Clinical effect of torsemide in a horse with congestive heart failure and atrial fibrillation.

In this case report, a high dose of torsemide (6mg/kg, every 12 hours for 3 days followed by 12mg/kg, every 12 hours for 4 days) was administered orally to a horse with congestive heart failure (CHF) and atrial fibrillation. Blood samples for measurement of plasma torsemide concentrations were obtained one hour after each drug administration. Pharmacodynamic effects of oral torsemide were evaluated by daily physical examination, electrocardiography, and serum biochemistry. The horse tolerated administration of torsemide. A decrease in ventral oedema and venous congestion was subjectively noted at day 7. Torsemide plasma concentration markedly increased at day 5 (peak concentration of 15.41 µg/mL). Evidence of an increase in renal markers was observed throughout the study period. Electrolyte measurements revealed mild hyponatremia and hypochloremia, and moderate hypokalaemia. No electrocardiographic changes related to torsemide administration were observed. After seven days of treatment, the horse was euthanised due to his disease stage and poor prognosis. Results indicate that torsemide was absorbed after oral administration and was well tolerated in this horse. Furthermore, clinical improvement in this single case indicates that torsemide might be utilized as an oral alternative to furosemide in the management of equine patients in CHF. The high doses of torsemide used in this case report should be reserved for cases without clinical response to lower doses and with close monitoring of electrolytes and renal function parameters. Further investigation of torsemide clinical efficacy and safety in horses with CHF with a larger cohort and prolonged administration is warranted.

Persistent phosphaturic mesenchymal tumor causing tumor-induced osteomalacia treated with image-guided ablation.

Phosphaturic mesenchymal tumors (PMTs) can present with vague symptoms of diffuse bone pain with pathologic fractures that often lead to a delayed diagnosis. We present a 60-year-old patient with a PMT that was persistently hypophosphatemic after resection, who was then successfully treated with cryoablation of the tumor. Tumor-induced osteomalacia (TIO) is a rare cause of hypophosphatemia characterized by vague symptoms of gradual muscle weakness and diffuse bone pain with pathologic fractures that often lead to a delayed diagnosis. This condition is usually caused by benign phosphaturic mesenchymal tumors (PMTs). Here, we present a case of persistent PMT after surgical resection treated with image-guided ablation. We present the patient's clinical examinations and laboratory findings (phosphorus, 1,25 (OH)2D, FGF-23, Intact PTH). Representative histologic images of a PMT are also presented. A 61-year-old male was evaluated for persistent hypophosphatemia and presumed osteomalacia. Six years earlier, he underwent surgical excision of a left ischial mass after presenting with TIO. The pathology was consistent with a PMT; however, hypophosphatemia persisted suggesting incomplete resection. He was treated with calcitriol and phosphate salts. A PET Ga68 dotatate scan of the patient revealed an avid left ischial mixed lytic and sclerotic lesions with marked amount of radiotracer uptake, suggesting persistent tumor. The patient was resistant to re-excision of the tumor due to the extended recovery period from his prior surgery and was treated instead with cryoablation of the tumor. His biochemical findings of hypophosphatemia and elevated FGF23 resolved after the ablation and have remained normal for 5 months after surgery. In patients with TIO, wide surgical excision is the treatment of choice. When this is not possible, image-guided ablation is an alternative therapeutic option.

Disposition of levetiracetam in healthy adult horses.

