Joris H. Robben

Aldosterone-to-Renin and Cortisol-to-Adrenocorticotropic Hormone Ratios in Healthy Dogs and Dogs with Primary Hypoadrenocorticism

In dogs with primary hypoadrenocorticism, hypocortisolism and hypoaldosteronism usually are present, but these deficiencies also may occur in isolated forms. The diagnosis is commonly made by measuring plasma cortisol concentration before and after stimulation with ACTH, thereby ignoring aldosterone. In search of an alternative approach that would include assessment of glucocorticoid and mineralocorticoid production, 2 pairs of endocrine variables were measured: (1) plasma concentration of cortisol and ACTH, and (2) plasma aldosterone concentration and plasma renin activity. In addition, the cortisol-to-ACTH ratio (CAR) and the aldosterone-to-renin ratio (ARR) were calculated. Reference intervals were established in a population of 60 healthy dogs. In these dogs, CAR ranged from 1.1 to 26.1 and ARR ranged from 0.1 to 1.5. The variables were compared with those of 22 dogs with spontaneous primary hypoadrenocorticism. Plasma concentration of cortisol and ACTH in both groups of dogs overlapped, whereas CAR did not. Similarly, plasma aldosterone concentration and plasma renin activity overlapped, whereas ARR did not. These observations indicate that measurement of these endogenous variables (in one blood sample) allows the specific diagnoses of primary hypocortisolism and primary hypoaldosteronism.

Dexmedetomidine constant rate infusion for 24 hours during and after propofol or isoflurane anaesthesia in dogs

OBJECTIVE To evaluate cardiovascular and respiratory effects and pharmacokinetics of a 24-hour intravenous constant rate infusion (CRI) of dexmedetomidine (DMED) during and after propofol (PRO) or isoflurane (ISO) anaesthesia in dogs. STUDY DESIGN Prospective, randomized, cross-over study. ANIMALS Ten healthy adult Beagles. METHODS Instrumented dogs received a DMED-loading bolus (25 microg m(-2)) at time 0 followed by a 24-hour CRI (25 microg m(-2) hour(-1)), with PRO or ISO induction/maintenance of anaesthesia during the first 2 hours (PRO and ISO treatment groups, respectively). Cardiovascular, respiratory, blood gas, airway gas, serum chemistry variables and DMED plasma concentration data were collected at -15, 5, 15, 30, 45, 60, 90 and 120 minutes. A number of cardiorespiratory and tissue oxygenation variables were calculated from the above data. After the 2-hours of anaesthesia, heart and respiratory rates and electrocardiograms were recorded and DMED plasma concentrations were determined for up to 26 hours. RESULTS Vasopressor effects and the decrease in heart rate (HR) and cardiac index induced by DMED were greater for PRO than ISO, but were within clinically acceptable ranges. Adequate oxygenation was maintained above the critical O(2) delivery level. The overall incidence of unfavourable arrhythmias was low and tended to vary inversely with HR. Mean DMED plasma concentration ranged from 0.23 to 0.47 ng mL(-1) for both groups during the 24-hour CRI with a mean elimination half-life of approximately 0.46 hour. CONCLUSION AND/CLINICAL RELEVANCE: DMED CRI resulted in typical alpha(2)-agonist induced haemodynamic changes with minimal respiratory effects, and appeared to be an efficacious adjunct during and after PRO or ISO anaesthesia in healthy dogs.

Clinical evaluation of the efficacy and safety of a constant rate infusion of dexmedetomidine for postoperative pain management in dogs.

OBJECTIVE To compare postoperative analgesia provided by a constant rate infusion (CRI) of dexmedetomidine (DMED) to that of a well-established positive control [morphine (MOR)] in critically ill dogs. The sedative, cardiorespiratory effects and clinical safety of a 24-hour DMED CRI were also evaluated. STUDY DESIGN Prospective, randomised, blinded, positive-controlled parallel-group clinical study. ANIMALS Forty hospitalised, client-owned dogs requiring post-operative pain management after invasive surgery. METHODS After surgery, a loading dose of either DMED (25 microg m(-2)) or MOR (2500 microg m(-2)) followed by a 24-hour CRI of DMED (25 microg m(-2) hour(-1)) or MOR (2500 microg m(-2) hour(-1)) was administered. Pain was measured using the Short Form of the Glasgow Composite Measure Pain Scale, sedation and physiological variables were scored at regular intervals. Animals considered to be painful received rescue analgesia and were allocated to a post-rescue protocol; animals which were unresponsive to rescue analgesia were removed from the study. Data were analysed with anova, two-sample t-tests or Chi-square tests. Time to intervention was analysed with Kaplan-Meier methodology. RESULTS Forty dogs were enrolled. Twenty dogs (9 DMED and 11 MOR) did not require rescue analgesia. Eleven DMED and eight MOR dogs were allocated to the post-rescue protocol and seven of these removed from the study. Significant differences in pain scores between groups were not observed during the first 12 hours, however, DMED dogs were less (p = 0.009) painful during the last 12 hours. Sedation score over the entire 24-hour study was not significantly different between groups. CONCLUSION / CLINICAL RELEVANCE: Dexmedetomidine CRI was equally effective as MOR CRI at providing postoperative analgesia and no clinically significant adverse reactions were noted. This study shows the potential of DMED to contribute to a balanced postoperative analgesia regimen in dogs.

