitor than PBZ and was more selective for the inducible form of COX in vivo.
A study was designed to investigate the association between heart rate, respiratory rate and pupil dilation and a subjective pain score allocated using a numerical rating scale (NRS). Four groups of dogs (n = 17 to 20 per group) were included: orthopaedic surgery cases, soft tissue surgery cases, dogs with medical conditions and healthy dogs. Each dog was examined by five veterinary surgeons within a four-hour period. When examining each dog, the observers recorded heart rate, respiratory rate, pupil dilation (present or absent) and a pain score using a NRS (range 0 to 10). For surgical cases, all study assessments were carried out between 21 and 27 hours following the end of surgery. The correlation coefficients between physiological parameters and NRS score were small but, depending on the analysis, were significant for heart rate and NRS score (P < 0.05). However, the size of the coefficient, 0.168, indicated that the relationship was not biologically significant. There was no association between respiratory rate and NRS score. Analysis of the relationship between NRS score and pupil dilation indicated that there was an association between this factor and pain, depending on the analysis. This was significant for the surgical groups (P < 0.05) but not for the other groups. These findings indicate that heart rate and respiratory rate are not useful indicators of pain in hospitalised dogs. It is also unlikely that pupil dilation will be a useful tool in the assessment of pain.
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The pharmacokinetics of propofol were investigated in two groups of five Scottish blackface sheep undergoing surgery for the implantation of subcutaneous tissue pouches. After premedication with acepromazine and papaveretum, anaesthesia was induced with either propofol at 4 mg kg-1 intravenously (group 1) or with a mixture of propofol at 3 mg kg-1 and ketamine at 1 mg kg-1 intravenously (group 2). Anaesthesia was maintained with a variable infusion rate of either propofol alone (group 1) or propofol and ketamine (group 2). Both regimens produced satisfactory conditions for superficial surgery of the body surface. The mean (SD) duration of anaesthesia was 64.8 (3.1) minutes for group 1 and 60 (0) minutes for group 2; the mean total dose of propofol given to the sheep in group 1 was 801 (84) mg, and the sheep in group 2 received 470 (46) mg of propofol and 267 (30) mg of ketamine. The mean elimination half-life of propofol was 56.6 (13.1) minutes in group 1 and 50.3 (21.4) minutes in group 2; the mean volume of distribution at steady state was 1.037 (0.480) litre kg-1 in group 1 and 1.515 (0.939) litre kg-1 in group 2; the mean body clearance was 85.4 (28.0) ml kg-1 min-1 in group 1 and 128.0 (35.0) ml kg-1 min-1 in group 2; the mean residence time corrected for a bolus injection was 12.1 (4.2) minutes in group 1 and 11.9 (6.6) minutes in group 2; for the infusion, the mean residence time was 72.1 (4.2) minutes in group 1 and 69.9 (7.9) minutes in group 2. There were wide variations in the blood propofol concentrations reached in individual sheep by using this standard dosing regimen. All the sheep recovered quickly from anaesthesia; the mean times to extubation, sternal recumbency and standing for the animals in group 1 were 2.8 (0.4), 6.3 (1.2) and 10.9 (1.6) minutes from the end of the infusion, and the times for group 2 were 5.3 (0.9), 11.2 (1.7) and 15.1 (2.2) minutes.
The pharmacokinetics of propofol were investigated in six unpremedicated dogs aged between eight-and-a-half and 10.5 years. After the induction of anaesthesia with a bolus dose of 5 mg kg-1 propofol administered intravenously, the trachea was intubated and anaesthesia was maintained with halothane in a gas mixture of oxygen and nitrous oxide. The mean (sd) t1/2 beta was 83.9 (14.8) minutes, the mean (SD) residence time was 99.0 (10.8) minutes, the mean body clearance was 34.5 (12.1) ml kg-1 minute-1 and the mean volume of distribution at steady state was 3864 (1647) ml kg-1. The dose of propofol was lower than that recommended in the data sheet (6.5 mg kg-1) and was associated in some of these dogs over eight years of age with post-induction apnoea. The clearance of propofol was also slower than that previously reported in young dogs. These results have implications for infusion rates when propofol is used to maintain anaesthesia in dogs.
The antinociceptive effect of flunixin meglumine was assessed in healthy and lame sheep by using a noxious mechanical stimulus. Sheep suffering from the chronically painful condition, footrot, have previously been shown to have lower thresholds to noxious mechanical stimuli than healthy animals. In the present study, 22 sheep suffering from footrot did not have a lower mean mechanical threshold than 25 matched healthy animals, but it was significantly greater than that recorded from eight experimental sheep (5.0 [2.5], 4.9 [2.1] and 3.0 [1.0] Newtons, respectively). Doses of 1.0 or 2.0 mg kg-1 of flunixin meglumine had no effect on the thresholds to noxious mechanical stimulation in either experimental sheep tested over six hours, or in lame sheep tested over a period of 30 minutes. The repeated administration of flunixin to sheep suffering from footrot over a period of three days reduced their thresholds to noxious mechanical stimulation.
