Pharmacokinetics and effect on renal function and average daily gain in lambs after castration and tail docking, of firocoxib and meloxicam.

AIMS: To evaluate and compare the pharmacokinetics of IM and oral firocoxib, and IM meloxicam, and detect their effect on renal function and average daily gain (ADG) in lambs undergoing tail docking and castration. METHODS: Seventy-five male Romney lambs, aged 3-6 weeks, were randomised into five treatment groups (n = 15 per group): IM firocoxib (1 mg/kg); oral firocoxib (1 mg/kg); IM meloxicam (1 mg/kg); normal saline (approximately 2 mL, oral); or sham. Following the treatment administration, hot-iron tail docking and rubber ring castration were performed in all groups except the sham group, which did not undergo the procedures, but the animals were handled in the same manner as castrated and tail docked lambs. Blood samples were collected before and 1, 2, 4, 6, 8, 24, 48, 72, 96 and 120 hours after treatment administration, and drug concentrations in plasma were quantified by liquid chromatography and mass spectrometry. Plasma urea and creatinine concentrations were determined at a commercial laboratory. Lamb body weights were recorded before and 2, 4 and 8 weeks after tail docking and castration. The pharmacokinetic analysis was carried out using a non-compartmental approach. Between-group and between-time-point differences were compared using mixed model analyses. RESULTS: There was no evidence for a difference in plasma elimination half-life between firocoxib given IM (LSM 18.6 (SE 1.4) hours), firocoxib given orally (LSM 18.2 (SE 1.4) hours), and meloxicam given IM (LSM 17. 0 (SE 1.4) hours). Firocoxib (IM) had a significantly greater volume of distribution (LSM 3.7 (SE 0.2) L/kg) than IM meloxicam (LSM 0.2 (SE 0.2) L/kg). Lambs in the meloxicam group had higher (p < 0.05) plasma urea and creatinine concentrations than those in the firocoxib, saline and sham groups. Lambs' ADG was decreased (p < 0.01) compared to the other treatment groups in the 0-2 week period following meloxicam administration. CONCLUSIONS AND CLINICAL RELEVANCE: Both formulations of firocoxib had a long plasma elimination half-life and large volume of distribution. There was a transient reduction in ADG in the meloxicam group, possibly due to mild renal toxicity. Comparative studies on dose-response effects of firocoxib and meloxicam in lambs following the procedures are required.Abbreviations: ADG: Average daily gain; Cmax: Maximum concentration; COX: Cyclooxygenase; LOD: Limit of detection; NSAID: Non-steroidal anti-inflammatory drugs; CL: Plasma clearance; T1/2el: Plasma elimination half-life; Tmax: Time to achieve Cmax; Vd: Volume of distribution.

Euthanasia of dogs and cats by veterinarians in New Zealand: protocols, procedures and experiences.