Plasma superwarfarin levels and vitamin K1 treatment in dogs with anticoagulant rodenticide poisoning.

The plasma concentration, plasma half-life (t1/2), and mean residence time (MRT) of rodenticide anticoagulants were determined in 21 dogs in which a preliminary diagnosis of anticoagulant rodenticide poisoning had been made. Brodifacoum, difethialone, and difenacoum were detected by high-performance liquid chromatography (HPLC) in the plasma of 13, 3, and 2 dogs, respectively. At presentation the plasma concentration ranged from below the detection limit (10 ng/L) to 851 ng/L. Toxin could not be detected in 3 dogs, despite these animals showing characteristic coagulation disturbances and a positive response to therapy with vitamin K1. In 7 dogs the estimated t1/2 of brodifacoum ranged from 0.9 to 4.7 (median 2.4) days with a MRT of 1.9 to 3.7 (median 2.8) days. In 2 dogs the individual t1/2 of difethialone was 2.2 and 3.2 days and the MRT was 2.3 and 2.8 days, respectively. Two dogs died during emergency treatment. Treatment in the remaining 19 dogs consisted of the administration of vitamin K1 and supportive therapy. The dose of vitamin K1 was reduced in a stepwise manner as long as the prothrombin time remained within physiological limits. The variation in initial plasma concentrations of the anticoagulants combined with the results of treatment support the idea that an individual therapeutic approach is warranted.

Pyothorax in nine dogs.

Summary The results of treatment of pyothorax using systemic antibiotics, drainage, and lavage of the pleural space, are reported for 9 dogs. All 9 dogs recovered completely. In 8 of the 9 dogs the follow‐up period was at least 6 months and in none was there a relapse. The results obtained with this treatment are excellent in comparison with the results that have been reported for treatment with systemic antibiotics and drainage of the pleural space but without lavage. Apart from the addition of pleural lavage to the treatment protocol, the better result might be because migrating plant related foreign bodies did not seem to play an important role in the pathogenesis of pyothorax in this group of dogs.

Plasma creatinine in dogs: intra- and inter-laboratory variation in 10 European veterinary laboratories

BackgroundThere is substantial variation in reported reference intervals for canine plasma creatinine among veterinary laboratories, thereby influencing the clinical assessment of analytical results. The aims of the study was to determine the inter- and intra-laboratory variation in plasma creatinine among 10 veterinary laboratories, and to compare results from each laboratory with the upper limit of its reference interval.MethodsSamples were collected from 10 healthy dogs, 10 dogs with expected intermediate plasma creatinine concentrations, and 10 dogs with azotemia. Overlap was observed for the first two groups. The 30 samples were divided into 3 batches and shipped in random order by postal delivery for plasma creatinine determination. Statistical testing was performed in accordance with ISO standard methodology.ResultsInter- and intra-laboratory variation was clinically acceptable as plasma creatinine values for most samples were usually of the same magnitude. A few extreme outliers caused three laboratories to fail statistical testing for consistency. Laboratory sample means above or below the overall sample mean, did not unequivocally reflect high or low reference intervals in that laboratory.ConclusionsIn spite of close analytical results, further standardization among laboratories is warranted. The discrepant reference intervals seem to largely reflect different populations used in establishing the reference intervals, rather than analytical variation due to different laboratory methods.

Locally produced growth hormone in canine insulinomas.

