Dispersal pattern of injectate following CT-guided perineural infiltration in the canine thoracolumbar spine: a cadaver study.

An increasing proportion of canine patients are presented with chronic thoracolumbar back pain and without compressive spinal lesions. In humans, spinal perineural infiltrations have been reported to have a favorable effect on pain control. The purpose of this prospective cadaver study was to describe the dispersal pattern of injectate following CT-guided spinal perineural infiltration in the canine thoracolumbar region. Seven fresh canine cadavers were first scanned using multislice CT and then CT-guided spinal perineural infiltration was performed at 42 sites from T13/L1 to L6/L7. The injectate for each site was a mixture of new methylene blue and iodinated contrast medium. Immediately following CT-guided injection, cadavers were frozen, cut, and dissected macro- and mesoscopically (using a magnifying glass) to identify anatomic structures that were infiltrated. In the majority of sites (64.3%), complete epidural and hypaxial staining of spinal nerve components (including the spinal ganglion, trunk, and ventral branch) was successfully achieved. However, no (11.9%) or unpredictable staining (9.5%) of nervous tissue occurred in some sites despite careful CT guidance and the application of relatively large volumes of injectate. Optimal results were achieved when the needle tip was positioned periforaminally ventral to the cranial contour of the cranial articular process. Findings from this ex vivo study indicated that CT-guided spinal perineural infiltration is feasible for testing in the canine thoracolumbar region and that successful nerve tissue infiltration would likely occur in the majority of sites. Future in vivo studies are needed to determine the safety and efficacy of this technique.

Electroencephalographic examination of epileptic dogs under propofol restraint.

The main aim of this study was to identify interictal epileptiform discharges in a group of dogs with seizures of known aetiology (symptomatic epilepsy, SE) and in dogs with idiopathic epilepsy (IE). Propofol was used for chemical restraint in all dogs. We found electroencephalographic (EEG) changes that could be considered epileptiform discharges (EDs) in 5 out of 40 dogs (12.5%). The EEG changes identified were spikes in four cases and periodic epileptiform discharges in one case. All EDs were seen in the SE group. We conclude that the interictal electroencephalographic examinations of propofolanaesthetised dogs suffering from IE and SE rarely show epileptic discharges and that the diagnostic value of such EEGs in the work-up for epilepsy seems to be low as epileptic discharges were unlikely to be detected. However, positive findings are more likely to be connected with SE. We found frequent, transient EEG phenomena (spindles, K-complexes, vertex waves, positive occipital sharp transients of sleep, cyclic alternating patterns), which are non-epileptic but their differentiation from epileptic phenomena is challenging.

Targeted inactivation of a developmentally regulated neural plectin isoform (plectin 1c) in mice leads to reduced motor nerve conduction velocity.

Cytolinker proteins stabilize cells mechanically, regulate cytoskeleton dynamics, and provide scaffolds for signaling molecules. For plectin, the prototype of these proteins, an unusual diversity of isoforms has been reported, which show distinct expression patterns, subcellular localizations, and functions. Plectin has been shown to have important functions in skin and muscle, but little is known about its role in neural cells. To address this issue, we generated two knock-out mouse lines, one which was selectively lacking plectin 1c (P1c), the major isoform expressed in neural cells, and another in which plectin was conditionally deleted in neuronal precursor cells. Using isoform-specific antibodies, we found P1c to be expressed late in development and to associate with postsynaptic dendrites of central nervous system neurons, motorneurons of spinal cord, sciatic nerve axons, and Schwann cells. Motor nerve conduction velocity was found significantly reduced in sciatic nerve from P1c-deficient as well as from conditional knock-out mice. This defect was traceable to an increased number of motor nerve fibers with small cross-sectional areas; the thicknesses of axons and of myelin sheaths were unaffected. This is the first report demonstrating an important role of plectin in a major nerve function.

Impaired heart contractility in Apelin gene-deficient mice associated with aging and pressure overload.

