Novel findings from a beta coronavirus outbreak on an American Miniature Horse breeding farm in upstate New York.

This case report describes an outbreak and novel findings associated with a beta coronavirus (BCoV) infection that occurred on an American Miniature Horse (AMH) breeding farm in upstate New York, in January and February of 2013. Twenty-nine AMH and one donkey were present on the farm when the outbreak occurred. One 10-year-old Quarter Horse mare, stabled at a separate location and owned by an employee of the farm, also tested positive. A polymerase chain reaction (PCR) assay for the detection of BCoV was performed at the Animal Health Diagnostic Center (AHDC) at Cornell on all faecal samples. The PCR assay used detects multiple beta coronaviruses, including, but not limited to, equine enteric coronavirus (ECoV). Novel findings regarding this BCoV infection in horses were recognised in this outbreak study. To the authors' knowledge, this is the largest outbreak of BCoV described thus far in a closed herd on a single premise. The case fatality rate was 0% unlike that described in a previous outbreak of ECoV involving miniature horses and a miniature donkey (Fielding et al. 2015). The morbidity rate was lower in this outbreak than in previously described studies (Oue et al. 2013; Pusterla et al. 2013). This outbreak also demonstrated the potential for BCoV transmission via farm personnel. The duration of shedding of virus in the faeces among some asymptomatic horses in this outbreak was longer than previously described clinical cases of ECoV (Pusterla et al. 2013; Nemoto et al. 2014). This study suggests that asymptomatic animals may play a role in the maintenance of BCoV during an outbreak; therefore, the need for diagnostic testing of both clinically affected and apparently clinically normal horses on a premises followed by appropriate biosecurity and control measures.

miRNA-regulated transcription associated with mouse strains predisposed to hypnotic effects of ethanol.

INTRODUCTION: Studying innate sensitivity to ethanol can be an important first step toward understanding alcohol use disorders. In brain, we investigated transcripts, with evidence of miRNA modulation related to a predisposition to the hypnotic effect of ethanol, as measured by loss of righting reflex (LORR). METHODS: Expression of miRNAs (12 samples) and expression of mRNAs (353 samples) in brain were independently analyzed for an association with LORR in mice from the LXS recombinant inbred panel gathered across several small studies. These results were then integrated via a meta-analysis of miRNA-mRNA target pairs identified in miRNA-target interaction databases. RESULTS: We found 112 significant miRNA-mRNA pairs where a large majority of miRNAs and mRNAs were highly interconnected. Most pairs indicated a pattern of increased levels of miRNAs and reduced levels of mRNAs being associated with more alcohol-sensitive strains. For example, CaMKIIn1 was targeted by multiple miRNAs associated with LORR. CAMK2N1 is an inhibitor of CAMK2, which among other functions, phosphorylates, or binds to GABAA and NMDA receptors. CONCLUSIONS: Our results suggest a novel role of miRNA-mediated regulation of an inhibitor of CAMK2 and its downstream targets including the GABAA and NMDA receptors, which have been previously implicated to have a role in ethanol-induced sedation and sensitivity.

Leukoencephalomyelopathy of mature captive cheetahs and other large felids: a novel neurodegenerative disease that came and went?

A novel leukoencephalomyelopathy was identified in 73 mature male and female large captive felids between 1994 and 2005. While the majority of identified cases occurred in cheetahs (Acinonyx jubatus), the disease was also found in members of 2 other subfamilies of Felidae: 1 generic tiger (Panthera tigris) and 2 Florida panthers (Puma concolor coryi). The median age at time of death was 12 years, and all but 1 cheetah were housed in the United States. Characteristic clinical history included progressive loss of vision leading to blindness, disorientation, and/or difficulty eating. Neurologic deficits progressed at a variable rate over days to years. Mild to severe bilateral degenerative lesions were present in the cerebral white matter and variably and to a lesser degree in the white matter of the brain stem and spinal cord. Astrocytosis and swelling of myelin sheaths progressed to total white matter degeneration and cavitation. Large, bizarre reactive astrocytes are a consistent histopathologic feature of this condition. The cause of the severe white matter degeneration in these captive felids remains unknown; the lesions were not typical of any known neurotoxicoses, direct effects of or reactions to infectious diseases, or nutritional deficiencies. Leukoencephalomyelopathy was identified in 70 cheetahs, 1 tiger, and 2 panthers over an 11-year period, and to our knowledge, cases have ceased without planned intervention. Given what is known about the epidemiology of the disease and morphology of the lesions, an environmental or husbandry-associated source of neurotoxicity is suspected.