A tourniquet was used in conjunction with a mechanical threshold testing device to investigate the suitability of the technique for the investigation of analgesic drugs in sheep. The changes to the mechanical thresholds to noxious stimulation during and after the inflation of a pneumatic tourniquet on a limb were recorded, and the influence of pre-treatment with two non-steroidal anti-inflammatory drugs was studied. Fentanyl, an opioid agonist with known analgesic properties in sheep, was used as a positive control. The tourniquet significantly reduced the mechanical thresholds on the ipsi- but not the contralateral limb. Pretreatment with either flunixin meglumine or carprofen attenuated the development of mechanical hyperalgesia, and fentanyl initially caused a significant anti-nociceptive effect. The time to aversion was not significantly different between the treatments. These results suggest that hyperalgesia induced by a tourniquet may be a useful technique for the investigation of the anti-nociceptive effects of analgesic drugs in sheep.
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Pharmacokinetic variables of propofol were investigated in 6 mixed-breed dogs, and the effect of medetomidine (10 micrograms/kg of body weight) on these kinetics was investigated using a two-way crossover design. On 2 occasions, dogs received either a bolus dose of propofol sufficient to allow endotracheal intubation, followed by an infusion of propofol (0.4 mg/kg/min) for 120 minutes, or medetomidine (10 micrograms/kg, IM), 15 minutes prior to induction of anesthesia as described, followed by infusion of propofol (0.2 mg/kg/min). Dogs given medetomidine received atipamezole (50 micrograms/kg, IM) at the end of the 120-minute propofol infusion. Blood propofol concentration was measured, using high-performance liquid chromatography with fluorescence detection. Mean elimination half-life, blood clearance, mean residence time, and mean volume of distribution at steady state, were 486.2 minutes, 34.4 ml/kg/min, 301.8 minutes, and 6.04 L/kg, respectively, in the absence of medetomidine, and 136.9 minutes, 36.2 ml/kg/min, 215.1 minutes, and 3.38 L/kg, respectively, in the presence of medetomidine. Mean time to walking without ataxia was 174 minutes in the nonpremedicated dogs (with a median blood propofol concentration of 2.2 micrograms/ml) and was 160 minutes in the premedicated dogs in which median blood propofol concentration was 1.03 microgram/ml.
An improved technique to photographically record 2-Dimensional shoe sole impressions "to scale" is described. This technique was developed as a result of continual attacks in court in relation to the question of precise SCALE. Staff at our laboratory are routinely required to examine shoe sole impressions evidence that has been collected by our Scenes of Crime Officers. The Scenes of Crime Officers have been instructed in the appropriate photographic techniques which should be used to record 2-Dimensional shoe sole impressions, however, for one reason or another, including inexperience, this technique is not rigidly adhered to. We have seventy-five (75) Scenes of Crime Officers throughout Queensland, and nearly all of the shoe sole interpretation work is done in the Brisbane Headquarters. It is the case that the Scenes of Crime Officers record the scene and other photographers record the Test Impression. There are three problems that affect the quality of the scale photographs submitted. 1. The camera is not directly over the center of the subject. 2. The camera is not exactly parallel to the subject. 3. The designs of the camera lens. These problems are highlighted when barristers compare the scale photos of the test impressions made in the laboratory, with the scale photos of the scene impressions. Barristers actually measure the distance between features and usually a discrepancy (albeit slight) is found. The GRID allows us to demonstrate to Lay persons and Lawyers the interrelationship of identification features, by reference to a particular GRID.
Flunixin meglumine was administered intravenously and intramuscularly in sheep and the pharmacokinetics of the drug studied. Plasma concentrations of flunixin were measured by high performance liquid chromatography. The decline in plasma flunixin concentration with time was best fitted by a triexponential equation. The pharmacokinetics following intravenous administration of 1.0 mg/kg indicate that flunixin has a rapid distribution half-life (t1/2 pi = 2.3 min), a slow body clearance rate (Clb = 0.6 ml/kg/min) and an elimination half-life of 229 min. Similarly, at 2.0 mg/kg, flunixin is rapidly distributed from the plasma, t1/2 pi = 2.7 min, has a slow body clearance rate (Clb = 0.7 ml/kg/min) and an elimination half-life of 205 min. Following intramuscular injection flunixin is rapidly and well absorbed from the injection site. It had a mean maximum concentration (Cmax) of > or = 5.9 micrograms/ml when administered at a dose rate of 1.1 mg/kg, and a relative bioavailability of 70%. Plasma concentrations increase proportionally to dose over the range 1.1 mg/kg-2.2 mg/kg when administered by the intramuscular route.
