Ingeborgh Polis

Ghent University, Gand, Flanders, Belgium

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Publications (66)106.54 Total impact

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    ABSTRACT: Thyroid carcinoma is a common endocrine tumor in the dog. Local invasive growth frequently precludes surgical excision and, in up to 38% of dogs, the tumor has already metastasized by the time of diagnosis. Therefore, it is important to investigate new treatment modalities that may be useful for the large number of dogs with inoperable tumors or metastatic disease. To investigate the immunohistochemical expression of potential therapeutic targets in canine thyroid tumors. 74 dogs with thyroid neoplasia. Immunohistochemistry was performed for thyroglobulin, calcitonin, vascular endothelial growth factor (VEGF), p53, cycloxygenase-2 (cox-2), and P-glycoprotein (P-gp). Fifty-four (73%) tumors were classified as follicular cell thyroid carcinomas (FTCs) and 20 (27%) as medullary thyroid carcinomas (MTCs). Eighty percent of FTCs and all MTCs had a high percentage (76-100%) of neoplastic cells immunopositive for VEGF. Thirteen percent of FTCs and 50% of MTCs expressed cox-2. Seven percent of FTCs and 70% of MTCs expressed P-gp. No tumor was immunopositive for p53 expression. Expression of VEGF (P = .034), cox-2 (P = .013), and P-gp (P < .001) was significantly higher in MTCs compared to FTCs. VEGF is a potential therapeutic target in both FTC and MTC in dogs. Cox-2 and P-gp may be useful molecular targets in canine MTC.
    Journal of Veterinary Internal Medicine 02/2014; · 2.06 Impact Factor
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    ABSTRACT: Infections by antibiotic-resistant bacteria are becoming a great risk for human health, leading to an urgent need for new efficient antibacterial therapies. The short, proline-rich antimicrobial peptides from insects gained a lot of interest as a potential antibacterial treatment, having a low toxicity profile and being mainly active against Gram-negative bacteria. To know whether these antimicrobial peptides can be used for the treatment of cerebral infections, the blood-brain barrier transport characteristics of these peptides were investigated. This study describes the results of the in vivo blood-brain barrier experiments in mice, as well as the in vitro metabolic stability in mouse plasma and brain of apidaecin Api137, oncocin, drosocin and drosocin Pro5Hyp. The four investigated peptides showed a significant influx into the brain with a Kin ranging between 0.37 and 0.86 µL/g × min and brain distribution volumes of 19.6 to 25.8 µL/g. Only for drosocin, a significant efflux was determined, with a kout of 0.22 min-1. After entering the brain, oncocin was for approximately 80% trapped in the endothelial cells, while the other peptides reached the brain parenchyma for about 70%. All peptides were stable in plasma and brain during the experiments, with estimated metabolic half-lives ranging between 47 min and 637 min. We conclude that the investigated short, proline-rich antimicrobial peptides show an influx into the brain, which make them a promising antibacterial treatment of cerebral infections.
