Reference intervals and echocardiographic findings in Leonberger dogs.

INTRODUCTION: Leonbergers are large-breed dogs believed to be predisposed to dilated cardiomyopathy, yet the normal echocardiographic measurements of these dogs are unknown. The aim of this study was to describe echocardiographic findings and propose breed-specific reference intervals (RIs) for Leonbergers. ANIMALS: A total of 42 clinically healthy dogs were involved in this study. MATERIALS AND METHODS: This study was designed as a cross-sectional study of 42 Leonberger dogs undergoing complete transthoracic echocardiographic studies at a national show. Reference intervals were determined using robust method with bootstrapping. The effects of age, sex, and body weight (BW) on linear and volumetric dimensions were evaluated by regression analysis. Intra- and interobserver variability were evaluated by coefficient of variation from 10 of the studies. RESULTS: There were significant linear correlations with BW for many of the cardiac variables evaluated. However, despite the statistical significance, most regression equations had small slopes, necessitating large changes in BW for small changes in two-dimensional echocardiographic variables. As such, this study resulted in breed-specific RIs irrespective of BW. Trace mitral insufficiency (n = 18), trace aortic insufficiency (n = 15), or both (n = 1) was identified in 81% of dogs in this population. Coefficients of variation were <9% for all two-dimensional, volumetric, and motion mode measurements. CONCLUSIONS: This study describes echocardiographic findings and provides RIs, which may be useful in echocardiographic evaluations of Leonbergers and may aid in early identification of heart disease within the breed.

Quantitative assessment of two- and three-dimensional transthoracic and two-dimensional transesophageal echocardiography, computed tomography, and magnetic resonance imaging in normal canine hearts.

INTRODUCTION: The objective of the study was to evaluate the accuracy of two- and three-dimensional (2D, 3D) transthoracic echocardiography (TTE), 2D transesophageal echocardiography, and computed tomography angiography (CTA) compared with cardiac magnetic resonance imaging (CMR) in normal dogs and to assess repeatability of 2D and 3D TTE for the assessment of left ventricular (LV) and left atrial (LA) dimensions. ANIMALS: The study was performed on six healthy dogs. MATERIALS AND METHODS: Transthoracic echocardiography, transesophageal echocardiography, CTA, and CMR were performed on each dog. Right ventricular (RV) and LV volumes (in systole and diastole), ejection fraction (EF), and LA and right atrial (RA) volumes were assessed. Repeatability and intrarater and interrater measurements of variability were quantified by average coefficient of variation (CV) for 2D and 3D TTE. RESULTS: No clinically relevant differences in LV volume were detected between CMR and all modalities. Importantly, 3D TTE had the lowest CV (6.45%), correlated with (rs = 0.62, p = 0.01), and had the highest overlap in distribution with CMR (OVL >80%). Left ventricular EF and LA size via CTA compared best with CMR and RV and RA volumes were best estimated by 3D TTE. Assessment of LV and LA volumes via 3D TTE had moderate repeatability (15-21%) compared with LV M-mode measurements and 2D LA-to-aortic ratio (<10%), respectively. For LV size, interrater CV for 3D TTE (19.4%) was lower than 2D TTE (23.1%). CONCLUSIONS: Measurements of LV, RV, and RA volumes via 3D TTE and LA volume and LV EF assessed by CTA compared best with CMR. Three-dimensional echocardiography had lower interrater and intrarater CV compared with 2D TTE.

Development of a perceived exertion scale for dogs using selected physiologic parameters.

