Clinical, echocardiographic, and electrocardiographic abnormalities in Boxers with cardiomyopathy and left ventricular systolic dysfunction: 48 cases (1985-2003)

OBJECTIVE: To identify clinical, echocardiographic, and electrocardiographic abnormalities in Boxers with cardiomyopathy and echocardiographic evidence of left ventricular systolic dysfunction. DESIGN: Retrospective study. ANIMALS: 48 mature Boxers. PROCEDURE: Medical records were reviewed for information on age; sex; physical examination findings; and results of electrocardiography, 24-hour ambulatory electrocardiography, thoracic radiography, and echocardiography. RESULTS: Mean age of the dogs was 6 years (range, 1 to 11 years).Twenty (42%) dogs had a systolic murmur, and 9 (19%) had ascites. Congestive heart failure was diagnosed in 24 (50%) dogs. Seventeen (35%) dogs had a history of syncope. Mean fractional shortening was 14.4% (range, 1% to 23%). Mean left ventricular systolic and diastolic diameters were 4.5 cm (range, 3 to 6.3 cm) and 5.3 cm (range, 3.9 to 7.4 cm), respectively. Twenty-eight (58%) dogs had a sinus rhythm with ventricular premature complexes (VPCs), and 20 had supraventricular arrhythmias (15 with atrial fibrillation and 5 with sinus rhythm and atrial premature complexes). Sixteen of the dogs with supraventricular arrhythmias also had occasional VPCs. Morphology of the VPCs seen on lead II ECGs was consistent with left bundle branch block in 25 dogs, right bundle branch block in 8, and both in 11. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that Boxers with cardiomyopathy and left ventricular dysfunction frequently have arrhythmias of supraventricular or ventricular origin. Whether ventricular dysfunction was preceded by electrical disturbances could not be determined from these data, and the natural history of myocardial disease in Boxers requires further study.     

Assessment of plasma brain natriuretic peptide concentration in Boxers with arrhythmogenic right ventricular cardiomyopathy

OBJECTIVE: To determine whether Boxers with a clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) have increased plasma concentrations of brain natriuretic peptide (BNP), compared with concentrations in clinically normal dogs. ANIMALS: 13 Boxers with ARVC, 9 clinically normal Boxers, 10 clinically normal non-Boxer dogs, and 5 hound dogs with systolic dysfunction. PROCEDURE: All Boxers were evaluated via 24-hour ambulatory electrocardiography and echocardiography; the number of ventricular premature contractions (VPCs) per 24 hours was assessed. Hound dogs with cardiac pacing-induced systolic dysfunction (positive control dogs) and clinically normal non-Boxer dogs (negative control dogs) were evaluated echocardiographically. Three milliliters of blood was collected from each dog for measurement of plasma BNP concentration by use of a radioimmunoassay. RESULTS: Mean +/- SD plasma BNP concentration for the ARVC-affected Boxers, clinically normal Boxers, negative control dogs, and positive control dogs was 11.0 +/- 4.6 pg/mL, 7.9 +/- 3.2 pg/mL, 11.5 +/- 4.9 pg/mL, and 100.8 +/- 56.8 pg/mL, respectively. Compared with findings in the positive control group, plasma BNP concentration in each of the other 3 groups was significantly different. There was no significant difference in BNP concentration between the 2 groups of Boxers. A significant correlation between plasma BNP concentration and number of VPCs per 24 hours in the ARVC-affected Boxers was not identified. CONCLUSIONS AND CLINICAL RELEVANCE: A significant difference in BNP concentration between Boxers with ARVC and clinically normal Boxers was not identified. Results suggest that BNP concentration may not be an indicator of ARVC in Boxers.     

Pharmacokinetics and pharmacodynamics of pantoprazole in clinically normal neonatal foals

REASONS FOR PERFORMING STUDY: Proton pump inhibitors (PPIs) are a mainstay of treatment for acid-related ulceration in man and horses. Currently, only an oral preparation of omeprazole is approved for use in horses in the USA. Intravenous administration of a PPI would provide a useful therapeutic alternative for those foals in which oral medication is not feasible. OBJECTIVE: To investigate the pharmacokinetics and pharmacodynamics of pantoprazole following i.v. or intragastric administration in healthy neonatal foals. METHODS: Seven healthy foals age 6-12 days at the start of the study were evaluated. Treatments included no drug administration, i.v. pantoprazole (1.5 mg/kg bwt) and intragastric pantoprazole (1.5 mg/kg bwt). Intragastric pH was recorded for 24 h after drug administration for pharmacodynamic evaluation. Plasma pantoprazole concentrations were measured using high-performance liquid chromatography. RESULTS: Plasma concentrations of pantoprazole were detectable at the 5 min sampling point following i.v. or intragastric administration. Bioavailability of intragastric-administered pantoprazole was 41%. Baseline mean hourly pH was 1.5-6.1. There was a statistically significant increase in mean hourly pH relative to untreated foals 2-24 h after i.v. or intragastric pantoprazole administration. CONCLUSIONS: Based on these data, i.v. or intragastric administration of pantoprazole results in a significant, prolonged increase in intragastric pH. POTENTIAL RELEVANCE: The i.v. formulation of pantoprazole may provide a clinically useful alternative means of acid suppression in foals unable to tolerate enteral administration of a PPI, such as those with pyloric outflow obstruction.     

