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Pericardiectomy in dogs: 22 cases (1978-1994).

OBJECTIVE: To determine long-term outcome of dogs with neoplastic and nonneoplastic pericardial disease that undergo pericardiectomy. DESIGN: Retrospective study. ANIMALS: 22 dogs. PROCEDURE: Dogs that underwent pericardiectomy and in which the diagnosis had been confirmed histologically were included. Data collected from each record included signalment, history, clinical signs, results of diagnostic evaluations, operative management, postoperative complications, histologic diagnosis, and outcome. Dogs were grouped on the basis of underlying cause of pericardial disease (neoplastic vs nonneoplastic), and survival times were determined by means of Kaplan-Meier analyses. RESULTS: 9 dogs had neoplastic pericardial disease (chemodectoma, 4; hemangiosarcoma, 2; malignant mesothelioma, 2; lymphoblastic lymphoma, 1). Thirteen dogs had nonneoplastic pericardial disease (benign idiopathic pericarditis, 10; lymphocytic plasmacytic pericarditis, 2; osseous metaplasia of unknown cause, 1). Thoracic radiography and echocardiography were the most specific methods for diagnosis of pericardial effusion. Pleural effusion was the most common postoperative complication (8/22 dogs). Prevalence of postoperative complications was not associated with underlying cause of pericardial disease, surgical approach, or surgical procedure (subtotal vs total pericardiectomy). Median survival time of dogs with neoplastic disease (52 days) was significantly shorter than median survival time of dogs with nonneoplastic disease (792 days). Dogs that developed pleural effusion > 30 days after pericardiectomy had a poor prognosis for survival. CLINICAL IMPLICATIONS: Radiography and echocardiography are useful for diagnosis of pericardial effusion in dogs. Dogs with neoplastic pericardial disease have a significantly shorter survival time than do dogs with nonneoplastic pericardial disease.

Animals↗

Effect of staphylococcal alpha-toxin pancreatitis on glucose tolerance in the dog.

Acute pancreatitis was experimentally produced in dogs to study the effect of the disease on glucose tolerance. The k value (glucose disappearance coefficient measured in percentage decrease of glucose/min) calculated from the high-dose intravenous glucose-tolerance test was used to evaluate the glucose tolerance of each dog. Thirty dogs were allotted to 3 groups of 10 dogs each as follows: group I--nonsurgical control dogs; group II--surgical control dogs; and group III--pancreatitis-affected dogs. To increase their susceptibility to diabetes, 50% partial pancreatectomies and ductal catheterizations were performed on group II and III dogs. Saline solution was infused into the ductal systems of group II dogs, and staphylococcal alphatoxin was infused into the ductal systems of group III dogs to produce pancreatitis. The results indicated that (1) high-dose intravenous glucose-tolerance test was an effective tool for determining decreased glucose tolerance in dogs; (2) glucose tolerance of group III dogs was markedly decreased compared with that of group I and II dogs; (3) staphylococcal alpha-toxin produced signs of moderately severe pancreatitis; and (4) 50% partial pancreatectomy and saline solution infusion produced clinical and clinicopathologic signs of mild pancreatitis. To determine if a simplified k value (calculated using 2 or 3 blood samples) could closely approximate the standard k value (calculated using 6 blood samples), simplified k values were derived from the 5- and 60-minute blood sample values. These values closely approximated the standard k values, indicating the simplified value may be used in the clinical situation. The standard k value, however, is preferred for investigative work.

Animals↗

Systemic hypertension and proteinuria in dogs with diabetes mellitus.