Apelin constitutes a novel endogenous peptide system suggested to be involved in a broad range of physiological functions, including cardiovascular function, heart development, control of fluid homeostasis, and obesity. Apelin is also a catalytic substrate for angiotensin-converting enzyme 2, the key severe acute respiratory syndrome receptor. The in vivo physiological role of Apelin is still elusive. Here we report the generation of Apelin gene-targeted mice. Apelin mutant mice are viable and fertile, appear healthy, and exhibit normal body weight, water and food intake, heart rates, and heart morphology. Intriguingly, aged Apelin knockout mice developed progressive impairment of cardiac contractility associated with systolic dysfunction in the absence of histological abnormalities. We also report that pressure overload induces upregulation of Apelin expression in the heart. Importantly, in pressure overload-induced heart failure, loss of Apelin did not significantly affect the hypertrophy response, but Apelin mutant mice developed progressive heart failure. Global gene expression arrays and hierarchical clustering of differentially expressed genes in hearts of banded Apelin(-/y) and Apelin(+/y) mice showed concerted upregulation of genes involved in extracellular matrix remodeling and muscle contraction. These genetic data show that the endogenous peptide Apelin is crucial to maintain cardiac contractility in pressure overload and aging.

Chemotherapy in canine acute megakaryoblastic leukemia: a case report and review of the literature.

Acute myeloid leukemia (AML) in dogs is a rare disease with poor prognosis. In most subjects, palliative treatment or euthanasia is performed. A 3.5-year-old male castrated labrador with AML-M7, which was treated with induction polychemotherapy (8 cycles) using vincristine (0.5 mg/m(2)/cycle), daunorubicin (20 mg/m(2)/cycle), cytosine arabinoside (ARA-C, 100 mg/m(2)/cycle) and prednisolone (1 mg/kg/day) is reported. Treatment was well tolerated and complete remission was achieved. Postinduction chemotherapy consisted of ARA-C, daunorubicin and prednisolone. After 3, 5 and 18 months, the subject relapsed. Each relapse was treated with ARA-C (up to 1,000 mg/m(2)) and etoposide or daunorubicin. Again, no severe side-effects occurred and the disease was controlled, with 37 chemotherapy-cycles (ARA-C, 3 x 1,000 mg/m(2)/cycle), for 24 months. Based on a literature-search, this is the first report documenting a long-term response of canine AML, probably resulting from the high-dose ARA-C. Clinical trials using high-dose ARA-C are now required to confirm antileukemic efficacy in canine leukemias.

Effect of radiation on vascular endothelial growth factor expression in the C2 canine mastocytoma cell line.

OBJECTIVE: To establish the radiosensitivity and effect of irradiation on vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) expression in the canine mastocytoma cell line C2. SAMPLE POPULATION: Canine mastocytoma cell line C2. PROCEDURES: C2 cells were irradiated with single doses of 2, 4, 6, and 8 Gy. The 3-(4, 5-di-methyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide assay and proliferation assays with (methyl-hydrogen 3) thymidine were used for radiosensitivity experiments. Expression of VEGFR was determined via flow cytometry and apoptotic rate via annexin assay. Human and canine VEGF ELISA kits were evaluated in crossover assay experiments, and the canine kit was used thereafter. RESULTS: C2 cells secreted VEGF constitutively. Radiation did not induce a significant increase in VEGF secretion, regardless of radiation dose. Consistently, radiation did not up-regulate VEGFR. Cell survival rates decreased in a dose-dependent manner. The apoptotic cell fraction had a dose-dependent increase that reached its maximum 24 to 48 hours after radiation. CONCLUSIONS AND CLINICAL RELEVANCE: The C2 cell line was radiosensitive, and a fraction (up to 40%) of cells died via apoptosis in a dose-dependent manner. In response to radiation, C2 cells did not upregulate VEGF production or VEGFR. Further studies are needed to determine whether tumor control could be improved by combining radiotherapy with VEGFR inhibitors or apoptosis-modulating agents.

