Luteal phase decrease in packed cell volume in healthy non-pregnant and pregnant bitches.

OBJECTIVES: To establish packed cell volume (PCV) ranges for non-pregnant, pregnant and post-partum bitches from day 10 of proestrus, investigating any relationship with parity and litter size. METHODS: This prospective cohort study used 37 healthy breeding bitches to examine PCV counts from routine blood samples collected every 4 weeks, from day 10 of proestrus, as part of routine PCV monitoring. RESULTS: For pregnant (n = 19) and non-pregnant (n = 18) bitches, PCV decreased until week 8 (corresponding to 8.5 ± 1.1 days before whelping for pregnant bitches) and recovered by 16-20 weeks after the initial sample; bitches that whelped average and large litters showed greater declines. PCV began to recover sooner for bitches that had previously whelped one or two litters compared to bitches that had previously whelped three or more litters. There was a significant three-way interaction between time after the onset of proestrus, litter size and the number of previous litters which demonstrated that the large decrease in PCV for bitches that had previously whelped three or more litters only occurred in bitches that were expecting an average or large sized litter. CLINICAL SIGNIFICANCE: Chronological variation in PCV for pregnant and non-pregnant bitches was established during the reproductive cycle. There was no evidence to suggest that routine PCV measurement for normal, healthy bitches would be beneficial. However, knowledge from this study may be useful when deciding whether to prospectively monitor a bitch where there is a history of previous pregnancy-related anaemia, when performing a caesarean section due to the anticipated blood loss during surgery, or when examining blood profiles for post-litter bitches.

Differential effects of lipopolysaccharide on cognition, corticosterone and cytokines in socially-housed vs isolated male rats.

Social isolation is an established risk factor for mental illness and impaired immune function. Evidence suggests that neuroinflammatory processes contribute to mental illness, possibly via cytokine-induced modulation of neural activity. We examined the effects of lipopolysaccharide (LPS) administration and social home cage environment on cognitive performance in the 5-Choice Serial Reaction Time Task (5CSRTT), and their effects on corticosterone and cytokines in serum and brain tissue. Male Long-Evans rats were reared in pairs or in isolation before training on the 5CSRTT. The effects of saline and LPS (150 µg/kg i.p.) administration on sickness behaviour and task performance were then assessed. LPS-induced sickness behaviour was augmented in socially-isolated rats, translating to increased omissions and slower response times in the 5CSRTT. Both social isolation and LPS administration reduced impulsive responding, while discriminative accuracy remained unaffected. With the exception of reduced impulsivity in isolated rats, these effects were not observed following a second administration of LPS, revealing behavioural tolerance to repeated LPS injections. In a separate cohort of animals, social isolation potentiated the ability of LPS to increase serum corticosterone and IL-6, which corresponded to increased IL-6 in the orbitofrontal and medial prefrontal cortices and the nucleus accumbens. Basal IL-4 levels in the nucleus accumbens were reduced in socially-isolated rats. These findings are consistent with the adaptive response of reduced motivational drive following immune challenge, and identify social isolation as an exacerbating factor. Enhanced IL-6 signalling may play a role in mediating the potentiated behavioural response to LPS administration in isolated animals.

Dissociable effects of systemic and orbitofrontal administration of adrenoceptor antagonists on yohimbine-induced motor impulsivity.

The α2-adrenoceptor antagonist, yohimbine, is commonly used as a pharmacological stressor. Its behavioural effects are typically attributed to elevated noradrenaline release via blockade of central, inhibitory autoreceptors. We have previously reported that yohimbine increases motor impulsivity in rats on the five-choice serial reaction time task (5CSRTT), a cognitive behavioural assessment which measures motor impulsivity and visuospatial attention. Furthermore, this effect depended on cyclic adenomonophosphate (cAMP) signalling via cAMP response element binding (CREB) protein in the orbitofrontal cortex (OFC). However, the role of specific adrenoceptors in this effect is not well-characterised. We therefore investigated whether the pro-impulsive effects of systemic yohimbine could be reproduced by direct administration into the OFC, or attenuated by intra-OFC or systemic administration of prazosin and propranolol-antagonists at the α1- and ß-adrenoceptor, respectively. Male Long-Evans rats were trained on the 5CSRTT and implanted with guide cannulae aimed at the OFC. Systemically administered α1- or ß-adrenoceptor antagonists attenuated yohimbine-induced increases in premature responding. In contrast, local infusion of yohimbine into the OFC reduced such impulsive responding, while blockade of α1- or ß-adrenoceptors within the OFC had no effect on either basal or yohimbine-stimulated motor impulsivity. Direct administration of selective antagonists at the α1-, α2- or ß-adrenoceptor into the OFC therefore produce clearly dissociable effects from systemic administration. Collectively, these data suggest that the pro-impulsivity effect of yohimbine can be modulated by adrenergic signalling in brain areas outside of the OFC, in addition to non-adrenergic signalling pathways within the OFC.

