Electroencephalogram-based anaesthetic depth monitoring in laboratory animals

Objective measurements of physiological parameters controlled by the autonomic nervous system such as blood pressure, heart rate and respiration are easily obtained nowadays during anaesthesia by the use of monitors: oscillometers, pulseoximeters, electrocardiograms and capnographs are available for laboratory animals. However, the effect-site of hypnotic drugs that cause general anaesthesia is the central nervous system (the brain). In the present, the adjustment of hypnotic drugs in veterinary anaesthesia is performed according to subjective evaluation of clinical signs which are not direct reflexes of anaesthetic effects on the brain, making depth of anaesthesia (DoA) assessment a complicated task. The difficulties in assessing the real anaesthetic state of a laboratory animal may not only result in welfare-threatening situations, such as awareness and pain sensation during surgery, but also in a lack of standardization of experimental conditions, as it is not easy to keep all animals from an experiment in the same DoA without a measure of anaesthetic effect. A direct measure of this dose-effect relationship, although highly necessary, is still missing in the veterinary market. Meanwhile, research has been intense in this subject and methods based on the brain electrical activity (electroencephalogram) have been explored in laboratory animal species. The objective of this review is to explain the achievements made in this topic and clarify how far we are from an objective measure of DoA for animals.     

Guardians' Perceptions of Dogs' Welfare and Behaviors Related to Visiting the Veterinary Clinic

A large survey of Italian dog guardians (n = 906) was conducted to assess dog behavior and welfare at the veterinary clinic and to investigate how guardians and veterinarians affect them. This study confirmed that the veterinary clinic is a source of stress for most dogs, who showed impaired welfare in all phases: in the waiting room, entering the examination room, on the examination table, and when approached by the vet. This study also characterizes some factors related to the guardians' and veterinarians' behavior that affect the dogs' behavior and welfare during the veterinary examination. If dogs had not been examined by a vet since puppyhood, if they did not accept treatments by their guardians, and if they were scolded when refusing a treatment, the risk for having problems with dog welfare and behavior at the veterinary clinic increased. The attention paid by the vet to the dog was found to be positively related with a good response of the dog to the vet. Prevention seems to be the key for the protection of dog welfare related to veterinary care.     

Species differences in tumour responses to cancer chemotherapy

Despite advances in chemotherapy, radiotherapy and targeted drug development, cancer remains a disease of high morbidity and mortality. The treatment of human cancer patients with chemotherapy has become commonplace and accepted over the past 100 years. In recent years, and with a similar incidence of cancer to people, the use of cancer chemotherapy drugs in veterinary patients such as the dog has also become accepted clinical practice. The poor predictability of tumour responses to cancer chemotherapy drugs in rodent models means that the standard drug development pathway is costly, both in terms of money and time, leading to many drugs failing in Phase I and II clinical trials. This has led to the suggestion that naturally occurring cancers in pet dogs may offer an alternative model system to inform rational drug development in human oncology. In this review, we will explore the species variation in tumour responses to conventional chemotherapy and highlight our understanding of the differences in pharmacodynamics, pharmacokinetics and pharmacogenomics between humans and dogs. Finally, we explore the potential hurdles that need to be overcome to gain the greatest value from comparative oncology studies.     

Management of 41 persons exposed to a rabid dog: unplanned experience with human diploid vaccine.

Thirty-six persons -- veterinarians, technicians and students at a veterinary clinic -- were unwittingly exposed to a rabid dog over a period of 21/2 days. One veterinarian received a penetrating bite, two other individuals were grabbed by the dog but the skin was not penetrated, and many were exposed to saliva or urine or both. In addition, the owner of the dog and his wife and three children, while not bitten, were exposed to saliva. The diagnosis was made post mortem when specimens of the dog''s brain were examined by indirect fluorescent antibody testing. All but one of the students had been vaccinated against rabies with hamster kidney vaccine, but eight members of the veterinary college''s staff had not been so vaccinated. Treatment started with duck embryo vaccine; if necessary, rabies (human) immune globulin was also given. When one student reacted severely to the first dose of duck embryo vaccine permission was sought to bring a human diploid vaccine into Canada. In five patients the human diploid vaccine was substituted for the duck embryo vaccine because of severe reactions to the latter. Twenty-five staff members and the family of five received both vaccines. Reactions to the human diploid vaccine were minor and transient. Recommendations include the early licensing of the human diploid vaccine in Canada.     

