Determination of plasma and skin concentrations of orbifloxacin in dogs with clinically normal skin and dogs with pyoderma

Plasma and skin concentrations of orbifloxacin (Orbax tablets, Schering-Plough Animal Health) were assessed in 14 clinically normal dogs and 14 dogs with pyoderma following oral administration of the drug at 7.5 mg/kg once daily for 5 to 7 days. Skin biopsies and whole blood samples were obtained before dosing and at the time of the expected maximum concentration in skin (3 hours after dosing) on the first and on the fifth to seventh day of dosing. Skin biopsies and plasma were analyzed for orbifloxacin concentrations by high-performance liquid chromatography. Dogs with pyoderma had significantly higher mean skin concentrations of orbifloxacin within 3 hours of administration (Day 0: 7.80 +/- 3.40 mcg/g, Days 4 to 6: 9.47 +/- 6.23 mcg/g) than did dogs with normal skin (Day 0: 3.85 +/- 1.08 mcg/g, Days 4 to 6: 5.43 +/- 1.02 mcg/g). After dosing on Day 0 and after five to seven daily treatments, dogs with pyoderma had significantly higher mean orbifloxacin skin:plasma ratios (1.40 and 1.44, respectively) than did clinically normal dogs (0.81 and 0.96, respectively). The accumulation of orbifloxacin in diseased skin may contribute to the efficacy of this compound for the treatment of bacterial skin infections.     

Isoamylases in clinically normal dogs

Isoenzymes of canine serum amylase were evaluated by electrophoresis on cellulose acetate membranes in a discontinuous buffer system. Two isoamylase groups were identified in the serum of clinically normal dogs. Most of the serum amylase activity was the more cathodal isoamylase. The anodal isoamylase was rarely observed in serum from normal dogs and, when present, accounted for little of the enzymatic activity. Amylase activities of various tissues were determined and isoenzymes were identified. The anodal isoenzyme was found in the pancreas and uterus. The cathodal isoamylase had its origin mainly from the intestinal tract. Activities of other tissues were not greater than was serum amylase activity. Effects of feeding upon total serum amylase activity and isoenzyme composition also were examined over a period of 5 minutes to 7 hours. Feeding did not markedly alter the serum amylase activity.     

Ureterocolonic anastomosis in clinically normal dogs

Ureterocolonic anastomosis was evaluated in 13 clinically normal dogs. Urinary continence was maintained after surgery, and the procedure was completed without technique errors in all but 2 dogs. Three dogs died within 5 weeks (2 of undetermined causes and 1 of aspiration pneumonia and neurologic disease), and 1 dog was euthanatized 4 months after surgery because of neurologic signs. Two healthy dogs were euthanatized 3 months after surgery for light microscopic evaluation of their kidneys. Five dogs were euthanatized 6 months after surgery for light microscopic evaluation of their kidneys. Gastrointestinal and neurologic disturbances developed in 4 dogs at various postoperative intervals. Plasma ammonia concentration measured in 2 dogs with neurologic signs was increased. Plasma ammonia concentration measured in 5 dogs without neurologic signs was within normal limits. All 5 dogs, in which metabolic acidosis was diagnosed, had high normal or above normal serum chloride concentration. Serum urea nitrogen values were increased after surgery because of colonic absorption of urea. Serum creatinine concentration was increased in 1 dog 6 months after surgery. Individual kidney glomerular filtration rate was reduced in 38% (3/8) of the kidneys from 4 other dogs at 6 months after surgery. Of 5 dogs euthanatized at 3 to 4 months after surgery, 4 had bilateral pyelitis, and 1 had unilateral pyelonephritis. Six months after surgery, pyelonephritis was diagnosed in 40% (4/10) of the kidneys from 5 dogs. The ureterocolonic anastomosis procedure is a salvage procedure that should allow complete cystectomy. However, variable degrees of metabolic acidosis, hyperammonemia, and neurologic disease may result.     

