Liver enzyme activity and histological changes in the liver of silver foxes (Vulpes vulpes fulva) experimentally infected with opisthorchiid liver flukes. A contribution to the pathogenesis of opisthorchiidosis.

Blood samples from silver foxes experimentally infected with Opisthorchis felineus and Metorchis bilis, respectively, were examined for the activity of liver enzymes. The average activities of aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), alkaline phosphatase and alanine aminotransferase in uninfected control animals were 20, 1.8, 57 and 44 units/l, respectively. The liver enzymes in infected foxes reacted differently, depending on dose, species of flukes and individual peculiarities. The highest individual deviation of infected from control animals was registered in the case of GLDH, reaching increases of up to 200-fold. In contrast, AST showed the lowest deviation from control values (less than 10-fold). By the end of the study period, enzyme activities had declined. The prepatent periods for M. bilis and O. felineus in foxes were 2 weeks and 4 weeks, respectively. High egg per gram values were established at the beginning of the patent period. At necropsy, chronic inflammatory reactions were found in the bile ducts and in the wall of the gall bladder. The number of flukes at the end of the study was low.

Genetic variability and prevalence of Bartonella henselae in cats in Berlin, Germany, and analysis of its genetic relatedness to a strain from Berlin that is pathogenic for humans.

Nineteen Bartonella henselae strains and one Bartonella clarridgeiae strain were isolated from blood samples of 97 pet cats and 96 stray cats from Berlin, Germany, indicating prevalence rates of 1 and 18.7%, respectively, for B. henselae and 0 and 1%, respectively, for B. clarridgeiae. Eighteen of 19 B. henselae isolates corresponded to 16S rRNA type II. Pulsed-field gel electrophoresis (PFGE) analysis revealed seven different PFGE types among the feline B. henselae strains. Interestingly, all feline isolates displayed low genetic relatedness to B. henselae strain Berlin-1, which is pathogenic for humans.

[Insufficient success in the treatment of epilepsy--mistakes in therapy or resistance to therapy?]. / Ungenügender Behandlungserfolg bei der Epilepsie--Therapiefehler oder Therapieresistenz?

Frequently either no results or inadequate results are obtained in the therapy of canine and feline epilepsy. This is often not due to a primary resistance to therapy, but rather, caused by other factors and, above all, by mistakes made in therapeutic management. The possible causes of a faulty or insufficient treatment and the most common mistakes made in therapeutic regime are described. At the same time suggestions for an optimal course of therapy are given.

[Effectiveness of bromide in therapy resistant epilepsy of dogs]. / Wirksamkeit von Bromid bei den therapieresistenten Epilepsien des Hundes.

In therapy lasting between 8 and 79 (means = 31) months 22 epileptic dogs had been unsuccessfully treated with phenobarbital and/or primidone. Both drugs had been administered in their maximum dosages. In an add-on therapy, these dogs were given potassium bromide at a rate of 17 to 58 mg/kg daily for a period of 7 to 61 (means = 21) months. We could quantitatively evaluate the seizure data from 19 of the dogs: four became free of seizures; seven showed a greater than 50% reduction in seizure frequency; in two dogs, the seizures were reduced by greater than 50% but the number of seizure-days by less than 50%; in the remaining six dogs the therapy was unsuccessful. We achieved the best therapeutic results in animals that suffered only grand mal seizures. Grand mal in addition to other types of seizures and tonic seizures were affected to a lesser extent if at all. At the beginning of the therapy we saw temporary side effects--weakness in the hind limbs and sedation; these were temporary and dependent on the dosage. Serum concentrations differed even with the same dosage among individual dogs. The therapeutic range of bromide serum concentration was from 0.7 to 2.0 mg/ml. Most of the animals tolerated concentrations up to 1.5 mg/ml quite well. To begin an add-on therapy with potassium bromide we would recommend a daily dose of 30 to 40 mg/kg. During treatment, the dose should be determined for each individual dog.

[Lafora disease (progressive myoclonic epilepsy) in the Bassett hound--possibility of early diagnosis using muscle biopsy?]. / Lafora-Erkrankung (progressive Myoklonusepilepsie) beim Bassethund--Möglichkeit der Früherkennung mittels Muskelbiopsie? Vergleich der Einschlusskörperchen in Hirn und Muskel, dargestellt an zwei ausgewerteten Fällen.