Correlation of surface electromyography of the vastus lateralis muscle in dogs at a walk with joint kinematics and ground reaction forces.

OBJECTIVE: To describe the activity pattern of the vastus lateralis muscle in dogs at walk measured by surface electromyography (EMG) in relation to kinematics and kinetics of the pelvic limb. STUDY DESIGN: Experimental. ANIMALS: Malinois dogs (n=11). METHODS: Dogs (mean +/- SD age, 5.5 +/- 2.9 years; weight, 27.3 +/- 3.8 kg; shoulder height, 62.7 +/- 3.3 cm) walked on a treadmill system with integrated force plates, which allowed simultaneous analysis of kinematics, kinetics, and EMG data from all limbs. The maxima, minima, and their time of occurrence in the motion cycle of the EMG and the pelvic limb kinematics and kinetics were calculated; correlations between joint movement patterns, ground reaction forces (GRF), and activity pattern of the muscle group were investigated. RESULTS: The vastus lateralis muscle had an activity pattern with 2 peaks and a close positive correlation with GRF. The 1st peak occurred in early stance, followed by a decrease in activity during mid-stance. The 2nd peak occurred directly before the quick activity decrease in late stance phase, reaching its minimum early in swing phase. CONCLUSIONS: These results suggest that the vastus lateralis muscle supports the vertical position and elevation of the pelvis during stance and push-off. During early stance, the muscle acts as a coantagonist to the hamstring muscle group and the gastrocnemius muscle, and restrains flexion during the late stance. CLINICAL RELEVANCE: Results of this study could enhance diagnosis of locomotor system disorders and facilitate monitoring effects of treatments (e.g., therapeutic exercises) on gait ability and muscle function.

Clonality testing as complementary tool in the assessment of different patient groups with canine chronic enteropathy.

Differentiation between canine chronic enteropathy (CCE) and intestinal lymphoma is a diagnostic challenge as histopathology might fail to yield unequivocal results. Detection of clonal rearrangements of the T-cell-receptor gamma (TCRG) chain and IG heavy chain (IGH) V-J genes offer a useful solution. In this retrospective study, histopathology samples of 35 CCE patients and 7 healthy Beagle dogs underwent clonality testing. Patients suffered either from inflammatory bowel disease (IBD), food responsive diarrhea (FRD) or protein loosing enteropathy secondary to IBD (PLE/IBD). Healthy Beagles served as controls (CO). Canine IBD activity index (CIBDAI) and histopathological WSAVA-grading differed significantly (p<0.001) between groups. CIBDAI improved significantly after appropriate therapy (p < 0.0001). Intestinal biopsies of all CO showed polyclonal patterns for B- and T-cell primers. All samples from CCE patients showed polyclonal patterns for the B-cell primers. Targeting TCRG, 4 patients showed a monoclonal or oligoclonal pattern of the lymphocytic infiltrates in the duodenum and/or colon. Clinical improvement was observed in all dogs. Although a small cell lymphoma cannot be excluded in view of the short follow up duration, a false positive result, in the sense of a canonical rearrangement or unspecific amplification due to a antigenic stimulation in a non-neoplastic inflammatory process is possible.

Clinical symptoms and diagnosis of encephalitozoonosis in pet rabbits.