AIMS: To collect data on protocols used by New Zealand veterinarians to perform euthanasia of dogs and cats, and to explore opinions towards the training they received in euthanasia during veterinary school. METHODS: A cross-sectional survey was administered to all veterinarians registered with the Veterinary Council of New Zealand. The survey asked respondents about their practices' policies for euthanasia; protocols for performing euthanasia of dogs and cats; opinions towards euthanasia training received in veterinary school; and subsequent experiences with euthanasia in practice. Descriptive statistics were provided for all quantitative study variables and thematic analysis was performed on the free-text comments. RESULTS: The survey was completed by 361/1,448 (24.9%) veterinarians in companion or mixed animal practice. The mean numbers of dogs and cats euthanised each month were 7.2 (median 5; min 0; max 60) and 7.9 (median 5; min 0; max 60), respectively. Fewer than half of respondents reported that their clinic had a standard protocol for euthanising dogs (147/361; 40.7%) or cats (157/361; 43.5%). For euthanasia of dogs, 119/361 (32.9%) always used sedation while 71/361 (19.7%) indicated that they would not use sedation. For euthanasia of cats, 170/361 (47.1%) always used sedation while 53/361 (14.7%) indicated that they would not use sedation. Placement of IV catheters, methods for patient restraint, preferences towards the presence of owners during euthanasia, services provided with euthanasia, and discussions with owners were also highly variable and handled case-by-case depending on the client, patient, and clinical scenario. When asked about the euthanasia training received at veterinary school, it was generally ranked as below satisfactory, with approximately one-third of respondents indicating that they received no training in dealing with emotional clients (113/361; 31.3%), sedation protocols for euthanasia (107/361; 29.6%), or managing compassion fatigue (132/361; 36.6%). Most respondents (268/361; 74.2%) received no formal training in euthanasia after graduation and learned from experience or discussions with colleagues. Providing animals and owners with a good experience during the euthanasia process was highlighted as important for managing compassion fatigue. CONCLUSIONS: Euthanasia is a common procedure in companion animal practice and there is considerable variation in how veterinarians approach both the technical and non-technical elements. Training provided during veterinary school was generally considered below satisfactory, particularly regarding managing compassion fatigue and clients' emotional needs. CLINICAL RELEVANCE: Providing veterinarians with additional training on adapting their euthanasia protocols to different clinical scenarios may improve the experience for patients, owners and veterinary staff.

Practices and opinions of New Zealand sheep farmers towards pain management in lambs during castration and/or tail docking.

AIMS: To collect baseline data from New Zealand sheep farmers on techniques for docking and castrating lambs, their perceptions of the level of pain lambs experience following these procedures, and their opinions about the use of pain relief. METHODS: From a voluntary cross-sectional survey of New Zealand sheep farmers, descriptive statistics were provided for quantitative study variables. Thematic analysis was performed on the free-text comments. Univariable logistic regression was used to assess factors associated with farmers indicating they would consider using a device allowing administration of pain relief simultaneously with castration and tail docking. RESULTS: There were 432 survey responses containing sufficiently complete data for analysis. Of the 340 individuals (77.5%) always or sometimes performing castration of ram lambs, 242 (72.2%) used rubber rings for complete castration, 23 (6.9%) used the short scrotum method for cryptorchid castration, and 75 (22.4%) used a combination of both methods. Of the 423 individuals (97.9%) who indicated that they always or sometimes performed tail docking, 245 (57.9%) used a hot iron only, 148 (35.0%) used a rubber ring only, 26 (5.8%) used both methods, 3 (0.7%) used a surgical knife, and 1 (0.2%) provided no response. Less than 2% of respondents always or sometimes used pain relief for these procedures. Of the 432 respondents, 139 (32.2%) and 180 (41.7%) strongly agreed that castration and tail docking do not cause sufficient pain to warrant using pain relief, respectively. Time and cost were identified as major barriers to providing pain relief. In the unadjusted logistic regression analyses, respondents who were female, had high levels of education, had been farming < 20 years, who believed lambs experienced high levels of pain following the procedures, and who believed pain lasted longer than 6 hours, were more likely to indicate willingness to use pain control devices. CONCLUSION AND CLINICAL RELEVANCE: Our results suggest very few New Zealand sheep farmers currently provide lambs with pain relief following tail docking or castration. This is likely due to the perception that the procedures are not painful enough to warrant pain relief, and concern over time and cost. This highlights the need to educate farmers about lamb pain and distress following tail docking and castration, and its negative impact on animal welfare. Farmers also need pain relief techniques and tools that can be administered simultaneously with these procedures to save time and labour cost.

Evaluation of analgesic interaction between morphine, maropitant and dexmedetomidine in dogs undergoing ovariohysterectomy.

