Inner ear morphology in a bilaterally deaf Dogo Argentino pup.

Two bilaterally deaf and three unilaterally deaf pups were identified from a litter of 10 Dogo Argentino pups presented for hearing evaluation by electrophysiological investigation. One pup, a bilaterally deaf female aged 43 days, was available for histopathology. Examination of both inner ears revealed bilateral cochlear degeneration with atrophy of the stria vascularis, collapse of the cochlear duct, degeneration of the organ of Corti, and abnormal tectorial membrane. The left vestibule, including the sacculus, was normal. The spiral and vestibular ganglia were essentially normal. This is the first histopathological description of lesions associated with deafness in a Dogo Argentino, but abnormalities were similar to those previously described in deaf Dalmatian pups and in other white hair-coated breeds. The defect was classified as a cochleosaccular degeneration. It was probably congenital and genetic causes were suspected.

The in vitro pharmacology of the beta-adrenergic receptor pet ligand (s)-fluorocarazolol reveals high affinity for cloned beta-adrenergic receptors and moderate affinity for the human 5-HT1A receptor.

RATIONALE: s-Fluorocarazolol [(S)-FCZ] is the major positron emission tomography (PET) ligand currently used to visualize central beta-adrenergic receptors in vivo, although its pharmacology is incompletely known. OBJECTIVE: Our objective was to comprehensively characterize the in vitro pharmacology of (S)- and (R)-FCZ to determine its suitability for study of central and peripheral beta-adrenergic receptors. METHODS: We characterized the in vitro pharmacology of (S)-FCZ at 42 biogenic amine receptors and transporters in vitro using the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. RESULTS: As expected (R)- and (S)-FCZ had high affinities for beta-adrenergic receptors (Ki values=0.08-0.45 nM) and negligible affinities (Ki values>100 nM) for nearly all other tested receptors and transporters with the exception of the h5-HT1A receptor for which (S)-FCZ had high affinity (Ki=34 nM). Interestingly, (R)-FCZ had low affinity for the h5-HT1A receptor (Ki=342 nM). CONCLUSION: The high affinity of (S)-FCZ for the h5-HT1A receptor is not likely to interfere with studies of peripheral beta-adrenergic receptors, since 5-HT1A receptors are expressed at very low levels outside the central nervous system. Indeed, computer simulations predict that even at low ligand concentrations, 5-HT1A binding in brain regions like hippocampus are likely to be substantial. Thus, (S)-FCZ may not be a suitable PET ligand for studies of central nervous system beta-adrenergic receptors unless the contribution by 5-HT1A sites can be shown to be negligible.

A modified bilateral transfrontal sinus approach to the canine frontal lobe and olfactory bulb: surgical technique and five cases.

Five adult dogs presented for an acute onset of seizure activity. Magnetic resonance imaging revealed lesions in the olfactory bulbs, frontal lobes of the cerebrum, or both. A modified bilateral transfrontal sinus craniotomy was performed on each patient. The goal of removing the lesion was to relieve clinical signs and to provide tissue for histopathological diagnosis. In each instance, excision of the lesion was possible using this approach. No postoperative complications were observed. The modified bilateral transfrontal sinus craniotomy provides excellent access to the canine olfactory bulbs and frontal lobes.

Tip-link integrity on chick tall hair cell stereocilia following intense sound exposure.

Hair bundle tip links have been implicated in the process of hair cell transduction, and previous studies have shown that acoustic overstimulation or exposure to low calcium can disrupt them. Severed tip links would thus be expected to cause a loss in hair cell function. This study investigates the presence of tip links on chick tall hair cells at three exposure durations and three recovery durations. After 4, 24, or 48 h of exposure, and 24, 96, and 288 h of recovery, the basilar papilla was harvested and prepared for scanning electron microscopy. Photomicrographs of hair bundles from sound-exposed and age-matched control ears were obtained in regions of the papilla adjacent to the 'patch' lesion. The percentage of tip links present on these hair bundles was determined from the photomicrographs. After 4, 24, or 48 h of exposure, an average of 49%, 41.1% and 52% of the observed sensory hairs exhibited links. This was significantly lower than that seen in the control ears (71.2%). There also was a reliable recovery of tip links between 24 and 48 h of exposure. The recovery continued and by 24 h post exposure, tip links were present on 61.3% of the sensory hairs. At subsequent recovery intervals, the mean number of tip links on sound-exposed tall hair cells was statistically the same as seen on control cells. The results indicated a predictable loss in the number of tip links during the exposure and their restoration within a relatively short time after the exposure. This structural damage to the tall hair cell, and its recovery, could account for some of the loss and recovery of function in the auditory periphery of these sound-damaged chicks.

A case of canine central nervous system cryptococcosis: management with fluconazole.