A progressive, hereditary disease has been observed in Basset Hounds, which appears clinically and neuromorphologically as myoclonus epilepsy (ME) and is similar to Lafora-Glueck disease in humans. The characteristic intracellular accumulations are typical myoclonus inclusion bodies. Four forms of inclusion bodies (IB) can be distinguished: a) very small, homogeneous, PAS-positive IBs, b) IBs consisting of an accumulation of PAS-positive particles, c) IBs with a concentric internal structure and a smooth or radial outer zone, and d) IBs with a homogeneous center, concentric layering, light intermediate zone, and a smooth outer zone. The occurrence of IBs is restricted largely to nerve cells. Here they are located mainly in pericarya, to a lesser extent in dendrites, and rarely in the neurites of the peripheral nervous system. IBs are also found in samples of skeletal muscle where they lie between myofibrils or beneath the sarcolemma. They are slightly basophilic in HE-staining and markedly PAS-positive. In transmission electron micrographs IBs prove to consist of chain-like filamentous material of varying density with focal concentrations. They are similar to IBs of the brain. Both muscular and neuronal IBs lack surrounding membranes. Diagnosis of Lafora disease in dogs by examination of muscle biopsies is discussed.

[The clinical picture of multiple enchondromatosis in the dog]. / Zur Klinik der multiplen Enchondromatose beim Hund.

The clinical and radiological findings of three related Miniature Poodles with multiple enchondromatosis (Ollier's disease) are presented. Persisting, in part ossified growth plate cartilage foci were found bilaterally in the humerus, radius, ulna, femur, tibia and fibula of each dog and in one dog in some metacarpal and metatarsal bones. The ribs and many vertebral bodies were also affected. There was evidently no bone formation in the sternebrae. All three dogs first attracted attention at the ages of four to six months, with spontaneous bilateral femoral neck fractures. The mode of inheritance of the condition is not yet clear, but based on the known pedigree data a dominant effect appears unlikely.

Feline epilepsy.

In approximately two-thirds of the epileptic cats in this article, an idiopathic epilepsy had to be assumed. It began between six and 36 months of age with a single seizure, which usually occurred during rest or sleep. Symptomatic epilepsy was frequently observed during the first two years of life and in old age, beginning frequently with multiple seizures or status epilepticus and less often during sleep or rest. In both types, grand mal seizures are predominant. Seizure clusters or status epilepticus caused extensive neuron necroses and scleroses in Ammon's horn. Diazepana and phenobarbital are antiepileptics of first choice for the cat; primidone and phenytoin are less suitable.

Turnover and urinary excretion of circulating diiodotyrosine.

The MCR of diiodotyrosine (DIT) was determined by measuring serum DIT concentrations by RIA after a single injection of 200 micrograms DIT and noncompartmental analysis. Comparison of the stable DIT method with the tracer DIT technique in dogs yielded good agreement of measured DIT MCRs. The mean (+/- SD) MCR and blood production rate of DIT were 122 +/- 29 L/day X 70 kg and 24.2 +/- 12.7 nmol/day X 70 kg (10.5 micrograms/day X 70 kg), respectively, in 10 normal subjects. Urinary DIT was measured by RIA after its immunoprecipitation from urine. Acid hydrolysis had no effect on measured urinary DIT concentrations, suggesting the presence of predominantly unconjugated DIT. Mean urinary DIT excretion was 1.23 +/- 0.43 (+/- SD) nmol/24 h (533 ng/24 h) or 0.108 +/- 0.048 nmol/nmol creatinine in 32 normal individuals. In patients with defective thyroidal iodine metabolism, urinary DIT was extremely elevated, ranging from 1.2-17.7 nmol/mmol creatinine. Comparison of normal production and excretion rates suggests that about 5% of the daily extrathyroidal DIT turnover is excreted in the urine unchanged or in a DIT-like form.

Low levels of gamma-aminobutyric acid in cerebrospinal fluid of dogs with epilepsy.

gamma-Aminobutyric acid (GABA) levels were determined in cisternal cerebrospinal fluid (CSF) of 19 epileptic dogs with generalized tonic-clonic (grand mal) seizures using a radioreceptor assay. Thirty-four healthy age-matched dogs served as controls. The average CSF GABA level in epileptic dogs (40 pmol/ml) was significantly lower than that determined in controls (66 pmol/ml). Treatment with phenobarbital or primidone seemed not to affect CSF GABA levels.

Therapeutic efficacy of phenobarbital and primidone in canine epilepsy: a comparison.

The efficacy of phenobarbital and primidone against canine epilepsy was compared in a controlled study. Thirty-five dogs showing generalized tonic-clonic seizures (grand mal), treated for a minimum of 6 months, were included in the study; fifteen of these were treated with phenobarbital, the other twenty with primidone. Both drugs were dosed according to the clinical requirement; the daily doses ranged from 5-17 mg/kg phenobarbital and from 17-70 mg/kg primidone. The plasma concentrations of phenobarbital, or of primidone and its metabolites phenobarbital and phenylethylmalondiamide (PEMA), were routinely monitored. Complete control of tonic-clonic seizures for 6 months, at least, was attained in six out of fifteen dogs of the phenobarbital group, and in five out of twenty dogs in the primidone group. A further six dogs on phenobarbital, and seven dogs on primidone, were classified as 'improved', i.e. the rate of seizures was reduced by at least 50%. The rest of the dogs were not improved by the treatment. The difference between the efficacy of phenobarbital and primidone was not significant, but primidone gave rise to signs of liver toxicity in fourteen out of twenty dogs, as indicated by considerable elevations of liver enzyme values (alanine transferase, glutamate dehydrogenase, alkaline phosphatase). Phenobarbital is, therefore, regarded as the drug of first choice for the treatment of canine epilepsy.