    Protein and Peptide Letters 01/2014; 21(4). · 1.99 Impact Factor
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    ABSTRACT: Down-stream neuronal alterations, including changes in the 5-HT-2A receptor system, play an important role in the etiology and treatment of depression. The present study examined the effect of prolonged opioid treatment on cerebral 5-HT2A receptors. Cerebral 5-HT2A receptor availability was estimated in seven healthy five-year-old female neutered Beagle dogs pre and post 10-day morphine treatment (oral sustained release morphine 20 mg twice daily for ten days) with 123I-R-91150, a 5-HT2A selective radioligand, and SPECT. 5-HT2A receptor binding indices (BI) for the frontal, parietal, temporal and occipital cortex and the subcortical region were calculated. Statistical analysis was performed using a linear mixed-effect model with treatment as fixed effect and dog as random effect. Morphine treatment significantly (p≤0.05) lowered 5-HT2A BIs in the right and left frontal cortex, the right and left temporal cortex, the right and left parietal cortex, and the subcortical region. The decreased cerebral 5-HT2A receptor availability following prolonged morphine exposure provides further evidence for an interaction between the opioid and serotonergic system.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 01/2014; · 3.68 Impact Factor
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    ABSTRACT: To compare sedation and antinociception after oral transmucosal (OTM) and intramuscular (IM) administration of a dexmedetomidine-buprenorphine combination in healthy adult cats. Randomized, 'blinded' crossover study, with 1 month washout between treatments. Six healthy neutered female cats, weighing 5.3-7.5 kg. A combination of dexmedetomidine (40 μg kg(-1) ) and buprenorphine (20 μg kg(-1) ) was administered by either the OTM (buccal cavity) or IM (quadriceps muscle) route. Sedation was measured using a numerical rating scale, at baseline and at various time points until 6 hours after treatment. At the same time points, analgesia was scored using a dynamic and interactive visual analogue scale, based on the response to an ear pinch, and by the cat's response to a mechanical stimulus exerted by a pressure rate onset device. Physiological and adverse effects were recorded, and oral pH measured. Signed rank tests were performed, with significance set at p < 0.05. Data are presented as median and range. There were no differences in sedation or antinociception scores between OTM and IM dosing at any of the time points. Nociceptive thresholds increased after both treatments but without significant difference between groups. Buccal pH remained between 8 and 8.5. Salivation was noted after OTM administration (n = 2) and vomiting after both OTM (n = 4), and IM (n = 3) dosing. In healthy adult cats, OTM administration of dexmedetomidine and buprenorphine resulted in comparable levels of sedation and antinociception to IM dosing. The OTM administration may offer an alternative route to administer this sedative-analgesic combination in cats.
    Veterinary Anaesthesia and Analgesia 08/2013; · 1.34 Impact Factor
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    ABSTRACT: Objective-To assess the agreement between CT and MRI for enabling detection of intracranial lesions in cats and dogs. Design-Evaluation study. Animals-51 dogs and 7 cats with suspected intracranial lesions. Procedures-During a 2-year-period, dogs and cats with suspected intracranial pathological changes underwent MRI and CT (single slice) of the head. Radiologists evaluated images produced with both techniques without awareness of subject identity. Agreement between methods was assessed for allowing detection of solitary or multiple lesions, selected lesion characteristics (via the Cohen κ statistic), and lesion dimensions (via Bland-Altman plots). Results-CT and MRI had substantial agreement for allowing detection of lesions and identification of whether the lesions were solitary or multiple. The techniques agreed almost perfectly for allowing identification of a mass effect and contrast medium enhancement, which were considered principal diagnostic imaging signs. A lower degree of agreement was attained for allowing identification of enhancement patterns and aspects of lesion margins. Agreement was substantial to almost perfect for lesion visualization in most anatomic brain regions but poor for identification of lesion dimensions. Conclusions and Clinical Relevance-Degrees of agreement between CT and MRI for allowing the detection and characterization of intracranial lesions ranged from poor to almost perfect, depending on the variable assessed. More investigation is needed into the relative analytic sensitivity and possible complementarities of CT and MRI in the detection of suspected intracranial lesions in dogs and cats.