OBJECTIVE: To determine prevalence and severity of systemic arterial hypertension and proteinuria in dogs with naturally developing diabetes mellitus (DM) and to determine whether these abnormalities were related to age, sex, duration of DM, or degree of control of glycemia. DESIGN: Case series and cohort study. ANIMALS: Fifty dogs with naturally developing DM. PROCEDURES: Blood pressure was measured in all 50 dogs. Thirty-eight dogs were evaluated once, and 12 were evaluated sequentially. Thirty-five were evaluated for proteinuria by determining protein-to-creatinine ratio in urine (n = 35) or by electrophoresis of urine (33). RESULTS: Hypertension was detected in 23 on the basis of a systolic pressure > 160 mm HG (12 dogs), a diastolic pressure > 100 mm HG (21), or a mean pressure > 120 mm HG (23). All dogs with systolic hypertension had concurrent diastolic and mean hypertension, and 19 of 21 dogs with diastolic hypertension had concurrent high mean pressure. Ten of 12 dogs reevaluated at subsequent visits had no change in blood pressure. Blood pressure remained consistent in 3 dogs tested at different times during the day on a single visit. Duration of DM and presence of proteinuria were significant predictors of hypertension. Seven of 35 (20%) dogs had an increased protein-to-creatinine ratio in their urine. Albumin concentration and albumin-to-creatinine ratio were significantly higher in urine from diabetic dogs, compared with healthy, nondiabetic dogs. Hypertension was associated with an increased albumin-to-creatinine ratio. CLINICAL IMPLICATIONS: Systemic hypertension and proteinuria may be common in diabetic dogs, but the clinical importance of these findings are, as yet, unknown.

Age Factors↗

Comparative pharmacokinetics of [14C]metosulam (N-[2,6-dichloro-3-methylphenyl]-5,7-dimethoxy-1,2,4- triazolo[1,5a]-pyrimidine-2-sulfonamide) in rats, mice and dogs.

This study was conducted to provide data on the pharmacokinetics of [14C]metosulam (N-[2,6-dichloro-3-methylphenyl]-5,7-dimethoxy-1,2,4-triazolo-[1,5a]- pyrimidine-2-sulfonamide). Groups of male Sprague-Dawley rats, CD-1 mice and Beagle dogs were given a single oral gavage dose of 100 mg [14C]metosulam kg-1 body weight and blood, urine, feces and selected tissue specimens were collected up to 168 h for rats and mice and 216 h post-dosing for dogs. Two of these dogs received a second oral dose of 100 mg kg-1 and were humanely euthanized at 12 h post-dosing and selected tissues were collected. The third dog was administered an intravenous dose of 1 mg kg-1 and plasma, urine and feces were collected for 72 h post-dosing. Specified tissue specimens were analyzed for 14C activity and selected tissues were evaluated for localization of 14C activity by histoautoradiography. Selected urine and plasma specimens were also profiled for metabolites by high-performance liquid chromatography. [14C]Metosulam was absorbed rapidly (t1/2 < 1 h) in all three species. Mice and dogs absorbed ca. 20% of the orally administered dose of [14C]metosulam, compared to > 70% absorption in the rat. Analysis of 14C activity and histoautoradiography of the dog eyes indicated that the retina, a target for toxicity in the dog, did exhibit affinity for the radiotracer. There was no evidence of 14C localization in the kidneys of dogs or in the eyes of rats. In rats and mice the 14C plasma time-course was fit to a two-compartment pharmacokinetic model, whereas the dog was fit to a one-compartment model. The half-lives for the rapid initial (alpha) and slower terminal phases (beta) were 9 h and 60 h for the rat and 20 h and 155 h for mice, respectively. The dog had an elimination t1/2 of 73 h. In all three species, [14C]metosulam and metabolites were excreted in the urine and quantitatively the relative amount of [14C]metosulam metabolism followed the pattern of mice > rats > dogs. These data suggest that the observed ocular lesion in dogs is due to metosulam and may in part be due to its selective affinity for the dog retina.

Administration, Oral↗

Maximum oxygen consumption and catecholamines in thyroidectomized dogs.