AIMS: To compare the analgesic effect of morphine combined with maropitant and/or dexmedetomidine to morphine alone but at a higher dose, and to evaluate the pharmacokinetics of the drug combinations, in dogs undergoing ovariohysterectomy (OHE). METHODS: Forty client-owned dogs were randomised into four treatment groups (n = 10 per group) each to receive a different analgesic protocol. After premedication with I/M acepromazine, anaesthesia was induced with propofol to effect and maintained with isoflurane in 100% oxygen delivered via a circle system. The heart rate, respiratory rate, blood pressure, haemoglobin oxygen saturation, end-tidal partial pressure of carbon dioxide, electrocardiogram and rectal temperature were monitored during anaesthesia. The test drugs (Mor: 0.6 mg/kg morphine; Maro + Mor: 0.3 mg/kg morphine and 1 mg/kg maropitant; Dex + Mor: 0.3 mg/kg morphine and 10 µg/kg dexmedetomidine; Dex + Maro + Mor: 0.2 mg/kg morphine, 7 µg/kg dexmedetomidine and 0.7 mg/kg maropitant) were administered I/M after induction of anaesthesia and 30 minutes before the expected start time of ovariohysterectomy, which was carried out by veterinary students under veterinary supervision. The short form of the Glasgow composite measure pain scale (CMPS-SF) and visual analogue scale (VAS) were used for pain assessment at 15 and 30 minutes and 1, 2, 3, 6, 9 and 24 hours after extubation. Dogs with CMPS-SF pain score ≥ 6 received rescue analgesia with S/C buprenorphine (0.02 mg/kg). Blood samples were collected before, 15, 30, 60 and 120 minutes after injection of the test drugs and concentration of the test drugs in plasma was determined by liquid chromatography-mass spectrometry. RESULTS: Dogs that received Dex + Mor had significantly lower CMPS-SF (estimate of difference = -1.53 (SE 0.58); p = 0.010) and VAS (estimate of difference = -0.67 (SE 0.25); p = 0.007) scores compared to the dogs that received morphine alone. There was no evidence of a difference in the number of dogs requiring rescue between groups. All dogs that received dexmedetomidine showed cardiac arrhythmia and second-degree heart block. Mean (SD) maximum concentrations (Cmax,) of morphine in plasma were 6.8 (4.56), 9.56 (8.29), 9.30 (3.35) and 18.99 (9.41) ng/mL for the groups Dex + Mor, Dex + Maro + Mor, Maro + Mor and Mor respectively. The Cmax of morphine was significantly lower in the Dex + Mor (p = 0.004), Dex + Maro + Mor (p = 0.034) and Maro + Mor (p = 0.018) groups compared to the Mor group. CONCLUSIONS: For dogs undergoing ovariohysterectomy, lower doses of morphine (0.2 and 0.3 mg/kg) combined with dexmedetomidine or maropitant may provide analgesia equivalent to or better than morphine when given alone at a higher dose (0.6 mg/kg).Abbreviations: AUC: Area under curve; Cmax: Maximum concentration in plasma; CMPS-SF: Glasgow composite measure pain scale - short form; NK1: Neurokinin-1; OHE: Ovariohysterectomy; Tmax: Time to Cmax; T1/2: Half-life of terminal elimination phase; VAS: Visual analogue scale.

Cross-sectional survey of surgical techniques used to perform dog and cat spays in New Zealand veterinary practice.