Population-based study of presentation and adverse outcomes after femoral hernia surgery.

BACKGROUND: Rates of emergency admission with femoral hernia are high compared with those for other hernias. This study aimed to determine the modes and consequences of presentation to primary care before admission to hospital. METHODS: This was a population-based cohort study using healthcare records from the Clinical Practice Research Datalink linked to Hospital Episode Statistics data from 1997 to 2007. Length of hospital stay, bowel resection rates and 30-day mortality were calculated. RESULTS: A total of 885 patients (690 female, 78.0 per cent) underwent femoral hernia repair, with 406 operations (45·9 per cent) performed as an emergency. The majority of patients who were admitted as an emergency (331, 81·5 per cent) presented to the general practitioner for the first time with symptoms of a hernia in the 7 days before admission, compared with just ten (2·1 per cent) of 479 patients admitted electively (P < 0·001). The median (i.q.r.) length of stay for patients undergoing elective surgery was 1 (0-2) day compared with 5 (3-9) days for those having an emergency repair (P < 0·001). Adverse events were more common among patients operated on as emergency, with 94 (23·2 per cent) having a small bowel resection compared with one (0·2 per cent) who had elective surgery. There were no deaths within 30 days in the elective group, but seven (1·7 per cent) in the emergency group. CONCLUSION: A large proportion of patients with femoral hernia present late to primary care and are operated on as an emergency, with worse outcomes.

Therapeutic plasma concentrations of epsilon aminocaproic acid and tranexamic acid in horses.

BACKGROUND: Antifibrinolytic drugs such as epsilon aminocaproic acid (EACA) and tranexamic acid (TEA) are used to treat various bleeding disorders in horses. Although horses are hypofibrinolytic compared to humans, dosing schemes have been derived from pharmacokinetic studies targeting plasma concentrations in humans. HYPOTHESIS/OBJECTIVES: We hypothesized therapeutic plasma concentrations of antifibrinolytic drugs in horses would be significantly lower than in humans. Our objective was to use thromboleastography (TEG) and an in vitro model of hyperfibrinolysis to predict therapeutic concentrations of EACA and TEA in horses and humans. ANIMALS: Citrated plasma collected from 24 random source clinically healthy research horses. Commercial pooled human citrated plasma with normal coagulation parameters was purchased. METHODS: Minimum tissue plasminogen activator (tPA) concentration to induce complete fibrinolysis within 10 minutes was determined using serial dilutions of tPA in equine plasma. Results used to create an in vitro hyperfibrinolysis model with equine and human citrated plasma, and the minimum concentrations of EACA and TEA required to completely inhibit fibrinolysis for 30 minutes (estimated therapeutic concentrations) determined using serial dilutions of the drugs. RESULTS: Estimated therapeutic concentrations of EACA and TEA were significantly lower in horses (5.82; 95% CI 3.77-7.86 µg/mL and 0.512; 95% CI 0.277-0.748 µg/mL) than in humans (113.2; 95% CI 95.8-130.6 µg/mL and 11.4; 95% CI 8.62-14.1 µg/mL). CONCLUSIONS AND CLINICAL IMPORTANCE: Current dosing schemes for EACA and TEA in horses may be as much as 20× higher than necessary, potentially increasing cost of treatment and risk of adverse effects.

Transcriptome analysis of Inbred Long Sleep and Inbred Short Sleep mice.

Many studies have utilized the Inbred Long Sleep and Inbred Short Sleep mouse strains to model the genetic influence on initial sensitivity to ethanol. The mechanisms underlying this divergent phenotype are still not completely understood. In this study, we attempt to identify genes that are differentially expressed between these two strains and to identify baseline networks of co-expressed genes, which may provide insight regarding their phenotypic differences. We examined the whole brain and striatal transcriptomes of both strains, using next generation RNA sequencing techniques. Many genes were differentially expressed between strains, including several in chromosomal regions previously shown to influence initial sensitivity to ethanol. These results are in concordance with a similar sample of striatal transcriptomes measured using microarrays. In addition to the higher dynamic range, RNA-Seq is not hindered by high background noise or polymorphisms in probesets as with microarray technology, and we are able to analyze exome sequence of abundant genes. Furthermore, utilizing Weighted Gene Co-expression Network Analysis, we identified several modules of co-expressed genes corresponding to strain differences. Several candidate genes were identified, including protein phosphatase 1 regulatory unit 1b (Ppp1r1b), prodynorphin (Pdyn), proenkephalin (Penk), ras association (RalGDS/AF-6) domain family member 2 (Rassf2), myosin 1d (Myo1d) and transthyretin (Ttr). In addition, we propose a role for potassium channel activity as well as map kinase signaling in the observed phenotypic differences between the two strains.