Comparisons have been made in 7 dogs between maximum oxygen consumption recorded before (N dogs) and after thyroidectomy (T dogs). The comparisons were performed under two conditions 1) during severe cold stress (CVo2 max), 2) during a short period of exhaustive work (Ex Vo2 max). Heart rate, plasma catecholamine and substrate concentrations (glucose, lactic acid, FFA) were measured under each condition. 1. Thyroidectomy induced a more substantial decrease in CVo2 max than in Ex Vo2 max. 2. At CVo2 max, average plasma epinephrine and norepinephrine concentrations rose to a higher level in T dogs than in N dogs. In T dogs, correlations were found between plasma epinephrine concentrations and CVo2 max values, and between plasma norepinephrine concentrations and CVo2 max values. At Ex Vo2 max, average plasma norepinephrine concentrations were similar in N dogs and in T dogs, and average plasma epinephrine concentrations were not significantly different from each other. 3. At Ex Vo2 max, average plasma concentrations of the various substrates were not significantly different in N dogs and T dogs. At CVo2 max, plasma FFA levels were higher in T dogs. It may be concluded that in dogs, thyroidectomy affects mechanisms which are more specifically involved in heat production than in muscular exercise. The increased catecholamine secretion in response to cold which occurred in T dogs appeared merely to limit the decrease in heat production. It seems possible that increased catecholamine secretion compensates for the decreased sensitivity of beta receptors to catecholamine but it cannot fully account for the effects of thyroidectomy.

Animals↗

Hypercholeresis with cholate infusion in dogs with pigment gallstones.

We previously reported that dogs with pigment gallstones infused with taurocholate produce higher bile flow than normal dogs due to an increase in bile-acid independent bile flow. Since dogs with pigment gallstones are taurine-depleted and secrete large amounts of unconjugated bile salt, we hypothesized that the observed increased bile flow is secondary to the presence of unconjugated bile salts in the biliary tract, and cholate infusion was compared in normal and pigment gallstone dogs. Cholate increased bile flow significantly (P < 0.05) from 5.2 and 8.2 to 31 and 57 microliter/kg/min in normal and pigment gallstones dogs, respectively. Plots of bile flow versus bile acid output yielded separate linear relationships with a higher slope in gallstone dogs, but mannitol clearance indicated that excess flow originated in the canaliculus. Extended cholate infusion (570 min) severely taurine depleted normal dogs and increased cholate secretion, but bile flow remained significantly lower (P < 0.05) in normal dogs than in gallstone dogs. Choleretic activity of cholate in normal dogs was similar to that of taurocholate, but was nearly twice that of taurocholate in gallstone dogs. Choleretic activity increased in both groups with extended cholate infusion, suggesting adaptive changes in a biliary system bathed with unconjugated bile salts. These results are important since the increased bile flow in dogs with pigment gallstones would increase delivery of all biliary components to the gallbladder contributing to the high concentrations of gallbladder bile calcium previously observed in these dogs. It also has important physiological implications concerning the formation of bile in the proximal biliary tree. The data are most consistent with either direct hepatocyte stimulation to secrete another anion or with cholate/anion exchange at the canalicular, rather than ductal, level.

Animals↗

Oral absorption of CGS-20625, an insoluble drug, in dogs and man.

Oral bioavailability of highly water-insoluble drugs is often quite limited and variable, requiring the development of improved formulations. Animal models are an essential aspect of the design and testing of such formulations designed to improve absorption in man. The present report compares the absorption of CGS-20625, an insoluble drug, in dog and man after oral administration of the drug as a powder, a solid dispersion capsule, and after gastric and duodenal administration in PEG 400 solution. CGS-20625 powder (20 mg) given orally exhibited slow, delayed absorption in both dog and man, with a Cmax of 0.26 +/- 0.07 microgram/ml at Tmax of 3 hr in dog, and 0.01 +/- 0.004 microgram/ml at 2 hr in man. Administration of CGS-20625 in PEG 400 solution improved absorption in dog and man, with a Cmax of 1.2 +/- 0.10 microgram/ml at Tmax of 0.25 hr in dog, and a Cmax of 0.10 +/- 0.04 microgram/ml at 0.5 hr in man. Tmax after administration of the hard gelatin capsule formulation was 0.9 and 1.0 hr in dog and man, with Cmax of 0.89 +/- 0.16 and 0.052 +/- 0.014 microgram/ml, respectively. Absolute bioavailability of CGS-20625 powder in the dog was 0.67 +/- 0.21, whereas the bioavailabilities of the powder and the capsule relative to the PEG 400 solution were 0.84 and 1.1, respectively, in dog, and 0.41 and 0.85 respectively, in man. No significant benefits of duodenal administration were observed. Plasma levels were approximately 10-fold greater and oral clearance was approximately 5-fold less in the dog than in man. Furthermore, pharmacokinetic data were less variable and relative bioavailability was greater in dogs than in humans. Physiological factors in the gastrointestinal tract or greater first-pass metabolism in man may account for these species differences. The relative rate and extent of CGS-20625 absorption were similar between dog and man, in the order of powder < capsule < PEG 400 solution. In addition, in vivo absorption rates in both species reflect in vitro dissolution differences between the powder and the capsule. These data strongly support the use of the dog as a model for developing improved formulations of CGS-20625. Further investigation of the dog as a model to evaluate insoluble drug absorption is warranted.

