Marjatta Snellman

Increasing evidence suggests that endoglin (CD105) is a new powerful marker of neovascularization in solid malignancies; thus, using breast cancer as a model, we investigated whether targeting of CD105 by monoclonal antibody (mAb) MAEND3 can be used for in vivo imaging of solid tumors. Immunohistochemistry and flow cytometry identified differential expression of CD105 on breast cancer and endothelial cells; in fact, neoplastic cells were weakly and rarely stained by mAb MAEND3, which in contrast, strongly and invariably stained blood vessel endothelia within the breast adenocarcinomas investigated and cultured endothelial cells. Moreover, in contrast to CD31, which currently represents the reference marker to assess angiogenetic activity, CD105 expression was highest in semiconfluent and actively proliferating endothelial cells, and it progressively decreased as cells reached tight confluency and low [3H]thymidine uptake. i.v. administration of 18 MBq of 125I-labeled mAb MAEND3 efficiently imaged spontaneous mammary adenocarcinomas in two dogs; the uptake of radiolabeled mAb was rapid and intense because tumor: background ratios of 8.2:1 and 9.3:1 were reached 8 h after mAb administration, in the absence of immediate and/or long-term clinical side effects. Altogether, our present data suggest that targeting of CD105 on tumor-associated blood vessels may represent a new strategy for in vivo imaging of solid malignancies, regardless of their histological origin.

Abstract Background:Idiopathic childhood epilepsies with benign outcomes are well recognized in human medicine, but are not reported in veterinary literature. We recognized such a neurologic syndrome in Lagotto Romagnolo dogs. Animals: Twenty-five Lagotto Romagnolo puppies from 9 different litters examined because of simple or complex focal seizures and 3 adult Lagotto Romagnolo dogs exhibiting similar clinical signs were used. Methods: Clinical and diagnostic evaluations of affected dogs were conducted, including electromyography, electroencephalography, and other testing. Results: Seizures in puppies began at 5 to 9 weeks of age and usually resolved spontaneously by 8 to 13 weeks. Those with the most severe seizures also had signs of neurologic disease between these seizures, including generalized ataxia and hypermetria. There were no abnormalities in routine laboratory screenings of blood, urine, and cerebrospinal fluid. Electromyography, brainstem auditory-evoked potentials, and magnetic resonance imaging revealed no specific and consistent abnormalities. Fourteen of 16 (87.5%) affected puppies and 2 of 3 (67%) adult dogs revealed epileptiform activity in the electroencephalogram. Histopathologic examination in 1 puppy and 1 adult dog revealed lesions of Purkinje cell inclusions and vacuolation of their axons restricted to the cerebellum. Pedigree analysis suggests an autosomal recessive mode of inheritance. Conclusions and Clinical Importance: This disorder, with simple or complex focal seizures and cerebellar lesions, represents a newly recognized epileptic syndrome in dogs.

BACKGROUND: Idiopathic childhood epilepsies with benign outcomes are well recognized in human medicine, but are not reported in veterinary literature. We recognized such a neurologic syndrome in Lagotto Romagnolo dogs. ANIMALS: Twenty-five Lagotto Romagnolo puppies from 9 different litters examined because of simple or complex focal seizures and 3 adult Lagotto Romagnolo dogs exhibiting similar clinical signs were used. METHODS: Clinical and diagnostic evaluations of affected dogs were conducted, including electromyography, electroencephalography, and other testing. RESULTS: Seizures in puppies began at 5 to 9 weeks of age and usually resolved spontaneously by 8 to 13 weeks. Those with the most severe seizures also had signs of neurologic disease between these seizures, including generalized ataxia and hypermetria. There were no abnormalities in routine laboratory screenings of blood, urine, and cerebrospinal fluid. Electromyography, brainstem auditory-evoked potentials, and magnetic resonance imaging revealed no specific and consistent abnormalities. Fourteen of 16 (87.5%) affected puppies and 2 of 3 (67%) adult dogs revealed epileptiform activity in the electroencephalogram. Histopathologic examination in 1 puppy and 1 adult dog revealed lesions of Purkinje cell inclusions and vacuolation of their axons restricted to the cerebellum. Pedigree analysis suggests an autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: This disorder, with simple or complex focal seizures and cerebellar lesions, represents a newly recognized epileptic syndrome in dogs.

