Anticoagulant rodenticides in urban bobcats: exposure, risk factors and potential effects based on a 16-year study.

Anticoagulant rodenticides (ARs) are increasingly recognized as a threat to nontarget wildlife. High exposure to ARs has been documented globally in nontarget predatory species and linked to the high prevalence of an ectoparasitic disease, notoedric mange. In southern California, mange associated with AR exposure has been the proximate cause of a bobcat (Lynx rufus) population decline. We measured AR exposure in bobcats from two areas in southern California, examining seasonal, demographic and spatial risk factors across landscapes including natural and urbanized areas. The long-term study included bobcats sampled over a 16-year period (1997-2012) and a wide geographic area. We sampled blood (N = 206) and liver (N = 172) to examine exposure ante- and post-mortem. We detected high exposure prevalence (89 %, liver; 39 %, blood) and for individuals with paired liver and blood data (N = 64), 92 % were exposed. Moreover, the animals with the most complete sampling were exposed most frequently to three or more compounds. Toxicant exposure was associated with commercial, residential, and agricultural development. Bobcats of both sexes and age classes were found to be at high risk of exposure, and we documented fetal transfer of multiple ARs. We found a strong association between certain levels of exposure (ppm), and between multiple AR exposure events, and notoedric mange. AR exposure was prevalent throughout both regions sampled and throughout the 16-year time period in the long-term study. ARs pose a substantial threat to bobcats, and likely other mammalian and avian predators, living at the urban-wildland interface.

Pharmacokinetics and selected pharmacodynamics of cobalt following a single intravenous administration to horses.

Cobalt has been used by human athletes due to its purported performance-enhancing effects. It has been suggested that cobalt administration results in enhanced erythropoiesis, secondary to increased circulating erythropoietin (EPO) concentrations leading to improvements in athletic performance. Anecdotal reports of illicit administration of cobalt to horses for its suspected performance enhancing effects have led us to investigate the pharmacokinetics and pharmacodynamic effects of this compound when administered in horses, so as to better regulate its use. In the current study, 18 horses were administered a single intravenous dose of cobalt chloride or cobalt gluconate and serum and urine samples collected for up to 10 days post administration. Cobalt concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS) and pharmacokinetic parameters determined. Additional blood samples were collected for measurement of equine EPO concentrations as well as to assess any effects on red blood cell parameters. Horses were observed for adverse effects and heart rate monitored for the first 4 h post administration. Cobalt was characterized by a large volume of distribution (0.939 L/kg) and a prolonged gamma half-life (156.4 h). Cobalt serum concentrations were still above baseline values at 10 days post administration. A single administration of cobalt had no effect on EPO concentrations, red blood cell parameters or heart rate in any of the horses studied and no adverse effects were noted. Based on the prolonged gamma half-life and prolonged residence time, regulators should be able to detect administration of a single dose of cobalt to horses.

An outbreak of sodium fluoroacetate (1080) intoxication in selenium- and copper-deficient sheep in California.

Sodium fluoroacetate is an organofluorine compound toxic to mammals, insects, and birds, currently registered for use only in livestock protection collars as a predacide in some North American states, with restricted use in California. A flock of 445 lambs and ewes in California were moved into a native pasture on a municipal refuse disposal site. Within 24 hours, 14 ewes were found dead, and the remaining sheep were moved off the site. Both ewes and lambs exhibited disoriented running, followed by apparent blindness, weakness, ataxia, coma, and death. Over the next 4 days, 63 ewes and 80 lambs died with a peak at 3 days after grazing the suspect pasture (157/445, 35% mortality). Two dead 4-month-old lambs and 2 ewes were submitted to the California Animal Health and Food Safety laboratory for necropsy. Grossly, there were bilateral diffuse pulmonary congestion and edema, hydrothorax and hydropericardium with fibrin clots, and multifocally extensive areas of epicardial petechiae, ecchymoses, and pallor. In 1 ewe, there was regional caudodorsal pulmonary hemorrhage and intraluminal tracheal clotted blood. Microscopically in all cases, there was multifocal acute myocardial degeneration and necrosis with nonsuppurative pleocellular myocarditis. Sodium fluoroacetate was detected in kidney from a lamb and a ewe at 27.5 and 12.5 parts per billion, respectively. All sheep were selenium deficient, and concurrent copper deficiency was diagnosed in 3. The pathological and toxicological findings were consistent with 1080 poisoning, possibly exacerbated by micronutrient deficiency. This outbreak raised an alert about the use of restricted products with potential lethal effect in animals in California.