Toxicity of Halogenated Oxyquinolines in Dogs. A Clinical Study

LANNEK, BIRGITTA and PAUL LINDBERG: Toxicity of halogenated oxyquinolines in dogs. A clinical study. III. Intoxication experiments. Acta vet. scand. 1974, 15, 398–418. — Oxyquinoline drugs, which are normally well tolerated by dogs, will cause disease when a dog’s resistance is occasionally lowered. In a series of experiments in dogs we tried to reproduce the disease pattern of spontaneous cases of poisoning. Most of these experiments, using even high single or repeated oral doses, failed. It was observed, more or less by chance, that the intestinal absorption of 125I-labelled vioform was greatly increased when the dog was not fasted. The consumption of fat, but not of protein or carbohydrates, was found to be the responsible factor. When the oxyquinoline drug was given in a fat emulsion, approx. 1/3 of the dogs fell ill. When fouled fish was also added, the dose necessary to produce disease was lowered to the range used in vioform therapy. We believe that phenolic substances, which may be produced from bacterial degradation of proteins in intestinal disorders, compete with oxyquinolines in metabolic and elimination processes. vioform; oxyquinolines; dogs; convulsions; heart injury; liver injury; poisoning; diarrhoea; phenolic substances.     

An introduction to metabolomics and its potential application in veterinary science

Metabolomics has been found to be applicable to a wide range of fields, including the study of gene function, toxicology, plant sciences, environmental analysis, clinical diagnostics, nutrition, and the discrimination of organism genotypes. This approach combines high-throughput sample analysis with computer-assisted multivariate pattern-recognition techniques. It is increasingly being deployed in toxico- and pharmacokinetic studies in the pharmaceutical industry, especially during the safety assessment of candidate drugs in human medicine. However, despite the potential of this technique to reduce both costs and the numbers of animals used for research, examples of the application of metabolomics in veterinary research are, thus far, rare. Here we give an introduction to metabolomics and discuss its potential in the field of veterinary science.     

Diffuse cutaneous candidiasis in a dog. Diagnosis by PCR-REA

The authors describe a clinical case of cutaneous candidiasis in a dog with dermatological lesions, characterized by persistent alopecia, crusts, ulcers and scales. Predisposing factors such as the use of corticosteroids, the concomitan presence of an autoimmune disease (pemphigus foliaceus) and an infection of ehrlichiosis caused by Ehrlichia canis were observed. Histopathological findings included signs of orthokeratotic hyperkeratosis, moderate follicular keratosis and light epidermic acanthosis. The reactive process included an infiltrative superficial dermatitis and a mural folliculitis with prevalent participation of macrophages and lymphocytes. The application of PCR-Restriction Enzyme Analysis (REA) method on cutaneous specimens in veterinary medicine is an extremely interesting diagnostic tool. Its use, together with other techniques, such as mycologic, cytologic and histological examinations, allowed us to identify Candida albicans as aetiological agent in this particular case.     

Feline Histoplasmosis in Brazil: Clinical and Laboratory Aspects and a Comparative Approach of Published Reports

The present study described clinical and epidemiological aspects of three cases of feline histoplasmosis and compared them to previously described cases. A detailed mycological identification and antifungal susceptibility profile of each isolate are presented. Secondarily, a serological survey for anti-Histoplasma antibodies was performed with domestic and wild cats. Diseased animals presented nodular to ulcerated skin lesions and respiratory disorders as main clinical signs. H. capsulatum var. capsulatum was isolated and the strains showed to be susceptible to antifungal drugs. Considering that feline histoplasmosis is uncommonly observed in veterinary clinics, diagnosis, and clinical management in endemic areas should be improved.     