OBJECTIVE: To develop a perceived exertion scale for dogs exercising on a treadmill and to assess intra- and inter-observer variability. MATERIALS AND METHODS: Fifteen healthy client-owned dogs participated in paired exercise trials. Measurements of lactate, glucose, heart rate, temperature, respiratory rate and regional tissue oximetry were obtained before, during and after exercise. Perceived exertion scale scores were recorded during exercise and using video recordings to evaluate inter-observer variability. Correlations were evaluated using the Spearman's non-parametric method. RESULTS: Thirteen dogs completed both trials. Dogs walked or trotted on the treadmill with an average perceived exertion score of 2 in both trials. Holter heart rate was positively correlated with perceived exertion scale scores from all observers for both trials. In trial 1, plasma glucose decreased in association with increase in perceived exertion and, in trial 2, cutaneous oximetry decreased, respiratory rate increased and temperature increased with increases on the perceived exertion scale. Inter-observer perceived exertion scale scores were positively correlated in both trials. There was no intra-observer variability between trials. CLINICAL SIGNIFICANCE: The perceived exertion scale correlated with the measured physiologic parameters in dogs exercising at mild to moderate intensity. The perceived exertion scale was consistent and repeatable but larger study numbers and further validation are needed before it can be widely applied.

Effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor velagliflozin, a new drug with therapeutic potential to treat diabetes in cats.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are used in the treatment of human diabetics. They increase glucose excretion and correct hyperglycemia. We examined the investigational SGLT2 inhibitor velagliflozin in two groups of six neutered adult obese cats (equal gender distribution). Placebo (Pl) or drug (D; 1 mg/kg) was administered for 35 days. Routine blood examinations, fructosamine, beta-hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), glucagon, adiponectin, and leptin were measured before and after treatment, also water intake, and urinary electrolytes, glucose, and volume. Indirect calorimetry, an intravenous glucose tolerance test (IVGTT; 0.8 g/kg) and insulin tolerance test (IVITT) were conducted. All cats tolerated treatment well. Significant changes with D included a decrease in the respiratory exchange ratio, an increase in cholesterol, a small increase in albumin, and a rise in BHB and NEFA. Glucose clearance was unaltered, although less insulin was secreted during the IVGTT (p = .056) suggesting improved insulin sensitivity. IVITT was unchanged. Treatment did not affect glucagon, leptin, or adiponectin. Water intake, urine output, urinary glucose excretion, and the glucose/creatinine ratio but not urinary electrolytes were significantly higher post-D. We conclude that velagliflozin is a promising drug, which increases urinary glucose excretion in cats and could thereby be beneficial for the treatment of hyperglycemia.

Physiological and biochemical variables in captive tigers (Panthera tigris) immobilised with dexmedetomidine and ketamine or dexmedetomidine, midazolam and ketamine.

Physiological and biochemical variables in captive tigers (Panthera tigris) immobilised with dexmedetomidine and ketamine or dexmedetomidine, midazolam and ketamine were evaluated. Thirty tigers received either dexmedetomidine (0.025 mg/kg) and ketamine (3 mg/kg) (group DK) or dexmedetomidine (0.0125 mg/kg), midazolam (0.1 mg/kg) and ketamine (3 mg/kg) (group DMK). Heart rate, SPO2 and blood pressure were measured at five-minute intervals. Arterial pH, PO2, PCO2, glucose, K+ and arterial and venous lactate were measured at 15 and 45 minutes after immobilisation. A generalised linear mixed model was used for statistical comparison. There was no difference within or between groups at any time point for any measured variable. Measured PO2 was 73.2±17.5 mm Hg and SPO2 was 88.9±10.8 per cent. Systolic, mean and diastolic blood pressures were 170.5±48.4, 138.9±41.8 and 121.8±37.2 mm Hg, respectively. Venous lactate was higher than arterial lactate within groups at each time point. Seizure-like behaviour was observed in 25 per cent of tigers in group DK but not in group DMK. The addition of midazolam into a protocol for immobilisation of tigers did not result in a difference in any of the measured variables but may have prevented the development of seizure-like behaviour.

Emotion regulation: quantitative meta-analysis of functional activation and deactivation.

Emotion regulation is hypothesized to be a multifaceted process by which individuals willfully modulate the intensity and direction of emotional response via prefrontally mediated inhibition of subcortical response-related regions of the brain. Here we employ activation likelihood estimation (ALE) meta-analysis of functional magnetic resonance imaging studies to (1) reveal a consistent network of structures active during emotion regulation, (2) identify the target regions inactivated by the willful regulation process, and (3) investigate the consistency of activated structures associated with downregulation and upregulation. Results reveal signal change in bilateral amygdala/parahippocampal gyrus that decreased in downregulated states and increased in upregulated states, while cortical regions including superior frontal gyrus, cingulate, and premotor areas exhibited enhanced activity across all regulation conditions. These results provide consistent evidence for the role of amygdala activity in experienced emotional intensity, where intentional dampening and exaggeration are clearly expressed. However, the execution of emotional upregulation and downregulation may involve distinct subsets of frontocortical structures.