Acid-base balance and ventilation during sternal and lateral recumbency in field immobilized black rhinoceros (Diceros bicornis) receiving oxygen insufflation: a preliminary report.

Posture, ventilation, and acid-base balance using auricular venous blood values (pH, lactate, base excess [BE], HCO(3)(-), PO(2), SO(2), and PCO(2)), oxygen saturation of hemoglobin (SpO(2)), and end-tidal carbon dioxide (P(ET)CO(2)) were compared between sternal (STE) and lateral (LAT) recumbency in free-ranging black rhinoceros (Diceros bicornis bicornis) receiving oxygen insufflation. Data are reported as median, minimum, and maximum (median [minimum, maximum]). Thirty-six desert-adapted black rhinoceros (20 male, 16 female; age 8 [1.5, 33] yr) were immobilized in Namibia in March and April of 2008, from a helicopter, by remote intramuscular injection with etorphine HCl, azaperone, and hyaluronidase. Time from darting to recumbency was 6.0 (3, 15.5) min. Data were organized into two sampling periods: sample period 1 (P1, collected within 0-20 min postdarting; 13 [6.5, 19] min) and sample period 2 (P2, collected between 20-40 min postdarting; 32 [22.3, 39] min). All animals were acidemic (pH 7.24 [7.07, 7.32]) and hypoxemic (PO(2) 51 [38, 95.2]; SO(2) 78 [64, 96] mmHg) after capture. Lactate at P1 was 7.2 (3.2, 16.8) mmol/l and decreased (P=0.01) to 4.6 (1.2, 10.9) mmol/l at P2. At P2, lactate was less (P=0.06) in LAT 3.5 (1.2, 8.6) mmol/l than in STE posture 7.4 (3.1, 10.9) mmol/l. In P2, PO(2), SO(2), and SpO(2) were higher (P=0.02, 0.10, and 0.01, respectively) in STE than in LAT. End-tidal carbon dioxide in LAT was 38 (26, 47) mmHg and increased (P<0.001) rapidly to 48 (37, 55) mmHg when animals were moved into STE; no corresponding change in PCO(2) was observed. These preliminary findings suggest that STE posture in recumbent black rhinoceros reduces dead-space ventilation and improves oxygenation. Lateral posture was associated with lower blood lactate, quicker lactate recovery, or both. It is possible that the posture of recumbent rhinoceros after capture affects lactate accumulation and clearance, or both, and procedures should consider positioning in order to enhance perfusion.

Need for a new kind of partnership on animal health.

The report from the England Advisory Group on Responsibility and Cost Sharing recommends a new approach built around the idea of an England Partnership Board. Rosemary Radcliffe, the group's chair, gives her perspective.

A major QTL for acute ethanol sensitivity in the alcohol tolerant and non-tolerant selected rat lines.

The Alcohol Tolerant and Alcohol Non-Tolerant rats (AT, ANT) were selectively bred for ethanol-induced ataxia as measured on the inclined plane. Here we report on a quantitative trait locus (QTL) study in an F(2) intercross population derived from inbred AT and ANT (IAT, IANT) and a follow-up study of congenics that were bred to examine one of the mapped QTLs. Over 1200 F(2) offspring were tested for inclined plane sensitivity, acute tolerance on the inclined plane, duration of the loss of righting reflex (LORR) and blood ethanol at regain of the righting reflex (BECRR). F(2) rats that were in the upper and lower 20% for inclined plane sensitivity were genotyped with 78 SSLP markers. Significant QTLs for inclined plane sensitivity were mapped on chromosomes 8 and 20; suggestive QTLs were mapped on chromosomes 1, 2 and 3. Highly significant QTLs for LORR duration (LOD = 12.4) and BECRR (LOD = 5.7) were mapped to the same locus on chromosome 1. Breeding and testing of reciprocal congenic lines confirmed the chromosome 1 LORR/BECRR QTL. A series of recombinant congenic sub-lines were bred to fine-map this QTL. Current results have narrowed the QTL to an interval of between 5 and 20 Mb. We expect to be able to narrow the interval to less than 5 Mb with additional genotyping and continued breeding of recombinant sub-congenic lines.