Maxillomandibulocardiac reflex in a dog

Background

The trigeminocardiac reflex (TCR) is a brainstem reflex that may be observed in anaesthesia during surgical procedures stimulating the intracranial or peripheral portion of the trigeminal nerve. The peripheral TCR is divided into the oculocardiac reflex and the maxillomandibulocardiac reflex based on the affected sensory branches of the trigeminal nerve. In veterinary medicine the oculocardiac reflex has been described, however the maxillomandibulocardiac reflex has never been reported.

Case presentation

A 5-year-old male Epagneul Breton was presented for surgical management of an upper lip mass. During surgery, a sudden severe bradycardia and a decrease in systemic arterial blood pressure developed. The occurrence of a maxillomandibulocardiac reflex was suspected on the basis of the temporary link between surgical stimulation and haemodynamic changes. Three doses of atropine were given before starting a dopamine infusion due to lack of response. The dopamine infusion normalized heart rhythm and blood pressure. The dog recovered uneventfully and he was discharged 24 h later with a sinus rhythm and no sign of recurrence of arrhythmias.

Conclusion

The TCR is a rare but potentially life-threatening complication of procedures involving the sensory areas innervated by the three branches of the trigeminal nerve and it may cause bradycardia with hypotension. The use of a β1-adrenergic receptor agonist such as dopamine may be indicated in cases of a refractory response to the conventional treatment with atropine.

     

Does halothane anaesthesia decrease the metabolic and endocrine stress responses of newborn infants undergoing operation?

Concern about the side effects of various anaesthetic agents in newborn infants has led to the widespread use of anaesthesia with unsupplemented nitrous oxide and oxygen with muscle relaxants in such patients. To investigate the efficacy of such a regimen 36 neonates undergoing operations were randomised to two groups: one group received anaesthesia with nitrous oxide and curare alone and the other was additionally given halothane. Concentrations of metabolites and hormones were measured before and at the end of operation and at six, 12, and 24 hours after operation and the values compared between the two groups. Neonates given halothane anaesthesia showed decreased hormonal responses to operation, with significant differences between the two groups in the changes in adrenaline, noradrenaline, and cortisol concentrations and the ratio of insulin to glucagon concentration. Changes in blood concentrations of glucose and total ketone bodies and plasma concentrations of non-esterified fatty acids were also decreased in neonates receiving halothane anaesthesia. Neonates given anaesthesia with unsupplemented nitrous oxide showed significantly greater increases in the urinary ratio of 3-methylhistidine to creatinine concentration and their clinical condition was also more unstable during and after operation.Unless specifically contraindicated potent anaesthesia with halothane or other anaesthetic agents should be given to all neonates undergoing surgical operations as it decreases their stress responses and improves their clinical stability during and after operation.     

Veterinary science student preferences for the source of dog cadavers used in anatomy teaching

Live animals and cadavers are integral to veterinary education. In the year of this survey (2008), and in at least the five preceding years, cadavers obtained by euthanasia of healthy pound dogs and ex-racing greyhounds were dissected by students, during their veterinary anatomy classes at the University of Queensland School of Veterinary Science. Students may have ethical concerns about this. An alternative approach was to use donated dog cadavers. These are owned pet dogs that have died of natural causes or have been euthanised for medical reasons, and have been donated by their owners for the purposes of veterinary education. Veterinary students at the School were surveyed in 2008, in order to determine their preferences for cadaver source. Data from 406 questionnaires were analysed. Third-year and fifth-year veterinary students were more likely than first-year students to prefer pound-dog/greyhound cadavers over donated cadavers for anatomy dissection (p ≤ 0.002). Between 32% and 45% of the students had no preference for either source of cadaver. These findings are consistent with the hypothesis that veterinary students become more accepting of the euthanasia of unwanted healthy animals for education as they progress through the veterinary programme, in contexts such as the current study. This could occur due to increased acceptance of the euthanasia of healthy animals generally, a decline in moral development, desensitisation, and/or the belief that healthy animal cadavers offer a superior learning experience.     

Molecular identification and genetic analysis of Rhipicephalus sanguineus sensu lato of dogs in Nigeria,West Africa

Experimental and Applied Acarology - The brown dog tick, Rhipicephalus sanguineus sensu lato, is a ubiquitous and taxonomically controversial pest of dogs with immense veterinary and public health...     