Aims: To describe the variation in surgical techniques used by veterinarians to perform routine dog and cat spays in first-opinion veterinary practice in New Zealand, and how these techniques differed with the number of years since the veterinarian graduated.Methods: A cross-sectional survey of veterinarians registered to practice in New Zealand was conducted online between 1 April and 30 May 2018. Respondents were asked their year of graduation and about the procedures, they would use to perform a routine spay of a healthy, 5 kg, young adult, female domestic shorthair cat, and a healthy, 20 kg, young adult, female mixed-breed dog. The number of years since graduation was calculated by subtracting the reported year of graduation from 2018.Results: Overall, 282 respondents provided details about dog spays, and 361 about cat spays, and the median number of years since graduation was 14 (min 0, max 50). Only 54/282 (19.1%) respondents performing dog spays and 43/361 (11.9%) performing cat spays wore a surgical cap, gown, mask, and gloves. For dog spays, 278 (98.6%) respondents used a ventral midline approach and 147 (52.1%) used manual exteriorisation of the uterus. Most used two clamps (168; 59.6%) and used two encircling ligatures (152; 53.9%) for removal of the uterus. For cat spays, 254 (70.4%) respondents used a ventral midline approach and 313 (86.7%) used a spay hook for exteriorising the uterus. Most used two clamps (250; 69.3%) with one encircling ligature (213; 59.0%) for removal of the uterus. Simple interrupted external or intradermal patterns were mostly used for skin closure for both dog and cat spays. For cat spays, the percentage of respondents using the ventral midline approach decreased with increasing years since graduation (p < 0.001). For both dog and cat spays, the percentage of respondents using two encircling ligatures and transfixation ligation of the uterus, and using a simple continuous suture pattern for the closure of the abdomen, decreased with number of years since graduation (p < 0.05).Conclusions and clinical relevance: Veterinarians responding to this survey used a wide range of techniques to perform routine dog and cat spays, some of which were associated with the number of years since graduation. It may be beneficial to provide veterinarians with resources to reflect on their current approaches for performing routine spays. However further research is needed to determine whether any surgical techniques are superior to others.

Analgesic efficacy of articaine hydrochloride for velvet antler removal in red deer (Cervus elaphus) and analysis of drug residues in the harvested velvet antlers.

AIMS: To investigate the analgesic efficacy of articaine hydrochloride for antler removal in red deer (Cervus elaphus) following S/C administration as a ring block, and to quantify the residue concentrations of articaine compared to lignocaine in the harvested antlers. METHODS: Articaine hydrochloride (40 mg/mL) was administered to 10 male red deer as a ring block around the base of each antler at 1 mL/cm of pedicle circumference. Analgesia was evaluated by determining the response to a saw cut test every 1-minute, until no response was observed. Behaviour during and following removal of antlers was also recorded. Twenty commercially harvested velvet antlers were also collected following S/C administration of 2% lignocaine hydrochloride. A liquid chromatography-mass spectrometry (LC-MS) method for quantification of residues of articaine and lignocaine in velvet antlers was developed and validated. RESULTS: In red deer administered 4% articaine hydrochloride as a ring block, the median interval to analgesia was 4 (min 3, max 5) minutes and no deer showed withdrawal responses during antler removal. There were no signs of toxicity or adverse effects up to 2 hours after administration. The sample preparation method developed for the LC-MS was simple and had acceptable extraction recoveries of articaine and lignocaine from the velvet antlers. The lower limits of quantification of lignocaine and articaine were 5 and 50 ng/g, respectively. Mean concentrations of articaine in antlers following ring block with 4% articaine hydrochloride were 1.50 (SD 1.09) mg/kg, and of lignocaine following ring block with 2% lignocaine hydrochloride were 0.66 (SD 0.71) mg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: A ring block with 4% articaine hydrochloride at a dose of 1 mL/cm of pedicle circumference provided effective analgesia for velvet antler removal in red deer. The LC-MS method developed and validated to quantify articaine and lignocaine was simple and sensitive. Based on these results, articaine hydrochloride appears to be an effective alternative to lignocaine hydrochloride for velvet antler removal. However, further studies to evaluate the safety and residue concentrations of articaine and articainic acid are required before it can be recommended for use in deer.Abbreviations: DMA: 2,6-dimethylaniline; LC-MS: Liquid chromatography-mass spectrometry; MEGX: Monoethylglycinexylidide; MRL: Maximum residue level.

Pharmacogenetics of opioid analgesics in dogs.