Absorption↗

Alpha-tocopherol concentrations of the nervous system and selected tissues of adult dogs fed three levels of vitamin E.

The effects of dietary vitamin E levels on tissue alpha-tocopherol (alpha-T) concentrations in different parts of the nervous system are largely unknown. Therefore, we measured the alpha-T contents of nervous and other tissues obtained from beagle dogs fed for two years a vitamin E-deficient diet (-E, 0.05 +/- 0.02 mg vitamin E/kg diet, n = 2), a vitamin E-supplemented diet (+E, 114 +/- 14 mg/kg, n = 2), or a standard chow diet (En, 74 +/- 6 mg/kg, n = 3). Brain regions and spinal cords of +E dogs contained about double the alpha-T concentrations of En dogs, and about 10-fold those of -E dogs. The various brain regions of -E dogs, compared with En dogs, retained 12-18% of the alpha-T concentrations, with the exception of the caudal colliculus, which retained 48%. Peripheral nerve alpha-T concentrations in +E dogs (67 ng/mg wet weight) were nearly 5-fold higher than in En dogs (13.4 +/- 5.9 ng/mg) and 80-fold higher than in -E dogs (0.8 ng/mg). Within each dietary group, the lowest alpha-T concentrations in the central nervous system (CNS) were in the spinal cord. Peripheral nerves were the most susceptible to vitamin E repletion or depletion: in +E dogs, nerves contained higher concentrations of alpha-T than most brain regions; in En dogs, they contained similar concentrations; but in -E dogs, they contained less alpha-T than most brain regions. Muscles and other tissues of -E dogs retained from 1 to 10% of En values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Preclinical toxicity of a geldanamycin analog, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), in rats and dogs: potential clinical relevance.