Nine horses received 20 mg/kg of intravenous (LEVIV ); 30 mg/kg of intragastric, crushed immediate release (LEVCIR ); and 30 mg/kg of intragastric, crushed extended release (LEVCER ) levetiracetam, in a three-way randomized crossover design. Crushed tablets were dissolved in water and administered by nasogastric tube. Serum samples were collected over 48 hr, and levetiracetam concentrations were determined by immunoassay. Mean ± SD peak concentrations for LEVCIR and LEVCER were 50.72 ± 10.60 and 53.58 ± 15.94 µg/ml, respectively. The y-intercept for IV administration was 64.54 ± 24.99 µg/ml. The terminal half-life was 6.38 ± 1.97, 7.07 ± 1.93 and 6.22 ± 1.35 hr for LEVCIR , LEVCER, and LEVIV , respectively. Volume of distribution at steady-state was 630 ± 73.4 ml/kg. Total body clearance after IV administration was 74.40 ± 19.20 ml kg-1  hr-1 . Bioavailability was 96 ± 10, and 98 ± 13% for LEVCIR and LEVCER , respectively. A single dose of Levetiracetam (LEV) was well tolerated. Based on this study, a recommended dosing regimen of intravenous or oral LEV of 32 mg/kg every 12 hr is likely to achieve and maintain plasma concentrations within the therapeutic range suggested for humans, with optimal kinetics throughout the dosing interval in healthy adult horses. Repeated dosing and pharmacodynamic studies are warranted.

Pre-birth origins of allergy and asthma.

Allergy is a chronic disease that can develop as early as infancy, suggesting that early life factors are important in its aetiology. Variable associations between size at birth, a crude marker of the fetal environment, and allergy have been reported in humans and require comprehensive review. Associations between birth weight and allergy are however confounded in humans, and we and others have therefore begun exploring the effects of early life events on allergy in experimental models. In particular, we are using ovine models to investigate whether and how a restricted environment before birth protects against allergy, whether methyl donor availability contributes to allergic protection in IUGR, and why maternal asthma during pregnancy is associated with increased risks of allergic disease in children. We found that experimental intrauterine growth restriction (IUGR) in sheep reduced cutaneous responses to antigens in progeny, despite normal or elevated IgE responses. Furthermore, maternal methyl donor supplementation in late pregnancy partially reversed effects of experimental IUGR, consistent with the proposal that epigenetic pathways underlie some but not all effects of IUGR on allergic susceptibility. Ovine experimental allergic asthma with exacerbations reduces relative fetal size in late gestation, with some changes in immune populations in fetal thymus suggestive of increased activation. Maternal allergic asthma in mice also predisposes progeny to allergy development. In conclusion, these findings in experimental models provide direct evidence that a perturbed environment before birth alters immune system development and postnatal function, and provide opportunities to investigate underlying mechanisms and develop and evaluate interventions.

Placental restriction in multi-fetal pregnancies and between-twin differences in size at birth alter neonatal feeding behaviour in the sheep.

Most individuals whose growth was restricted before birth undergo accelerated or catch-up neonatal growth. This is an independent risk factor for later metabolic disease, but the underlying mechanisms are poorly understood. This study aimed to test the hypothesis that natural and experimentally induced in utero growth restriction increase neonatal appetite and milk intake. Control (CON) and placentally restricted (PR) ewes carrying multiple fetuses delivered naturally at term. Outcomes were compared between CON (n=14) and PR (n=12) progeny and within twin lamb pairs. Lamb milk intake and feeding behaviour and ewe milk composition were determined using a modified weigh-suckle-weigh procedure on days 15 and 23. PR lambs tended to have lower birth weights than CON (-15%, P=0.052). Neonatal growth rates were similar in CON and PR, whilst heavier twins grew faster in absolute but not fractional terms than their co-twins. At day 23, milk protein content was higher in PR than CON ewes (P=0.038). At day 15, PR lambs had fewer suckling bouts than CON lambs and in females light twins had more suckling attempts than their heavier co-twins. Birth weight differences between twins positively predicted differences in milk intakes. Lactational constraint and natural prenatal growth restriction in twins may explain the similar milk intakes in CON and PR. Within twin comparisons support the hypothesis that prenatal constraint increases lamb appetite, although this did not increase milk intake. We suggest that future mechanistic studies of catch-up growth be performed in singletons and be powered to assess effects in each sex.

A review of fundamental principles for animal models of DOHaD research: an Australian perspective.

Epidemiology formed the basis of 'the Barker hypothesis', the concept of 'developmental programming' and today's discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals. As knowledge in this discipline has accumulated, from studies of humans and other animals, the complexity of interactions between genome, environment and epigenetics, has been revealed. The vast nature of programming stimuli and breadth of effects is becoming known. As a result of our accumulating knowledge we now appreciate the impact of many variables that contribute to programmed outcomes. To guide further animal research in this field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in Melbourne, Australia in April 2015. This review summarizes the contributions of animal research to the understanding of DOHaD, and makes recommendations for the design and conduct of animal experiments to maximize relevance, reproducibility and translation of knowledge into improving health and well-being.

