Adverse extrapyramidal effects in four horse given fluphenazine decanoate

CASE DESCRIPTION: 4 racehorses were examined because of markedly abnormal behavior following administration of fluphenazine decanoate. CLINICAL FINDINGS: Clinical signs included restlessness, agitation, profuse sweating, hypermetria, aimless circling, intense pawing and striking with the thoracic limbs, and rhythmic swinging of the head and neck alternating with episodes of severe stupor. Fluphenazine was detected in serum or plasma from all 4 horses. The dose of fluphenazine decanoate administered to 3 of the 4 horses was within the range (25 to 50 mg) routinely administered to adult humans. TREATMENT AND OUTCOME: In 2 horses, there was no response to IV administration of diphenhydramine hydrochloride, but the abnormal behavior in these 2 horses appeared to resolve following administration of benztropine mesylate, and both horses returned to racing. The other 2 horses responded to diphenhydramine administration. One returned to racing. The other was euthanized because of severe neurologic signs, respiratory failure, and acute renal failure. CLINICAL RELEVANCE: Findings indicate that adverse extrapyramidal effects may occur in horses given fluphenazine decanoate. These effects appear to be unpredictable and may be severe and life threatening. Use of fluphenazine decanoate as an anxiolytic in performance horses is not permitted in many racing and horse show jurisdictions, and analytic procedures are now available to detect the presence of fluphenazine in serum or plasma.     

Effect of dorsal hip loading,sedation, and general anesthesia on the dorsolateral subluxation score in dogs

OBJECTIVE: To determine whether dorsal loading of the pelvis and type of chemical restraint affected the dorsolateral subluxation (DLS) score of dog hips. STYDY DESIGN: In vivo testing of diagnostic method. ANIMALS: Labrador retrievers, Greyhounds, and crosses between both breeds (n = 119 dogs). METHODS: Dorsal load was applied to the hips through a strap that was placed over the hips, and the peak vertical and steady-state vertical, ground-reaction forces exerted on the stifles were measured in the DLS position. The DLS score was measured with their hips under dorsal load and compared with the DLS score without load. For 24 dogs, the DLS score was measured both under chemical restraint (medetomidine) and under general anesthesia. Wilcoxon-signed rank test and paired t test was used to compare effects of dorsal load and restraint method on the left and right DLS hip score, and P <.05 was considered significant. RESULTS: Both stifles together accepted median 15% body weight in the vertical plane in the unloaded steady state. Loading the hips increased the steady-state, vertical ground-reaction force to 34% body weight. At 8 months of age, loading significantly decreased the DLS score from 65% +/- 11% (mean +/- SD) to 60% +/- 12% for left hips and 66% +/- 11% to 63% +/- 13% for right hips. The left hip DLS score was affected by load more consistently than the right hip. In general, loading the hips decreased the DLS score in all breeds by 4% to 6% except for the greyhounds, in which the DLS score was unchanged by dorsal loading. When grouped by their DLS scores, load significantly decreased DLS scores in dogs with unloaded scores greater than 55% (nondysplastic), whereas DLS scores of dogs with unloaded scores between 55% and 45% (dysplastic) and less than 45% did not change significantly with load. Unloaded scores did not change significantly when compared under sedation versus general anesthesia. However, load significantly decreased the DLS score under general anesthesia for the left hip but not for the right hip. CONCLUSIONS: Less than half of the vertical ground-reaction force normally exerted by the hindlegs of a standing dog was sufficient to induce hip subluxation in the DLS position. Although dorsal loading approximately doubled the steady-state, vertical ground-reaction force, the decrease in the DLS score under load was never greater than 6%. Furthermore, the DLS scores of dogs most likely to be dysplastic (based on DLS scores <45%) were not affected by load, whereas load slightly decreased DLS cores of dogs with DLS scores greater than 55%. CLINICAL RELEVANCE: External influences can change the DLS score significantly, but the magnitude of change is unlikely to be of clinical importance, making the method useful as a field screening test for both dysplastic and nondysplastic hips in young dogs.     