Blood leak alarm interference by hydoxocobalamin is hemodialysis machine dependent.

CONTEXT: Hydroxocobalamin has been reported to interfere with the blood leak alarm on hemodialysis machines making it difficult to use this treatment modality after hydroxocobalamin infusion. OBJECTIVE: The objective was to determine if this interference with hydroxocobalamin occurs across hemodialysis machines by different manufacturers. Additionally, we aimed to see if this represented a colorimetric interference alone or if it is the optical properties of hydroxocobalamin. MATERIALS AND METHODS: Hydroxocobalamin was reconstituted per package insert. Food coloring was added to 0.9% saline to create the colors of the visual spectrum. Optical properties of absorbance and transmittance were measured. Hydroxocobalamin and the saline solutions were infused into the Fresenius 2008K™ and the Gambro Phoenix X36™ machines. Times were recorded from the start of the machine until the solution finished or the alarm triggered. RESULTS: When evaluating the Gambro Phoenix X36™ machine and dialysis circuit; the alarm did not trigger. In contrast, the blood leak alarm on the Fresenius 2008K™ machine was tripped by both the red solution and hydoxocobalamin infused per the package insert. The alarm stopped the machine between 128 and 132 seconds for the red solution and between 30 and 35 seconds with the hydroxocobalamin. Membranes of the circuits where the alarm tripped were examined and remained intact without blood. Results were validated on different machines with new circuits. DISCUSSION: Hydroxocobalamin infusion per package insert and the red saline solution prepared with Red Dye 40 both triggered the blood leak alarm and stopped the Fresenius 2008K™ machine. However, this was not true for the Gambro Phoenix X36™ machine as the alarm never triggered. The interference with the Fresenius 2008K™ appears colorimetric due to normal saline with Red Dye 40 triggering the alarm. CONCLUSION: We alert physicians to become familiar with the properties of individual dialysis machines prior to use of hydroxocobalamin. When facing difficulties with hemodialysis after the administration of hydroxocobalamin, consider attempting with a different manufactures machine or model if available or contact the manufacturer directly.

Death by caffeine: presumptive malicious poisoning of a dog by incorporation in ground meat.

BACKGROUND: A 4-year-old, 37 kg, male German shepherd developed hyperthermia, tachycardia, and agitation following consumption of ground meat found in the backyard of its owner. When presented to a veterinary clinic, plasma ethylene glycol (EG) testing was positive, and the dog was given ethanol and lactated Ringer's solution intravenously. Approximately 11 h postexposure the dog died. DISCUSSION: Among tissues submitted for toxicological analysis, urine was negative for EG, ground meat was negative for certain drugs of abuse, and gastric contents were negative for zinc/aluminum phosphide and metaldehyde. Analysis of gastric contents by gas chromatography-mass spectrometry confirmed the presence of caffeine. Caffeine concentration in the ground meat was estimated at 1 %. Caffeine is a methylxanthine alkaloid with a reported canine oral median lethal dose (MLD(50)) of 140 mg/kg (range 120-200 mg/kg). A commercially available 200-mg tablet formulation of caffeine was considered to be a possible source but this was not confirmed. By conservative estimates, the dog would need to ingest approximately 500-550 g of the meat to reach the MLD(50). Acute intoxication affects the cardiovascular, pulmonary, neurologic, gastrointestinal, and metabolic systems. Although no tablet remnants were observed in the bait, tablets could have been crushed and/or dissolved. Other potential caffeine sources include guarana, brewed and concentrated coffee, and caffeine-containing beverages. Based on the history, clinical signs, and the detection of caffeine in the gastric contents and meat, a presumptive diagnosis of malicious caffeine poisoning was made. A suggested treatment regimen for caffeine intoxication in dogs is described. While few cases of accidental ingestion of caffeine by dogs have been described, the intentional use of a concentrated caffeine source to cause mortality in a dog has not been previously reported.