Placental restriction in multi-fetal pregnancies increases spontaneous ambulatory activity during daylight hours in young adult female sheep.

Intrauterine growth restriction (IUGR) has adverse effects on metabolic health and early life, whereas physical activity is protective against later development of metabolic disease. Relationships between birth weight and physical activity in humans, and effects of IUGR on voluntary activity in rodents, are mixed and few studies have measured physical activity in a free-ranging environment. We hypothesized that induced restriction of placental growth and function (PR) in sheep would decrease spontaneous ambulatory activity (SAA) in free-ranging adolescent and young adult progeny from multi-fetal pregnancies. To test this hypothesis, we used Global Positioning System watches to continuously record SAA between 1800 and 1200 h the following day, twice during a 16-day recording period, in progeny of control (CON, n=5 males, 9 females) and PR pregnancies (n=9 males, 10 females) as adolescents (30 weeks) and as young adults (43 weeks). PR reduced size at birth overall, but not in survivors included in SAA studies. In adolescents, SAA did not differ between treatments and females were more active than males overall and during the day (each P<0.001). In adults, daytime SAA was greater in PR than CON females (P=0.020), with a similar trend in males (P=0.053) and was greater in females than males (P=0.016). Adult SAA was negatively correlated with birth weight in females only. Contrary to our hypothesis, restricted placental function and small size at birth did not reduce progeny SAA. The mechanisms for increased daytime SAA in adult female PR and low birth weight sheep require further investigation.

Effect of Age, Season, Body Condition, and Endocrine Status on Serum Free Cortisol Fraction and Insulin Concentration in Horses.

BACKGROUND: Increased free cortisol fraction is associated with insulin dysregulation (ID) in people with Metabolic Syndrome and Cushing's Disease. Free cortisol has not been investigated in equine endocrine disorders. HYPOTHESES: (1) In healthy horses, sex, age, body condition score (BCS), and season impact free cortisol; (2) free cortisol is increased in horses with Pituitary Pars Intermedia Dysfunction (PPID) or Equine Metabolic Syndrome (EMS). ANIMALS: Fifty-seven healthy horses; 40 horses and ponies with PPID (n = 20) or EMS (n = 20). METHODS: Prospective study. Serum collected seasonally from healthy animals and archived serum from PPID and EMS animals was analyzed for insulin, total and free cortisol concentrations, and free cortisol fraction (FCF). Linear mixed models were used to determine effects of age, sex, season, and BCS on hormones in controls. Hormone measurements were compared between disease groups and age- and season-matched controls with t-tests. EMS and hyperinsulinemic PPID animals were combined in an ID (hyperinsulinemia) group. RESULTS: Free cortisol concentrations were increased in overweight/obese controls (0.3 ± 0.1 µg/dL) compared to lean controls (0.2 ± 0.1 µg/dL; P = .017). Mean FCF was significantly higher in animals with PPID (8.8 ± 5.8 µg/dL, P = .005) or ID (8.8 ± 10.2 µg/dL, P = .039) than controls (5.0 ± 0.9 µg/dL), but total cortisol concentrations were similar (P ≥ .350) (PPID: 4.2 ± 4.3 µg/dL; ID: 5.0 ± 4.5 µg/dL; controls: 4.6 ± 1.7 and 5.1 ± 2.1 µg/dL). CONCLUSIONS AND CLINICAL IMPORTANCE: Increased FCF is associated with obesity in healthy horses and with ID (hyperinsulinemia) in horses and ponies with endocrine disease. Decreased plasma cortisol-binding capacity could be a component of these endocrine disorders in horses.

Experimental transmission of Corynebacterium pseudotuberculosis biovar equi in horses by house flies.