Genetic variation causes interindividual variability in drug absorption, distribution, metabolism and excretion. These pharmacokinetic processes will influence the observed efficacy and toxicity of a drug. Polymorphisms in the genes encoding the metabolizing enzymes, transport proteins and receptors have been linked to the inconsistency in responses to opioid treatment in humans and laboratory animals. Pharmacogenetics is relatively less developed field in veterinary medicine compared to significant advances in knowledge on genetic basis of variation in drug responses and clinical applications in human medicine. This review discusses the opioid drug metabolism and possible genetic polymorphism of metabolizing enzymes in dogs. Polymorphism of genes encoding opioid drug transporter proteins and its effect on opioid response and opioid receptor gene variants are also discussed. Due to the scarcity of studies reported on opioid pharmacogenetics in dogs, relevant studies in humans and rodents have also been discussed to indicate current trends and potential targets for research in dogs.

Pharmacokinetics of articaine hydrochloride and its metabolite articainic acid after subcutaneous administration in red deer (Cervus elaphus).

AIM: To develop and validate a simple and sensitive method using liquid chromatography-mass spectrometry (LC-MS) for quantification of articaine, and its major metabolite articainic acid, in plasma of red deer (Cervus elaphus), and to investigate the pharmacokinetics of articaine hydrochloride and articainic acid in red deer following S/C administration of articaine hydrochloride as a complete ring block around the antler pedicle. METHODS: The LC-MS method was validated by determining linearity, sensitivity, recovery, carry-over and repeatability. Articaine hydrochloride (40 mg/mL) was administered S/C to six healthy male red deer, at a dose of 1 mL/cm of pedicle circumference, as a complete ring block around the base of each antler. Blood samples were collected at various times over the following 12 hours. Concentrations in plasma of articaine and articainic acid were quantified using the validated LC-MS method. Pharmacokinetic parameters of articaine and articainic acid were estimated using non-compartmental analysis. RESULTS: Calibration curves were linear for both articaine and articainic acid. The limits of quantifications for articaine and articainic acid were 5 and 10 ng/mL, respectively. Extraction recoveries were >72% for articaine and >68% for articainic acid. After S/C administration as a ring block around the base of each antler, mean maximum concentrations in plasma (Cmax) of articaine were 1,013.9 (SD 510.1) ng/mL, detected at 0.17 (SD 0.00) hours, and the Cmax for articainic acid was 762.6 (SD 95.4) ng/mL at 0.50 (SD 0.00) hours. The elimination half-lives of articaine hydrochloride and articainic acid were 1.12 (SD 0.17) and 0.90 (SD 0.07) hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The LC-MS method used for the quantification of articaine and its metabolite articainic acid in the plasma of red deer was simple, accurate and sensitive. Articaine hydrochloride was rapidly absorbed, hydrolysed to its inactive metabolite articainic acid, and eliminated following S/C administration as a ring block in red deer. These favourable pharmacokinetic properties suggest that articaine hydrochloride should be tested for efficacy as a local anaesthetic in red deer for removal of velvet antlers. Further studies to evaluate the safety and residues of articaine hydrochloride and articainic acid are required before articaine can be recommended for use as a local anaesthetic for this purpose.

Attitudes and perceptions of veterinary paraprofessionals in New Zealand to postoperative pain in dogs and cats.