An eight month randomized controlled exercise intervention alters resting state synchrony in overweight children.

Children with low aerobic fitness have altered brain function compared to higher-fit children. This study examined the effect of an 8-month exercise intervention on resting state synchrony. Twenty-two sedentary, overweight (body mass index ≥85th percentile) children 8-11 years old were randomly assigned to one of two after-school programs: aerobic exercise (n=13) or sedentary attention control (n=9). Before and after the 8-month programs, all subjects participated in resting state functional magnetic resonance imaging scans. Independent components analysis identified several networks, with four chosen for between-group analysis: salience, default mode, cognitive control, and motor networks. The default mode, cognitive control, and motor networks showed more spatial refinement over time in the exercise group compared to controls. The motor network showed increased synchrony in the exercise group with the right medial frontal gyrus compared to controls. Exercise behavior may enhance brain development in children.

Long-term survival in horses with strangulating obstruction of the small intestine managed without resection.

REASONS FOR PERFORMING STUDY: Although many studies have described results after small intestinal resection and anastomosis in horses, few have described the outcome in horses with strangulating lesions managed without resection. OBJECTIVES: To examine short- and long-term recoveries in horses with strangulated small intestine that was judged to be viable during surgery and not resected. STUDY DESIGN: Retrospective analysis of case records. METHODS: Data were reviewed from all cases (35 horses) with colic caused by small intestinal strangulation that underwent surgery between 1996 and 2011 at 2 university hospitals and that were managed without resection by 2 surgeons who used a clinical grading system to assess intestinal viability. Kaplan-Meier analyses were used to examine long-term survival. RESULTS: Survival to discharge from the hospital was 100%, and post operative complications developed in 11 horses (31%). Three horses (8.6%) required repeat coeliotomy because of persistent pain with or without reflux, and they responded favourably to decompression of distended intestine. Ten horses died after discharge, and 12 were still alive at follow-up from 20 to 192 months after surgery. Information was available on 13 horses after discharge, but these were eventually lost to follow-up. Kaplan-Meier analyses yielded a median survival probability of 120 months. CONCLUSIONS: A subjective method of assessing small intestinal viability in strangulated small intestine in horses, as used in this study, could reduce the need for resection and anastomosis, with the associated complications and costs. Also, the favourable post operative course in these horses provides strong evidence that early referral could avoid the need for resection and improve survival. The numbers of horses with the most severe changes that were not resected were too small to allow a conclusion that such segments should be left in place, and additional criteria might be needed to guide that decision in such cases.

The effects of hyperglycemia and endotoxemia on coagulation parameters in healthy adult horses.

BACKGROUND: Hyperglycemia and endotoxemia have been associated with coagulation abnormalities in horses. Studies in humans suggest greater disturbances in coagulation with hyperglycemia and concurrent endotoxemia. OBJECTIVES: To compare coagulation parameters in horses administered with lipopolysaccharide (LPS) with and without concurrent hyperglycemia. ANIMALS: Twelve healthy adult horses. METHODS: Hyperglycemia (180-240 mg/dL) was maintained for 6 hours in 6 horses (GLU-LPS) using 140 mg/kg IV bolus of dextrose followed by a 20% dextrose constant rate infusion. A similar volume of saline was administered to an additional 6 horses (SAL-LPS). LPS (20 ng/kg) was administered to each horse. Fibrogen concentration, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin antithrombin concentration (TAT), and thromboelastometry were measured at baseline and after 1, 1.5, 2, 2.5, 3, 4, 6, and 22 hours. Repeated measures analysis of variance was used to examine temporal changes. RESULTS: Increases in PT (P = .001) and TAT (P = .027) were observed in the GLU-LPS group. Changes in thromboelastometry parameters including increased clot formation time (In-TEM, P = .006; Ex-TEM, P = .002) and decreased alpha angle (Ex-TEM, P = .04) and maximal clot firmness (Ex-TEM, P = .014) were observed in the SAL-LPS group. Differences between SAL-LPS and GLU-LPS groups were limited to increased maximal clot firmness (Ex-TEM) at 3, 6, and 22 hours (P < .001) in the SAL-LPS group. CONCLUSIONS AND CLINICAL IMPORTANCE: Minor alterations in coagulation parameters identified for each group are most likely not clinically relevant. Observed differences between groups do not suggest that concurrent hyperglycemia and endotoxemia are associated with greater coagulation abnormalities in horses.