BACKGROUND: The route of Corynebacterium pseudotuberculosis infection in horses remains undetermined, but transmission by insects is suspected. OBJECTIVES: To investigate house flies (Musca domestica L.) as vectors of C. pseudotuberculosis transmission in horses. ANIMALS: Eight healthy, adult ponies. METHODS: Randomized, controlled, blinded prospective study. Ten wounds were created in the pectoral region where cages for flies were attached. Three ponies were directly inoculated with C. pseudotuberculosis. Four ponies were exposed for 24 hours to 20 hours C. pseudotuberculosis-inoculated flies. One negative control pony was exposed to noninoculated flies. Ponies were examined daily for swelling, heat, pain, and drainage at the inoculation site. Blood was collected weekly for CBC and biochemical analysis, and twice weekly for synergistic hemolysis inhibition titers. RESULTS: Clinical signs of local infection and positive cultures were observed in 7/7 exposed ponies and were absent in the negative control. In exposed ponies, peak serologic titers (1:512 to 1:2,048) were obtained between days 17 and 21. Seroconversion was not observed in the negative control. Neutrophil counts were higher in the positive and fly-exposed groups than in the negative control (P = .002 and P = .005) on day 3 postinoculation. Serum amyloid A concentrations were higher in the positive control than in the negative control and fly-exposed ponies on days 3 (P < .0001) and 7 (P = .0004 and P = .0001). No differences were detected for other biochemical variables. CONCLUSIONS AND CLINICAL IMPORTANCE: House flies can serve as mechanical vectors of C. pseudotuberculosis and can transmit the bacterium to ponies.

Effects of intravenous and subcutaneous heartworm homogenate from doxycycline-treated and untreated donor dogs on bronchial reactivity and lung in cats.

A controlled, blind research study was conducted to define the innate response of lungs in specific pathogen free (SPF) cats to intravenous (n=10) or subcutaneous (n=4) administration of homogenate of adult Dirofilaria immitis from donor dogs compared with lung response in control cats (n=6). There was no difference in cats that received heartworm homogenate IV for 18 days from donor dogs treated with doxycycline for 1 month compared with cats given heartworm homogenate from untreated donor dogs. Cats did not develop clinical signs, and no radiographic changes were noted. Cats given SC heartworm homogenate at lower concentration than IV groups did not develop histologic changes. Cats that received IV heartworm homogenate for 18 days developed mild interstitial and peribronchial myofibrocyte proliferation and smooth muscle proliferation of the pulmonary arteries. Bronchial ring contractility in vitro was blunted in the IV homogenate cats to the agonists acetylcholine and 5-hydroxytryptamine. Cats in the SC group had increased sensitivity to histamine at high concentrations but normal contractility and relaxation responses to other agonists. No increase in mast cells was noted in lung tissues of cats given homogenate. In the absence of bronchial wall remodeling, cats given IV homogenate had blunted responses to bronchial constriction, but normal relaxation to nitroprusside and substance P and increased sensitivity to histamine. In the absence adult heartworms, the homogenate of adult heartworms in the circulation of SPF cats induced a direct effect on lung parenchyma and altered bronchial ring reactivity.

Effect of pre-cardiac and adult stages of Dirofilaria immitis in pulmonary disease of cats: CBC, bronchial lavage cytology, serology, radiographs, CT images, bronchial reactivity, and histopathology.