Acute respiratory distress in an alpaca.

An alpaca was presented with a history of respiratory difficulty and death. Histology of the phrenic nerves and diaphragm revealed degenerative changes consistent with denervation atrophy, and a diagnosis of diaphragmatic paralysis was established. No gross or histological abnormalities were observed in the spinal cord or other organs. The etiology of the phrenic nerve neuropathy could not be determined. The need to examine phrenic nerves and diaphragm in camelids with respiratory distress is emphasized, as failure to examine these samples will preclude a diagnosis of diaphragmatic paralysis.

Amanitin toxicosis in two cats with acute hepatic and renal failure.

Amanitin is a toxic cyclopeptide present in several species of poisonous mushrooms. Amanitin toxicosis was diagnosed in 2 cats from separate premises. Both cats initially had lethargy and vomiting, and they rapidly developed depression and neurological signs over 24-48 hours. Marked elevation of alanine aminotransferase was the primary finding, with subsequent serum chemistry values compatible with hepatic and renal failure. Histopathological findings consisted of submassive to massive acute hepatic necrosis, renal proximal tubular epithelial necrosis, and foci of necrosis and inflammation in the gastrointestinal tract. Amanitin exposure was confirmed postmortem by detection of α-amanitin in the kidney by liquid chromatography-mass spectrometry. A similar clinical course and pathological changes are reported in human and canine amanitin intoxication; however, gastrointestinal lesions are not typically described.

Osteoporosis associated with pulmonary silicosis in an equine bone fragility syndrome.

California horses incur a bone fragility syndrome manifested by pathologic fractures. This study investigated gross, radiographic, and histologic features of the disorder as well as relationships with silicosis and levels of heavy metals and trace minerals through a postmortem study of 9 affected and 3 unaffected horses. Bones and soft tissues were evaluated grossly and histologically. Bones, lymph nodes, and lung tissue were evaluated radiographically. Tissues were evaluated for silicon levels, intracytoplasmic crystals, heavy metals, and trace minerals. All 9 affected horses had osteoporosis and clinical or subclinical pulmonary disease due to silicosis (8/9) or pneumoconiosis (1/9). All affected horses had radiographic findings consistent with osteopenia and histologic evidence of osteoporosis characterized by osteopenia, numerous resorption cavities, cement lines, and a mosaic lamellar pattern indicative of multiple remodeling events. Silicosis was characterized by widespread pulmonary granuloma formation with fibrosis; variable tracheobronchiolar and mediastinal granulomatous lymphadenitis; intracellular crystals within lung and lymph node macrophages; and pronounced lymph node fibrosis, focal necrosis, and dystrophic calcification. Crystals in lung (6/9) and lymph node (8/9) tissues were identified as cytotoxic silica dioxide polymorphs. Lung and liver tissue from affected horses had elevated levels of elemental silicon. Osteoporosis was highly correlated (r = 0.8, P < .01) with silicosis. No abnormalities in heavy metal or trace minerals were detected. This evaluation indicated that horses with bone fragility disorder have systemic osteoporosis associated with fibrosing pulmonary silicosis. The etiopathogenesis of the bone fragility syndrome is unknown; however, this study provides circumstantial evidence for a silicate associated osteoporosis.

Retrospective study of melamine/cyanuric acid-induced renal failure in dogs in Korea between 2003 and 2004.