Effects of γ-acetylenic GABA and γ-vinyl GABA on electrically-induced spinal cord convulsions and on spinal cord GABA concentration

The effects of γ-acetylenic GABA and γ-vinyl GABA on electrically-induced spinal cord convulsions were compared to the effects of these same drugs on spinal cord GABA concentration. The data show that the effects of these two compounds on seizure activity do not correlate either positively or negatively with changes in GABA concentration. Although both drugs produced marked increases in the amount of GABA in the spinal cord, their effects on spinal cord convulsions were qualitatively different and failed to correlate temporally with alterations in GABA concentration.     

Cerebral metabolic response to systematic kainic acid: 14-C-deoxyglucose studies

Kainic acid (KA) given once intravenously in a dose of 12 mg/kg results successively in staring spells, wet dog shakes, and overt behavioral convulsions over a 90 minute time period. Convulsions last up to 18 hours and are followed by aphagia, adipsia and startle. behavior. Five minutes after KA, deoxyglucose autoradiography reveals a 3–6 fold increase in glucose utilization in ventral CA3 of hippocampus, ventral subiculum, lateral septum with a less intense increase in dorsal hippocampus. During severe behavioral convulsions the entire limbic system and its subcortical projections are metabolically active, while sensory pathways and neocortex are depressed. One to three days following convulsions many limbic areas that participated in seizures are necrotic, while metabolism in the rest of the brain has returned toward normal.     

Changes in plasma IL-1beta, TNF-alpha and IL-6 after total hip replacement surgery in general or regional anaesthesia

Different anaesthetic methods influence the neuro-immuno-endocrine biologic responses to surgery and may thus possibly interfere with the postoperative course and development of complications. The neuroendocrine system is closely related to the cytokine network. In this study, the effects of general anaesthesia (n=6) and regional spinal/epidural anaesthesia (n=6) on the cytokine response (IL-1beta, TNFalpha, IL-6) to uncemented total hip replacement surgery were evaluated. The postoperative clinical course was uneventful in every case. In both groups, only very low values of plasma IL-beta were measured perioperatively, whereas plasma IL-6 increased postoperatively with peak values 4 h after surgery. The changes in plasma TNF-alpha were not significant. No significant differences in plasma TNF-alpha or IL-6 were found between patients operated in general or in regional anaesthesia. This suggests minor influence of plasma cytokines on the possible beneficial effects of regional anaesthesia on the clinical course after surgery in low risk patients. There were slightly higher TNF-alpha and IL-6 levels after the operation and significantly lower cortisol levels during the operation in the regional anaesthesia group compared to the general anaesthesia group, giving rise to a significant inverse correlation between peak values of IL-6 and peak values of cortisol. This supports the theory that after surgery the inhibitory effect of cortisol on monocyte cytokine production overrides adrenergic stimulation.     

Myonecrosis by Clostridium septicum in a dog,diagnosed by a new multiplex-PCR

Clostridial myositis is an acute, generally fatal toxemia that is considered to be rare in pet animals. The present report describes an unusual canine clostridial myositis that was diagnosed by a new multiplex-PCR (mPCR) designed for simultaneous identification of Clostridium sordellii, Clostridium septicum, Clostridium perfringens type A, Clostridium chauvoei, and Clostridium novyi type A. A ten-month-old male Rottweiler dog, that had displayed lameness and swelling of the left limb for 12 h, was admitted to a veterinary hospital. The animal was weak, dyspneic and hyperthermic, and a clinical examination indicated the presence of gas and edema in the limb. Despite emergency treatment, the animal died in only a few minutes. Samples of muscular tissue from the necrotic area were aseptically collected and plated onto defibrinated sheep blood agar (5%) in anaerobic conditions. Colonies suggestive of Clostridium spp. were submitted to testing by multiplex-PCR. Impression smears of the tissues, visualized with Gram and also with panoptic stains, revealed long rod-shaped organisms, and specimens also tested positive using the fluorescent antibody technique (FAT). The FAT and mPCR tests enabled a diagnosis of C. septicum myonecrosis in the dog.     