PURPOSE: 17-DMAG is a hydrophilic derivative of the molecular chaperone inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG; NSC-330507), which is currently being evaluated for the treatment of cancer in clinical trials. 17-DMAG offers a potential advantage over 17-AAG because its aqueous solubility eliminates the need for complicated formulations that are currently used for administration of 17-AAG. In addition, 17-DMAG undergoes only limited metabolism compared to 17-AAG. The present results are from preclinical toxicity studies evaluating 17-DMAG in rats and dogs. METHODS: Doses of 0, 2.4, 12 and 24 mg/m2 per day were administered to rats, while dogs received doses of 0, 8 or 16 mg/m2 per day. In both species, 17-DMAG was administered i.v. (slow bolus for rats; 1-h infusion for dogs) daily for 5 days. An additional cohort of dogs received 16 mg/m2 per day orally for 5 days. Clinical observations were noted, and standard hematology and clinical chemistry parameters were monitored. Selected tissues were evaluated microscopically for drug-related lesions. Tissue and plasma 17-DMAG concentrations were measured by HPLC/MS at selected time-points on days 1 and 5. RESULTS: Daily i.v. administration of 17-DMAG at doses of 24 mg/m2 per day in rats or 16 mg/m2 per day in dogs produced lethality on day 6, approximately 24 h following the last dose. Body weight loss was common in rats and dogs. Drug-related gastrointestinal, bone marrow and hepatic toxicities were also common in rats and dogs. Dogs also exhibited signs of renal and gallbladder toxicity. Plasma concentrations of 17-DMAG increased proportionately with dose in rats and disproportionately with dose in dogs. In rat tissues, however, only fourfold to sixfold increases in 17-DMAG concentrations were observed with a tenfold increase in dose. The highest concentrations of 17-DMAG were found in the liver of rats, with progressively lower concentrations in the spleen, lung, kidney and plasma. Regardless of the route of administration, higher drug concentrations were present in plasma (rat and dog) and tissue (rat) samples obtained on day 5 compared to those obtained on day 1. Although plasma concentrations decreased with time, 17-DMAG was still detected in dog plasma for at least 24 h after drug administration. CONCLUSIONS: With the recent approval of 17-DMAG for clinical use, the data generated from these preclinical studies will provide guidance to clinicians as they administer this drug to their patients. The MTD of 17-DMAG was 12 mg/m2 per day in rats and 8 mg/m2 per day in dogs; therefore, the recommended starting dose for phase I trial is 1.3 mg/m2 per day for 5 days. Gastrointestinal and bone marrow toxicity were dose-limiting in rats, and gastrointestinal, renal, gallbladder and bone marrow toxicity were dose-limiting in dogs. All adverse effects were fully reversible in surviving animals after treatment was complete.

Administration, Oral↗

Renal tubule reabsorption of amino acids after lysine loading of cystinuric dogs.

The renal reabsorption of cystine, lysine, arginine, and ornithine as well as other amino acids has been determined before and after lysine infusion in four normal and five cystinuric dogs. The large filtered load of lysine caused defective reabsorption of cystine in three of four normals and augmented the basal defect in all of the cystinuric dogs. Two of the cystinuric dogs responded with cystine clearances in excess of the glomerular filtration rate. The magnitude of increase of the reabsorptive defect for cystine observed after lysine infusion into the cystinuric dogs was unrelated to the extent of the basal defect. Two of the normal dogs and four of the five cystinuric dogs demonstrated defective arginine reabsorption after lysine loading, one of the cystinuric dogs having greater arginine excretion than the filtered load. Although normal dogs showed a moderate inability to reabsorb the large filtered load of lysine, three of the cystinuric dogs exhibited a -60 to -70% reabsorption, consistent with lysine secretion. Both normal and cystinuric dogs showed defective glycine absorption after lysine loading, but only cystinuric dogs showed variable defects in threonine, serine, histidine, methionine, and tyrosine when the basic amino acid was infused. Each cystinuric dog responded to lysine infusion in a different way, and the overall pattern of response differed from the normal, with evidence of induced secretion of cystine, lysine, and arginine in the affected dogs.

Absorption↗

Lectin histochemistry on the skin of hairless descendants of Mexican hairless dogs.

The skin of hairless descendants of Mexican hairless dogs was investigated lectin-histochemically. Haired dogs were also used for comparative study. In the epidermis of infant pups, lectin staining revealed marked differences between hairless and haired dogs. Griffonia simplicifolia-I (GS-I) bound moderately to the cytoplasm of the stratum basale of hairless dogs, while no binding to that of haired dogs was observed. Bauhinia purpurea (BPA) showed positive staining for the stratum spinosum and basale of hairless dogs, while it was negative or weakly positive for the cytoplasm of both epidermal layers of haired dogs. Maclura pomifera (MPA) showed moderate to intense staining for the intercellular area of the stratum basale of hairless dogs, while no or weak staining was detected in that of haired dogs. Urex europeus-I (UEA-I) bound weakly to moderately to the cytoplasm and the intercellular area of the stratum spinosum of hairless dogs, whereas no or very weak staining was observed in those of haired dogs. Most of the lectins exhibited significant alterations in the epidermal staining pattern between infants and adults. Significant differences were not observed in adult canine epidermis between hairless and haired dogs. In conclusion, lectin histochemistry in hairless dogs revealed that there were different development steps in the epidermal cells between infants and adults.