In early 2007, American pet food ingredients leading to nephrotoxic renal failure of dogs and cats raised serious concerns about the safety of pet foods. Major pet food companies recalled more than 1,000 commercial pet foods in consideration of pet safety. A similar pet food-associated outbreak of nephrotoxic renal failure occurred in Asia, in late 2003 and 2004, resulting in a similar extensive pet food recall. At that time, contamination of ingredients with a nephrotoxin-producing fungus at a pet food production facility was suspected. However, toxicologic evidence to substantiate a mycotoxicosis was lacking. Moreover, the renal lesions were not typical of those reported with fungal nephrotoxins. During 2003 and 2004, 14 dogs were presented to the Veterinary Medical Teaching Hospital of Konkuk University, Seoul, Korea, with renal failure and distinctive renal pathologic findings. Grossly, the kidneys were greenish in color with greenish uroliths in the renal pelvis or bladder. Histologically, characteristic crystals with pinwheel radiating striations were present in distal tubular segments. Toxicologic analysis identified melamine, cyanuric acid, and ammelide in deparaffinized formalin-fixed kidney samples.

Clostridium piliforme infection in two farm-raised white-tailed deer fawns (Odocoileus virginianus) and association with copper toxicosis.

Necropsy of 2 white-tailed deer fawns who died acutely revealed diarrhea and melena in case No. 1 and no gross changes in case No. 2. Histologically, the livers of both deer displayed multifocal coagulative necrosis, with infiltrations of neutrophils, macrophages, and lymphocytes. By Warthin-Starry staining, bundles of filamentous bacteria were identified within hepatocytes at the periphery of the necrotic foci in case No. 1. There was multifocal myocardiocyte necrosis in case No. 1 and multifocal lymphoid necrosis of the Peyer's patches in case No. 2. Clostridium piliforme 16S ribosomal ribonucleic acid gene was detected in both livers by polymerase chain reaction (PCR) with C. piliforme-specific primers. The liver copper levels in both cases were normal to slightly elevated. The kidney copper level in case No. 2 was elevated. This represents the first published cases of Tyzzer's disease in deer, a novel use of PCR for the diagnosis of C. piliforme infection, and a possible association between copper toxicosis and Tyzzer's disease.

Pharmacokinetics of imipenem-cilastatin following intravenous administration in healthy adult horses.

In two studies, six healthy adult horses were given imipenem-cilastatin by slow intravenous (i.v.) infusion at an imipenem dosage of 10 mg/kg (study 1) and 20 mg/kg (study 2). The same horses were used in each dosage schedule, with a 2-week washout period between studies. In each dosage group, serial blood and synovial fluid samples were collected for 6 h after completion of the infusion. HPLC was used to determine the imipenem concentration in all samples. Imipenem was well tolerated by all horses at both dosages; no adverse effects were noted during the study period or during the 24-hour postinfusion observation period. The pharmacokinetic profiles of imipenem in the plasma and synovial fluid indicate that an imipenem dosage of 10-20 mg/kg by slow i.v. infusion q6h (every 6 h) is appropriate for most susceptible pathogens.

Cefotaxime kinetics in plasma and synovial fluid following intravenous administration in horses.

Cefotaxime powder was diluted with sterile water to a concentration of 100 mg/mL. The volume of solution was adjusted for each experimental horse to provide a total dose of 15, 20, and 25 mg/kg and was administered by infusion through a jugular vein catheter over a 10-min period. All three doses were administered to each of the six experimental horses at three different times. Cefotaxime concentrations in plasma and synovial fluid samples were measured by high-performance liquid chromatography (HPLC). Standard compartmental analysis techniques and the WinSAAM modeling program were used to determine standard pharmacokinetic parameters for cefotaxime. The plasma and synovial fluid data from the five horses administered the 25 mg/kg dose was analyzed. Plasma cefotaxime concentrations appeared to be linearly related to dose infused and declined in parallel, suggesting linear drug kinetics. Moreover, cefotaxime concentrations declined monotonically suggesting that its disposition kinetics could essentially be described by a one-compartment model rather than the fact that sampling occurred after the infusion was discontinued. Maximum concentration of cefotaxime in plasma occurred immediately after cessation of the infusion. Minimum inhibitory concentrations were determined for Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, common isolates from septic arthritis in horses. Based on our pharmacokinetic data, a regimen of 25 mg/kg administered i.v. every 6 h appears appropriate for susceptible joint infections in adult horses.