Clinical evaluation of pimecrolimus eye drops for treatment of canine keratoconjunctivitis sicca: a comparison with cyclosporine A

The aim of this study was to evaluate the efficacy of pimecrolimus oil-based eye drops in alleviating the clinical signs of keratoconjunctivitis sicca (KCS) in dogs and to compare the efficacy with that of cyclosporine A (CsA) ointment. An open-label, multicenter study enrolling 44 dogs previously untreated with CsA was conducted. Dogs were randomly assigned to a treatment group and medicated twice daily for 8 weeks. After that time the mean increase (+/-SEM) in the Schirmer tear test was 9.2+/-1.6 mm/min in the pimecrolimus group and 5.8+/-1.1 mm/min in the CsA group (P=0.085). The improvement in clinical signs of inflammation in eyes treated with pimecrolimus was significantly greater than in eyes treated with CsA (P=0.02). The results show that 1% pimecrolimus oily eye drops are as safe as and more effective than CsA ointment in controlling KCS in dogs.     

Insulin sensitivity and glucose dynamics during pre-weaning foal development and in response to maternal diet composition

Nutritional management of animals during pregnancy can affect glucose and insulin dynamics in the resulting offspring through influences on fetal development. Additionally, high starch feeding in mature horses is associated with reduced insulin sensitivity and an increased risk for diseases such as obesity and laminitis. However, no study has yet evaluated the effect of feeding a high starch diet to pregnant mares on glucose and insulin dynamics in their offspring. Twenty late-gestation mares maintained on pasture were provided two-thirds of digestible energy requirements from isocaloric, isonitrogenous low starch (LS, n = 10) or high starch (HS, n = 10) feed. Their foals were assessed with an insulin-modified frequently sampled intravenous glucose tolerance test at 5, 40, 80, and 160 d of age. Baseline glucose concentrations, insulin sensitivity, and insulin-independent glucose clearance in 5-d foals were all greater than values observed in mature horses and declined towards mature values as foals reached 160 d of age. Baseline glucose concentrations were all within normal range, but higher in foals born from HS mares through 80 d of age. Insulin sensitivity was not different between dietary groups until a trend for lower insulin sensitivity in HS foals emerged at 160 d of age. These data are the first to characterize decreasing insulin sensitivity and glucose tolerance in Thoroughbred foals from 5 to 160 d of age. This study also presents the first data examining glucose and insulin dynamics in developing foals in response to maternal high starch diet.     

VH1-44 gene usage defines a subset of canine B-cell lymphomas associated with better patient survival

The use of specific immunoglobulin heavy chain variable region (VH) genes has been associated with increased patient survival in human B-cell lymphomas (hBCL). Given the similarity of human and canine BCL (cBCL) in morphology and clinical treatment, we examined the choice of VH in cBCL and determined whether VH gene selection was a distinct feature associated with survival time in dogs. VH gene selection and mutational status in 52 cBCL, including 29 diffuse large B-cell lymphomas (cDLBCL, the most common subtype of cBCL), were analyzed by comparison with the 80 published canine germline VH gene sequences. We further examined the prognostic impact of the subgroups defined by these features on canine survival. We found that VH1-44 was preferentially expressed in the majority of the 52 cBCLs (60%) as well as in the majority of the cDLBCL subset (59%). VH1-44 gene expression was associated with a statistically better overall survival (p = 0.039) in cBCL patients, as well as in the cDLBCL subset of patients (p = 0.038). These findings suggest that VH gene selection in cBCL is not random and may therefore have functional implications for cBCL lymphomagenesis, in addition to being a useful prognostic biomarker.     

Glucose and insulin responses to different dietary energy sources in Thoroughbred broodmares grazing cool season pasture