Animals↗

Prevalence of zoonotic agents in dogs visiting hospitalized people in Ontario: implications for infection control.

Visitation of hospitalized people by dogs is becoming commonplace, but little is known about the potential health risks of introducing dogs to healthcare settings. This cross-sectional study evaluated the prevalence of zoonotic agents in a group of 102 visitation dogs from a variety of sources across Ontario. Between May and July 2004, owners were interviewed by a standardized questionnaire while dogs underwent a standardized physical examination. One specimen of faeces, hair-coat brushings and one rectal, aural, nasal, oral and pharyngeal swab were collected from each dog and tested for 18 specific pathogens. All dogs were judged to be in good health. Zoonotic agents were isolated from 80 out of 102 (80%) dogs. The primary pathogen was Clostridium difficile, which was isolated from 58 (58%) faecal specimens. Seventy-one percent (41/58) of these isolates were toxigenic. Extended-spectrum beta-lactamase Escherichia coli was isolated from one (1%) dog, extended-spectrum cephalosporinase E. coli was isolated from three (3%) dogs, and organisms of the genus Salmonella were isolated from three (3%) dogs. Pasteurella multocida or Pasteurella canis was isolated from 29 (29%) oral swabs, and Malassezia pachydermatis was isolated from eight (8%) aural swabs. Giardia antigen was present in the faeces of seven (7%) dogs, while Toxocara canis and Ancylostoma caninum were detected in two (2%) dogs and one (1%) dog, respectively. Methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Campylobacter spp., Microsporum canis, group A streptococci, Pseudomonas aeruginosa and Cryptosporidium spp. were not detected. Further information is needed before the full implications of these findings for infection control can be assessed properly.

Animals↗

Molecular characterization of dog albumin as a cross-reactive allergen.

Indoor allergens comprise a group of allergenic proteins that are commonly derived from house dust mite and cat and dog dander. In addition to the two major dog allergens (molecular weights: 19 and 23 kd), dog albumin represents an important allergen for up to 35% of patients who are allergic to dogs. In IgE immunoblot inhibition studies and histamine release tests it has been demonstrated that patients who react to dog albumin exhibit IgE reactivity with purified albumins from cat, mouse, chicken, and rat. The proportion of dog-specific IgE directed against dog albumin was determined for patients allergic to dog albumin, and it ranges from 70% to 90%. By IgE immunoscreening of a lambda gt11 expression library from a dog salivary gland, we identified a number of reactive complementary DNA clones. All patients with IgE reactivity against natural dog albumin displayed IgE reactivity to the beta-galactosidase fusion protein encoded by clone 54c, which was therefore assumed to contain major IgE epitopes of dog albumin. The deduced amino acid sequence of clone 54c was compared with the Swiss-Prot library, and significant sequence homologies were found with albumins from different species (human: 82.6%, pig: 81.8%, cattle: 77.3%, sheep: 78.8%, mouse: 75.8%, and rat: 76.2%). Several other IgE-positive clones hybridized with oligonucleotides that were prepared according to this sequence. Partial complementary DNA coding for dog albumin fragments may be considered a useful tool for further characterization of major IgE epitopes of dog albumin.

Allergens↗

Castration, other management practices and socio-economic implications for dog keepers in Nsukka area, Enugu state, Nigeria.

Structured interviews were used to obtain information from 258 respondents from among 625 people who were selected by stratified random sampling from villages in five of seven local government areas of Nsukka area. Information included gender and literacy status of the respondents, whether the respondents had (between 1990 and 1995) presented any of their dogs for castration, the comparative market value of the dogs, and dog use and owner preference for castrates in performance of such duties. Information on bathing, vaccinations, confinements, use of veterinarians and cultural and religious uses of dogs also were sought. Also, 208 (80%) of the respondents had their dogs castrated. Of the respondents, 23% were literate, 37% semiliterate and 40% illiterate. Of the 367 non-respondents, 63% were not available during the time of contact and 37% resented dog keeping and therefore refused to talk. About 958 dogs were owned by respondents, of these dogs, 56%, 27% and 17% were females, intact males and castrates, respectively. There was no association between the respondent's literacy status and dog-sex preference in performance of such uses as security, hunting, and "economic reasons". The three most-important reasons for dog keeping were security, pet and hunting. However, the use of castrates for security was favoured by most keepers irrespective of literacy status. Most of the respondents agreed that dogs are used as gifts and 72% of the respondents agree that dog meat is a protein source. Castration should be encouraged because of its market value. Usage was low of veterinary services, confinement, and bathing of dogs.