Background: Qualitative and quantitative electroencephalography (EEG) parameters of healthy and Finnish Spitz dogs with epilepsy have not been determined. Objective: To determine if EEG can provide specific characteristics to distinguish between healthy dogs and dogs with epilepsy. Animals: Sixteen healthy and 15 Finnish Spitz dogs with epilepsy. Methods: A prospective clinical EEG study performed under medetomidine sedation. Blinded visual and quantitative EEG analyses were performed and results were compared between study groups. Results: Benign epileptiform transients of sleep and sleep spindles were a frequent finding in a majority of animals from both groups. The EEG analysis detected epileptiform activity in 3 Finnish Spitz dogs with epilepsy and in 1 healthy Finnish Spitz dog. Epileptiform activity was characterized by spikes, polyspikes, and spike slow wave complexes in posterior-occipital derivation in dogs with epilepsy and with midline spikes in control dog. The healthy dogs showed significantly less theta and beta activity than did the dogs with epilepsy (P < .01), but the only significant difference between healthy dogs and dogs with untreated epilepsy was in the alpha band (P < .001). Phenobarbital treatment increased alpha, beta (P < .001), and theta (P < .01), and decreased delta (P < .001) frequency bands compared with dogs with untreated epilepsy. Conclusions and Clinical Importance: Benign epileptiform transients of sleep could be easily misinterpreted as epileptiform activity. Epileptiform activity in Finnish Spitz dogs with epilepsy seems to originate from a posterior-occipital location. The EEG of dogs with epilepsy exhibited a significant difference in background frequency bands compared with the control dogs. Phenobarbital treatment markedly influenced all background activity bands. Quantitative EEG analysis, in addition to visual analysis, seems to be a useful tool in the examination of patients with epilepsy.

Abstract Background: Qualitative and quantitative electroencephalography (EEG) parameters of healthy and Finnish Spitz dogs with epilepsy have not been determined. Objective: To determine if EEG can provide specific characteristics to distinguish between healthy dogs and dogs with epilepsy. Animals: Sixteen healthy and 15 Finnish Spitz dogs with epilepsy. Methods: A prospective clinical EEG study performed under medetomidine sedation. Blinded visual and quantitative EEG analyses were performed and results were compared between study groups. Results: Benign epileptiform transients of sleep and sleep spindles were a frequent finding in a majority of animals from both groups. The EEG analysis detected epileptiform activity in 3 Finnish Spitz dogs with epilepsy and in 1 healthy Finnish Spitz dog. Epileptiform activity was characterized by spikes, polyspikes, and spike slow wave complexes in posterior-occipital derivation in dogs with epilepsy and with midline spikes in control dog. The healthy dogs showed significantly less theta and beta activity than did the dogs with epilepsy (P &amp;lt; .01), but the only significant difference between healthy dogs and dogs with untreated epilepsy was in the alpha band (P &amp;lt; .001). Phenobarbital treatment increased alpha, beta (P &amp;lt; .001), and theta (P &amp;lt; .01), and decreased delta (P &amp;lt; .001) frequency bands compared with dogs with untreated epilepsy. Conclusions and Clinical Importance: Benign epileptiform transients of sleep could be easily misinterpreted as epileptiform activity. Epileptiform activity in Finnish Spitz dogs with epilepsy seems to originate from a posterior-occipital location. The EEG of dogs with epilepsy exhibited a significant difference in background frequency bands compared with the control dogs. Phenobarbital treatment markedly influenced all background activity bands. Quantitative EEG analysis, in addition to visual analysis, seems to be a useful tool in the examination of patients with epilepsy.