AIM: To survey the attitudes and perceptions of veterinary paraprofessionals in New Zealand to postoperative pain in dogs and cats. METHODS: In December 2011, veterinary paraprofessionals (VP) from throughout New Zealand were invited to participate in an online survey. Eleven questions, which were divided into five sections, were used to determine demographic information, the respondents' assessment of pain after commonly performed surgeries in dogs and cats, their opinions on provision of analgesia, who had responsibility for pain monitoring and the use of any formal pain scoring system in the practice. RESULTS: Data from 165 respondents were able to be used, and 162 (98%) respondents to the survey were female. According to the respondents' estimates, fracture repair in dogs and repair of diaphragmatic hernias in cats had the highest pain score following surgery. Neutering procedures involving dogs were scored higher than for cats (p<0.01). All respondents agreed that animals benefit from perioperative analgesia. The veterinary nurse was reported to be predominantly responsible for monitoring pain in animals postoperatively by 116/165 (70.3%) respondents. Of 165 respondents, 154 (93%) considered that their knowledge of pain and assessment of pain could be enhanced. CONCLUSIONS: This survey reflects the attitudes and perceptions of a sample of VP in New Zealand to postoperative pain in dogs and cats. The results indicate that all respondents believe that surgery results in sufficient pain to warrant analgesic therapy. Routine neutering surgeries were considered to be more painful in dogs than in cats. The current survey also provides information to educators on potential areas of focus, given that 93% of respondents felt that their knowledge of pain and assessment of pain could be enhanced.

Electroencephalographic evaluation of decapitation of the anaesthetized rat.

The objective of this study was to evaluate the changes in electroencephalographic (EEG) power spectrum in response to decapitation of anaesthetized rats, in order to assess the nociception or otherwise of this procedure. Ten young adult male Sprague-Dawley rats were anaesthetized with halothane in oxygen and anaesthesia was maintained at a stable concentration of halothane between 1.20% and 1.25%. The rat's head and neck were placed through the opening of a small animal guillotine so that the blade of the guillotine was positioned over the atlanto-occipial joint of the rat's neck. The EEG was recorded in a five-electrode montage, bilaterally. After recording a 15 min baseline the rat was decapitated by swiftly pressing the guillotine blade and the EEG recording was continued until the signal was isoelectric on both channels. Changes in the median frequency (F50), 95% spectral edge frequency (F95) and total power of the EEG (Ptot) were used to investigate the effects of decapitation. During the first 15 s following decapitation, there were significant increases in the F50 and F95, and a decrease in the Ptot compared with baseline values. There was a clear window of time immediately following decapitation where changes in the EEG frequency spectrum were obvious; these changes in the EEG indices of nociception could be attributed as responses generated by the rat's cerebral cortex following decapitation.

Cytotoxic activity of extracts from Hypochaeris radicata.

Pasture-associated stringhalt is an acquired equine disease characterized by peripheral neuropathy and hyperflexion of the pelvic limbs. The disease occurs most commonly during periods of drought in horses grazing pastures heavily contaminated by Hypochaeris radicata. We hypothesized that stringhalt is caused by neurotoxins elaborated by H. radicata in response to the stress of drought conditions. Supernates were collected from H. radicata that were stressed (or not) by immersion in copper chloride solution, then extracted with ethyl acetate and dried. Dilutions of extracts from stressed (SE) and control, unstressed (UE) plants were incubated with myelinating spinal cord cultures (MSCC) established from fetal Swiss mice, and with spinal ganglion cultures (SGC) and dermal fibroblast cultures derived from neonatal mouse tissues. Cytotoxicity in culture monolayers was evaluated both morphologically by microscopy and by release of lactate dehydrogenase activity into culture supernates. Three different SGC preparations were exposed to a single H. radicata extract and single preparations of fibroblasts and MSCC were exposed to three different extracts. Repin, a plant-derived sesquiterpene lactone neurotoxin, was included as a positive control. Significant dose-dependent cytotoxicity was seen within 24 h in all three culture types when incubated with SE or repin. Complete morphologic destruction of culture monolayers was induced by the highest concentrations tested of SE (100 µg/mL) and repin (30 µg/mL). Cytotoxic effect of SE was significantly greater than that of UE for all three cell types and was not due to copper contamination of the extract. This study has identified a cytotoxic activity in leaf exudates of H. radicata that was upregulated by the model stressor, copper chloride.

Effects of tramadol or morphine in dogs undergoing castration on intra-operative electroencephalogram responses and post-operative pain.