A three-year-old, female Labrador retriever was presented for acute generalized seizures. Disseminated cryptococcosis with central nervous system (CNS) involvement was diagnosed by serum and cerebrospinal fluid (CSF) fungal titers, histopathological examination, and magnetic resonance imaging (MRI). Fluconazole therapy resulted in prolonged, substantial clinical improvement for a period of one year. This report documents the diagnosis of a case of cryptococcal meningoencephalitis and its management with the new antifungal agent, fluconazole.

Inherited deafness among nervous pointer dogs.

A high incidence of deafness, confirmed by brainstem auditory evoked response testing, was found in a colony of pointer dogs selectively bred for excessive nervous behavior. The results of outcross and F1 backcross breedings were consistent with an autosomal recessive mode of inheritance of deafness in this family of dogs.

Glycogen storage disease type IV: inherited deficiency of branching enzyme activity in cats.

Glycogen storage disease type IV due to branching enzyme deficiency was found in an inbred family of Norwegian forest cats, an uncommon breed of domestic cats. Skeletal muscle, heart, and CNS degeneration were clinically apparent and histologically evident in affected cats older than 5 mo of age, but cirrhosis and hepatic failure, hallmarks of the human disorder, were absent. Beginning at or before birth, affected cats accumulated an abnormal glycogen in many tissues that was determined by histochemical, enzymatic, and spectral analysis to be a poorly branched alpha-1,4-D-glucan. Branching enzyme activity was less than 0.1 of normal in liver and muscle of affected cats and partially deficient (0.17-0.75 of normal) in muscle and leukocytes of the parents of affected cats. These data and pedigree analysis indicate that branching enzyme deficiency is a simple autosomal recessive trait in this family. This is the first reported animal model of human glycogen storage disease type IV. A breeding colony derived from a relative of the affected cats has been established.

Hepatotoxicity of phenobarbital in dogs: 18 cases (1985-1989).

The medical records of 18 dogs that had hepatic disease and received phenobarbital as an anticonvulsant for 5 to 82 months were reviewed. Clinical signs included sedation and ataxia in all dogs, 5 dogs were also anorectic, 2 had coagulopathy, 3 were icteric, and 5 had ascites. Serum biochemical analysis revealed serum albumin concentration less than or equal to 2.2. g/dl in 12 dogs, serum alkaline phosphatase activity greater than or equal to 169 U/L in 18 dogs, serum alanine transaminase activity greater than or equal to 57 U/L in 15 dogs, and total bilirubin concentration greater than or equal to 1 mg/dl (in the absence of lipemia) in 7 dogs. Serum phenobarbital concentration was greater than or equal to 40 micrograms/ml in 12 of 17 dogs. Sulfobromophthalein excretion was prolonged in 8 of 10 dogs. Preprandial serum bile acid concentrations were high in 8 of 10 dogs, and 2-hour postprandial serum bile acid concentrations were high in 9 of 10 dogs. Two of 4 dogs tested had resting plasma ammonia concentrations greater than 200 mg/dl. An ammonia tolerance test was performed on 2 other dogs; both had ammonia concentration greater than or equal to 200 mg/dl in the plasma 30 minutes after receiving 100 mg of ammonium chloride/kg of body weight, PO. Nine dogs died, 1 was euthanatized, and necropsies were performed on these 10 dogs. Biopsies and necropsies of 6 dogs revealed chronic hepatic fibrosis with nodular regeneration (cirrhosis). One dog had hepatocellular carcinoma and mild cirrhosis. In 1 dog, after phenobarbital had been withheld, necropsy revealed complete recovery of the previously observed lesions.

Clinical evaluation of gamma-vinyl-gamma-aminobutyric acid for control of epilepsy in dogs.

Gamma-vinyl-gamma-aminobutyric acid is a novel antiepileptic drug that exerts its effects by increasing the concentration of gamma-aminobutyric acid in the brain. The mechanism of action involves irreversible inhibition of the metabolic pathway of gamma-aminobutyric acid. The drug was administered to 14 dogs in conjunction with other anticonvulsants, in an attempt to control refractory epilepsy. Four of these dogs had clinically relevant evidence of decreased seizure frequency. In 4 dogs, response to the drug was no better than response to phenobarbital alone. In 2 dogs, seizure control improved, but gamma-vinyl-gamma-aminobutyric acid was withdrawn because of development of hemolytic anemia. For various reasons, the therapeutic effect in the remaining 4 dogs could not be evaluated. This study of only 14 dogs illustrates some of the problems that confound our ability to judge the efficacy of anticonvulsant treatment.

Identification of gonadal steroid receptors in meningiomas from dogs and cats.