Seeing through the smoke: Human and animal studies of cannabis use and endocannabinoid signalling in corticolimbic networks.

Public opinion surrounding the recreational use and therapeutic potential of cannabis is shifting. This review describes new work examining the behavioural and neural effects of cannabis and the endocannabinoid system, highlighting key regions within corticolimbic brain circuits. First, we consider the role of human genetic factors and cannabis strain chemotypic differences in contributing to interindividual variation in the response to cannabinoids, such as THC, and review studies demonstrating that THC-induced impairments in decision-making processes are mediated by actions at prefrontal CB1 receptors. We further describe evidence that signalling through prefrontal or ventral hippocampal CB1 receptors modulates mesolimbic dopamine activity, aberrations of which may contribute to emotional processing deficits in schizophrenia. Lastly, we review studies suggesting that endocannabinoid tone in the amygdala is a critical regulator of anxiety, and report new data showing that FAAH activity is integral to this response. Together, these findings underscore the importance of cannabinoid signalling in the regulation of cognitive and affective behaviours, and encourage further research given their social, political, and therapeutic implications.

A rare ophthalmic presentation of pituitary metastases.

Metastasis to the pituitary gland is very uncommon and a first presentation of any systemic tumour through pituitary metastasis is rare. The authors report an 82-year-old Caucasian woman, well-controlled hypertensive and moderate smoker who presented with worsening diplopia. On ocular motility examination she had partial right third nerve paralysis along with reduced vision in the right eye and headache. MRI brain showed a large growth in the pituitary gland consisting with radiological features of pituitary macroadenoma. The initial chest x-ray showed a non-specific shadow that raised some suspicions and a CT scan of her thorax confirmed a right central bronchial carcinoma. The authors suggest that pituitary gland metastases be considered as part of the differential diagnosis for any patient presenting with a pituitary lesion, as pituitary disease could be the first manifestation of an underlying malignancy.

Observations of the potency and duration of vecuronium in isoflurane-anesthetized horses.

OBJECTIVE: To evaluate the potency and duration of three subparalyzing doses of vecuronium (VEC) in isoflurane-anesthetized horses. STUDY DESIGN: Prospective experimental study. ANIMALS: Thirteen healthy adult horses undergoing arthroscopic surgery. METHODS: During isoflurane anesthesia, horses received one of three doses of vecuronium (25, 50, or 100 µg kg(-1)). Neuromuscular transmission was monitored with acceleromyography (AMG) with train-of-four (TOF) stimulation of the radial nerve. Maximal depression of the first twitch (T1), and onset time were recorded for each dose. Recovery time to a TOF ratio >90% was also evaluated. RESULTS: Vecuronium 25 µg kg(-1) produced no observable T1 depression in four horses. VEC 50 µg kg(-1) (n = 5) produced a maximal T1 depression of [median (min, max)] 41 (20, 71) % in four horses, and no neuromuscular block was seen in the fifth. VEC 100 µg kg(-1) was given to four horses and produced a T1 depression of 73 (64, 78) %. Of the four horses in which VEC 50 µg kg(-1) produced a measurable neuromuscular block, three recovered spontaneously 43 (40, 52) minutes after VEC administration; a fourth subject received edrophonium to reverse residual block at the end of the surgery. Spontaneous recovery after VEC 100 µg kg(-1) occurred by 112 minutes in one horse, and had to be facilitated by edrophonium in the remaining three horses, more than 2 hours after VEC had been given. CONCLUSIONS AND CLINICAL RELEVANCE: A dose of 100 µg kg(-1) VEC in isoflurane anesthetized horses failed to produce complete paralysis. The partial neuromuscular block lasted at least 2 hours after this dose had been administered. Edrophonium was required to reverse the neuromuscular block in three of four horses. It is likely that more than 100 µg kg(-1) VEC would be necessary for complete neuromuscular blockade in horses, and that this dose will last >2 hours.

Strabismus surgery for internuclear ophthalmoplegia with exotropia in multiple sclerosis.