Animal Husbandry↗

Vitamin D3 metabolism in dogs.

Plasma concentrations of the main vitamin D(3) metabolites (i.e., 25(OH)D(3), 1,25(OH)(2)D(3), and 24,25(OH)(2)D(3)) were measured in 14 weeks old large- and small-breed dogs (adult body weight 60 kg vs. 6 kg), raised under the same conditions. Levels of 25(OH)D(3) (approx. 22 microg/l) and 1,25(OH)(2)D(3) (approx. 40 ng/l) were similar in both groups, whereas plasma 24,25(OH)(2)D(3) concentrations were lower in large-breed dogs (7 microg/l vs. 70 microg/l, large- vs. small-breed dogs, respectively). The lower plasma 24,25(OH)(2)D(3) concentrations could be explained by the higher plasma GH and IGF-I concentrations in the large- vs. small-breed dogs, and these hormones are known to suppress 24-hydroxylation. Plasma 24,25(OH)(2)D(3) concentrations increased during Ca supplementation in small-breed but not in large-breed dogs (100 microg/l vs. 7 microg/l, respectively). Hypophosphatemia induced by a high dietary Ca content was only seen together with increased plasma 1,25(OH)(2)D(3) concentrations in euparathyroid dogs and not in hypoparathyroid dogs. Hyperparathyroidism due to Ca deficiency was accompanied by increased plasma 1,25(OH)(2)D(3) concentrations and decreased plasma 24,25(OH)(2)D(3) concentrations in both large- and small-breed dogs, together with generalized osteoporosis. Large-breed pups fed on a standard diet supplemented with Ca and P had decreased plasma concentrations of both 25(OH)D(3) and 1,25(OH)(2)D(3), which may indicate an increased clearance of these metabolites; the low plasma concentrations of the di-hydroxylated vitamin D metabolites were considered responsible for the disturbance in cartilage maturation (i.e., osteochondrosis) in these dogs. Even lower concentrations of all vitamin D(3) metabolites were seen in young dogs raised on a vitamin D(3)-deficient diet, and led to disturbed osteoid and cartilage mineralization (i.e., rickets). These studies indicate that there is a hierarchy of factors regulating vitamin D(3) metabolism in dogs, i.e., GH and IGF-I suppress 24-hydroxylase more than hypercalcemia or hypophosphatemia does; 1,25(OH)(2)D(3) and 24,25(OH)(2)D(3) are only reciprocally related in hyperparathyroidism; excessive Ca and P intake increases the turnover of vitamin D(3) metabolites; and the synergism between parathyroid hormone and 1,25(OH)D(3) seems to play a role in skeletal mineralization. The low plasma 24,25(OH)(2)D(3) concentrations in large-breed dogs raised on standard dog food may play a role in the etiology of disturbances in endochondral ossification during the rapid growth phase.

Animals↗

Proarrhythmic effects of ventricular electrical catheter ablation in dogs.