Canine Gastrointestinal Pythiosis Treatment by Combined Antifungal and Immunotherapy and Review of Published Studies

Pythium insidiosum is an oomycete, a fungal like microorganism, which infects mammals, causing pythiosis in animals and humans, especially in tropical and subtropical regions around the world. The treatment for this infection is very difficult, and therapeutic options commonly comprise surgery, immunotherapy and antimicrobial drugs. The present report describes the clinical healing of a dog with gastrointestinal pythiosis by treatment with a combination of antifungals and immunotherapy, as well as reviews the cases reported in the literature that used some type of therapy for canine pythiosis. A 2.5-year-old male beagle initially showed sporadic vomiting episodes, and this symptom became more frequent 5 months after the onset of clinical signs. Celiotomy procedure found thickness of the stomach wall extending to the pylorus and duodenum. A biopsy was performed, and the diagnosis of pythiosis was made by mycological, histopathological analyses and molecular identification. Therapy was based on an association of terbinafine plus itraconazole during 12 months and immunotherapy for 2.5 months. The healing of the dog reported here allows us to propose the use of immunotherapy associated with antifungal therapy to treat canine gastrointestinal pythiosis. However, additional studies should be performed on a larger number of patients to establish a standard treatment protocol for canine pythiosis.     

Long-term anaesthesia with alfentanil and midazolam for lung transplantation in the dog

An anaesthetic regime was developed for lung transplantation in the dog using a continuous infusion of alfentanil and midazolam. This combination of agents provided excellent analgesia and also produced loss of consciousness. Cardiovascular stability was well maintained over a 24-h period of anaesthesia following lung transplantation. Although no animals were allowed to recover from anaesthesia in the present series, the regime described is likely to be suitable for recovery anaesthesia, particularly since both of the agents used can be reversed with specific antagonists.     

CpG motif identification for veterinary and laboratory species demonstrates that sequence recognition is highly conserved.

Oligodinucleotides containing CpG motifs stimulate vertebrate immune cells in vitro, have proven efficacy in murine disease models and are currently being tested in human clinical trials as therapies for cancer, allergy, and infectious disease. As there are no known immunostimulatory motifs for veterinary species, the potential of CpG DNA as a veterinary pharmaceutical has not been investigated. Here, optimal CpG motifs for seven veterinary and three laboratory species are described. The preferential recognition of a GTCGTT motif was strongly conserved across two vertebrate phyla, although a GACGTT motif was optimal for inbred strains of mice and rabbits. In a subsequent adjuvanticity trial, the in vitro screening methodology was validated in sheep, representing the first demonstration of CpG DNA efficacy in a veterinary species. These results should provide candidate immunostimulant and therapeutic drugs for veterinary use and enable the testing of CpG DNA in large animal models of human disease.     

Denial of effective treatment and poor quality of clinical information in placebo controlled trials of ondansetron for postoperative nausea and vomiting: a review of published trials.

OBJECTIVE--To determine how many patients were deprived of treatment by being given placebo as comparator in trials of ondansetron for postoperative nausea and vomiting. DESIGN--Review of published trials of ondansetron during 1991 to July 1994. SETTING--Medline search in a university department of anaesthesia. SUBJECTS--8806 patients who had been included in 18 indexed placebo controlled trials of ondansetron as prophylaxis against or treatment of postoperative nausea and vomiting. RESULTS--Five studies (1236 patients) had been published by July 1992. All were placebo controlled trials. By July 1994, 8806 patients had been included in 18 indexed placebo controlled studies of prophylaxis or treatment. Only 462 patients had been in studies that compared ondansetron with other drugs, and there were no indexed comparative trials of treatment of nausea and vomiting. Roughly 2180 patients had been given placebo as prophylaxis and 440 had been given placebo when already experiencing postoperative nausea or vomiting. CONCLUSIONS--Around 2620 patients in the reviewed studies were denied existing drugs, which, though not completely effective or without side effects, do bring some relief from postoperative nausea and vomiting. Drug regulatory bodies should collaborate with drug companies to ensure better comparison of new with established drugs. This would avoid placebos being given to more than the fewest patients necessary to confirm effect and would allow doctors to be informed more quickly about relative efficacies.