    Journal of the American Veterinary Medical Association 08/2013; 243(3):367-75. · 1.72 Impact Factor
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    ABSTRACT: Subanesthetic doses of ketamine can be used as a rapid-acting antidepressant in patients with treatment-resistant depression. Therefore, the brain kinetics of (123)I-5-I-R91150 (4-amino-N-[1-[3-(4-fluorophenyl)propyl]-4-methylpiperidin-4-yl]-5-iodo-2-methoxybenzamide) and the influence of ketamine on the postsynaptic serotonin-2A receptor (5-hydroxytryptamine-2A, or 5-HT2A) status were investigated in cats using micro-SPECT. This study was conducted on 6 cats using the radioligand (123)I-5-I-R91150, a 5-HT2A receptor antagonist, as the imaging probe. Anesthesia was induced and maintained with a continuous-rate infusion of propofol (8.4 ± 1.2 mg kg(-1) followed by 0.22 mg kg(-1) min(-1)) 75 min after tracer administration, and acquisition of the first image began 15 min after induction of anesthesia. After this first acquisition, propofol (0.22 mg kg(-1) min(-1)) was combined with ketamine (5 mg kg(-1) followed by 0.023 mg kg(-1) min(-1)), and the second acquisition began 15 min later. Semiquantification, with the cerebellum as a reference region, was performed to calculate the 5-HT2A receptor binding indices (parameter for available receptor density) in the frontal and temporal cortices. The binding indices were analyzed with Wilcoxon signed ranks statistics. The addition of ketamine to the propofol continuous-rate infusion resulted in decreased binding indices in the right frontal cortex (1.25 ± 0.22 vs. 1.45 ± 0.16; P = 0.028), left frontal cortex (1.34 ± 0.15 vs. 1.49 ± 0.10; P = 0.028), right temporal cortex (1.30 ± 0.17 vs. 1.45 ± 0.09; P = 0.046), and left temporal cortex (1.41 ± 0.20 vs. 1.52 ± 0.20; P = 0.046). This study showed that cats can be used as an animal model for studying alterations of the 5-HT2A receptor status with (123)I-5-I-R91150 micro-SPECT. Furthermore, an interaction between ketamine and the 5-HT2A receptors resulting in decreased binding of (123)I-5-I-R91150 in the frontal and temporal cortices was demonstrated. Whether the decreased radioligand binding resulted from a direct competition between ketamine and (123)I-5-I-R91150 or from a decreased affinity of the 5-HT2A receptor caused by ketamine remains to be elucidated.
    Journal of Nuclear Medicine 07/2013; · 5.77 Impact Factor
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    ABSTRACT: Objectives: To report the characteristics of two types of flexor enthesopathy, primary and concomitant, based on different diagnostic techniques. Materials and methods: Over a period of three years a prospective study was performed on dogs admitted for the complaint of elbow lameness. Based on the radiographic findings a selection of dogs underwent a complete series of different imaging modalities. With each technique, pathology of the medial epicondyle and the presence of other elbow disorders were recorded. All joints with signs of flexor pathology apparent with at least three techniques were selected. A distinction was made between primary and concomitant flexor enthesopathy based on the absence or presence of other elbow disorders. Results: Primary flexor enthesopathy was diagnosed in 23 joints and concomitant flexor enthesopathy in 20 joints. In 43% of the joints with primary and in 75% of the joints with concomitant flexor enthesopathy, pathology at the medial epicondyle was demonstrated by all techniques. All joints with concomitant flexor enthesopathy had a diagnosis of medial coronoid disease, osteochondritis dissecans, or both. Clinical significance: Pathology at the medial epicondyle is a sign of flexor enthesopathy. It may be present as the only sign in a joint with primary flexor enthesopathy or concomitant with other elbow pathology. In both groups flexor lesions can be demonstrated with different imaging techniques. The distinction between the primary and concomitant form is based on the presence or absence of other elbow pathology, mainly medial coronoid disease. Recognizing both types is important for a correct treatment decision.
    Veterinary and Comparative Orthopaedics and Traumatology 06/2013; 26(6). · 1.01 Impact Factor
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    ABSTRACT: According to human research, the location of fat accumulation seems to play an important role in the induction of obesity-related inflammatory complications. To evaluate whether an inflammatory response to obesity depends on adipose tissue location, adipokine gene expression, presence of immune cells and adipocyte cell size of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were compared between lean and obese cats. Additionally, the present study proposes the cat as a model for human obesity and highlights the importance of animal models for human research. A total of ten chronically obese and ten lean control cats were included in the present study. Body weight, body condition score and body composition were determined. T-lymphocyte, B-lymphocyte, macrophage concentrations and adipocyte cell size were measured in adipose tissue at different locations. Serum leptin concentration and the mRNA expression of leptin and adiponectin, monocyte chemoattractant protein-1, chemoligand-5, IL-8, TNF-α, interferon-γ, IL-6 and IL-10 were measured in blood and adipose tissues (abdominal and inguinal SAT, and omental, bladder and renal VAT). Feline obesity was characterised by increased adipocyte cell size and altered adipokine gene expression, in favour of pro-inflammatory cytokines and chemokines. Consequently, concentration of T-lymphocytes was increased in the adipose tissue of obese cats. Alteration of adipose tissue was location dependent in both lean and obese cats. Moreover, the observed changes were more prominent in SAT compared with VAT.