Infections with Encephalitozoon cuniculi in rabbits are observed at increasing frequency and are known as opportunistic infections in immunocompromised humans. 191 pet rabbits with suspected encephalitozoonosis, presented at the Animal Hospital of the Veterinary University of Vienna (Austria), were included in this study. Rabbits were serologically examined for antibodies against E. cuniculi (144 positive out of 184 rabbits with suspected encephalitozoonosis compared to 14 positive out of 40 clinically healthy rabbits tested as part of a standard health check) and Toxoplasma gondii (8 positive out of 157). Of the 144 seropositive rabbits with clinical signs, 75% showed neurological symptoms, 14.6% demonstrated phacoclastic uveitis and 3.5% suffered from renal failure. 6.9% of the animals had combined symptoms. Vestibular disease dominated within the rabbits that showed neurological symptoms. Polymerase chain reaction (PCR) could not detect parasite DNA in urine or cerebrospinal fluid (CSF), but did so in 4 out of 5 samples of liquefied lens material in cases with phacoclastic uveitis due to lens capsule rupture. Additionally further diagnostic procedures, such as inspection of the external ear canal (N=69), radiography of the tympanic bullae (N=65) were performed to rule out differential diagnosis. 54.2% of the patients exhibiting neurological symptoms recovered within a few days, while 87.5% of the rabbits suffering from renal failure died or had to be euthanized.

Microvessel density in normal lymph nodes and lymphomas of dogs and their correlation with vascular endothelial growth factor expression.

Microvessel density is a frequently used parameter of angiogenesis, which is a complex multistep process necessary for tumor progression. The aim of this study was to compare the microvessel density of normal lymph node biopsies with those diagnosed with lymphoma in dogs. Furthermore, we sought to determine if there was any correlation between microvessel density and vascular endothelial growth factor expression in canine lymphoma, representing a potential target for anti-angiogenic therapy. Combined immunohistochemistry (von Willebrand factor) and lectin histochemistry was used to highlight microvessels in 40 untreated canine lymphomas and 14 normal lymph nodes. To evaluate microvessel density, the number of profiles of blood vessels per unit area was calculated. Fifty image fields (a total area of 5.68 mm(2)) were sampled for each specimen in a systematic random, way. We found a significant difference between the microvessel densities (MVD) of normal and neoplastic lymph nodes (177+/-35 versus 241+/-72 microvessel profiles/mm(2)). Classifying lymphoma samples according to the working formulation and the Kiel classification system revealed no significant differences in MVD between different grade malignancies. Immunohistochemical demonstration of the proangiogenic protein vascular endothelial growth factor showed expression in 60% of canine lymphomas, although there was no correlation between microvessel density and vascular endothelial growth factor expression. As an increase in tumor angiogenesis was observed in lymphoma samples compared to normal canine lymph node tissue, additional anti-angiogenic therapy, besides conventional chemotherapy as a lymphoma treatment may be effective. The optimal target among many pro-angiogenic factors has yet to be elucidated.

Retrospective clinical comparison of idiopathic versus symptomatic epilepsy in 240 dogs with seizures.

In the present study, 240 cases of dogs with seizures were analysed retrospectively. The aim was to examine the underlying aetiology and to compare primary or idiopathic epilepsy (IE) with symptomatic epilepsy (SE) concerning signalment, history, ictal pattern, clinical and neurological findings. The diagnosis of symptomatic epilepsy was based on confirmed pathological changes in haematology, serum biochemistry, cerebrospinal fluid (CSF) analysis and morphological changes of the brain by CT/MRI or histopathological examination. Seizure aetiologies were classified as idiopathic epilepsy (IE, n = 115) and symptomatic epilepsy (SE, n = 125). Symptomatic epilepsy was mainly caused by intracranial neoplasia (39) and encephalitis (23). The following variables showed significant difference between the IE and SE group: age, body weight, presence of partial seizures, cluster seizures, status epilepticus, ictal vocalisation and neurological deficits. In 48% of the cases, seizures were found to be due to IE, while 16% were due to intracranial neoplasia and 10% to encephalitis. Status epilepticus, cluster seizures, partial seizures, vocalisation during seizure and impaired neurological status were more readily seen with symptomatic epilepsy. If the first seizure occurred between one and five years of age or the seizures occurred during resting condition, the diagnosis was more likely IE than SE.

Bidirectional Regulation of COX-2 Expression Between Cancer Cells and Macrophages.