Ulceration in the proximal portion of the urethra as a cause of hematuria in horses: four cases (1978-1985)

Sudden onset of hematuria was associated with mucosal ulceration of the proximal portion of the urethra in 1 stallion and 3 geldings. Hematuria was observed characteristically and consistently at the end of urination. Mucosal ulceration was identified endoscopically in the proximal portion of the urethra at the level of the ischial arch. Biopsy of an ulcerated area of the proximal urethra in one gelding revealed transitional cell carcinoma. Treatment regimens varied from systemic antimicrobial and/or vasoactive therapy to diversion of urinary flow via a temporary perineal urethrostomy. Hematuria resolved in 14 to 24 days (average, 20 days) after treatment was begun, except in one gelding that died of undetermined causes during an initial examination. In the 3 remaining horses, hematuria had not recurred for up to 9 years (average, 1 year).     

Nitrogen kinetics of infectious bovine rhinotracheitis-stressed calves

Eight crossbred feeder steers were used in two consecutive N balance studies to investigate the effects of infectious bovine rhinotracheitis virus (IBRV) on N kinetics. Balance Study 1, which followed a 10-d acclimation phase, consisted of 7 d of sample collection referred to as the healthy phase (d -7 to d -1). Study 2, the IBRV-infected phase, began 2 d after a nasal IBRV challenge and continued for 6 d (d 2 to d 8). A stable isotope, [15N]-glycine, was used to determine N kinetics in both studies. Steers weighed 203 kg at the beginning of the study, 208 kg at IBRV infection and 194 kg at the end of study. Infection with IBRV increased (P less than .05) urinary N excretion from 17.9 to 31.5 g/d. Daily N balance was reduced (P less than .05) during infection from 21.2 to -3.3 g/d. Total serum proteins increased (P less than .05) during infection from 6.6 to 7.1 g/100 ml, the increase being predominantly in the alpha and gamma globulin fractions. Blood urea-N increased (P less than .05) during infection from 6.5 to 12.9 mg/100 ml. The urine excretion curve of the stable isotope and the N balance data indicated that IBRV infection increased N turnover and altered tissue utilization of N.     

Bovine spongiform encephalopathy: case-control studies of calf feeding practices and meat and bonemeal inclusion in proprietary concentrates

Following the identification of meat and bonemeal as the most likely source of exposure for the occurrence of bovine spongiform encephalopathy (BSE) in Great Britain case-control studies were initiated to investigate this hypothesis. These involved a comparison of the consumption of specific proprietary calf feedstuffs, and whether or not meat and bonemeal had been included, between animals born in 1983-84 in BSE-unaffected herds and confirmed cases of BSE also born in 1983-84. The feeding of proprietary concentrates containing meat and bonemeal was found to be a statistically significant risk factor for the occurrence of BSE. These studies therefore support the initial hypothesis that BSE occurred as a result of exposure to a scrapie-like agent via meat and bonemeal.     

Effects of short-term early gestational exposure to endophyte-infected tall fescue diets on plasma 3,4-dihydroxyphenyl acetic acid and fetal development in mares

Consumption of wild-type (toxic) endophyte-infected tall fescue (E+) by horses during late gestation is known to adversely affect pregnancy outcome; however, little is known of the potential disruptive consequences of E+ consumption by mares during the critical phases of placentation and fetal development in early pregnancy. The objective of this study was to evaluate the detrimental effects of feeding E+ to mares during early gestation. Mares (n = 12) paired by stage of gestation (d 65 to 100) were assigned to diets (six per diet) consisting of endophyte-free (E-) or E+ tall fescue seed (50% E- or E+ tall fescue seed, 45% sweet feed, and 10% molasses fed at 1.0% of BW/d). Mares also had ad libitum access to E+ or E- annual ryegrass hay, and were fed diets for 10 d. Following removal from the tall fescue diet on d 11, mares were placed on common bermudagrass pasture and monitored until d 21. Morning and evening rectal temperatures were recorded and daily blood samples were collected for progesterone and prolactin (PRL) analyses, whereas samples for 3,4-dihydroxyphenyl acetic acid (a catecholamine metabolite) analysis were collected on alternate days. For clinical chemistry analysis, blood samples were collected on d 0, 5, 10 and 21. Daily urine samples were collected for ergot alkaloid analysis, and ultrasonography was performed for presence of echogenic material in fetal fluids. Rectal temperatures (E+ 37.76+/-0.03; E- 37.84+/-0.03 degrees C) and serum PRL concentrations (E+ 14.06< or =0.76; E- 12.11+/-0.76 ng/mL) did not differ (P = 0.96) between treatments. Measuring the change in basal serum concentration from d 0 over time, progesterone concentrations did not differ (-0.64 +/-1.49 and -0.55+/-1.47 ng/mL for E+ and E- mares, respectively). There was no negative pregnancy outcome, and ultrasonography indicated no increase in echogenic material in fetal fluids. Plasma 3,4-dihydroxyphenyl acetic acid concentrations decreased (P < 0.05) in E+ compared with E- mares (2.1+/-0.14 and 4.4+/0.43 ng/mL, respectively). Urinary ergot alkaloid concentration was greater (P < 0.01) in mares consuming E+ compared with E- (532.12+/- 52.51 and 13.36+/-2.67 ng/mg of creatinine, respectively). Although no fetal loss was observed during the current study, elevated concentrations of urinary ergot alkaloid were consistent with depressed endogenous catecholamine activity, suggestive of an endocrine disruptive effect of hypothalamic origin.     

Conservation of RET regulatory function from human to zebrafish without sequence similarity

Evolutionary sequence conservation is an accepted criterion to identify noncoding regulatory sequences. We have used a transposon-based transgenic assay in zebrafish to evaluate noncoding sequences at the zebrafish ret locus, conserved among teleosts, and at the human RET locus, conserved among mammals. Most teleost sequences directed ret-specific reporter gene expression, with many displaying overlapping regulatory control. The majority of human RET noncoding sequences also directed ret-specific expression in zebrafish. Thus, vast amounts of functional sequence information may exist that would not be detected by sequence similarity approaches.