Disposition of flunixin meglumine injectable preparation administered orally to healthy horses.

An injectable preparation of flunixin meglumine was administered orally and intravenously at a dose of 1.1 mg/kg to six healthy adult horses in a cross-over design. Flunixin meglumine was detected in plasma within 15 min of administration and peak plasma concentrations were observed 45-60 min after oral administration. Mean bioavailability of the oral drug was 71.9 +/- 26.0%, with an absorption half-life of 0.76 h. The apparent elimination half-life after oral administration was 2.4 h. The injectable preparation of flunixin meglumine is suitable for oral administration to horses.

Common loon eggs as indicators of methylmercury availability in North America.

Increased anthropogenic mercury (Hg) deposition since pre-industrial times, and subsequent transformation of inorganic Hg to methylmercury (MeHg) in aquatic environments, has created areas in North America where Hg poses a relatively high risk to wildlife, especially long-lived, piscivorous species. From 1995 to 2001, we opportunistically collected 577 eggs abandoned by Common Loons from eight states. Egg-Hg concentrations ranged from 0.07 to 4.42 microg/g (ww) or 0.10 to 19.40 microg/g (dw). Mercury was higher in eastern than in western North America. Female blood-Hg concentrations strongly correlated with those of eggs from the same territory even though the mean intraclutch Hg difference was 25%. In New England, egg volume declined significantly as egg-Hg concentrations increased. Fertility was not related to egg-Hg concentrations. Based on existing literature and this study's findings, egg-Hg risk levels were established and applied to our US data set and an existing Canadian data set. Regionally, we found the greatest risk levels in northeastern North America. With few exceptions, loon eggs are suitable indicators of methylmercury availability on lakes with territorial pairs.

Clenbuterol ingestion causing prolonged tachycardia, hypokalemia, and hypophosphatemia with confirmation by quantitative levels.

BACKGROUND: Clenbuterol is a long acting beta2-adrenergic agonist used in the treatment of pulmonary disorders. Acute clenbuterol toxicity resembles that of other beta2-adrenergic agonists. Most previously reported cases of clenbuterol toxicity describe patients who ate livestock illicitly treated with clenbuterol. CASE REPORT: We report a case of human clenbuterol toxicity confirmed and correlated with qualitative and quantitative serum clenbuterol assays. This poisoned patient, a 28-year-old woman, developed sustained sinus tachycardia at 140/min, hypokalemia (2.4 mEq/L, 2.4 mmol/L), hypophosphatemia (0.9 mg/dL, 0.29 mmol/L), and hypomagnesemia (1.52 mg/dL, 0.76 mmol/L) after ingesting a reportedly small quantity of clenbuterol. The patient received repeated doses of metoprolol to treat her cardiovascular stimulation and potassium chloride to treat her hypokalemia. She remained symptomatic for more than 20 hours after the ingestion. Analysis by enzyme-linked immunosorbent assay and liquid chromatography/mass spectrometry revealed a serum clenbuterol concentration of 2.93 mcg/L 3 hours after the ingestion and an undetectable serum concentration 20 hours after ingestion. It is noteworthy that at a serum concentration below the limit of detection by liquid chromatography/mass spectrometry, the patient remained symptomatic. Acute clenbuterol toxicity is rarely reported following illicit use in humans, and this is the first such case to provide confirmatory toxicological analysis.

Lead toxicosis and trace element levels in wild birds and mammals at a firearms training facility.