Evaluation of epileptic dogs as an animal model of human epilepsy.

In 126 epileptic dogs with spontaneously recurring generalized tonic-clonic (grand mal) seizures, epidemiological aspects and the efficacy of chronic oral treatment with common antiepileptic drugs were studied. Furthermore, the pharmacokinetics of antiepileptic drugs in dogs was compared with the values known for man. As in man, idiopathic epilepsy appeared to be more common than symptomatic epilepsy in dogs. There was a preponderance of male vs. female animals. When the breeds of the epileptic dogs were compared to the distribution of breeds in the hospital population, breed-related differences in the prevalence of epilepsy were found. The highest prevalence was seen in Cocker spaniels, Miniature schnauzers, Collies and Bassets. The total prevalence of dogs with epilepsy was 0.55%. Comparison of pharmacokinetics of antiepileptic drugs showed that some drugs were suited for maintenance therapy in dogs (primidone, phenobarbital, ethosuximide, trimethadione) whereas others appeared not to be ideally suited because of their short half-lives (phenytoin, carbamazepine, valproic acid, diazepam, clonazepam, nitrazepam). This was confirmed by the evaluation of antiepileptic drug efficacy in epileptic dogs. 46 dogs were treated with primidone at daily doses of 14-104 mg/kg for 6-60 months. During medication with primidone, effective plasma levels of its metabolite phenobarbital could be maintained. Complete control of seizures or a reduction of seizure frequency by at least 75% was achieved in 39% of the dogs at phenobarbital concentrations of 5-49 micrograms/ml. Similar figures were obtained during chronic treatment with phenobarbital at daily doses of 2.5-13 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pharmacologic principles in the treatment of epilepsy in the dog and cat]. / Pharmakologische Grundlagen der Behandlung der Epilepsie bei Hund und Katze.

The pharmacokinetics of antiepileptic drugs used for the treatment of human epilepsies is reviewed for dogs and cats. In dogs, especially phenobarbital and primidone must be regarded as useful drugs for chronic treatment on account of their elimination rate and bioavailability. Phenytoin, carbamazepine, valproic acid and benzodiazepines are eliminated so rapidly that a therapeutic value cannot be expected. In cats, phenytoin, phenobarbital, valproic acid and diazepam must be regarded as suited for chronic treatment, but there is a definite lack of clinical experience. Phenobarbital and primidone are useful for treatment of clonic-tonic generalized seizures (grand mal) in dogs. The effect of primidone depends mostly on its metabolite phenobarbital. Since primidone, given in high dosage for longer periods of time, gives rise to liver damage, phenobarbital is regarded as the drug of first choice. A status epilepticus may be treated by i.v. injection of diazepam, clonazepam, phenytoin or lidocaine. In cats with grand mal, treatment with daily doses of about 1 mg/kg diazepam may be tried. It proved effective for longer time periods without development of tolerance. There is no reliable clinical experience with other drugs in this species.

Treatment of canine epilepsy with primidone.

Forty-seven dogs with a history of generalized recurrent seizures were treated with primidone at a daily oral dosage of 13 to 100 mg/kg of body weight, divided into 2 to 3 doses. During treatment, plasma concentrations of primidone and its metabolites, phenobarbital and phenylethylmalonamide, were determined at irregular intervals. Of the 30 dogs that finally could be evaluated, 20 were brought to excellent or good control of their seizures by daily primidone dosages ranging from 13 to 17 mg/kg and at plasma phenobarbital concentrations of 6 to 37 micrograms/ml. Of the other 10 dogs, 5 improved to a minor extent and 5 did not improve at all. It was concluded that treatment of seizures should start with a daily dosage of 10 to 15 mg/kg, with the dosage being increased to about 35 mg/kg within a few weeks. For dogs in which the seizures are not controlled by this dosage, a further increase should be tried until a plasma phenobarbital concentration of 30 to 40 micrograms/ml is reached or until signs of drug toxicosis develop. Monitoring of plasma phenobarbital concentrations is sufficient for the control of treatment with primidone.

Characterization of feline whole-blood cultures and determination of the frequency of radiation-induced dicentrics in human and feline lymphocytes.

The Ham's F-10 and PHA culture system was applied to whole feline blood and cell-cycle characteristics such as DNA synthesis and mitotic indices were studied. The results are comparable to those obtained from human whole-blood cultures. The yields of dicentrics were also determined in lymphocytes from X-irradiated human and feline blood. The ratio between the experimental yields of dicentrics in human as compared to feline lymphocytes was 1:0.27.