The objectives of this study were to characterize the glycemic and insulinemic responses of Thoroughbred broodmares fed late spring pasture only or a mixture of pasture and a high starch or low starch feed and to test hypotheses about differences in the glycemic and insulinemic effects of these dietary regimes. A group of 15 mares were divided into three treatment groups; pasture and high starch feed (PHS), pasture and low starch feed (PLS), and pasture only (PO) and maintained in these groups for 4.5 months prior to this study. These groups were maintained on a single pasture that was temporarily divided into three sections. The study protocol was conducted over two days. On day 1 the mares were fed their respective treatments and on day 2 all mares were allowed access to pasture only. On both days plasma glucose and insulin were measured in samples taken over a 7.5 h period. Baseline measurements for glucose and insulin were not different between any of the treatment groups on either day (P > 0.05). The baseline insulin concentrations of these pasture-kept mares (26.7 ± 8.3 mIU/L) were high compared to those reported from stall-kept horses. Plasma glucose and insulin on day 1 were influenced by treatment group, sample time, and an interaction between treatment and time (P < 0.05). On day 2 there was no significant influence of treatment group (P > 0.05). Glucose and insulin rose to higher (P < 0.01) peak concentrations in the PHS group on day 1 when compared to the PLS and PO groups, with no difference (P > 0.05) detected between the PLS and PO groups. These results are reflected in greater areas under the concentration-time curves for glucose and insulin in the PHS group on day 1 (P < 0.05). On day 2 there were no differences in any of the glucose and insulin characteristics for any of the treatment groups (P > 0.05). These results indicate a clear difference in the glycemic and insulinemic effect of the PHS feed compared to the PLS and PO groups. Of further interest are the glucose and insulin characteristics of these pasture-kept mares that indicate a low insulin sensitivity and high insulin secretory response. This study provides further information on factors influencing glycemic and insulinemic responses in horses.     

Relationship between incidence of gastric dilatation-volvulus and biometeorologic events in a population of military working dogs

OBJECTIVE: To calculate the monthly incidence of gastric dilatation-volvulus (GDV) in a population of military working dogs during a 5-year period and determine whether there was an association with synoptic climatologic indices. SAMPLE POPULATION: Medical records of all military working dogs housed at Lackland Air Force Base,Tex, from Jan 1, 1993 to Dec 31, 1997. PROCEDURE: Confirmed cases of GDV were identified from evaluation of medical records and used to calculate incidence of GDV. Factor analysis of local climatologic data was used to classify each day into 1 of 8 meteorologically homogeneous types of days for this location. Occurrence of GDV was compared with frequency of occurrence of synoptic climatologic days. RESULTS: 48 cases of GDV were identified from January 1993 through December 1997 Mean monthly incidence was 2.5 cases/1,000 dogs at risk (range, 0 to 18.5 cases/1,000 dogs; median, 2.5 cases/1,000 dogs). A seasonal increase in incidence of GDV was detected, because half of the episodes were during November, December, and January. An association with a specific synoptic climatologic day was not detected. CONCLUSIONS AND CLINICAL RELEVANCE: Seasonal fluctuations in incidence of GDV may be associated with external factors that precipitate physiologic changes resulting in GDV. Although a specific cause-effect relationship was not documented, clinicians must be alert for the potential of seasonal variation in incidence of GDV and accordingly heighten their index of suspicion for the condition, particularly in populations of dogs that are predisposed to development of GDV.     

Comparative laboratory evaluation of the acute and chronic toxicology of diflubenzuron,hexaflumuron and teflubenzuron against II instar desert locust (Schistocerca gregaria) (Orthoptera: Acrididae)

The acute and chronic toxicities of three benzoylphenyl ureas, diflubenzuron, hexaflumuron and teflubenzuron were assessed under laboratory conditions against two-day-old second (II) instar Desert Locust, Schistocerca gregaria (ForskÅl) nymphs. Following exposure by ingestion of a single precise dose applied to short pieces of spring barley, nymphs were monitored for two moults until the fourth (IV) instar. Analysis of acute response data gave three significantly different LD₅₀ statistics (P < 0·05), 68·0, 26·6 and 0·71 μg per nymph respectively for diflubenzuron, hexaflumuron and teflubenzuron. The probit regression slopes also differed significantly, indicating distinct tolerance distributions for the three compounds, the narrowest response being to diflubenzuron and the widest range of response being to teflubenzuron. The timing of death was found to vary between the compounds; most nymphs died during the first moult following treatment with either hexaflumuron or teflubenzuron. However, the majority of nymphs that died after exposure to diflubenzuron did so after completing the first moult after treatment, but before the second. The mean development times of nymphs during the II and especially third (III) instars were significantly longer (P < 0·05) than those of the controls following exposure to diflubenzuron and hexaflumuron. Teflubenzuron had no significant effect (P < 0·05) on the duration of the II instar. The potential of the three compounds to control S. gregaria populations in the field is discussed with particular reference to the timing and nature of acute and chronic responses.