The production and release of GH has been demonstrated in a variety of extra-pituitary tissues. In this respect insulin-producing pancreatic tumours are also of interest because it has been observed that GH may promote islet cell proliferation. However, these effects have only been related to GH of pituitary origin and the possibility of local production of GH with autocrine-/paracrine effects has not been considered. In this study, a reverse transcriptase polymerase chain reaction (RT-PCR) was used to demonstrate the presence of GH mRNA in pancreatic tissue of five healthy dogs and insulinomas of 14 dogs. After Southern blotting of the RT-PCR products, blots were hybridized using a canine-specific GH-probe and quantified using phosphor imaging. GH gene expression was further demonstrated by in situ hybridization using a canine digoxigenin-labelled GH-specific cDNA probe. In addition, GH immunohistochemistry was performed. In five samples of normal pancreatic tissue a weak hybridization signal was found. This signal was significantly higher in nine of 12 primary tumours. In ten of 11 metastases there was a positive hybridization signal, and this signal was also significantly higher than in the primary tumours. In situ hybridization in one sample demonstrated that GH mRNA was only produced in the tumour cells. The local production of GH was confirmed by positive staining of tumour tissue with anti-GH antibodies in ten of 12 samples. It is concluded that canine insulinomas express the gene encoding GH mRNA. The locally produced GH may have an autocrine/paracrine effect on tumour progression. The relatively high expression levels in metastases of these tumours may be related to the low inhibitory influence of somatostatin outside the pancreas.

Expression of insulin-like growth factor-1 by canine insulinomas and their metastases

The long-term prognosis after surgical resection of canine insulinoma is poor. Signs of hypoglycaemia often recur soon after surgery because tumour tissue has only been resected partially and/or functional (micro-)metastases were present. Using quantitative real-time PCR, the expression of 16 target genes was compared between primary canine insulinomas and their corresponding metastases. There was significantly higher expression of genes encoding for growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in metastases compared to their primary tumours. Immunohistochemical examination of proteins of the GH-IGF-1 axis revealed expression of GH, IGF-1 and GH receptor (GHR) in both primary insulinomas and metastases. Immunohistochemical staining for IGF-1 was significantly higher in metastases compared to primary tumours.

Response of cats to familiar and unfamiliar human contact using continuous direct arterial blood pressure measurement.

Continuous direct measurement of feline arterial blood pressure (ABP) was carried out via a modified method with percutaneous, ultrasound guided catheterization of the common carotid artery. In 21 healthy, conscious cats the ABP was measured during rest, alertness and activity. Furthermore, the ABP response to being petted by familiar and unfamiliar persons was assessed. Linear mixed modelling revealed that the mean blood pressure (MBP) in resting cats (114.6mmHg) was lower (P<0.001) than in alert cats (122.7mmHg), which was lower (P<0.001) than that of active cats (136.8mmHg). The MBP during petting by a familiar person (144.7mmHg) tended to be higher (P=0.065) than that during petting by an unfamiliar person (139.4mmHg). The MBP of active cats was lower (P=0.003) than MBP of cats petted by a familiar person, but not different from MBP of cats petted by an unfamiliar person. The MBP returned to resting values between 16 and 20min after the familiar person had left, whereas resting values were reached between 11 and 15min after the unfamiliar person had left. The complications of the described method were limited considering the potential risks of continuous direct ABP measurement. In conclusion, the described technique enables accurate measurement of feline ABP, which is influenced by the cats activity level and the familiarity of persons.

Biodistribution of [111In-DTPA-d-Phe1]-octreotide in dogs: uptake in the stomach and intestines but not in the spleen points towards interspecies differences

The purpose of the present study was to establish the tissue distribution in abdominal organs and the excretion of radioactivity after intravenous administration of [(111)In-DTPA-D-Phe(1)]-octreotide in healthy dogs. In five Beagle dogs computed tomography and single photon emission computed tomography (SPECT) at 24 h after injection of [(111)In-DTPA-D-Phe(1)]-octreotide revealed accumulation of radioactivity in the kidneys, gall bladder, gastric fundus and cardia, intestinal tract, but not in the spleen. These findings were confirmed by in vitro scintigraphy of single abdominal organs. This also demonstrated accumulation of radioactivity in the pancreas and located the radioactivity in the gastrointestinal tract primarily in the wall itself. In vitro autoradiography with (125)I-[Tyr(3)]-octreotide on tissue samples in two dogs revealed sst receptors in the medullary part of the kidney, the basal two-thirds of the gastric mucosa of the cardia and fundus, Peyers patches and neural plexus of the gastrointestinal tract. No sst receptors were demonstrated in the liver, spleen, and pancreas. These results differ to findings in man, where there is uptake in the spleen but not in the stomach, most likely caused by interspecies variations in sst receptor subtype expression.