Clinical comparison between a continuous Lembert pattern wrapped in a carboxymethylcellulose and hyaluronate membrane with an interrupted Lembert pattern for one-layer jejunojejunostomy in horses.

REASONS FOR PERFORMING STUDY: Although experimental studies have demonstrated differences in performance between methods for handsewn jejunojejunostomy in horses, information on clinical results after different methods of anastomosis are rare. HYPOTHESIS: A continuous Lembert pattern wrapped in a carboxymethylcellulose and hyaluronate membrane would perform better than an interrupted Lembert pattern for jejunojejunostomy in horses. METHODS: Data was reviewed on 32 horses that underwent jejunojejunostomy from 1993-2002. Kaplan-Meier analyses and rates for post operative colic and death were used to compare outcomes after an interrupted Lembert pattern (15 horses with strangulating lesions and 5 horses with nonstrangulating lesions) and a continuous Lembert pattern with membrane (12 horses with strangulating diseases). RESULTS: None of the 32 horses had post operative ileus or post operative endotoxaemia. One horse with a continuous pattern required a repeat celiotomy for anastomotic impaction. Short-term survivals for the interrupted Lembert were 100% (nonstrangulating lesions) and 93% (strangulating lesions) and for the continuous pattern 92% (all strangulating). Long-term rates for mortality and colic episodes were less for the continuous Lembert pattern with membrane compared with the interrupted Lembert for strangulating lesions (P<0.05) and were less for strangulating lesions than for nonstrangulating lesions (P<0.05). For strangulating lesions, Kaplan-Meier analyses yielded a survival probability of 70% for up to 9 years after the interrupted Lembert pattern and 80% for up to 5 years for the continuous Lembert pattern. CONCLUSIONS AND RELEVANCE: Both Lembert patterns performed well in clinical use, although the continuous pattern with the carboxymethylcellulose and hyaluronate membrane had superior long-term outcomes with less colic and mortality from colic.

Nonsteroidal anti-inflammatory agents and musculoskeletal injuries in Thoroughbred racehorses in Kentucky.

Injuries sustained by horses during racing have been considered as an unavoidable part of horse racing. Many factors may be associated with the musculoskeletal injuries of Thoroughbred race horses. This study surveyed the amounts of nonsteroidal anti-inflammatory agents (NSAIDs) in injured horse's biological system (plasma) at Kentucky racetracks from January 1, 1995 through December 31, 1996. During that period, there were 84 catastrophic cases (euthanized horses) and 126 noncatastrophic cases. Plasma concentrations of NSAIDs were determined by High Performance Liquid Chromatography in injured and control horses. The possible role of anti-inflammatory agents in musculoskeletal injuries of Thoroughbred race horses was investigated by comparing the apparent concentrations of NSAIDs in injured horses to concentrations in control horses. The plasma concentrations of phenylbutazone and flunixin were higher in injured horses than in control horses. Most injured and control horses did not have a detectable level of naproxen in their plasma samples. Further studies must be carried out to determine whether horses with higher plasma concentrations of NSAIDs have an altered risk of musculoskeletal injuries compared with other horses.

Two-generation reproductive toxicity study of implanted depleted uranium (DU) in CD rats.