BACKGROUND/AIM: Our aim was to investigate the crosstalk between tumor and immune cells (M2 macrophages) and its effects on cyclo-oxygenase-2 (COX2) regulation in canine mammary tumors (CMT). MATERIALS AND METHODS: Sh1b CMT cells and human BT474 mammary or HT29 colon cancer cells were co-cultured with canine peripheral blood mononuclear cells (PBMCs) or with macrophage-like differentiated THP1 monocytes (dTHP1). Intracellular COX2 expression by PBMCs, dTHP1 and cancer cells was evaluated by flow cytometry. RESULTS: Co-culturing of Sh1b and canine PBMCs induced COX2 overexpression in CMT cells. In turn, COX2 expression by PBMCs, mostly CD68+ macrophages, was attenuated by co-culture with Sh1b (p=0.0001). In accordance, co-culture with dTHP1 prompted intracellular production of COX2 in both Sh1b CMT cells and HT29 human colon cancer cells and reduced production of COX2 in BT474 human mammary cancer cells. The intracellular COX2 expression from dTHP1 decreased when treated with conditioned medium from cultured Sh1b and HT29 cancer cells. CONCLUSION: Bidirectional COX2 regulation between cancer and monocytes/macrophages might shape a tolerogenic tumor microenvironment in CMT.

Detection of vascular endothelial growth factor (VEGF) and VEGF receptors Flt-1 and KDR in canine mastocytoma cells.

Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis and a potential autocrine growth factor for neoplastic cells in various malignancies. In the present study, we have investigated expression of VEGF and VEGF receptors in canine mastocytomas and the canine mastocytoma cell line C2. As assessed by immunostaining of tissue sections and cytospin slides, primary neoplastic mast cells (MC) and C2 cells were found to express the VEGF protein. In Northern blot and RT-PCR experiments, C2 cells expressed VEGF mRNA in a constitutive manner. VEGF mRNA expression in C2 cells was counteracted by LY294002 and rapamycin, suggesting involvement of the PI3-kinase/mTOR pathway. Moreover, C2 cells were found to express VEGF receptor-1 (Flt-1) and VEGF receptor-2 (KDR). However, recombinant VEGF failed to promote (3)H-thymidine uptake in C2 cells, and a neutralizing anti-VEGF antibody (bevacizumab) failed to downregulate spontaneous proliferation in these cells. In addition, rapamycin decreased the expression of VEGF in C2 cells at the mRNA and protein level without suppressing their proliferation. Together, canine mastocytoma cells express VEGF as well as VEGF receptors. However, despite co-expression of VEGF and its receptors, VEGF is not utilized as an autocrine growth regulator by canine mastocytoma cells.

Antineoplastic effect of the cyclooxygenase inhibitor meloxicam on canine osteosarcoma cells.

A decisive role in cancer development has been attributed to cyclooxygenase-2 (COX-2) activity, but the significance of COX-2 inhibitors in cancer treatment still needs to be thoroughly investigated. We studied the influence of meloxicam, a non-steroidal antiinflammatory drug with preferential inhibitory effects on COX-2 compared to COX-1, on canine osteosarcoma (D-17) cells. We demonstrated that D-17 cells expressed mRNA and COX-2 protein. Treatment with meloxicam induced a time- and dose-dependent inhibition of cellular growth. To determine if apoptosis plays a role in meloxicam-induced cell death, we performed agarose gel electrophoresis and found a DNA-ladder pattern, typically seen in apoptosis, as well as early apoptotic changes by Annexin V tests. Furthermore, electron microscopy revealed ultrastructural alterations typical of apoptosis. Quantification of apoptotic cells by immunohistochemical staining of caspase 3 confirmed the results. However, further studies with meloxicam are necessary to assess its potential use for treatment of osteosarcomas in dogs.

Pollen Allergies in Humans and their Dogs, Cats and Horses: Differences and Similarities.

