Treatment of a Myasthenic Dog with Mycophenolate Mofetil

A ten‐year‐old, male castrated Springer Spaniel was presented for dysphagia, ptyalism, and regurgitation. Evidence of megaesophagus and mild aspiration pneumonia were apparent on thoracic radiographs. A diagnosis of focal acquired myasthenia gravis was suspected and subsequently confirmed with a positive serum acetylcholine (ACh) receptor antibody concentration (3.87 nM/L). A gastrostomy tube was placed shortly after presentation; food and drugs (including azathioprine) were administered through the tube. After transient improvement, the dog suddenly deteriorated clinically, experiencing frequent episodes of regurgitation and developing severe aspiration pneumonia. Mycophenolate mofetil (MMF), a novel immunosuppressive drug with relative specificity for lymphocytes, was instituted every twelve hours via the gastrostomy tube. Within four days of beginning MMF therapy, both clinical evidence of pharyngeal/esophageal dysfunction and radiographic evidence of megaesophagus had resolved. Initially, clinical side‐effects of combined MMF/AZA administration were not apparent, but the patient experienced several vomiting episodes during the third week of treatment. The vomiting resolved after decreasing the dose of both drugs. The patient made a full recovery, and a one‐month follow‐up ACh receptor antibody concentration was normal (0.26 nM/L). After one month of combination therapy, the patient was weaned off of AZA and maintained on MMF as the sole immunosuppressive drug. The dog was subsequently weaned off of MMF on two occasions. Mycophenolate mofetil was reinstituted after the first discontinuation due to the development of profound appendicular muscle weakness two days after stopping MMF; the weakness resolved within 24 hours of reinstituting MMF. A positive ACh receptor antibody concentration (0.89 nM/L) after the second MMF weaning prompted the second reinstitution of MMF. Two months following this second MMF reinstitution, the dog was again serologically negative (0.51 nM/L) for myasthenia gravis. At the time of last followup, the dog remained in clinical remission eight months after initial presentation. The use of MMF to treat acquired myasthenia gravis in dogs has not been reported previously. The literature concerning MMF and its potential use in treating patients with autoimmune diseases is discussed.     

The cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in cats

ObjectiveTo determine the cardiorespiratory and anesthetic effects of 0, 5, 15, and 50 mg kg^?1 intravenous (IV) alfaxalone in hydroxypropyl beta cyclodextrin (Alfaxan; Jurox Pty Ltd, Rutherford, NSW, Australia) in cats.Study designFour treatments of alfaxalone were administered in sequential order.AnimalsEight healthy adult cats (four male; four female) weighing between 3.71 and 5.91 kg.MethodsCats were instrumented for hemodynamic measurements. Four (0, 5, 15, and 50 mg kg^?1) IV doses of alfaxalone were administered over one minute, with a 3-hour washout period between doses 0, 5, and 15 mg kg^?1 on Day 0. The 50 mg kg^?1 treatment was administered 24 hours later. Measurements of heart rate, aortic systolic, mean, and diastolic blood pressures, pulmonary arterial and right atrial mean pressures, cardiac output, respiratory rate, tidal and minute volumes, and arterial blood pH and blood gases (PaO₂, PaCO₂) were performed at pre-determined intervals. Systemic vascular resistance and rate pressure product were calculated. The quality of induction, maintenance, and recovery from anesthesia and the response to noxious stimulation were categorically scored.ResultsAlfaxalone administration resulted in dose-dependent cardiorespiratory depression. Decreases in arterial blood pressure and increases in heart rate occurred at higher doses. Most variables returned to baseline by 15-30 minutes. Respiratory rate, minute volume, and PaO₂ decreased. Apnea was the most common side effect. Induction and maintenance quality were judged to be good to excellent at all doses and quality of recovery good to excellent at all but the 50 mg kg^?1 dose. The duration of anesthesia and unresponsiveness to noxious stimulation increased with dose. The administration of the 50 mg kg^?1 dose produced marked cardiorespiratory depression and apnea.Conclusions and clinical relevanceAlfaxalone produced dose-dependent anesthesia, cardiorespiratory depression and unresponsiveness to noxious stimulation in unpremedicated cats. Hypoventilation and apnea were the most common side effects.     

Effect of detomidine on visceral and somatic nociception and duodenal motility in conscious adult horses

ObjectiveTo evaluate the effects of detomidine on visceral and somatic nociception, heart and respiratory rates, sedation, and duodenal motility and to correlate these effects with serum detomidine concentrations.Study designNonrandomized, experimental trial.AnimalsFive adult horses, each with a permanent gastric cannula weighing 534 ± 46 kg.MethodsVisceral nociception was evaluated by colorectal (CRD) and duodenal distension (DD). The duodenal balloon was used to assess motility. Somatic nociception was assessed via thermal threshold (TT). Nose–to–ground (NTG) height was used as a measure of sedation. Serum was collected for pharmacokinetic analysis. Detomidine (10 or 20 μg kg^?1) was administered intravenously. Data were analyzed by means of a three–factor anova with fixed factors of treatment and time and random factor of horse. When a significant time × treatment interaction was detected, differences were compared with a simple t–test or Bonferroni t–test. Significance was set at p < 0.05.ResultsDetomidine produced a significant, dose–dependent decrease in NTG height, heart rate, and skin temperature and a significant, nondose–dependent decrease in respiratory rate. Colorectal distension threshold was significantly increased with 10 μg kg^?1 for 15 minutes and for at least 165 minutes with 20 μg kg^?1. Duodenal distension threshold was significantly increased at 15 minutes for the 20 μg kg^?1 dose. A significant change in TT was not observed at either dose. A marked, immediate decrease in amplitude of duodenal contractions followed detomidine administration at both doses for 50 minutes.Conclusions and clinical relevanceDetomidine caused a longer period of visceral anti–nociception as determined by CRD but a shorter period of anti–nociception as determined by DD than has been previously reported. The lack of somatic anti–nociception as determined by TT testing may be related to the marked decrease in skin temperature, likely caused by peripheral vasoconstriction and the low temperature cut–off of the testing device.