Depleted uranium (DU) munitions and armor plating have been used in several conflicts over the last 17 yr, including the Persian Gulf War and the Iraq War. Because of its effectiveness and availability, DU will continue to be used in military applications into the foreseeable future. There is much controversy over the use of DU in weapons and equipment because of its potential radiological and toxic hazards, and there is concern over the chronic adverse health effects of embedded DU shrapnel in war veterans and bystanders. This study evaluated the effects of long-term implantation of DU on the reproductive success of F0 generation adults and development and survival of subsequent F1 and F2 generations in a two-generation reproductive toxicity study. F0 generation Sprague-Dawley rats, 8 wk of age, were surgically implanted with 0, 4, 8, 12, or 20 DU pellets (1 x 2 mm). Inert implant control animals were implanted with 12 or 20 tantallum (Ta) pellets. The F0 generation was then mated at 120 d post DU implantation. In the F0 generation, when measured on postimplantation d 27 and 117, uranium was present in the urine of DU-implanted animals in a dose-dependent manner. F0 reproductive success was similar across treatment groups and the maternal retrieval test revealed no changes in maternal behavior. DU implantation exerted no effect on the survival, health, or well-being of the F0 generation. Necropsy results of F0 animals were negative with the exception of a marked inflammatory response surrounding the implanted DU pellets. For the F1 generation, measures of F1 development through postnatal day (PND) 20 were unremarkable and no gross abnormalities were observed in F1 offspring. No uranium was detected in whole-body homogenates of PND 4 or PND 20 pups. Necropsy findings of F1 PND 20 pups were negative and no instances of ribcage malformation were observed in F1 PND 20 pups. Body weight and body weight gain of F1 rats through PND 120 were similar across treatment groups. Eight of 414 F1 animals observed from PND 20 to 120 died of unknown causes; 7 were from litters of DU-implanted F0 mating pairs. F1 mating success at 10 wk of age was an overall 70% compared with 91% for F0 mating pairs. Mating success was similar between F1 animals derived from DU-implanted F0 adults and those derived from F0 implant control adults suggesting that the comparatively low mating success was not due to F1 DU exposure. The gestational index of F1 animals derived from mid-dose F0 mating pairs was found to be lower compared with F1 controls. The average gestation duration of F1 animals derived from high-dose F0 mating pairs was found to be significantly longer than F1 controls. F1 sperm motility analyses did not differ among experimental groups and no gross abnormalities were identified at necropsy among surviving F1 animals at PND 120. Histopathology of kidneys, spleen, thymus, bone marrow, ovaries, and testes of F1 high-dose animals did not differ from F1 controls. F1 high-dose females had significantly higher mean relative liver and heart weights compared with F1 controls; the biological relevance of this finding could not be determined. For the F2 generation, measures of F2 development through PND 20 were unremarkable and no gross abnormalities were observed in F2 offspring. Necropsy findings of F2 PND 20 pups were negative and no instances of ribcage malformation were observed in F2 PND 20 pups. Body weight and body weight gain of F2 rats through PND 90 were similar across treatment groups. Mean relative heart weights of males derived from high-dose F0 parents were significantly lower compared with F2 controls. Sperm motility and concentration analysis of F2 males at PND 90 were similar across F2 groups. Overall, the consistent absence of positive findings in this study seems to suggest that DU is not a significant reproductive or developmental hazard, particularly when one considers that mid- and high-dose rats were implanted with the equivalent of 0.3 and 0.5 lb of DU in a 70-kg human, respectively. However, the findings that seven of eight F1 adults that died postweaning were from DU-implanted F0 mating pairs, and that mean relative heart weights were elevated in high-dose F1 and F2 pups, suggest conservatism is warranted in characterizing the reproductive and teratogenic hazards of embedded DU until further studies are completed.

Evolution of the treatment of canine radial and tibial fractures with external fixators.