Both humans and their most important domestic animals harbor IgE and a similar IgE receptor repertoire and expression pattern. The same cell types are also involved in the triggering or regulation of allergies, such as mast cells, eosinophils or T-regulatory cells. Translational clinical studies in domestic animals could therefore help cure animal allergies and at the same time gather knowledge relevant to human patients. Dogs, cats and horses may spontaneously and to different extents develop immediate type symptoms to pollen allergens. The skin, nasal and bronchial reactions, as well as chronic skin lesions due to pollen are in principle comparable to human patients. Pollen of various species most often causes allergic rhinitis in human patients, whereas in dogs it elicits predominantly eczematous lesions (canine atopic dermatitis), in horses recurrent airway obstruction or hives as well as pruritic dermatitis, and in cats bronchial asthma and so-called cutaneous reactive patterns (eosinophilic granuloma complex, head and neck pruritus, symmetric self-induced alopecia). In human allergy-specific IgE detection, skin tests or other allergen provocation tests should be completed. In contrast, in animals IgE and dermal tests are regarded as equally important and may even replace each other. However, for practical and economic reasons intradermal tests are most commonly performed in a specialized practice. As in humans, in dogs, cats and horses allergen immunotherapy leads to significant improvement of the clinical symptoms. The collected evidence suggests that canines, felines and equines, with their spontaneous allergies, are attractive model patients for translational studies.

Inhibition of nociceptive neuronal responses in the cat's spinal dorsal horn by electrical stimulation and morphine microinjection in nucleus raphe magnus.

The descending inhibitions produced by morphine microinjection and electrical stimulation in the nucleus raphe magnus (NRM) on dorsal horn neurons excited by noxious heating of the skin and/or electrical stimulation of hind limb nerves were examined in the cat. The responses to A-volleys were inhibited to 60.1% (mean, n = 9), those to C-volleys to 64.8% of control (mean, n = 6) and responses to skin heating to 25.3% (mean, n = 8) by electrical NRM stimulation. Morphine (e.g., 10 or 20 micrograms) microinjected into the NRM markedly reduced the responses elicited by afferent C-fiber stimulation (mean 55.6%, n = 8) and the responses to noxious skin heating (mean 38.1%, n = 8), while responses to A-volleys in hind limb nerves were less attenuated (mean 73.6%, n = 8). The effects of morphine were partially or completely blocked by microinjection (10 micrograms) of naloxone into the NRM. It is concluded that morphine microinjection into the NRM generates descending inhibition on the transmission of nociceptive information in the dorsal horn of the spinal cord. This may partly explain the mechanisms of morphine analgesia.

Treatment and long-term follow-up of cats with suspected primary epilepsy.

We report an evaluation of the treatment and outcome of cats with suspected primary epilepsy. Phenobarbital therapy was used alone or in combination with other anti-epileptic drugs. Outcome after treatment was evaluated mainly on the basis of number of seizures per year and categorised into four groups: seizure-free, good control (1-5 seizures per year), moderate control (6-10 seizures per year) and poor control (more than 10 seizures per year). About 40-50% of cases became seizure-free, 20-30% were considered good-to-moderately controlled and about 30% were poorly controlled depending on the year of treatment considered. The duration of seizure events after treatment decreased in 26/36 cats and was unchanged in eight cats. The subjective severity of seizure also decreased in 25 cats and was unchanged in nine cats. Twenty-six cats had a good quality of life, nine cats an impaired quality of life and one cat a bad quality of life. Despite being free of seizures for years, cessation of treatment may lead to recurrence of seizures in most cats.

[ESBL-producing E. coli and EHEC in dogs and cats in the Tyrol as possible source of human infection]. / ESBL-produzierende E. coli und EHEC bei Hunden und Katzen in Tirol als mögliche Quelle für humane Infektionen.