    The British journal of nutrition 05/2013; · 3.45 Impact Factor
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    ABSTRACT: Portosystemic shunts (PSS), congenital or acquired, occur uncommonly in the feline population. The diagnostic approach is similar to one in dogs suspected of a PSS based on the clinical signs and haematological and biochemical changes. Diagnostic imaging, however, is key for the confirmation of a PSS. Although abdominal ultrasound is the first-choice diagnostic imaging modality, the results are not always unequivocal. Transsplenic portal scintigraphy (TSPS) using (99m)Tc-pertechnetate is a well-established technique in canine medicine, providing relatively fast and easy confirmation of the presence or absence of a PSS. As the prevalence of PSS is much lower in the feline population, this technique has not been widely used in cats. This retrospective study of 12 cases gives an overview of the potential of TSPS in the diagnostic work-up of PSS in cats (2005-2012).
    Journal of feline medicine and surgery. 05/2013;
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    ABSTRACT: Objective: To evaluate the use of intra-articular anaesthesia combined with positive contrast arthrography (collectively called 'anaesthetic arthrography' [AA]) in the shoulder in order to identify and confirm the source of pain in lame dogs. Methods: Anaesthetic arthrography was performed in 30 dogs with shoulder joint lameness with a mixture of contrast medium (iohexol: 240 mg I/ml) and a local anaesthetic (mepivacaine 2%: 20 mg/ml). The effect of intra-articular anaesthesia was evaluated by an objectified visual scoring system and the arthrograms were evaluated for their diagnostic value. Results: This study showed that AA was positive in 28 out of 30 dogs. Dilution of the contrast medium with a local anaesthetic produced an arthrogram of good quality for each shoulder joint. In 16 out of 18 cases of osteochondritis dissecans, a cartilage flap could be identified following arthrography. In all cases the flap was not identified from plain radiographs. Biceps brachii tendon pathology was diagnosed on arthrography in seven dogs but was missed in two dogs. Calcification at the caudal rim of the glenoid cavity was diagnosed in three dogs, but was of clinical importance in only two dogs. In addition one infection was diagnosed during synovial aspiration. Conclusion: Anaesthetic arthrography of the shoulder is a simple, safe, and reliable diagnostic test to confirm shoulder joint pain and simultaneously identify a lesion. This procedure may be of particular importance in cases of occult shoulder joint lameness when clinical findings and plain radiographs are inconclusive.
    Veterinary and Comparative Orthopaedics and Traumatology 04/2013; 26(4). · 1.01 Impact Factor
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    ABSTRACT: Functional imaging provides important insights into canine brain pathologies such as behavioral problems. Two (99m) Tc-labeled single photon emission computed tomography (SPECT) cerebral blood flow tracers-ethylcysteinate dimer (ECD) and hexamethylpropylene amine oxime (HMPAO)-are commonly used in human medicine and have been used previously in dogs but intrasubject comparison of both tracers in dogs is lacking. Therefore, this study investigated whether regional distribution differences between both tracers occur in dogs as is reported in humans. Eight beagles underwent two SPECT examinations first with (99m) Tc-ECD and followed by (99m) Tc-HMPAO. SPECT scanning was performed with a triple head gamma camera equipped with ultrahigh resolution parallel hole collimators. Images were reconstructed using filtered backprojection with a Butterworth filter. Emission data were fitted to a template permitting semiquantification using predefined regions or volumes of interest (VOIs). For each VOI, perfusion indices were calculated by normalizing the regional counts per voxel to total brain counts per voxel. The obtained perfusion indices for each region for both tracers were compared with a paired Student's T-test. Significant (P < 0.05) regional differences were seen in the subcortical region and the cerebellum. Both tracers can be used to visualize regional cerebral blood flow in dogs, however, due to the observed regional differences, they are not entirely interchangeable.