OBJECTIVES: To determine if indications for external fixator treatment of radial and tibial fractures, management of the fractures, or outcomes have changed over three decades. METHODS: Three groups of dogs were identified from discrete time spans within three decades and the medical records and radiographs were evaluated. The groups were compared in order to determine whether indications (signalment, etiology, fracture type and configuration), reduction method, equipment and implants, frame types and pin numbers, numbers of radiographic reevaluations, use of destabilization, frequency of pin track osteolysis, frame removal times and percentage of complications remained the same over the decades. RESULTS: The indications for external fixator treatment of radial and tibial fractures remained consistent over three decades. The equipment and implants changed over the decades. Frame construction changed from the predominately Type II frames constructed in the 1980's and 1990's to a variety of modified Type II, Type Ia, Type Ib and hybrid frames constructed in the 2000's. The frequency of pin track osteolysis decreased significantly over the decades. Frame removal times have not changed significantly over the past three decades. Complications (nonunion, delayed union, osteomyelitis, implant failure and premature frame loss) have decreased over this time. CLINICAL SIGNIFICANCE: Improvements in techniques and equipment have led to decreased complications with external fixators.

Clinical, clinicopathological and histological changes observed in 14 cats treated with glucocorticoids.

Fourteen cats were given immunosuppressive doses of either prednisolone (4.4 mg/kg/day) or dexamethasone (0.55 mg/kg/day) for 56 days. Complete blood counts, serum biochemistry profiles and urinalyses were performed on days 0 and 56, and liver biopsies were taken laparoscopically on day 56, because of evidence of hepatic disease on the serum biochemistry profiles. There were significant increases in the cats' mean white blood cell counts, neutrophil counts and monocyte counts, and significant decreases in their mean lymphocyte counts and eosinophil counts. There were consistent increases in the serum concentrations of albumin, glucose, triglycerides and cholesterol. Glycogen deposition, consistent with a steroid hepatopathy, was present to varying degrees in all the liver biopsies. One of the cats developed adverse clinical signs including anorexia, icterus, pruritus and medial curling of the pinnae, some of which were suspected to be related to the glucocorticoid therapy.

Quantitation of canine regulatory T cell populations, serum interleukin-10 and allergen-specific IgE concentrations in healthy control dogs and canine atopic dermatitis patients receiving allergen-specific immunotherapy.

Canine atopic dermatitis (AD) shares many clinical and immunological similarities with human AD. Regulatory T cells (Treg) are a distinct lineage of T lymphocytes with various immunosuppressive properties including the down-regulation of allergic inflammation associated with IgE production. Antigen-induced Treg typically regulate immune homeostasis via productions of cytokines such as interleukin-10. Given the immunological similarities with human AD, it is likely that Tregs and the cytokines they produce play an important role in diseases of dogs as well. A cross-reactive FoxP3 antibody was used to identify a subset of CD4(+) T cells in the blood of both healthy dogs and dogs with atopic dermatitis undergoing immunotherapy over a year period. There was no significant difference in the Treg percentage over time in the healthy dogs. The immunotherapy group showed a significant increase in Treg percentage at 6, 9, and 12 months when compared to the healthy dogs. For the immunotherapy group, the mean Treg percentage at the beginning of the study was 4.94+/-0.71 and 10.86+/-2.73 at the completion. A commercially available ELISA kit was also used to quantitate the concentration of IL-10 in the serum of the same subsets of dogs. There was no significant difference in the IL-10 concentrations over time in the healthy dogs. The immunotherapy group showed a significant increase in serum IL-10 concentrations at 6, 9, and 12 months when compared to the control group. The mean serum IL-10 concentration at the initiation of immunotherapy was 20.40+/-3.52ngL(-1) and 37.26+/-15.26ngL(-1) at the completion of the study. The immunotherapy group also showed a significant decrease in serum IgE levels over the 1-year treatment period for specific allergens identified during ASIT. We conclude from these studies that similar to humans undergoing immunotherapy, increasing Treg populations likely play a significant role in the success of this particular type of therapy for atopic dermatitis and other allergic conditions.

Evaluation of the effect of implanted depleted uranium (DU) on adult rat behavior and toxicological endpoints.