BACKGROUND: Internuclear ophthalmoplegia (INO) is a disabling condition affecting up to 40% of patients with multiple sclerosis (MS). Management of bilateral internuclear ophthalmoplegia (BINO) with exotropia in MS has been controversial because of the uncertain course of MS. Diplopia associated with INO severely impacts the patient's quality of life and, therefore, treatment should be considered. METHODS: Three patients (ages 28, 62, and 82 years) who had BINO with exotropia and disabling diplopia secondary to MS underwent bilateral medial rectus resections with either unilateral or bilateral adjustable lateral rectus recession(s). Alignment was measured preoperatively and postoperatively, and symptoms were recorded. RESULTS: Preoperative exotropia ranged from 40(Delta) to 64(Delta) for distance fixation and from 50(Delta) to 70(Delta) for near fixation. Preoperatively, all patients had diplopia at distance and near fixation. Immediately after surgery, patients were adjusted to 10(Delta) to 18(Delta) ET at distance fixation with the expectation of an exotropic drift. None of the patients had a tropia at distance and near fixation 6 months after surgery, with single vision in primary position and reading. Two patients had a 2-year follow-up examination; 1 required a small amount of base-in prism for comfortable reading. CONCLUSIONS: Three patients who had BINO with exotropia secondary to MS all benefited from surgery. Surgery should be considered as an option for symptomatic patients who have BINO with exotropia caused by MS.

Quality of life in intermittent exotropia: child and parent concerns.

OBJECTIVE: To identify specific health-related quality-of-life (HRQOL) concerns for children with intermittent exotropia (IXT) and their parents. METHODS: Twenty-four children aged 5 to 17 years with IXT and 1 parent for each child were recruited. Individual interviews with the child and then the parent were audiotaped and transcribed. Transcripts were reviewed, phrases regarding effects of IXT on HRQOL recorded, and specific topic areas identified. Topic frequency was analyzed to determine children's perceptions of their own HRQOL, parents' perceptions of their child's HRQOL, and parents' own HRQOL. RESULTS: Child interviews generated 18 topics. Worry (10 of 24 patients [42%]) was most frequently mentioned. Parent interviews generated 22 topics regarding their children's HRQOL. The most frequently mentioned topic was comments from others (15 of 24 patients [63%]). Regarding the parents' own HRQOL, 14 topics were identified; the most frequently mentioned was worry regarding possible surgery (15 of 24 patients [63%]). CONCLUSIONS: Multiple individual interviews revealed specific HRQOL concerns, such as worry, in children with IXT and their parents. We will use the concerns identified to develop condition-specific HRQOL instruments for IXT.

C-terminal domains within human MT1 and MT2 melatonin receptors are involved in internalization processes.

Melatonin, a molecule implicated in a variety of diseases, including cancer, often exerts its effects through G-protein-coupled melatonin receptors, MT(1) and MT(2). In this study, we sought to understand further the domains involved in the function and desensitization patterns of these receptors through site-directed mutagenesis. Two mutations were constructed in the cytoplasmic C-terminal tail of each receptor subtype: (i) a cysteine residue in the C-terminal tail was mutated to alanine, thus removing a putative palmitoylation site, and a site possibly required for normal receptor function (MT(1)C7.72A and MT(2)C7.77A) and (ii) the C-terminal tail in the MT(1) and MT(2) receptors was truncated, removing the putative phosphorylation and beta-arrestin binding sites (MT(1)Y7.64 and MT(2)Y7.64). These mutations did not alter the affinity of 2-[(125)I]-iodomelatonin binding to the MT(1) or MT(2) receptors. Using confocal microscopy, it was determined that the putative palmitoylation site (cysteine residue) did not play a role in receptor internalization; however, this residue was essential for receptor function, as determined by 3',5'-cyclic adenosine monophosphate (cAMP) accumulation assays. Truncation of the C-terminal tail of both receptors (MT(1)Y7.64 and MT(2)Y7.64) inhibited internalization as well as the cAMP response, suggesting the importance of the C-terminal tail in these receptor functions.

Improvement in distance stereoacuity following surgery for intermittent exotropia.