A pilot study to test the effects of art-making classes for family caregivers of patients with cancer.

PURPOSE/OBJECTIVES: To test the effects of an art-making class (AMC) on reducing anxiety and stress among family caregivers of patients with cancer. DESIGN: A pretest and post-test quasi-experimental design. SETTING: A residential care facility near tertiary treatment centers in the southeastern United States. SAMPLE: The convenience sample of 69 family caregivers was aged 18-81 years (X = 48 years) and predominantly Catholic. Most had at least a high school education. Two-thirds were daughters, wives, or mothers of patients with cancer. METHODS: Participants completed a demographic data survey and a Beck Anxiety Inventory (BAI). Researchers collected a saliva sample from each participant to measure salivary cortisol, which indicates stress levels. Following pretesting, a two-hour AMC was delivered. Post-tests included a repeat BAI and a second saliva sample. MAIN RESEARCH VARIABLES: Anxiety and stress. FINDINGS: Anxiety was significantly reduced after AMC. Stress was reduced. CONCLUSIONS: The AMC appeared to reduce anxiety and stress. The addition of a control group and replication with larger numbers are suggested. The physiologic cortisol measure corroborated BAI findings but was difficult to obtain from some cultural groups and was expensive to analyze. IMPLICATIONS FOR NURSING: Family caregivers may benefit from participation in art-making interventions. Nurses should continue to investigate the use of creative approaches to promote holistic care.

Neurotensin levels in specific brain regions and hypnotic sensitivity to ethanol and pentobarbital as a function of time after haloperidol administration in selectively bred rat lines.

Evidence indicates that sensitivity to ethanol is a good predictor of the development of alcoholism. Thus, identification of neuronal processes that regulate ethanol sensitivity has been the subject of much recent research. The present studies were designed to further test the hypothesis that neurotensinergic processes mediate, in part, hypnotic sensitivity to ethanol. Single doses of haloperidol were administered to lines of rats [selectively bred for high and low sensitivity (HAS and LAS, respectively) to hypnotic effects of ethanol] to produce increases in neurotensin (NT) levels in brain regions. At 20 h after administration, haloperidol produced dose-dependent increases in NT immunoreactivity levels in nucleus accumbens (NA) and caudate putamen (CP) in both HAS and LAS lines. Levels of NT in NA and CP returned to control values at 48 h after 4 mg/kg haloperidol. These studies used two measures of hypnotic sensitivity to ethanol: duration of loss of righting reflex (sleep time) and blood ethanol concentration at regain of righting reflex (BECRR). At 20 h, but not 48 h, after haloperidol treatment, both HAS and LAS rats displayed increases in ethanol-induced sleep time with concomitant decreases in BECRR. Pentobarbital-induced sleep time was not increased 20 h after administration of 4 mg/kg haloperidol; however, hypnotic sensitivity to both pentobarbital and ethanol was increased by acute (30-min) pretreatment with 1 mg/kg. These results suggest that NT levels in NA, acting via NT receptors, enhance hypnotic sensitivity to ethanol, but not pentobarbital.

Quantitative genetics and mouse behavior.

Quantitative differences are observed for most complex behavioral and pharmacological traits within any population. Both environmental and genetic influences regulate such individual differences. The mouse has proven to be a superb model in which to investigate the genetic basis for quantitative differences in complex behaviors. Genetically defined populations of mice, including inbred strains, heterogeneous stocks, and selected lines, have been used effectively to document these genetic differences. Recently, quantitative trait loci methods have been applied to map the chromosomal regions that regulate variation with the goal of eventually identifying the gene polymorphisms that reside in these regions.

Ultrasonographic characterization of ovarian events and fetal gestational parameters in two southern black rhinoceros (Diceros bicornis minor) and correlation to fecal progesterone.