In 2002, the Naval Health Research Center Toxicology Detachment began a study to determine the effects of surgically implanted depleted uranium (DU) pellets on adult rat (e.g., P1 generation) health and reproduction. In this report, the effect of implanted DU on adult rat behavior and health is described. Adult Sprague-Dawley (SD) rats, 8 wk of age, were surgically implanted with 0, 4, 8, 12, or 20 DU pellets (1 x 2 mm); 20 DU pellets of size 1 x 2 mm approximates to 0.22 kg (0.5 lb) of DU in a 70-kg (154 lb) person. Control animals were implanted with 12 or 20 tantallum (Ta) pellets. The animals were then housed for up to 150 d postimplantation or 20% of an assumed 2-yr life span for rats. The concentration of uranium in urine directly correlated with the number of implanted DU pellets, indicating that DU was migrating into the body from the implanted pellets. Three male and 4 female animals died during the 150-d period of causes apparently not related to DU implantation. Behavioral testing found no definitive evidence of neurobehavioral perturbations associated with DU implantation. Uranium translocated to tissues known to sequester uranium (bone, teeth, and kidneys), but uranium concentrations varied considerably within each dose group and did not follow a dose-response pattern as anticipated. Serum chemistry values were within normal ranges for the SD rat. However, alanine aminotransferase measurements were significantly lower for rats implanted with 20 DU pellets as compared to sham surgery controls but not when compared to animals implanted with Ta pellets only. Phosphate measurements were significantly lower for female rats implanted with 20 DU pellets as compared to both sham surgery controls and animals implanted with Ta pellets only. Monocyte ratios were higher in adult rats implanted with 20 DU pellets as compared to sham surgery controls but not when compared to animals implanted with 20 Ta pellets. Mean platelet volume was found to be significantly lower for rats implanted with 20 DU pellets as compared to sham surgery controls but not when compared to animals implanted with 20 Ta pellets. Gross necropsy found no obvious tissue abnormalities in implanted rats, and the weights of major tissues did not differ between Ta- and DU-implanted animals. Histopathologic analysis of major tissues from animals implanted with 0 pellets, 20 Ta pellets, or 20 DU pellets found no differences between treatment groups. The findings of this study indicate that implantation of up to 20 DU pellets in adult rats did not have a significant negative impact on their general health and neurobehavioral capacities when assessed after 150 d of pellet implantation. However, the growing body of data on the potential health effects associated with DU exposure warrants further studies involving higher embedded DU body burdens in conjunction with longer surveillance periods postimplantation.

Acute and subacute dermal toxicity of Break-Free CLP: a weapons cleaning and maintenance compound.

Break-Free CLP((R)) is a commercial cleaning, lubricating and preserving compound used in both the military and civilian sectors for maintenance of small- and large-caliber weapons. Like many commercial mixtures, there is very little information available on the toxicity of Break-Free CLP. Studies were conducted to characterize the biological effects of single or repeat dermal application of Break-Free CLP to the clipped backs of CD-1 mice. Break-Free CLP was applied neat, 50 microl three times of week for up to 2 weeks. Foci of epithelial ulceration were observed in skin sections from 22% of Break-Free CLP-treated animals in conjunction with markedly thickened epithelium suggesting that robust epithelial regeneration was occurring in these animals. Skin histopathology of Break-Free CLP-treated animals closely matched the histopathology from mice treated repeatedly with 2% croton oil in acetone (dermal irritation positive control). Serum alkaline phosphatase activity was significantly (P < 0.05) lower for mice treated with Break-Free CLP, 2% croton oil or 7,12-dimethylbenz[a]anthracene (DMBA) compared with negative and vehicle control mice. Skin nitric oxide (NO) levels were not significantly elevated for mice treated with Break-Free CLP but were significantly elevated for mice treated with dermal irritation positive control compound DMBA. The cumulative skin changes in Break-Free CLP-treated animals support conducting a subchronic dermal application study. The observed decreases in serum alkaline phosphatase activity suggest that future studies should include the liver and bone as possible target organs. Additionally, dermal penetration studies could provide key health risk assessment information for characterizing the potential health risks associated with chronic dermal exposure to Break-Free CLP.

Reproducibility of a commercial in vitro allergen-specific assay for immunoglobulin E in dogs.