The pharmacokinetics of propofol, 6.5 mg/kg, administered as a bolus dose intravenously (i.v.) were studied in six dogs (group 1). The effect of maintaining anaesthesia with halothane and nitrous oxide in oxygen on propofol pharmacokinetics was also investigated in six dogs undergoing routine anaesthesia (group 2). Induction of anaesthesia was rapid in all animals. Post-induction apnoea was a feature in three of the 12 dogs. The blood propofol concentration-time profile was best described by a bi-exponential decline in two dogs in group 1 and in 3 dogs in group 2, and by a tri-exponential decline in four dogs in group 1 and 3 dogs in group 2. The elimination half-life was long in both groups (90.9 min and 75.2 min, respectively), the volume of distribution at steady state large (4889 and 4863 ml/kg) and the clearance rapid (58.6 and 56.3 ml/kg.min). There were no significant differences between the groups, thus indicating that maintenance of anaesthesia with halothane and nitrous oxide had no effect on the pharmacokinetics of propofol in the dog.
The pharmacokinetics of propofol, 4 mg/kg, administered as a bolus dose intravenously (i.v.) prior to the maintenance of anaesthesia with halothane in oxygen, were determined in five goats, and a clinical impression of its use as an induction agent was made. Induction of anaesthesia was rapid and smooth, providing satisfactory conditions for intubation in all animals. Post-induction apnoea occurred in one goat and minimal regurgitation of ruminal contents was recorded in two animals. Recovery times were rapid with a mean time to standing after halothane inhalation ceased of 13.7 min. The blood propofol concentration time profile was best described by a bi-exponential decline in all five goats. The mean elimination half-life was short (15.5 min), the volume of distribution at steady state large (2.56 l/kg) and the clearance rapid (275 ml/min.kg). Propofol was shown to be a very satisfactory induction agent in the goat.
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A study was designed to compare use of an numerical rating scale (NRS) and a visual analogue scale (VAS) for subjective assessment of lameness, using sheep as a model. The NRS consisted of 5 divisions, 0, 1, 2, 3, and 4; 4 of these divisions (1-4) described lameness. The VAS used a 100-mm horizontal line with vertical bars at either end; one end was labeled 'sound' and the other was labeled 'could not be more lame.' Two independent observers graded lameness in 62 sheep, and between- and within-observer differences were assessed for each scoring system to compare the NRS with the VAS. Results indicated no significant differences between the 2 observers scoring lameness, using either the VAS or the NRS. The scores obtained, using the VAS, were not normally distributed, although differences between scores for the 2 observers were. The NRS scores followed a normal distribution pattern. Investigation of repeated measurement for the same sheep, using both scales, revealed no significant difference between either. A comparison of the NRS and VAS scores made by each observer indicated that although correlation was good (observer 1; r = 0.94; observer 2; r = 0.95), there was not perfect agreement. The maximal NRS score of 4 was associated with VAS values > 68 mm, indicating that the NRS divisions did not reflect equal increases in lameness. The VAS and NRS scores for each observer were highly reproducible, although they were more variable for sheep that were regarded as moderately lame.(ABSTRACT TRUNCATED AT 250 WORDS)
Carprofen was administered intravenously to sheep at two dose rates (0.7 and 4.0 mg kg-1), and the pharmacokinetics of the drug studied. Plasma concentrations of the drug were measured by high performance liquid chromatography. Carprofen had a small volume of distribution (Vd[area], 95.5 and 118.4 ml kg-1), a prolonged elimination half-life (t1/2 beta, 26.1 and 33.7 hours) and a slow body clearance rate (Clb, 2.5 ml kg-1 h-1) in sheep.
The alpha 2 agonist xylazine produced a dose-dependent decrease in mean arterial blood pressure in conscious rabbits when injected intrathecally (i.t.) through a cannula previously implanted under general anaesthesia. Intrathecal administration of 200 and 400 micrograms of xylazine produced a significant reduction in arterial blood pressure from control values (maximum depressions of 25% and 33%, respectively). There was little effect on cardiac output and arterial carbon-dioxide tension and no effect on respiratory rate, arterial oxygen tension and pulse rate. Intrathecal injection of 100 microliters of 0.9% saline had no effect. Intravenous (i.v.) tolazoline (0.5 mg/kg) abolished xylazine-induced hypotension (200 micrograms) in four rabbits. Contrast radiography revealed that 100 microliters of solution injected i.t. in anaesthetized rabbits spread distally over eight vertebral spaces. There was little rostral spread. It was concluded that xylazine-induced hypotension following i.t. injection was due to local activation of alpha 2 adrenoceptors present in the thoracic spinal cord. It is postulated that spinal alpha 2 adrenoceptors may play an important role in the hypotension recorded in animals after parenteral injection of xylazine.