    Veterinary Radiology &amp Ultrasound 03/2013; · 1.41 Impact Factor
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    ABSTRACT: In this study the use of the high resolution Micro-Single Photon Emission Tomography (HiSPECT) system with a radioactive bonemarker, (99m)Tc-oxidronate, was evaluated in dogs with coronoid pathology and/or flexor enthesopathy. Sixty-five elbows of 34 dogs were included. CT and HiSPECT were performed on all elbows, arthroscopy on 59. Tracer uptake in 8 anatomical regions was graded according to two models. Increased activity in the medial epicondylar region was associated with flexor pathology on CT (P=0.0002) and arthroscopy (P<0.0001) and increased uptake in the medial coronoid (P<0.0001) and the medial condylar area (P<0.013) with coronoid pathology. Uptake in the remaining areas was not associated with both pathologies. In conclusion, the improved resolution of the HiSPECT system allows identification of increased tracer uptake in the anatomical regions involved in coronoid pathology and flexor enthesopathy. This modality may improve the diagnostic potential of the bone scan in canine elbow disease.
    Research in Veterinary Science 01/2013; · 1.77 Impact Factor
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    ABSTRACT: Single-photon emission computed tomography (SPECT) can be used to study the regional distribution of the cerebral blood flow in the feline brain without interference of anesthetics. When the tracer, 99mtechnetium-ethyl cysteinate dimer (99mTc-ECD), is injected in the awake animal, the acquisition can be performed afterward under general anesthesia, whereas the tracer distribution still represents the regional cerebral blood flow (rCBF) in the awake animal. The aim of this study was to look at the in vivo stability of 99mTc-ECD in the feline brain. For this purpose, 6 cats (n = 6) were used, and 3 serial acquisitions were performed starting at 40 (T40), 60 (T60), and 85 (T85) minutes after tracer injection. Total counts and perfusion indices (PIs), normalized to the total brain and to the cerebellum, were calculated. When T85 was compared with T40, total counts decreased, depending on the brain region, with 29% (left thalamus) to 51% (bulbus olfactorius). These regional differences in tracer clearance resulted in significantly altered PIs at T85 as compared with T40. This study shows that 99mTc-ECD SPECT can be used in cats for studying the rCBF and that the clearance of 99mTc-ECD in the feline brain is region dependent. As a result, the acquisition should be started between 40 and 60 minutes after tracer injection.
    Journal of Veterinary Behavior Clinical Applications and Research 01/2013; 8(6):444–449. · 1.65 Impact Factor
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    ABSTRACT: This study determines the influence of general anesthesia on serum cardiac troponin I (cTnI) concentrations in dogs. All dogs showed no abnormalities on clinical and echocardiographic examination. Venous blood samples were drawn within 12h of induction and 12h after discontinuation of anesthesia. Each dog was premedicated with methadone IV and induced with diazepam IV and propofol IV. Anesthesia was maintained using isoflurane in oxygen in combination with a continuous rate infusion of fentanyl. The cTnI concentrations were measured using a third generation chemiluminescent microparticle immunoassay with a detection limit of 0.01ng/mL (below this level '<0.01ng/mL'). Ten dogs (55%) had a post-anesthetic increase of cTnI concentration relative to their pre-anesthetic cTnI concentration, whereas a decrease was observed in two dogs (11%). This study shows that cTnI can increase in healthy dogs undergoing general anesthesia.
    Research in Veterinary Science 11/2012; · 1.77 Impact Factor
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    ABSTRACT: With the use of perfusion tracers, in vivo examination of the regional cerebral blood flow in cats can be performed with single photon emission computed tomography (SPECT). Reliable perfusion data of normal, healthy cats are necessary for future clinical studies or other research use. Therefore, this dataset of the regional perfusion pattern of the normal feline brain was created. Twelve cats were used in this study. Technetium-99m-ethyl cysteinate dimer ((99m)Tc-ECD) was injected intravenously and the acquisition, using a triple head gamma camera equipped with three multi-pinhole collimators (pinhole SPECT), was started 40 mins after tracer administration under general anaesthesia. Nineteen regions of interest were defined using 7T magnetic resonance images of the feline brain and a topographical atlas. Regional counts were normalised to the counts of two reference regions: the total brain and the cerebellum. The highest tracer uptake was noticed in the subcortical structures, and the lowest in the frontal cortex and the cerebellum. Also left-right asymmetry in the temporal cortex and a rostrocaudal gradient of 5% were observed.