A tremendous potential exists for the application of transrectal ultrasonography as a tool to enhance the captive management of endangered species. Reproductive study of two southern black rhinoceros (Diceros bicornis minor) females was performed daily to every other day for a approximately 60 day period to document ovarian changes, and three times weekly in early pregnancy to once monthly in late pregnancy in order to characterize changes in fetal parameters throughout gestation. All ovarian and fetal anatomical structures were measured in millimeters. The mean (+/- SD) length of the estrous cycle or interovulatory period was 26 +/- 1.4 days (n=2 cycles). Follicular growth rate of a dominant follicle was approximately 3 mm/day once the follicle reached 35 mm in diameter. Ovulation was observed to occur at a mean (+/- SD) follicular diameter of 49.5 +/- 2.6 mm (n=4) and within 48 to 72 h after observed estrus (n=2). Large ovarian structures [mean (+/- SD) diameter of 71.7 +/- 2.9 mm; n=3], considered analogous to equine anovulatory hemorrhagic follicles, were observed to form in the winter months and suggest seasonal periods of reduced fertility. Fecal progesterone assays confirmed ultrasonographic events. Although preliminary, the results of fetal sexing are presented and compared to the horse. Our data indicate that fetal eye or fetal foot diameter measurements can be used to accurately predict gestational age from about 2 months to term, providing useful information to managers of both captive and wild rhino populations. The ability to identify and quickly release animals in late term pregnancy in the wild and thereby reduce-abortions and neonatal mortalities in holding bomas is one potential practical conservation benefit of the fetal age predictive models.

An in vitro biomechanical comparison of interlocking nail constructs and double plating for fixation of diaphyseal femur fractures in immature horses.

OBJECTIVE: To compare the biomechanical properties of intact immature horse femurs and 3 stabilization methods in ostectomized femurs. ANIMAL OR SAMPLE POPULATION: Eighteen pairs of femurs from immature horses aged 1 to 15 months, and weighing 68 to 236 kg. METHODS: Thirty-four immature horse femurs were randomly assigned to 1 of 5 test groups: 1) interlocking intramedullary nail (IIN) (n = 6); 2) IIN with a cranial dynamic compression plate (I/DCP) (n = 6); 3) 2 dynamic compression plates (2DCP) (n = 8); 4) intact femurs tested to failure in lateromedial (LM) bending (n = 6); and 5) intact femurs tested to failure in caudocranial (CaCr) bending (n = 8). Mid-diaphyseal ostectomies (1 cm) were performed in all fixation constructs. Biomechanical testing consisted of 4 nondestructive tests: CaCr bending, LM bending, compression, and torsion, followed by bending to failure. All groups were tested to failure in LM bending with the exception of 1 group of intact femurs tested to failure in CaCr bending. Stiffness and failure properties were compared among groups. RESULTS: The 2DCP-femur construct had greater structural stiffness in nondestructive bending than the IIN-femur construct in either LM or CaCr bending, and the I/DCP-femur construct in LM bending. Only the I/DCP and 2DCP fixations were similar to intact bone in nondestructive-bending tests. In addition, the 2DCP-femur construct had greater structural and gap torsional stiffness than the I/DCP-femur construct, and greater gap torsional stiffness than the IIN-femur construct. However, all of the fixation methods tested, including the 2DCP-femur construct, had lower structural stiffness in torsional loading compared with intact bone. No significant differences in structural stiffness were found between intact bones and femur constructs tested nondestructively in compression. In resistance to LM bending to failure, the 2DCP-femur construct was superior to the IIN-femur construct, yet similar to the I/DCP-femur construct. Also, evaluation of yield and failure loads revealed no significant differences between intact bone and any of the femur constructs tested to failure in LM bending. CONCLUSIONS: In general, the 2DCP-femur construct provided superior strength and stiffness compared with the IIN and I/DCP-femur constructs under bending and torsion. CLINICAL RELEVANCE: Double plating of diaphyseal comminuted femoral fractures in immature horses may be the best method of repair, because in general, it provides the greatest strength and stiffness in bending and torsion.

The role of RNA editing of kainate receptors in synaptic plasticity and seizures.