Electrical catheter ablation of arrhythmogenic sites is a new therapy for ventricular tachycardia that is still being investigated. Recent studies have shown, however, that the procedure itself can provoke serious ventricular arrhythmias. The incidence, course and mechanism of these arrhythmias were studied in 10 beagles treated with a single R wave-synchronized cathodal shock delivered to the endocardial ventricular wall (5 dogs left ventricular, 5 dogs right ventricular). Shocks were delivered at 30 (four dogs), 80 (two dogs) or 250 J (four dogs). Each dog underwent programmed electrical stimulation at or near the ablation site before, within 1 hour after and 1 week after the shock. Holter electrocardiographic monitoring (24 hours) was performed during day 1 and 7 after the shock in all the dogs, and extended Holter monitoring was done during the first 5 days in four dogs. All dogs survived for 1 week. Within 10 minutes after the shock, a sustained ventricular tachycardia was recorded in nine dogs; deterioration into ventricular fibrillation occurred in two dogs. In nine dogs, 60 to 169 monomorphic ventricular tachycardia episodes (mean 101) occurred on day 1 and 0 to 11 (mean 3) occurred on day 7; Holter monitoring failed for technical reasons in one dog. Extended Holter monitoring showed a marked decline in the incidence of tachycardia during the first 3 days. Early activation during ventricular tachycardia was always derived at or near the ablation site, and the QRS configuration during pre- and postablation pacing at this site was identical to the tachycardia configuration. Ventricular tachycardia was never inducible with programmed stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Seizure-alert dogs: a review and preliminary study.

PURPOSE: Gather data on incidence of canine alerting/responding behavior with a defined patient population. Research development and use of purported alerting dogs. METHODS: Review of the literature was performed. A qualitative questionnaire was completed by epilepsy patients. Service dog trainers were identified. RESULTS: Of 63 patients, 29 owned pet dogs. Nine reported their dog responded to seizures, three also were reported to alert to seizure onset. There was no significant evidence of correlation between alerting/responding behavior and the patients' demographics, health, or attitude/opinion of pets. Seizure-alerting/responding behavior of the dog did not appear to depend on its age, gender or breed. A literature review revealed psychological and practical benefits of service dogs are well documented. Fifteen trainers of seizure-assist dogs were identified and interviewed. CONCLUSIONS: Findings suggest some dogs have innate ability to alert and/or respond to seizures. Suggests a trend in type of seizure/auras a dog may alert to. Success of these dogs depends largely on the handler's awareness and response to the dog's alerting behavior. Warrants further research to aid in the selection of patients who may benefit from seizure-assist dogs, for identification and further training of these dogs and possibly the development of seizure-alerting devices.

Adolescent↗

Oral formulations of adefovir dipivoxil: in vitro dissolution and in vivo bioavailability in dogs.

The effect of formulation on oral bioavailability of the antiviral nucleotide analogue adefovir from the prodrug adefovir dipivoxil was examined in beagle dogs. A suspension formulation of adefovir dipivoxil granules was administered to five fasted male beagle dogs (250 mg prodrug per dog; 135.7 mg-equiv of adefovir per dog). Tablets prepared from the same granulation (batch B94) were administered at 2 x 125 mg prodrug per dog. In addition, the same tablets were administered to dogs in the fed state or following pentagastrin pretreatment. Two further tablet batches (H94 and D501) with slight formulation changes were also evaluated in pentagastrin pretreated dogs (n = 5). Concentrations of adefovir in plasma were determined by HPLC following fluorescence derivatization. Tablet dissolution was examined at pH 2.0. One batch of adefovir dipivoxil tablets showed a 5-fold slower dissolution rate in vitro (B94 = H94 >> D501). Adefovir dipivoxil was completely converted to adefovir following oral absorption in dogs. The oral bioavailability of adefovir from the suspension was 35.0 +/- 8.9%. The oral bioavailability of adefovir from the tablet formulation was 34.7 +/- 10.3%, 37.2 +/- 4.5%, and 44.9 +/- 5.9% in fasted dogs, fed dogs and fasted dogs pretreated with pentagastrin, respectively. All three tablet batches had equivalent bioavailability in dogs. Oral bioavailability of adefovir from the prodrug in dogs (35-46%) was unaffected by formulation, food, or the acidic pH of the gastrointestinal tract. In vitro dissolution of adefovir dipivoxil tablets did not correlate with oral bioavailability. Oral bioavailability of adefovir dipivoxil appears to be limited by low permeability and biological conversion of the prodrug to adefovir.

Adenine↗