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Lead Poisoning
Accidental lead poisoning is one of the more common intoxications of dogs and cats [71-80]. It may occur from many sources including linoleum, putty, roofing felt, golf balls, old car batteries, lead weights, ingestion of contaminated soil, improperly glazed ceramic water bowls, and toys; however, lead-based paints are the most frequent source of poisoning [78,81]. Lead is believed to inhibit sulfhydryl groups of essential enzymes of cellular metabolism. One important consequence of this is inhibition of heme synthesis resulting in the circulation of immature erythrocytes [82]. Dietary factors, such as high-fat- low-calcium diets, may facilitate absorption of lead from the alimentary tract [83]. The majority of absorbed lead is deposited in bones, followed by liver and kidney, brain and spinal cord [84]. Lead can disrupt the blood-brain barrier by damaging capillary endothelial cells with resultant cerebral edema and hemorrhage. In the brain, morphological changes range from diffuse capillary proliferation to status spongiosus and cerebral cortical necrosis. In studies of experimental lead toxicosis of dogs, microscopic lesions were present in up to 89% of the lead-treated dogs [85,86]. Cerebrocortical lesions comprising spongiosis, vascular hypertrophy and gliosis predominated. These lesions were bilateral, had a predilection for gyri and were located mainly in the parietal and frontal cortex. There were bilaterally symmetrical spongiform changes in the brain stem. The cerebellum had spongiform changes in the roof nuclei and in the lingula there was spongiosis of the Purkinje cell layer and vacuolation of Purkinje cells. Axonal degeneration was evident in a sciatic nerve of only one dog. While peripheral neuropathy may occur sporadically with spontaneous lead poisoning, the inability to experimentally produce a polyneuropathy in dogs given chronic oral low level lead in another study [87], further suggests that dogs may be resistant to the toxic neuropathic effects of lead.
Lead poisoning is more commonly reported in dogs than cats [77]. Affected animals may be of any age (e.g., from 8 weeks to 16 years). In case reports of lead toxicoses from 2 major animal poison control centers in Europe and North America, 60% of dogs were less than 2 years old [81]. The incidence is reportedly higher in summer and early fall [81]. Clinical signs of central nervous system dysfunction usually are preceded or accompanied by gastrointestinal malfunction [74,78]. Signs may be acute or chronic. The most common gastrointestinal signs in dogs and cats are vomiting, anorexia, diarrhea, and in some animals, abdominal pain. Common neurological signs in dogs and cats include depression, generalized seizures, hysteria (barking and/or whining continuously, aimless running and snapping at objects), ataxia, blindness, head pressing, and jaw champing. Abdominal pain and hysteria may be more common in animals less than 1 year of age. Megaesophagus and partial laryngeal paralysis, believed to be due to lead-associated neuropathy, have been seen in a cat [88]. Megaesophagus may also be observed in dogs with lead poisoning. In some cats, clinical signs may be non-specific (e.g., weight loss). Low-level lead intake in young dogs can cause an early increase in blood pressure [89].
Diagnosis is suggested by finding rubricytosis and numerous nucleated erythrocytes in a stained blood smear [90]. The presence of basophilic stippling in red blood cells, anemia, increased packed cell volume, presence of diffuse radiopaque material in the gastrointestinal tract, and radiopaque bands in x-rays of long bone metaphyses of young dogs [84], also supports the diagnosis (chronic low dose lead intoxication results in bone storage and altered normal bone physiology [91]). Elevated urinary levels of delta aminolevulinic acid has been reported to have limited value as a diagnostic aid in canine lead poisoning [75,92]. Furthermore, recent studies suggest that theta-aminolevulinic acid dehydratase and zinc protoporphyrin were of poor predictive diagnostic value as markers of lead intoxication in dogs [93,94]. In some animals, leukocytosis, elevated liver enzyme levels, and increased serum concentrations of glucose and cholesterol may be found. Levels of 40 mg or more of lead/100 ml of whole blood is considered definitively diagnostic of lead poisoning [71,77]. There is no direct correlation between severity of clinical signs and blood level content. Electroencephalographic changes reported in nonsedated dogs were marked by intermittent high-amplitude slow wave activity [95].
Treatment with the chelating agent, calcium disodium ethylene diamine tetraacetate (EDTA), using a dose of 25 mg/kg IV, qid for 2 to 5 days, often results in rapid recovery within 36 to 48 hours. Oral administration (same dosage) has also been effective [96]. Alternatively, oral penicillamine may be given in a dose of 100 mg/kg, daily, for 1 to 2 weeks. Treatment is repeated over another 5-day period if signs persist. The prognosis is favorable in the majority of lead poisoning cases treated with chelating agents [78,97]. Recent studies in dogs with naturally acquired lead poisoning indicated that succimer (meso-2,3-dimercaptosuccinic acid), administered orally for 10 days (10 mg/kg of body weight, PO, q 8 h), also effectively reduced blood lead concentrations and eliminated clinical signs of lead poisoning [98]. Succimer is also effective in cats [214]. Succimer may also be given rectally as a solution in patients that are vomiting.

Levamisole
Levamisole is used as an anthelmintic, microfilaricide, and immunostimulant [1,99,100]. Clinical signs of toxicity may be seen at approximately 4 times the normal therapeutic dose (which is 10 to 11 mg/kg), although toxicity has been reported following a single oral dose of levamisole hydrochloride given at the rate of 12 mg/kg [101]. Levamisole is a nicotine-like ganglionic stimulant producing both muscarinic and nicotinic effects at cholinergic receptors [1]. Clinical signs and lesions of levamisole toxicosis include: nausea, vomiting, increased salivation, frequent urination and defecation, colic, dizziness, headache, muscle tremors, ataxia, anxiety, hyperesthesia with irritability, clonic convulsions, depression, rapid respiration, dyspnea, cardiac arrhythmias, prostration, collapse, hemorrhages in the subepicardium and thalamus, enteritis, hepatic degeneration and necrosis, and splenic congestion. Most of these signs and lesions are similar to those observed in nicotine poisoning [102]. Levamisole causes an electroencephalographic arousal and multiple foci of EEG irritation [101,102]. Treatment is largely supportive, including GI tract decontamination, seizure control, fluid therapy, and ventilation support [1].