A controlled, blind study was conducted to define the initial inflammatory response and lung damage associated with the death of precardiac stages of Dirofilaria immitis in cats as compared to adult heartworm infections and normal cats. Three groups of six cats each were used: UU: uninfected untreated controls; PreS I: infected with 100 D. immitis L3 by subcutaneous injection and treated topically with selamectin 32 and 2 days pre-infection and once monthly for 8 months); IU: infected with 100 D. immitis L3 and left untreated. Peripheral blood, serum, bronchial lavage, and thoracic radiographic images were collected from all cats on Days 0, 70, 110, 168, and 240. CT images were acquired on Days 0, 110, and 240. Cats were euthanized, and necropsies were conducted on Day 240 to determine the presence of heartworms. Bronchial rings were collected for in vitro reactivity. Lung, heart, brain, kidney, and liver tissues were collected for histopathology. Results were compared for changes within each group. Pearson and Spearman correlations were performed for association between histologic, radiographic, serologic, hematologic and bronchoalveolar lavage (BAL) results. Infected cats treated with selamectin did not develop radiographically evident changes throughout the study, were heartworm antibody negative, and were free of adult heartworms and worm fragments at necropsy. Histologic lung scores and CT analysis were not significantly different between PreS I cats and UU controls. Subtle alveolar myofibrosis was noted in isolated areas of several PreS I cats and an eosinophilic BAL cytology was noted on Days 75 and 120. Bronchial ring reactivity was blunted in IU cats but was normal in PreS I and UU cats. The IU cats became antibody positive, and five cats developed adult heartworms. All cats with heartworms were antigen positive at one time point; but one cat was antibody positive, antigen negative, with viable adult females at necropsy. The CT revealed early involvement of all pulmonary arteries and a random pattern of parenchymal disease with severe lesions immediately adjacent to normal areas. Analysis of CT 3D reconstruction and Hounsfield units demonstrated lung disease consistent with restrictive pulmonary fibrosis with an interstitial infiltrate, absence of air trapping, and decrease in total lung volume in Group IU as compared to Groups UU and PreS I. The clinical implications of this study are that cats pretreated with selamectin 1 month before D. immitis L3 infection did not become serologically positive and did not develop pulmonary arterial hypertrophy and myofibrosis.

Vasorelaxation responses to insulin in laminar vessel rings from healthy, lean horses.

Hyperinsulinemia causes laminitis experimentally and is a risk factor for naturally occurring laminitis. The aim of this study was to investigate the effects of insulin on laminar vascular relaxation and to induce insulin-associated vascular dysfunction in vitro. Relaxation responses of isolated laminar arterial and venous rings to acetylcholine and insulin were evaluated. To alter vascular function in response to insulin, all vessel rings were incubated with insulin or vehicle, submaximally contracted, administered insulin again and relaxation responses recorded. Laminar arteries were also incubated with the mitogen-activated protein kinase (MAPK) inhibitor, PD-98059. Relaxation in response to acetylcholine was not different between arteries and veins, but veins relaxed less in response to insulin than arteries. In arteries incubated with insulin, the subsequent relaxation response to insulin was blunted. Veins had minimal relaxation to insulin regardless of incubation. Arteries incubated with PD-98059 relaxed more in response to insulin than arteries not exposed to PD-98059, indicating that MAPK plays a role in maintenance of basal tone in laminar arteries. A differing response of laminar veins and arteries to insulin-induced relaxation may be important in understanding the link between hyperinsulinemia and laminitis. In vitro induction of vascular dysfunction in response to insulin in laminar arteries may be useful for testing therapeutic interventions and for understanding the pathophysiology of laminitis.

Lung histopathology, radiography, high-resolution computed tomography, and bronchio-alveolar lavage cytology are altered by Toxocara cati infection in cats and is independent of development of adult intestinal parasites.

This study presents clinical findings after oral ingestion of Toxocara cati eggs which resulted in rapid pulmonary lung migration and parenchymal disease, noted on clinically relevant diagnostic methods. Further, the study investigated the efficacy of pre-infection applications of preventative medication on larval migration through the lungs. A third aim of the study was to determine if adult cats infected with T. cati developed lung disease. Cats in infected groups were administered five oral doses of L3 T. cati larvae. Four-month-old specific pathogen free (SPF) kittens were divided into three groups (six per group): an infected untreated group, an uninfected untreated control group, and an infected treated group (topical moxidectin and imidacloprid, Advantage Multi for Cats, Bayer Healthcare LLC). Six 2- to 3-year-old adult multiparous female SPF cats were an infected untreated adult group. The cats were evaluated by serial CBCs, bronchial-alveolar lavage (BAL), fecal examinations, thoracic radiographs, and thoracic computed tomography (CT) scans and were euthanized 65 days after the initial infection. Adult T. cati were recovered in infected untreated kittens (5/6) and infected untreated adults (5/6) in numbers consistent with natural infections. Eggs were identified in the feces of most but not all cats with adult worm infections. No adult worms were identified in the uninfected controls or the infected treated group. All cats in the infected groups, including treated cats and untreated cats without adult worms, had lung pathology based on evaluation of radiography, CT scans, and histopathology. The infected cats demonstrated a transient peripheral eosinophilia and marked eosinophilic BAL cytology, but normal bronchial reactivity based on in vivo CT and in vitro ring studies. Lung lesions initially identified by CT on day 11 were progressive. Thoracic radiographs in infected cats had a diffuse bronchial-interstitial pattern and enlarged pulmonary arteries. Pulmonary arterial, bronchial, and interstitial disease were prominent histological findings. Infected treated cats had a subtle attenuation but not prevention of lung disease compared to infected cats. Significant lung disease in kittens and adult cats is associated with the early arrival of T. cati larvae in the lungs and is independent of the development of adult worms in the intestine. These data suggest that while the medical prevention of the development of adult parasites after oral exposure to T. cati is obviously beneficial, this practice even with good client compliance will not prevent the development of lung disease which can alter clinical diagnostic methods.