PURPOSE: To evaluate whether distance stereoacuity improves following surgery for intermittent exotropia using the Frisby Davis Distance (FD2) and Distance Randot stereotests. METHODS: Eighteen patients (median age, 24 years; range, 5 to 68 years) with intermittent exotropia were prospectively enrolled. Stereoacuity was measured pre- and 6 weeks postoperatively using the FD2 and Frisby near tests (real depth tests) and Preschool Randot and Distance Randot tests (polaroid vectographs). RESULTS: Distance stereoacuity measured with the FD2 improved from a median preoperative value of 80 to 40 arcsec postoperatively (p = 0.04) and stereoacuity measured with the Distance Randot improved from a median of nil to 200 arcsec (p = 0.06). In those that had subnormal stereoacuity preoperatively, there was even more marked improvement in distance stereoacuity (FD2 median nil vs 40 arcsec, p = 0.002; Distance Randot median nil vs 200 arcsec, p = 0.004). Near stereoacuity measured with Frisby and Preschool Randot remained unchanged pre- to postoperatively (median, 60 and 80 arcsec, respectively). CONCLUSIONS: There was improvement in distance stereoacuity measured with both the FD2 and the Distance Randot stereotests in patients who underwent surgery for intermittent exotropia. The FD2 and Distance Randot may be useful outcome measures in future clinical trials of interventions for intermittent exotropia.

Postoperative endophthalmitis caused by Sphingomonas paucimobilis.

We present a case in which a new organism, Sphingomonas paucimobilis, caused endophthalmitis after phacoemulsification in a 73-year-old woman. The case shows a recurrent acute endophthalmitis with complete resolution only after vitrectomy. This organism has not been described as a cause of endophthalmitis and was resistant to initial medical management. We also describe an interaction between this organism and a co-infective organism that may account for the unusual clinical course.

cis-Atracurium in dogs with and without porto-systemic shunts.

OBJECTIVE: To evaluate the non-depolarizing neuromuscular blocking drug cis-atracurium in dogs with porto-systemic shunts, and to compare it in clinically normal animals. ANIMALS: Thirteen dogs of mixed breed and sex, aged between 3 and 31 months old, weighing 2.2-25.5 kg, with ASA physical status II-IV, and undergoing surgical attenuation of porto-systemic shunt. A control group of 11 bitches of mixed breed, between 8 and 60 months old, and weighing 4.5-41.0 kg, all ASA physical status I, undergoing routine ovarohysterectomy were also studied. MATERIALS AND METHODS: Pre-anaesthetic medication was an opioid analgesic, given either alone or in combination with acepromazine. Following induction of general anaesthesia with intravenous (IV) propofol and oro-tracheal intubation, anaesthesia was maintained using isoflurane in either oxygen or oxygen and nitrous oxide. Ventilation was controlled. The train of four (TOF) technique was used to monitor neuromuscular blockade. An initial dose of 0.1 mg kg(-1)cis-atracurium was given IV and additional doses of 0.03 mg kg(-1)cis-atracurium were administered when at least one twitch of the TOF was present. RESULTS: Except for one dog that was killed during surgery because its anomaly was inoperable, all animals recovered satisfactorily from anaesthesia and surgery. In dogs with porto-systemic shunt, onset of neuromuscular blockade was 3.1 +/- 1.1 minutes (mean +/- SD) and in control dogs was 3.4 +/- 0.7 minutes (not significantly different). Neuromuscular blockade lasted 34 +/- 13 minutes in dogs with porto-systemic shunt and 29 +/- 17 minutes in control dogs (not significantly different). CONCLUSIONS: The presence of porto-systemic shunt did not affect the rate of onset or duration of action of cis-atracurium. CLINICAL RELEVANCE: cis-Atracurium may have a use in veterinary anaesthesia for producing neuromuscular blockade in dogs with hepatic insufficiency, including those with porto-systemic shunt.

Comparison of two thiopental infusion rates for the induction of anaesthesia in dogs.

OBJECTIVE: To compare the induction dose requirements of thiopental using two different infusion rates for induction of anaesthesia in dogs. STUDY DESIGN: Prospective, randomized study. ANIMALS: Fifty, healthy (ASA I or II) client-owned dogs with a mean age of 4.1 years and a mean mass of 20.4 kg undergoing elective surgery. MATERIALS AND METHODS: Animals were randomly assigned to receive an infusion of 2.5% thiopental at a rate of either 0.1 ml kg(-1) minute(-1) or 0.4 ml kg(-1)minute(-1), 30-40 minutes after pre-anaesthetic medication with intramuscular acepromazine (0.025 mg kg(-1)) and pethidine (3.5 mg kg(-1)). Thiopental administration was controlled by a precision syringe driver. Statistical analyses of the results, using the outcome 'mg kg(-1) required for induction' (log-transformed) included unpaired t-tests for all categorical data (thiopental infusion rate, breed, sex, obesity, sedation quality) and univariable linear regression for continuous variables (mass, age). All variables were then considered in a multivariable linear regression model. The quality of induction with the two different infusion rates was also assessed. RESULTS: After controlling for quality of sedation, the thiopental induction dose requirement was significantly less (p < 0.001) with the slower infusion rate (median = 7.5 mg kg(-1); range 4.9-13.7) compared with the faster infusion rate (median =11.0 mg kg(-1); range 6.6-18.0). The quality of sedation also affected the dose required (p = 0.03). The slower infusion rate was associated with a significantly poorer induction quality (p = 0.03) [corrected] CONCLUSIONS: Slow thiopental infusion (0.1 ml kg(-1) minute(-1)) for anaesthesia induction after acepromazine/pethidine pre-anaesthetic medication reduced the induction dose requirement, although the quality of induction was inferior. CLINICAL RELEVANCE: The induction dose of thiopental was reduced with a slower administration rate and so slow administration is recommended in thiopental-sensitive animals.