    Journal of feline medicine and surgery. 10/2012;
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    ABSTRACT: Brain neoplasia is diagnosed in an increasing number of dogs. Consequently, there is a higher need for an effective treatment. Chemotherapy is considered in cases where surgery or radiation is not optional. The objective of this retrospective study was to evaluate the difference in median survival time (MST) of dogs with intracranial masses, treated symptomatically with corticosteroids and anti-epileptic drugs, compared with the same symptomatic treatment supplemented with lomustine. The records of 71 dogs with intracranial masses were retrospectively evaluated. Fifteen dogs were treated symptomatically with corticosteroids and anti-epileptics, and 56 dogs received additional therapy with lomustine. There was no statistically significant difference in MST between both groups, being 60 and 93 days, respectively. Age, duration of symptoms, intracranial localization of the mass and intra- or extra-axial localization had no influence on survival time. However, female dogs survived significantly longer than male dogs.
    Veterinary and Comparative Oncology 06/2012; 9999(9999). · 1.56 Impact Factor
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    ABSTRACT: Objective  To investigate the clinical efficacy of four analgesia protocols in dogs undergoing tibial tuberosity advancement (TTA). Study design  Prospective, randomized, blinded study. Animals  Thirty-two client owned dogs undergoing TTA-surgery. Methods  Dogs (n = 8 per treatment) received an oral placebo (PM and PRM) or tepoxalin (10 mg kg(-1) ) tablet (TM and TRM) once daily for 1 week before surgery. Epidural methadone (0.1 mg kg(-1) ) (PM and TM) or the epidural combination methadone (0.1 mg kg(-1) )/ropivacaine 0.75% (1.65 mg kg(-1) ) (PRM and TRM) was administered after induction of anaesthesia. Intra-operative fentanyl requirements (2 μg kg(-1) IV) and end-tidal isoflurane concentration after 60 minutes of anaesthesia (Fe'ISO(60) ) were recorded. Post-operative analgesia was evaluated hourly from 1 to 8 and at 20 hours post-extubation with a visual analogue scale (VAS) and the University of Melbourne Pain Scale (UMPS). If VAS > 50 and/or UMPS > 10, rescue methadone (0.1 mg kg(-1) ) was administered IV. Analgesic duration (time from epidural until post-operative rescue analgesia) and time to standing were recorded. Normally distributed variables were analysed with an F-test (α = 0.05) or t-test for pairwise inter-treatment comparisons (Bonferonni adjusted α = 0.0083). Non-normally distributed data were analysed with the Kruskall-Wallis test (α = 0.05 or Bonferonni adjusted α = 0.005 for inter-treatment comparison of post-operative pain scores). Results  More intra-operative analgesia interventions were required in PM [2 (0-11)] [median (range)] and TM [2 (1-2)] compared to PRM (0) and TRM (0). Fe'ISO(60) was significantly lower in (PRM + TRM) compared to (PM + TM). Analgesic duration was shorter in PM (459 ± 276 minutes) (mean ± SD) and TM (318 ± 152 minutes) compared to TRM (853 ± 288 minutes), but not to PRM (554 ± 234 minutes). Times to standing were longer in the ropivacaine treatments compared to TM. Conclusions and clinical relevance  Inclusion of epidural ropivacaine resulted in reduction of Fe'ISO(60) , avoidance of intra-operative fentanyl administration, a longer duration of post-operative analgesia (in TRM) and a delay in time to standing compared to TM.
    Veterinary Anaesthesia and Analgesia 06/2012; 39(6):618-627. · 1.34 Impact Factor
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    ABSTRACT: Assessment of the effect of intra-articular anaesthesia on lameness caused by medial coronoid disease. This study included 90 dogs that were evaluated for the complaint of unilateral forelimb lameness. All dogs were suspected of having an elbow problem for which orthopaedic examination and radiographs showed inconclusive findings. Following a short sedation, mepivacaine was injected intra-articularly to determine whether lameness was caused by a suspected elbow problem. This effect was compared with the final diagnosis based on computed tomography and arthroscopy. Out of 90 dogs, 78 (87%) dogs had an improvement of lameness after injection of the local anaesthetic, which confirmed the elbow joint as the primary source of lameness. A positive response was seen in all types of medial coronoid lesions. A false negative result was observed in 12 dogs (13%). Medial coronoid disease is represented by different types of pathologic lesions including chondromalacia, fissures, fragments, and medial compartment disease. Diagnosis may be difficult because of limited clinical or radiographic signs or a combination of both. Intra-articular anaesthesia can be a helpful diagnostic tool to localize the problem by eliminating pain and reducing lameness to a great extent in all types of coronoid lesions.