Seasonal changes in the combined glucose-insulin tolerance test in normal aged horses.

BACKGROUND: Equine metabolic syndrome (EMS) is an increasingly recognized problem in adult horses. Affected horses are often obese and predisposed to the development of laminitis, especially in the spring and summer months. In addition, in the summer and fall months, increases in endogenous insulin concentrations, a marker of EMS, have been reported. HYPOTHESIS/OBJECTIVES: The purpose of this study was to evaluate seasonal changes in results of the combined glucose-insulin tolerance test (CGIT), a diagnostic test for EMS. ANIMALS: Nine healthy, aged horses with no history of laminitis and no clinical signs of EMS. METHODS: Horses were given dextrose (150 mg/kg) and insulin (0.1 U/kg) IV. Plasma glucose concentrations were measured at 0, 1, 5, 15, 30, 45, 60, 75, 90, and 150 minutes and serum insulin concentrations at 0, 5, and 75 minutes. Testing was performed in February, May, June, August, September, and November. Mean glucose concentrations, characteristics of the curve, and insulin concentrations during the CGIT were compared across months using repeated measures ANOVA (P < .05). RESULTS: No CGIT parameters indicated insulin resistance, but mean area under the curve for glucose concentrations was significantly lower in August and November compared to February and in November compared to June, indicating increased insulin-mediated glucose clearance. Glucose nadir was significantly lower in November compared to that in February. CONCLUSIONS AND CLINICAL IMPORTANCE: No clinically relevant differences were seen in the results of the CGIT, suggesting that season minimally affects results of this test in normal aged horses in the southeastern United States.

Seasonal changes in plasma adrenocorticotropic hormone and α-melanocyte-stimulating hormone in response to thyrotropin-releasing hormone in normal, aged horses.

BACKGROUND: Results of diagnostic tests for equine pituitary pars intermedia dysfunction (PPID), including endogenous ACTH concentration and the overnight dexamethasone suppression test (DST), are affected by season. New and potentially more sensitive diagnostic tests for equine PPID, such as thyrotropin-releasing hormone (TRH)-stimulated ACTH response, have been developed, but have had limited evaluation of seasonality. OBJECTIVE: Our purpose was to evaluate seasonal changes in plasma ACTH and alpha-melanocyte-stimulating hormone (α-MSH) responses to TRH administration. ANIMALS: Nine, healthy, aged horses with normal DST results. METHODS: Synthetic TRH (1 mg) was administered IV. Plasma ACTH and α-MSH concentrations were measured at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 180 minutes. Testing was performed in February, July, August, September, October, and November. Mean TRH-stimulated ACTH and α-MSH concentrations were compared across months and time by repeated measures analysis of variance. Significance was set at the P < .05 level. RESULTS: Concentrations of ACTH and α-MSH significantly increased after TRH administration. Endogenous and TRH-stimulated ACTH and α-MSH concentrations were significantly different across months with higher concentrations in the summer and fall compared with February. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma ACTH and α-MSH responses to TRH administration experience seasonal variation, with TRH-stimulated ACTH and α-MSH concentrations increasing from summer through fall. These results support previous evidence of a seasonal influence on the equine pituitary-adrenal axis. More research is warranted with a larger number of horses to determine if seasonal reference ranges for TRH stimulation testing need to be defined.

