Type 2 diabetes mellitus with pancreatic β cell dysfunction in 3 horses confirmed with minimal model analysis

Reasons for performing study: Type 2 diabetes mellitus (T2DM) is diagnosed rarely in equine practice although it may be under‐recognised. A greater awareness of the condition and therapeutic considerations would be to the benefit of such cases presenting in practice. More investigation into the pharmacological management of these cases is needed. Objectives: Three cases of diabetes mellitus were investigated using a specific test for insulin sensitivity and pancreatic β cell function in order to define accurately and characterise the existence of T2DM in all 3 subjects. Methods: The insulin‐modified frequently sampled i.v. glucose tolerance test was performed in each case and the data so obtained were subject to minimal model analysis of insulin‐glucose dynamics. Cases were then monitored following treatment using a combination of dietary modification, metformin, glibenclamide and pergolide. Results: Marked insulin resistance was identified in each case and, furthermore, severe pancreatic β cell dysfunction was present therefore classifying each case as end stage T2DM. Treatment was nevertheless associated with restoration of normoglycaemia in all cases. Conclusions: T2DM in horses may be more common than generally considered. In some cases individuals may respond to therapy aimed at restoring insulin sensitivity and pancreatic function. Drugs used in other species for the treatment of T2DM have not yet been adequately tested in horses. Potential relevance: T2DM should be considered as an important differential diagnosis in mature to elderly horses and ponies suffering from weight loss, polydipsia and polyuria. Clinicians should be encouraged to offer treatment and management advice when such cases are encountered.     

Aspects of the Pharmacokinetics of Albendazole Sulphoxide in Sheep

The plasma disposition kinetics of albendazole sulphoxide (ABZSO), ((+)ABZSO and (–)ABZSO) and its sulphone metabolite (ABZSO₂) were investigated in adult sheep. Six Corriedale sheep received albendazole sulphoxide by intravenous injection at 5 mg/kg live weight. Jugular blood samples were taken serially for 72 h and the plasma was analysed by high-performance liquid chromatography (HPLC) for albendazole (ABZ), ABZ sulphoxide (ABZSO) and albendazole sulphone (ABZSO₂). Albendazole was not detected in the plasma at any time after the treatment, ABZSO and ABZSO₂ being the main metabolites detected between 10 min and 48 h after treatment. A biexponential plasma concentration versus time curve was observed for both ABZSO and ABZSO₂ following the intravenous treatment. The plasma AUC values for ABZSO and ABZSO₂ were 52.0 and 10.8 (g.h)/ml, respectively. The ABZSO₂ metabolite was measurable in plasma between 10 min and 48 h after administration of ABZSO, reaching a peak concentration of 0.38 g/ml at 7.7 h after treatment. Using a chiral phase-based HPLC method, a biexponential plasma concentration versus time curve was observed for both ABZSO enantiomers. The total body clearance was higher for the (–) than for the (+) enantiomer, the values being 270.6 and 147.75 (ml/h)/kg, respectively. The elimination half-life of the (–) enantiomer was shorter than that of the (+) enantiomer, the values being 4.31 and 8.33 h, respectively. The enantiomeric ratio (+)ABZSO/(–)ABZSO at t ₀ was close to unity. However, the ratio in the plasma increased with time.     

Experimental infection with Mycobacterium avium, serotype 2, in pigs. 1. Intravenous inoculations

A porcine strain of Mycobacterium avium, Serotype 2, was used for intravenous inoculation of pigs in doses 5, 1, 10⁻¹, 10⁻² and 10⁻³ mg (1 mg = 78 × 10⁶ viable units), 2 pigs per dose.Dose 5 mg proved fatal for both of the inoculated pigs, which were killed in extremis 64 and 69 days, respectively, after inoculation. Dose 1 mg caused clinical disease in 1 of 2 pigs, but was not lethal. Post mortem, the clinically affected pigs showed a generalized granulomatous tuberculosis. The other pig given 1 mg and the pigs given smaller doses, showed no clinical signs, and lesions and presence of acid-fasts were mostly limited to the lymph nodes of the lung, liver and digestive tract.All the pigs showed delayed hypersensitivity to avian PPD tuberculin (1000 t.u.) and some of them cross-reacted with human PPD tuberculin (1000 t.u.). The clinically affected pigs gave a very weak response to tuberculin, the others a strong response.The smallest dose capable of establishing an infection and producing tuberculous lesions was not determined, but seems to be less than 10⁻³ mg (78000 viable organisms).     

A Prospective Study Of Intravenous Catheter Contamination

A one year prospective study was conducted to determine the association between intravenous catheter contamination and increased dwell time, and to identify any related risk factors. Intravenous catheters obtained from 23 cats and 98 dogs in the Intensive Care Unit at the Ontario Veterinary College with dwell times > 72 hours for the test group (n=58) and < 72 hours for a corresponding control group (n=63) were cultured between April 1991 and March 1992. One hundred and twenty one catheters were cultured, 16 jugular, 99 cephalic, and 6 saphenous. The overall contamination rate was 13 out of 121 catheters cultured (10.7%); 9/63 (14.3%) control and 4/58 (6.9%) test catheters. The bacteria isolated were E.aerogenes, S.aureus (3), P.aeruginosa, P.multocida, and Bacillus sp (7). The Bacillus sp positive catheters (5 control and 2 test) were placed during a five day period, and contaminated gauze squares were identified as the source of infection in these catheters. After these were removed from the study, the group infection rate was 6.9% control and 3.6% test. There was no significant difference between groups and no associated risk factors were identified. We conclude that intravenous dwell time need not be restricted to <72 hours.     