    Veterinary and Comparative Orthopaedics and Traumatology 06/2012; 25(4):307-13. · 1.01 Impact Factor
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    ABSTRACT: To evaluate the impact of modulation of the membrane-bound efflux pump P-glycoprotein (P-gp) on plasma concentrations of orally administered prednisolone in dogs. 7 healthy adult Beagles. Each dog received 3 treatments (control [no treatment], rifampicin [100 mg/d, PO, for 21 days, as an inducer of P-gp], and ketoconazole [100 mg/d, PO, for 21 days, as an inhibitor of P-gp]). A single dose of prednisolone (1 mg/kg, PO) was administered on day 8 of each treatment period. There was a 7-day washout period between subsequent treatments. Plasma concentrations of prednisolone were determined by use of a validated liquid chromatography-tandem mass spectrometry method. Duodenum and colon biopsy specimens were obtained endoscopically from anesthetized dogs and assessed for P-gp protein labeling via immunohistochemical analysis and mRNA quantification via real-time PCR assay. Total fecal collection was performed for evaluation of effects of P-gp modulation on digestion of nutrients. Rifampicin treatment upregulated duodenal P-gp in dogs and significantly reduced the area under the plasma concentration-time curve of prednisolone. Ketoconazole typically downregulated expression of duodenal P-gp, with a subsequent increase in the area under the plasma concentration-time curve of prednisolone. There was a noticeable interindividual difference in response. Digestion of nutrients was not affected. Conclusions and Clinical Relevance: Modulation of P-gp expression influenced plasma concentrations of prednisolone after oral administration in dogs. Thus, treatment response to prednisolone may be influenced by coadministration of P-gp-modulating medications or feed ingredients.
    American Journal of Veterinary Research 06/2012; 73(6):900-7. · 1.35 Impact Factor
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    ABSTRACT: To evaluate the evolution of clinical signs and their correlation with results of magnetic resonance imaging (MRI) and transcranial magnetic stimulation (TMS) and to assess potential prognostic variables after conservative medical treatment for disk-associated cervical spondylomyelopathy (DA-CSM) in dogs. Prospective cohort study. 21 client-owned dogs with DA-CSM. After neurologic grading, dogs underwent low-field MRI and TMS with measurement of onset latencies and peak-to-peak amplitudes from the extensor carpi radialis and cranial tibial muscles. Dimensions calculated from MRI images were remaining spinal cord area, spinal cord compression ratio, vertebral occupying ratio, vertebral canal height-to-body height ratio, vertebral canal height-to-body length ratio, and vertebral canal compromise ratio. Intraparenchymal signal intensity changes were graded. Dogs were reevaluated 1, 3, 6, 12, and 24 months after initial diagnosis. Outcome was successful in 8 of 21 dogs. Negative outcomes were characterized by rapid progression of clinical signs. All dogs with more severe clinical signs of DA-CSM 1 month after diagnosis had unsuccessful outcomes. Outcome was associated with the remaining spinal cord area and vertebral canal compromise ratio. Prognosis was not associated with severity of clinical signs or results of TMS. There were no significant correlations among clinical signs, MRI findings, and TMS results. Conservative medical treatment of DA-CSM was associated with a guarded prognosis. Selected MRI variables and clinical evolution 1 month after diagnosis can be considered prognostic indicators. The lack of correlation among clinical signs, results of diagnostic imaging, and results of electrophysiologic evaluation in dogs with DA-CSM warrants further investigation.
    Journal of the American Veterinary Medical Association 04/2012; 240(7):848-57. · 1.72 Impact Factor