In contrast to infections with enterohaemorrhagic E. coli (EHEC), which are thought to be classical zoonosis, the zoonotic potential of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is still widely unknown. The aim of our study was to determine the frequency of EHEC and ESBL-producing Enterobacteriaceae in domestic animals (dogs and cats) in the Tyrol. Among 228 fecal samples of dogs (n = 92) and cats (n = 136) three samples (1.3%) were positive in the EHEC-ELISA. In two of the three cases isolation of the organism was not possible, the third sample of a two-year-old crossbreed bitch yielded EHEC O103:H2. In twelve of 228 (5.3%) fecal samples 13 ESBL-producing Enterobacteriaceae (in ten cats and two dogs) were found.These animals mainly derived from homes for animals (ten animals, 83%). 75% of the isolates belonged to the CTX-M-1-group, 8% to the CTX-M-2-group and 17% to the CTX-M-9-group. One isolate was positive for CTX-M-1 and CTX-M-9. Typing of the 13 ESBL-producing isolates by multilocus sequence typing (MLST) showed ten different sequence types, which points out the importance of the horizontal transfer of mainly plasmid-coded ESBL genes. Transmission of EHEC and ESBL-producing Enterobacteriaceae from domestic animals to humans is possible, corroborated by the fact that the EHEC serotype found in one dog and the sequence types detected by MLST in several dogs and cats were previously reported to occur in severe human infection.

Comparative oncology: ErbB-1 and ErbB-2 homologues in canine cancer are susceptible to cetuximab and trastuzumab targeting.

To facilitate comparative oncology trials we compared the biological and molecular homologies of canine (dog; Canis lupus familiaris) and human tumor-associated antigens ErbB-1 and -2. Further, we investigated whether they could serve as targets for anti-ErbB-1 (cetuximab) and anti-ErbB-2 antibodies (trastuzumab), which are highly relevant in human clinical oncology. Immunohistochemistry of canine mammary cancer showed ErbB-1 overexpression in 3/10 patients and ErbB-2 in 4/10. We report 91% amino acid homology for ErbB-1 and 92% for ErbB-2 between canine and human molecules. Modeling of canine on human ErbB-1 revealed that the cetuximab epitope only differs by 4 amino acids: Lys443 is replaced by Arg, Ser468 by Asn, Gly471 by Asp, and Asn473 by Lys in canines. The trastuzumab binding site is identical in human and canine ErbB-2 apart from a single amino acid change (Pro557 to Ser). Binding of cetuximab and trastuzumab to canine mammary carcinoma cells CF33, CF41, Sh1b and P114 was confirmed by flow cytometry. Both antibodies significantly inhibited canine tumor cell proliferation partly due to growth arrest in G(0)/G(1) phase. We explain the lower efficiency on the tested canine than on human SKBR3 and A431 cells, by a 2-log lower expression level of the canine ErbB-1 and -2 molecules. Our results indicate significant homology of human and canine Erb-1 and -2 tumor associated antigens. The fact that the canine homologues express the cetuximab and trastuzumab epitopes may facilitate antibody-based immunotherapy in dogs. Importantly, the striking similarities of ErbB-1 and -2 molecules open up avenues towards comparative strategies for targeted drug development.

Complex partial cluster seizures in cats with orofacial involvement.

Seventeen cats were presented with acute onset of complex partial seizures with orofacial involvement (salivation, facial twitching, lip smacking, chewing, licking or swallowing), motor arrest (motionless starring) and behavioural changes. In 11 cats hippocampal necrosis (HN) was confirmed by histopathology. In a further six cats hippocampal changes were suggested by magnetic resonance imaging. The mean monitoring time of eight cats which were not euthanased in the acute phase of the disease, was 408 days (60-908): four cats are still alive. In all surviving cases, the owners reported a good quality of life. We conclude that an acute cluster of complex partial seizures with orofacial involvement are often associated with HN and that HN is not necessarily a fatal condition. Supportive and antiepileptic therapy can result in remission. The long-term outcome can be good to excellent; therefore, euthanasia should be avoided in the acute phase of the signs.