The ionotropic glutamate receptor subunit GluR6 undergoes developmentally and regionally regulated Q/R site RNA editing that reduces the calcium permeability of GluR6-containing kainate receptors. To investigate the functional significance of this editing in vivo, we engineered mice deficient in GluR6 Q/R site editing. In these mutant mice but not in wild types, NMDA receptor-independent long-term potentiation (LTP) could be induced at the medial perforant path-dentate gyrus synapse. This indicates that kainate receptors with unedited GluR6 subunits can mediate LTP. Behavioral analyses revealed no differences from wild types, but mutant mice were more vulnerable to kainate-induced seizures. Together, these results suggest that GluR6 Q/R site RNA editing may modulate synaptic plasticity and seizure vulnerability.

Confirmation of correlations and common quantitative trait loci between neurotensin receptor density and hypnotic sensitivity to ethanol.

BACKGROUND: In previous studies, genetic correlations were observed between hypnotic sensitivity to ethanol and high-affinity neurotensin receptor (NTS1) binding. Provisional quantitative trait loci (QTLs) were identified for these traits, and some of these QTLs were found on common chromosomal regions. In continued efforts to examine the relationship between NTS1 binding capacity and hypnotic sensitivity to ethanol, studies were designed to confirm correlations between NTS1 densities in the brain, duration of ethanol-induced loss of righting reflex (LORR), and blood ethanol concentrations at regain of righting reflex (BECRR). Another purpose of the study was to confirm QTLs for these traits. METHODS: ILS X ISS F2 mice and HAS X LAS F2 rats as well as the progenitors were tested for LORR, BECRR, and NTS1 densities. Phenotypic correlations were calculated between LORR and BECRR and between these measures and NTS1 densities in striatum from both mice and rats. The F2 mice were genotyped by using polymorphic markers for five previously reported QTLs for LORR to confirm QTLs for BECRR and NTS1 densities in striatum, ventral midbrain, and frontal cortex. RESULTS: Phenotypic correlations were found between LORR and BECRR (r = -0.66 to -0.74, p < 10(-9)) and between these measures and NTS1 densities in striatum (r = 0.28-0.38, p < 10(-2)) from both mice and rats. QTLs for LORR and BECRR (lod score = 2-6) were found in common regions of chromosomes 1, 2, and 15. By using the combined results from a previous LSXSS RI study and the current results, a suggestive QTL (lod score = 3.1) for striatal NTS1 receptor densities was found on chromosome 15 at approximately 60 cM, in the same region as the chromosome 15 LORR/BECRR QTL. CONCLUSIONS: The results are in agreement with previously reported correlations and QTLs for NTS1 receptor densities and measures of hypnotic sensitivity to ethanol in mice and extend those correlations to another species, the rat. These findings support a role for NTS1 in genetically mediated differences in hypnotic sensitivity to ethanol.

Confirmation of contextual fear conditioning QTLs by short-term selection.

A short-term selection study for contextual fear conditioning was conducted as a confirmational strategy to analyze the chromosomal locations of five previously mapped contextual fear conditioning quantitative trait loci (QTLs). The founding population was a C57BL/6 (B6) x DBA/2 (D2) F2 intercross. High and low lines were selected for three generations based on contextual fear conditioning scores. Fear conditioning was quantified as the percentage of time spent in a "frozen" posture when placed back into the chamber, where a mild footshock and a tone had been paired with exposure to the context 24 h earlier. Allele frequencies of at least three SSLP DNA markers linked to each of the five QTLs were determined in each generation. As the selection progressed, the frequency of D2 alleles decreased in the low line and increased in the high line for chromosomes 1 and 16, while the opposite was observed in chromosomes 2, 3, and 10. The direction of divergence for alleles on these five chromosomes is consistent with the original QTL mapping study. Differences between the lines in D2 allele frequencies were found to be significant for markers on chromosomes 2, 3, and 16 but did not reach significance on chromosomes 1 or 10. In general, the results are in good agreement with our original fear conditioning QTL mapping study and provide further evidence that these QTLs regulate variation in contextual fear conditioning in crosses of B6 and D2 mice.

Mapping of quantitative trait loci for hypnotic sensitivity to ethanol in crosses derived from the C57BL/6 and DBA/2 mouse strains.