AIM: To compare the effects of pre-operatively administered tramadol with those of morphine on electroencephalographic responses to surgery and post-operative pain in dogs undergoing castration. METHODS: Dogs undergoing castration were treated with either pre-operative morphine (0.5 mg/kg S/C, n = 8) or tramadol (3 mg/kg S/C, n = 8). All dogs also received 0.05 mg/kg acepromazine and 0.04 mg/kg atropine S/C in addition to the test analgesic. Anaesthesia was induced with thiopentone administered I/V to effect and maintained with halothane in oxygen. Respiratory rate, heart rate, end-tidal halothane tension (EtHal) and end-tidal CO2 tension (EtCO2) were monitored throughout surgery. Electroencephalograms (EEG) were recorded continuously using a three electrode montage. Median frequency (F50), total power (Ptot) and 95% spectral edge frequency (F95) derived from EEG power spectra recorded before skin incision (baseline) were compared with those recorded during ligation of the spermatic cords of both testicles. Post-operatively, pain was assessed after 1, 3, 6 and 9 h using the short form of the Glasgow composite measure pain scale (CMPS-SF). RESULTS: Dogs premedicated with tramadol had higher mean F50 (12.2 (SD 0.2) Hz) and lower Ptot (130.39 (SD 12.1) µv(2)) compared with those premedicated with morphine (11.5 (SD 0.2) Hz and 161.8 (SD 15.1) µv(2), respectively; p<0.05) during ligation of testicle 1. There were no differences in EEG responses between the two treatment groups during ligation of testicle 2 (p>0.05). The F95 of the EEG did not differ between the two groups during the ligation of either testicle (p > 0.05). Post-operatively, no significant differences in the CMPS-SF score were found between animals premedicated with tramadol and morphine at any time during the post-operative period. No dog required rescue analgesia. CONCLUSION AND CLINICAL RELEVANCE: Tramadol and morphine administered pre-operatively provided a similar degree of post-operative analgesia in male dogs at the doses tested.

Effects of tramadol, morphine or their combination in dogs undergoing ovariohysterectomy on peri-operative electroencephalographic responses and post-operative pain.

AIM: To compare the peri-operative electroencephalogram (EEG) responses and post-operative analgesic efficacy of pre-operative morphine or tramadol with a combination of low-dose pre-operative morphine and post-operative tramadol, in dogs undergoing ovariohysterectomy. METHODS: Dogs undergoing routine ovariohysterectomy were treated with either pre-operative morphine (0.5 mg/kg S/C, n=8), or tramadol (3 mg/kg S/C, n=8), or pre-operative low-dose morphine (0.1 mg/kg S/C) and post-operative tramadol (3 mg/kg I/V, n=8). All dogs received routine pre-anaesthetic medication, and anaesthesia was induced with I/V thiopentone to effect and maintained with halothane in oxygen. Respiratory rate, heart rate, end-tidal halothane tension (EtHal) and end-tidal CO2 tension (EtCO2) were monitored throughout surgery. The EEG was recorded continuously in a three electrode montage. Median frequency (F50), total power (Ptot) and 95% spectral edge frequency (F95) of the EEG power spectra were compared during different 100-second periods of surgery: prior to and during skin incision, ligation of each ovarian pedicle, ligation of uterine body and skin closure. Post-operatively, pain was assessed using the short form of the Glasgow composite measure pain scale (CMPS-SF). RESULTS: There was no difference in F50 or Ptot of the EEG between baseline and noxious surgical events within each treatment group, or between the three groups (p>0.05). The mean F95 was higher during the first three periods of surgery for dogs administered tramadol and low-dose morphine than those that received 0.5 mg/kg morphine (p=0.001). Dogs that received low-dose morphine and tramadol had lower CMPS-SF pain scores after ovariohysterectomy than those that received either tramadol or morphine alone (p=0.001). There was no difference in pain scores between dogs in the latter two groups. CONCLUSION AND CLINICAL RELEVANCE: Tramadol and morphine administered pre-operatively provided an equal degree of post-operative analgesia in dogs after ovariohysterectomy. A combination of pre-operative low-dose morphine and post-operative tramadol produced better post-operative analgesia than either drug administered alone pre-operatively. Administration of analgesics pre- and post-operatively could result in improved post-operative well-being of ovariohysterectomised dogs.