Samples of serum taken from 42 dogs with clinical signs and histories indicating pruritic skin disease and/or diseases of the ear were tested in a commercial allergen-specific assay for immunoglobulin E. Dogs which had been treated with glucocorticoids and/or antihistamines were not excluded. The samples were separated into two equal aliquots, given different randomised numbers, and analysed in two batches on two separate days. The laboratory was blinded to the identification numbers and the history of each dog, but knew the purpose of the study. The results for 48 allergens were expressed in modified absorbance units (MAU). The overall median MAU was 29. For each allergen the mean difference between the MAU values of the paired duplicates was determined and the difference was compared to zero by a paired t test. The number of means that were not 0 (P<0.05) in each allergen group were: seven of 10 grasses, seven of nine weeds, two of 13 trees, six of 10 fungi, and three of six environmental allergens. A single 2 x 2 table for the 48 allergens was created with MAU > or = 60 defined as 'positive' and < 60 as 'negative'. There were 116 of 188 (62 per cent) pairs that were reproducibly 'positive' and 1756 of 1828 (96 per cent) pairs that were reproducibly 'negative'.

Short-term survival after surgery for epiploic foramen entrapment compared with other strangulating diseases of the small intestine in horses.

REASONS FOR PERFORMING STUDY: Epiploic foramen entrapment (EFE) is one of the more common causes of colic in horses, but recent reports suggest a poor prognosis after surgical treatment. HYPOTHESIS: That EFE has a good prognosis compared with other small intestinal strangulating lesions. METHODS: Surgical findings, surgical procedures and short-term outcome were recorded for 157 horses that underwent surgery for strangulating lesions of the small intestine at the University of Illinois from 1994 to 2003. Horses were assigned to 3 groups for comparison; those with EFE, strangulation by lipoma and miscellaneous strangulating lesions. A logistic regression model and Monte Carlo tests of the binomial proportions were used to examine survival rates. The Kruskal-Wallis test was used to determine differences in usage of surgical treatments. Measurements of length and viability indices were analysed using a one-way analysis of variance followed by Tukey's HSD test, and viability scores were analysed using an exact Kruskal-Wallis test. Significance was set at P < 0.05. RESULTS: Horses with EFE were significantly more likely to be discharged (95%) than those with the other conditions (P < 0.05). The proportion of horses with ileal involvement was greater in horses with EFE than in the other 2 groups (P < 0.05), although this did not affect outcome. The distributions of viability grades for EFE and lipoma differed significantly (P < 0.05). CONCLUSIONS: The prognosis for horses that had surgery at this hospital for EFE was better than for those with the other conditions, although the greater proportion of horses with EFE with ileal involvement could influence outcome. Therefore, surgeons must consider ways of improving jejunocaecostomy and determining when bowel is viable, the latter to avoid jejunocaecostomy.

Study of the reproductive effects in rats surgically implanted with depleted uranium for up to 90 days.

In 2001, the Naval Health Research Center Toxicology Detachment was funded by the U.S. Army Medical Research Acquisition Activity (USAMRAA) to conduct a study of the effects of surgically implanted depleted uranium (DU) pellets on adult rat reproductive success and development across two successive generations. This article presents some of the findings for the group of offspring from adult rats mated at 30 d post surgical implantation of DU pellets. Adult male and female Sprague-Dawley rats (P1 generation) were surgically implanted with 0, 4, 8, or 12 DU pellets (1 x 2 mm). The P1 generation was then cross-mated at 30 d post surgical implantation. Urine collected from P1 animals at 27 d post surgical implantation showed that DU was excreted in the urine of DU-implanted animals in a dose-dependent manner. DU surgical implantation did not have a negative impact on P1 reproductive success, survival, or body weight gain through post surgical implantation d 90. There were no statistically significant differences in F1 birth weight, survival, and litter size at postnatal day (PND) 0, 5, and 20. No gross physical abnormalities identified in the offspring were attributable to neonatal DU exposure. A series of neurodevelopment and immune function assessments were also conducted on F1 offspring. No group differences were observed that were related to parental DU exposure. Studies are ongoing on the impact of leaving DU embedded in soft tissue for 120 d on rat reproduction and subsequent offspring survival and development.