BACKGROUND: Acute ethanol sensitivity is thought to be a predisposing factor toward the development of alcoholism. Accumulated evidence suggests that this characteristic may be at least partly heritable. A widely accepted approach for identifying genes thought to contribute to alcoholism is to map quantitative trait loci (QTLs) for various ethanol-related behaviors in rodent models. METHODS: Ethanol sensitivity QTLs were interval-mapped in a C57BL/6 (B6) X DBA/2 (D2) F2 intercross that contained 391 mice. Sensitivity was measured as the duration of loss of righting reflex (LORR) after 4.1 g/kg ip. LORR also was evaluated in a chromosome 1 marker-assisted congenic strain that had an approximately 30 centiMorgan (cM) portion of D2 DNA from the distal end of chromosome 1 introgressed onto a B6 background. RESULTS: A suggestive QTL was mapped on chromosome 1 (LOD = 3.3; approximately 80 cM) and a provisional QTL on chromosome 5 (LOD = 2.3; approximately 26 cM). The provisional chromosome 5 QTL was found to be sex-specific (LOD = 2.5 for males; LOD < 1 for females) with the D2 allele increasing LORR. The chromosome 1 D2 allele decreased LORR. Consistent with the F2 QTL mapping, congenic mice heterozygous for the chromosome 1 interval (B6/D2) had a significantly different mean (+/- SEM) LORR of 74.0 +/- 4.9 min (n = 36) compared with 90.8 +/- 6.2 min (n = 33) for their homozygous (B6/B6) littermates (p = 0.02). Blood ethanol concentration at regain of righting reflex was 377 +/- 10 mg% for the B6/D2 and 368 +/- 10 mg% (p = NS) for the B6/B6. CONCLUSIONS: LORR results in the chromosome 1 congenic mice were consistent with and very similar to what was predicted from the QTL analysis in the B6 X D2 F2 population. These results support a suggestive LORR QTL on the distal end of mouse chromosome 1. The results also indicate that there is a provisional sex-specific LORR QTL on chromosome 5.

Butorphanol and azaperone as a safe alternative for repeated chemical restraint in captive white rhinoceros (Ceratotherium simum).

Anesthesia in the white rhinoceros (Ceratotherium simum) has routinely involved potent narcotic anesthetic agents such as etorphine or carfentanil with their associated adverse side effects. In captive rhinoceroses conditioned to routine handling, a combination of butorphanol and azaperone at mean (+/- SD) doses of 69.3 +/- 18.0 mg and 103.1 +/- 20.9 mg, respectively, was used to produce levels of neuroleptanalgesia ranging from light "standing" sedation to deeper planes of anesthesia producing sternal and lateral recumbency. This combination was used for repeated (minimum repeat frequency of 3 days between events) anesthetic episodes (n = 26) in two animals, with the remaining episode performed in a white rhinoceros with chronic renal disease. The action of butorphanol was satisfactorily reversed with naltrexone (125 mg i.v. and 125 mg i.m.). Results (mean +/- SD) include sternal recumbency achieved in 14.1 +/- 8.1 min after i.m. dosing, standing and ambulation occurred in 1.7 +/- 0.6 min after reversal, heart rate was 62.0 +/- 10.1 beats/min, respiratory rate was 14.7 +/- 5.6 breaths/min, and percentage of oxygen saturation of hemoglobin (Spo2) was 89.2 +/- 3.0%. Without supplementation, the total elapsed time ranged from 44.9 min to 103.0 min, whereas elapsed times up to 214.3 min were achieved with supplementation (mean time to supplementation was 28.0 +/- 13.9 min after initial dosing). Butorphanol and azaperone produced adequate muscle relaxation and apparently adequate analgesia for minor surgical interferences, including abdominal laparoscopy. Respiratory rates and Spo2 measurements were improved compared with reports of using more potent opioids in this species.

Standing laparoscopic-guided uterine biopsy in a southern white rhinoceros (Ceratotherium simum simum).

Transrectal ultrasonography of a 35-yr-old captive female southern white rhinoceros (Ceratotherium simum simum) with a history of chronic mucohemorrhagic vulvar discharge revealed right transmural uterine horn enlargement. Abdominal laparoscopic surgery, although extremely difficult because of inadequate instrumentation, permitted uterine visualization and biopsy. Standing anesthesia, incorporating butorphanol and azaperone together with local anesthetic infiltration, facilitated the laparoscopy. A leiomyoma was suspected on the basis of history, physical examination, ultrasonographic appearance, and histopathology. Prior rhinoceros laparoscopies have failed, primarily from limitations imposed by recumbency.