Overdose during chemical restraint in a black rhinoceros (Diceros bicornis).

A juvenile female black rhinoceros (Diceros bicornis) was successfully treated after overdose of drugs used for chemical restraint. Subsequent general anaesthesia for surgical reduction of a recurrent rectal prolapse was uneventful. Over a 25-minute period before transportation to the veterinary hospital, the animal received a total dose of 1.225 mg etorphine, 30 mg acepromazine and 30 mg detomidine. Based on an estimated mass of 200 kg, these corresponded to doses of 6.1 microg kg(-1) etorphine, 150 microg kg(-1) acepromazine, and 150 microg kg(-1) detomidine which constitutes considerable overdose for each drug given separately, notwithstanding the synergy that probably resulted when the three drugs were present concurrently. The estimated body mass may have substantially overestimated the actual body mass and exacerbated overdosage. The animal was recumbent and apnoeic on arrival at the hospital. Heart sounds were auscultated and a weak peripheral pulse was palpated; no pulse deficits were detected, although the heart rate was low. The trachea was intubated, inspired breath was enriched with oxygen and the lungs ventilated manually. Diprenorphine (1.5 mg) was given intravenously and spontaneous breathing resumed 11 minutes later. After induction of general anaesthesia using isoflurane, emergency surgery for correction of rectal prolapse was performed, from which the animal recovered uneventfully. The case highlights some of the practical problems that may be encountered in dealing with dangerous and unfamiliar species.

Acid-base, blood gas, and physiologic parameters during laparoscopy in the head-down position in white-tailed deer (Odocoileus virginianus).

The objective of this project was to evaluate the acid-base, blood gas, and physiologic parameters of white-tailed deer (Odocoileus virginianus) during laparoscopy in the head-down position. Eleven white-tailed does were captured and then immobilized with xylazine (6 mg/kg i.m.) and ketamine (7 mg/kg i.m.). The deer were intubated orotracheally and maintained with isoflurane in oxygen. The deer were positioned in dorsal recumbency and positive pressure ventilated. Heart rate (HR), arterial blood pressure, end-tidal carbon dioxide concentration (FE/CO2), and CO2 insufflation pressure were recorded every 5 min. Respiratory parameters, plasma electrolytes, and peak inspiratory pressure were measured immediately before tilting deer in the head-down position (45-55 degrees), 5 min after tilting, and immediately before the end of the procedure (while tilted). Butorphanol (0.05 mg/kg i.m.) was administered at the end of the procedure and yohimbine (0.2 mg/kg i.v.) administered before release. The deer weighed 52 kg (28-70 kg) [median (minimum-maximum)]. The peak inspiratory pressure in dorsal recumbency while still horizontal was 25 cm H2O (16-28 cm H2O), which increased to 29 cm H2O (18-46 cm H2O) after tilting (P = 0.02). PaO2, PaCO2, FE/CO2, and pH did not change after tilting in the head-down position or after insufflation. HR did not change during the anesthetic period. Mean arterial pressure did not change after tilting or abdominal insufflation, but decreased by the end of the anesthetic period (approximately 1 hr). Time from intubation to extubation was 117 min (72-170 min) (n = 5) and surgery time was 31 min (17-60 min; n = 10). We conclude that captured white-tailed deer have minimal derangements to acid-base, blood gas, or physiologic parameters during laparoscopy in the head-down position with abdominal insufflation, and thus this procedure may be performed safely in ventilated white-tailed deer.

Diplopia following sub-Tenon's infiltration of local anesthesia.

A series of 3 patients with persistent diplopia following sub-Tenon's local anesthesia is presented. All 3 patients showed a pattern of vertical diplopia consistent with restriction of the inferior rectus muscle. The pathogenesis and significance of this complication are discussed.