Gynecomastia and mammary gland adenocarcinoma in a Nubian buck.

A 6-year-old Nubian buck was presented for bilateral mammary gland enlargement. Gynecomastia and mastitis were diagnosed, and bilateral mastectomy was performed. Histological examination showed mammary adenocarcinoma, active lactation, hyperplasia, and abscessation. Karyotyping showed a normal male. Clinical, therapeutic, etiologic, and epidemiologic aspects of gynecomastia and mammary gland adenocarcinoma are discussed.

Chronic renal failure associated with nephrolithiasis, ureterolithiasis, and renal dysplasia in a 2-year-old quarter horse gelding.

A 2-year-old quarter horse gelding presented for evaluation of polyuria and polydipsia. Azotemia was detected on serum chemistry profile. Small, misshapen, hyperechoic kidneys with decreased corticomedullary demarcation, hydronephrosis, and a right nephrolith were noted ultrasonographically. The diagnosis of end-stage kidney disease and dysplasia was made histopathologically using ultrasound-guided biopsy. Two ureteroliths were found in the right ureter via cystoscopy, and a nephrolith was seen in the right kidney at necropsy. Clinical, ultrasonographic, and pathologic features of equine urolithiasis and renal dysplasia are discussed.

Neuromuscular effects of doxacurium chloride in isoflurane-anesthetized dogs.

OBJECTIVE: To determine the neuromuscular effects of doxacurium chloride and to construct a dose-response curve for the drug in isoflurane-anesthetized dogs. DESIGN: Randomized, controlled trial. ANIMALS: Six healthy, adult, mixed-breed dogs (five female, one male) weighing 24.8 +/- 2.8 kg. METHODS: Anesthesia was induced with isoflurane in oxygen and maintained with 1.9% to 2.3% end-tidal isoflurane concentration. PaCO2 was maintained between 35 and 45 mm Hg with mechanical ventilation. Mechanomyography was used to quantitate the evoked twitch response of the paw after supramaximal train-of-four stimulation of the superficial peroneal nerve. After baseline values were recorded, the dogs received one of three doses of doxacurium (2.0, 3.5, 4.5 microg/kg of body weight) or a saline placebo intravenously in random order. All dogs received all treatments with at least 7 days between studies. After drug administration, the degree of maximal first twitch depression compared with baseline (T1%) was recorded. Dose-response relations of doxacurium were plotted in log dose-probit format and analyzed by linear regression to determine effective dose (ED50 and ED90) values for doxacurium. RESULTS: The median log dose-probit response curve showed good data correlation (r = .999) with estimates of the ED50 (2.1 microg/kg) and ED90 (3.5 microg/kg) for doxacurium in isoflurane-anesthetized dogs. Mean +/- SD values for T1% (first twitch tension compared with baseline) at maximal depression after drug administration, onset (time from drug administration to maximal depression of T1%), duration (time from maximal depression of T1% to 25% recovery of T1%), and recovery (time from 25% to 75% recovery of T1%) times were 92% +/- 4%, 40 +/- 5 minutes, 108 +/- 31 minutes, and 42 +/- 11 minutes for dogs treated with 3.5 microg/kg of doxacurium and 94% +/- 7%, 41 +/- 8 minutes, 111 +/- 33 minutes, and 37 +/- 10 minutes for dogs treated with 4.5 microg/kg of doxacurium. CONCLUSION AND CLINICAL RELEVANCE: We conclude that doxacurium is a long-acting neuromuscular blocking agent with a slow onset of action. Doxacurium can be used to provide muscle relaxation for long surgical procedures in isoflurane-anesthetized dogs. Interpatient variability, particularly of duration of drug action, may exist in the neuromuscular response to the administration of doxacurium in dogs.

Effect of ketorolac tromethamine on atracurium-induced neuromuscular blockade in anesthetized dogs.