In May 1999, lead poisoning was diagnosed in a yellow-rumped warbler (Dendroica coronata) and a gray squirrel (Sciurus carolinensis) found at the Federal Law Enforcement Training Center (FLETC), Glynn County, GA, based on detection of 6.2 and 90.0 ppm wet weight (WW) lead in the liver of the warbler and squirrel, respectively. From October 21--26, 1999, 72 wild animals (37 mammals and 35 birds), comprised of 22 different species, were collected from a 24-ha area surrounding the FLETC outdoor firearms shooting range complex to evaluate exposure to lead and other trace elements. Ten animals were used as controls (five mammals and five birds) and were collected from areas 1.5--3 km outside the shooting range area. Kidney and liver tissues were analyzed for lead, zinc, and other trace elements. Bird gizzards and white-tailed deer abomasums were examined grossly and radiographically to detect metallic objects. Twenty-four (33.3%) animals (11 species) had kidney or liver tissue lead levels > 1.00 ppm, and 12 of these (6 species) had levels > 2.00 ppm. Carcasses of one brown-thrasher (Toxostoma rufum) and two white-tailed deer (Odocoileus virginianus) contained lead fragments. Elevated liver tissue levels of zinc (111.0 ppm) were detected in one brown thrasher that also had elevated kidney and liver tissue lead levels. In February 2000, seven yellow-rumped warblers and one solitary vireo (Vireo solitarius) found dead near the FLETC firearms shooting range also were diagnosed with lead poisoning, with liver and kidney tissue lead levels from 1.77--11.6 and 4.55--17.8 ppm WW, respectively. This frequency of elevated tissue lead levels among the animals examined, in combination with confirmed lead toxicosis in both avian and mammalian species at FLETC, indicates significant lead exposure of local wild bird and mammal communities via bullets and fragments in and on the soil surface of the four outdoor ranges. Most FLETC firearms training is being shifted to new baffled ranges (four walls with semiopen top) with bullet recovery capabilities to preclude future deposition of lead in the environment; existing outdoor ranges will be remediated to remove existing lead.

Risks associated with the use of herbs and other dietary supplements.

The use of dietary supplements (herbs, vitamins, minerals, amino acids, enzymes, and other compounds) is common in horses. They are heavily marketed in retail stores, magazines, and on the Internet. There is the perception that since these compounds are "natural" they are devoid of toxicity, and, therefore, they are safe to use. Some of the active compounds in supplements, however, have inherent toxicity, and using them may cause adverse effects. Even relatively non-toxic ingredients may be toxic if used over-zealously or for a long period of time. By and large, these compounds have not been tested for safety or efficacy when used as marketed, and, unfortunately, there is little regulatory oversight for such products. Other deleterious consequences of dietary supplement use include interaction of compounds in the products with conventional drugs, resulting in unexpected adverse effects, or the occurrence of violative residues in urine samples collected from show or performance horses. This article provides a brief overview of potential problems associated with dietary supplements, primarily focusing on products containing herbs and essential oils.

Current environmental threats to animal health and productivity.

Livestock can be exposed to literally thousands of environmental contaminants. Fortunately, most do not cause significant livestock morbidity or mortality and relatively few present significant residue concerns in animal products intended for human consumption. Some environmental contaminants, however, present livestock health or residue concerns. The significance of specific environmental contaminants on livestock health and productivity can change with time and unforeseen threats can emerge as new chemicals or technologies are introduced or new knowledge about health effects of established chemicals emerges.

Respiratory failure attributable to moxidectin intoxication in a dog.

A 5-month-old 22-kg (48.4-lb) sexually intact male Collie was examined after ingesting a moxidectin-containing deworming medication. The dog was comatose and had respiratory arrest after progressively worsening lethargy, ataxia, and seizures. Exposure was confirmed by isolation of moxidectin from a biopsy specimen of adipose tissue, using liquid chromatography-mass spectroscopy methods. Treatment included use of intermittent positive-pressure ventilation, activated charcoal and cathartic administered enterally, nutrients administered via nasogastric tube, and intensive supportive care. The dog was weaned from a ventilator on day 6 after ingestion and was discharged on day 10. The dog was considered clinically normal during examination 24 days after ingestion. On the basis of the dog reported here and toxicologic data provided by the manufacturer of the deworming product, some Collies may have increased susceptibility to products containing high doses of moxidectin.