Cytosolic assay was used to detect gonadal steroid receptors in brain tumor tissue from 6 dogs and 2 cats. For 4 samples, the maximal number of binding sites and the equilibrium dissociation constant were calculated, using Scatchard analysis. The concentration of receptor protein that was discovered was similar to that detected in hormone-sensitive tumors.

The relationship between genetic deafness and fear-related behaviors in nervous pointer dogs.

Nervous pointer dogs have been extensively characterized as an animal model for some human pathological anxiety states. During our work with these animals suspicion developed that some of these dogs had a hearing deficit. We decided to systematically evaluate this observation and to study the relation between hearing status and fear-related behaviors in the nervous pointer dogs. Our results revealed that a majority of the nervous dogs in our colony (75%) suffer from bilateral deafness as demonstrated by complete absence of brain stem auditory evoked response. Furthermore, behavioral ratings revealed that hearing and deaf dogs do not differ in their pathological response to the characteristic fear-provoking stimuli (e.g., human interaction) and that both hearing and deaf nervous dogs markedly differ from normal dogs in that respect. The relation between these abnormalities and their implications for research involving breeding of animals for selected traits are further discussed in this report.

Subchronic toxicity studies of N-D-ornithyl amphotericin B methyl ester in dogs and rats.

Two subchronic studies were conducted to assess the potential toxicity of N-D-ornithyl amphotericin B methyl ester (OAME). In both studies the comparative control substance was amphotericin B (AMB). Dogs (5/sex/group) were given OAME (82% pure, based on high-pressure liquid chromatographic (HPLC) analysis) at 0.6, 2.5, and 10 mg/kg or AMB at 0.6 mg/kg intravenously once daily for 3 months. Two dogs per sex per group were retained for a 7-week postdose observation period. Rats (15/sex/group) were given daily doses of OAME at 4, 12, 24, and 36 mg/kg or AMB at 5 and 12 mg/kg intraperitoneally for 3 months. The principal organs of toxicity in both species were the liver, kidneys, and circulating erythrocytes. Hepatic changes in dogs consisted of periportal and centrilobular inflammation in animals of all dosed groups and were equivalent in dogs given 0.6 mg/kg OAME or AMB. In rats, acute hepatic necrosis with periportal, centrilobular, or panlobular distribution in animals of all OAME (except 4 mg/kg) and AMB-dosed groups was observed. These changes were equivalent in the 36-mg/kg OAME- and 12-mg/kg AMB-dosed animals. Renal changes, evidenced by increases in serum urea nitrogen water consumption, urine volume, decreased urine osmolality, and renal tubular changes (ranging from degeneration and regeneration to necrosis), were observed in both species. In dogs, these changes in the OAME-dosed animals were less severe at all doses than those observed in the AMB-dosed dogs. Renal changes in rats, which were mild in comparison to the dogs, were equivalent at doses of 5 and 12 mg/kg AMB and 36 mg/kg OAME. Decreased erythrocyte counts, hematocrit, and hemoglobin values were observed in both species. Unique to the dog study, however, were irreversible behavioral (somnolence, ataxia, tremors, and compulsive searching) and/or morphologic brain changes (gliosis with astrocytic hypertrophy and hyperplasia) at doses of 2.5 and 10 mg/kg OAME. Similar changes were observed in two dogs given 10 mg/kg OAME (100% pure, based on HPLC analysis) in a 6-week pilot study, indicating that the neurological changes were induced by OAME rather than by an impurity. These changes appear related to prolonged exposure to high plasma concentrations of OAME.

Acute idiopathic polyneuropathy in the dog.

From among a large group of dogs with acute tetraparesis, we identified 10 dogs with a distinct peripheral nerve disorder. Prior to the onset of signs, all of the dogs had been healthy, and none was known to have been exposed to a neurotoxin or raccoon bite. Weakness, with hypoactive or absent segmental reflexes, became progressively worse for 1 to 21 days. Results of electromyography and nerve conduction studies invariably were compatible with a diagnosis of polyneuropathy that predominantly affected proximal nerve segments. Appearance of nerve biopsy specimens and the short time course for functional recovery suggested a demyelinative component to the disorder. The extent of recovery was variable but often rapid and complete in dogs that did not succumb to complications in the early period. Corticosteroid therapy did not demonstrably influence the outcome. This acute idiopathic polyneuropathy in the dog shares many clinical and pathologic features with idiopathic polyradiculoneuritis (Coonhound paralysis).

A disorder of rapid eye movement sleep in a cat.

A young female cat with no neurologic abnormality during wakefulness was discovered to have violent motor activity during rapid eye movement sleep. Various characteristics of the disorder, which differentiated these episodes from epileptic seizures, suggested that the movements resulted from an exaggeration of phasic excitation during rapid eye movement sleep.