OBJECTIVE: The purpose of this study was to determine the effect of ketorolac tromethamine or placebo on the neuromuscular blockade induced by an infusion of atracurium in isoflurane-anesthetized dogs. DESIGN: Randomized, controlled trial. ANIMALS: Six healthy, adult mixed-breed dogs (five female, one male) weighing 24.8 +/- 2.8 kg. METHODS: Dogs were studied on two occasions with a minimum of 7 days between studies. Dogs were induced with 5% isoflurane in oxygen and maintained with 1.6 x minimum alveolar concentration (MAC) end-tidal isoflurane. Neuromuscular blockade was assessed using the train-of-four response. Once 50% depression of the first twitch (T1) was achieved, the atracurium infusion rate was held constant for 30 minutes. Then ketorolac, 0.5 mg/kg, or the same volume of placebo (0.9% sodium chloride solution) was administered intravenously and the atracurium infusion maintained for an additional 60 minutes. Before and at 2, 5, 10, 15, 30, and 60 minutes after ketorolac or placebo, the percent depression of T1 and the fourth twitch to the first twitch (T4/T1) ratio were recorded. The atracurium infusion was discontinued and the time for T1 to recover from 50% to 75% of its original value was recorded. At 75% T1, edrophonium, 0.5 mg/kg intravenously, was administered to antagonize the residual blockade. RESULTS: There was no significant difference in T1%, T4/T1 ratio, or recovery time after ketorolac administration compared with placebo. CONCLUSIONS: Ketorolac, 0.5 mg/kg intravenously, has no significant effect on either atracurium-induced neuromuscular blockade or recovery time for T1 in isoflurane-anesthetized dogs. CLINICAL RELEVANCE: The concurrent use of atracurium should not be a contraindication for the administration of ketorolac for intraoperative or postoperative analgesia.

Pharmacokinetics, effects on renal function, and potentiation of atracurium-induced neuromuscular blockade after administration of a high dose of gentamicin in isoflurane-anesthetized dogs.

OBJECTIVE: To determine pharmacokinetics, renal effects, and effect on atracurium-induced neuromuscular blockade of a high dose of gentamicin in isoflurane-anesthetized dogs. ANIMALS: 6 healthy, adult, mixed-breed dogs, anesthetized twice and receiving gentamicin (6 mg/kg of body weight, i.v.) or saline solution. PROCEDURE: Blood samples were collected before and at intervals after gentamicin administration. Pharmacokinetic values were evaluated by use of multivariant stepwise linear regression analysis. Gentamicin-induced renal changes were assessed by comparing pretreatment and 12- to 24-hour posttreatment values for serum urea nitrogen, serum creatinine, urine creatinine-to-gamma-glutamyl-transferase ratio, and urinalysis. Neuromuscular blockade, maintained by atracurium infusion, was assessed, using the train-of-four response. At stable 50% depression of first twitch (T1), gentamicin or saline solution was given. Before and at posttreatment intervals for 60 minutes, T1% and fourth twitch-to-T1 ratio were recorded. The infusion was discontinued and 50 to 75% T1 recovery time was recorded. At 75% T1, edrophonium (0.5 mg/kg) was administered i.v.. RESULTS: Mean values for volume of distribution and clearance were 0.263 L/kg and 2.0 ml/min/kg, respectively. Mean maximal serum concentration of gentamicin was 46.4 micrograms/ml. Pre and posttreatment values for serum urea nitrogen, serum creatinine, urine creatinine-to-gamma-glutamyltransferase ratio, and other urine analytes were not significantly different. Mean (+/- SD) values for T1% and fourth twitch-to-T1 ratio decreased significantly after gentamicin (depression was maximal at 5 minutes). Recovery time (50 to 75% T1) was not different between groups. Edrophonium restored twitch to baseline. CONCLUSIONS: Mean values for apparent volume of distribution and total body clearance of gentamicin were similar to values in unanesthetized dogs. Mean maximal serum concentration of gentamicin was greater than that in unanesthetized dogs. Renal function was unaffected. Gentamicin potentiated atracurium-induced neuromuscular blockade, but did not affect recovery time.