Minimum infusion rate and hemodynamic effects of propofol, propofol-lidocaine and propofol-lidocaine-ketamine in dogs

ObjectiveTo evaluate the effects of a constant rate infusion (CRI) of lidocaine alone or in combination with ketamine on the minimum infusion rate (MIR) of propofol in dogs and to compare the hemodynamic effects produced by propofol, propofol-lidocaine or propofol-lidocaine-ketamine anesthesia.Study designProspective, randomized cross-over experimental design.AnimalsFourteen adult mixed-breed dogs weighing 15.8 ± 3.5 kg.MethodsEight dogs were anesthetized on different occasions to determine the MIR of propofol alone and propofol in combination with lidocaine (loading dose [LD] 1.5 mg kg^?1, CRI 0.25 mg kg^?1 minute^?1) or lidocaine (LD 1.5 mg kg^?1, CRI 0.25 mg kg^?1 minute^?1) and ketamine (LD 1 mg kg^?1, CRI 0.1 mg kg^?1 minute^?1). In six other dogs, the hemodynamic effects and bispectral index (BIS) were investigated. Each animal received each treatment (propofol, propofol-lidocaine or propofol-lidocaine-ketamine) on the basis of the MIR of propofol determined in the first set of experiments.ResultsMean ± SD MIR of propofol was 0.51 ± 0.08 mg kg^?1 minute^?1. Lidocaine-ketamine significantly decreased the MIR of propofol to 0.31 ± 0.07 mg kg^?1 minute^?1 (37 ± 18% reduction), although lidocaine alone did not (0.42 ± 0.08 mg kg^?1 minute^?1, 18 ± 7% reduction). Hemodynamic effects were similar in all treatments. Compared with the conscious state, in all treatments, heart rate, cardiac index, mean arterial blood pressure, stroke index and oxygen delivery index decreased significantly, whereas systemic vascular resistance index increased. Stroke index was lower in dogs treated with propofol-lidocaine-ketamine at 30 minutes compared with propofol alone. The BIS was lower during anesthesia with propofol-lidocaine-ketamine compared to propofol alone.Conclusions and clinical relevanceLidocaine-ketamine, but not lidocaine alone, reduced the MIR of propofol in dogs. Neither lidocaine nor lidocaine in combination with ketamine attenuated cardiovascular depression produced by a continuous rate infusion of propofol.     

Pharmacokinetics of levosulpiride after single‐dose administration in goats (Capra hircus) by different routes of administration

Levosulpiride (LSP) is the l‐enantiomer of sulpiride, and LSP recently replacing sulpiride in several EU countries. Several studies about LSP in humans are present in the literature, but neither pharmacodynamic nor pharmacokinetic data of LSP is present for veterinary species. The aim of this study was to assess the pharmacokinetic profile of LSP after intravenous (IV), intramuscular (IM), and oral (PO) administration in goats. Animals (n = 6) were treated with 50 mg LSP by IV, IM, and PO routes according to a randomized cross‐over design (3 × 3 Latin‐square). Blood samples were collected prior and up to 24 hr after LSP administration and quantified using a validated HPLC method with fluorescence detection. IV and IM administration gave similar concentration versus time curve profiles. The IM mean bioavailability was 66.97%. After PO administration, the drug plasma concentrations were detectable only in the time range 1.5–4 hr, and the bioavailability (4.73%) was low. When the AUC was related to the administered dose in mg/kg, there was a good correlation in the IV and IM groups, but very low correlation for the PO route. In conclusion, the IM and IV administrations result in very similar plasma concentrations. Oral dosing of LSP in goats is probably not viable as its oral bioavailability was very low.     

The clinical efficacy of EMLA cream for intravenous catheter placement in client-owned dogs

Objective

To assess the reaction of client-owned dogs to intravenous (IV) catheter placement after applying a local anaesthetic (EMLA) or placebo cream for either 30 or 60 minutes.

INTRAVENOUS ALFAXALONE ANAESTHESIA IN LEOPARD GECKOS (EUBLEPHARIS MACULARIUS)

Intravenous alfaxalone, administered at a dose of 5 mg/kg in the jugular vein, was evaluated in 20 leopard geckos (Eublepharis macularius) to ascertain its ability to provide anesthesia. The induction time, time to loss of mandibular tone, interval of deep anesthesia, and full recovery time were 27.5 ± 30.7 seconds (10 to 56 seconds), 1.3 ± 1.4 minutes (11 seconds to 4 minutes), 12.5 ± 2.2 minutes (11.11 to 15.39 minutes), and 18.8 ± 12.1 minutes (10.4 to 52.31 minutes), respectively. A significant reduction in heart rate (74 ± 12.9 beats/minute) was recorded between 2 and 24 minutes after alfaxalone administration. A significant decrease in respiratory rate (26.8 ± 10.1 breaths/minute) was recorded 2 minutes after alfaxalone administration, and respiratory rate remained lower than the basal rate (31.4 ± 3.1 breaths/minute) for 24 minutes but without statistical significance. The intravenous administration of alfaxalone in leopard geckos achieved a rapid onset of anesthesia and a suitable recovery time. Based on this investigation, an afaxalone dose of 5 mg/kg intravenously proved to be suitable for sedation before tracheal intubation. Moreover, the administration route via the jugular vein, was acceptable in leopard geckos; a species in which other venipuncture sites can be challenging or inaccessible.