Salivary growth factors and cytokines are not deficient in patients with gastroesophageal reflux disease or Barrett's esophagus.

Growth factors, such as epidermal growth factor (EGF), are known to protect upper gut mucosa against irritants and to enhance healing of ulcerative lesions in animal models. A number of salivary growth factors are found in human saliva. The aim of this study was to determine if salivary growth factors and cytokines are deficient in patients with esophagitis or with Barrett's metaplasia. Fifteen healthy subjects, eight patients with esophagitis, and 13 patients with Barrett's metaplasia were included. Salivary concentration of EGF, FGF, IL-1, and IL-6 were measured during esophageal saline and hydrochloric acid perfusion and in the postprandial state. There was no statistically significant difference in the concentration of EGF or cytokines among the three study groups in each experimental condition or among the three experimental conditions in each group. FGF basic could not be detected in saliva. In conclusion, these findings do not support the hypothesis that a deficiency in salivary growth factors or cytokines plays a significant role in the development of mild to moderate reflux esophagitis or Barrett's metaplasia.

Colonic motor function in humans is not affected by gender.

Functional abdominal pain, including the irritable bowel syndrome, is more common in females. Our aim was to determine if differences in motility or biomechanical properties of the colon could account for this gender difference. In 18 healthy subjects (nine males), a catheter assembly incorporating a balloon and perfused side holes, connected to a barostat, was positioned in the left colon. The system was used to determine compliance, sensation in response to phasic balloon distension, and changes in motor activity and tone in response to a meal. There was no significant difference in any of these variables between males and females. We conclude that there is no gender difference in colonic motor function or sensation to balloon distension. The increased prevalence of irritable bowel syndrome in females may be related to psychosocial factors rather than differences in colonic motor function.

Intestinal motility in small bowel diverticulosis: a case report and review of the literature.

Small bowel diverticulosis is a rare disease that is usually associated with recurrent pseudo-obstruction, bacterial overgrowth, and malabsorption. The more severe complications include hemorrhage and perforation. There is evidence to suggest that this entity is a result of small bowel motor dysfunction. For this reason, it has been associated with disorders in which a myopathic or neuropathic process is involved, such as scleroderma. The majority of patients with jejunal diverticulosis do not require surgery and can be managed medically. We report a case of jejunal diverticulosis in a 63-year-old gentleman who presented with symptoms of pseudo-obstruction. Ambulatory duodenojejunal manometry revealed several abnormalities suggestive of small bowel motor dysfunction. Enteroclysis, however, did not find evidence of mechanical obstruction, and the patient had marked improvement with cisapride and antibiotics.

Saliva and esophageal protection.

There has been much interest in recent years in the potential protective role of saliva in the esophagus. Variables such as salivary volume and neutralizing capacity have been studied both during basal conditions and in response to esophageal acid exposure, in healthy subjects and in patients with esophagitis. In addition to its known neutralizing capacity, saliva also contains growth factors. These polypeptides (of which epidermal growth factor has been studied most) have cytoprotective and healing properties in various segments of the gastrointestinal tract. Therefore, a deficiency in one or more of these growth factors might be a contributing factor in the development of gastroesophageal reflux disease (GERD) or its complication, such as Barrett's metaplasia. However, human studies have produced contradictory results regarding salivary growth factor deficiency in such patients. Current methods of investigation make it difficult to assess the importance of saliva in GERD. This may be due in part to the multifactorial nature of the disease and the difficulty in long-term, selective manipulation of salivary function in humans. Given the present data in the literature, it is therefore unknown if saliva plays an important role in esophageal protection.