Diseased dogs isoamylases in clinically normal and diseased dogs

Isoamylases in normal canine sera were separated on cellulose acetate membranes using a discontinuous buffer system without EDTA. Four peaks of amylase activity were present in 17 of 24 sera. Normal values were established. The majority of activity was present in Peak 4 (cathodal isoamylase). Tissue extracts of pancreas, duodenum, kidney, lung, testis, spleen and uterus-ovaries contained Peak 4 isoamylase. Liver and salivary gland lacked all isoamylase activity. Pancreas contained Peak 3 in addition to Peak 4 isoamylase. A tissue origin for Peaks 1 and 2 was not identified. An overall lack of resolution resulted from the inclusion of EDTA in the electrophoresis buffer system. This may account for previous findings suggesting that pancreatic amylase is not present in normal canine serum. An increase in the Peak 3 isoamylase was present in dogs with pancreatitis while dogs with pancreatic atrophy had a decrease in all isoamylases. Total amylase activity was significantly (p < 0.05) decreased in dogs with pancreatic atrophy.     

Impedance audiometric measurements in clinically normal dogs

OBJECTIVE: To measure impedance audiometric values in clinically normal dogs that were sedated or anesthetized, evaluate effects of ear flushing on tympanometric measurements, and determine effects of performing acoustic reflex testing in a sound-attenuated room. ANIMALS: 35 mixed-breed and purebred client-owned dogs and 21 laboratory-bred Beagles. PROCEDURES: Tympanometry and acoustic reflex testing were performed on 27 mixed-breed and purebred dogs under isoflurane anesthesia in a non-sound-attenuated room and 21 Beagles under sedation in a sound-attenuated room. Tympanometry was performed on 8 mixed-breed dogs under halothane anesthesia before and after ear canal flushing. RESULTS: Among impedance audiometric values, ear canal volume and compliance peak were smaller in Beagles than in mixed-breed dogs; differences among other values were not detected. Ear canal volume was dependent on body weight. Differences were not found for tympanometric values measured before and after ear canal flushing. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study established reference range values for impedance audiometric measurements in clinically normal dogs under isoflurane anesthesia or sedation. Acoustic reflex testing does not need to be performed in a sound-attenuated room. The ear canals of clinically normal dogs can be flushed prior to performing tympanometry without altering the results. Impedance audiometry may be a useful noninvasive procedure for the diagnosis of otitis media in dogs.     

Sulphido-leukotriene production from peripheral leukocytes and skin in clinically normal dogs and house dust mite positive atopic dogs

Pathogenesis of canine atopy has not been completely elucidated. In humans, sulphido-leukotrienes (s-LT) play a role in atopy, and increased production of s-LT occurs in the skin and peripheral leukocytes after allergen challenge. The study population included 16 clinically normal and 13 atopic dogs. All atopic dogs had in common a positive reaction (4+) to the intradermal injection of house dust mite (allergen of reference). Blood samples and skin biopsies were collected. Sulphido-LT synthesis by peripheral leukocytes after stimulation was measured, and no statistically significant difference was found between clinically normal and atopic dogs. Sulphido-LT concentrations in skin samples from stimulated and unstimulated sites were measured, and no statistically significant difference was detected between clinically normal and atopic dogs or between lesional and nonlesional skin within the atopic group. Clinical signs of atopic dogs were graded by owners and no correlation was found between their severity and cutaneous concentrations of s-LT. In this study there was no increase in s-LT synthesis in atopic dogs.     

Use of chromametry and digital photography for objective measurement of skin color in clinically normal dogs

OBJECTIVE: To evaluate whether skin erythema in clinically normal dogs can be quantified by use of chromametry and image analysis of digital photographs. ANIMALS: 9 German Shepherd Dogs and 10 mixed-breed dogs. PROCEDURE: Hair was clipped at 7 sites on the body. Skin erythema was evaluated at the axillary region, right and left lateral aspect of thorax, right and left loin area (ie, part of the back between the thorax and pelvis), right and left groin area (ie, the junctional region between the abdomen and thigh), metatarsal digital pad, and on the nose. Replicate measurements were done by use of chromametry and image analysis of digital photographs, using erythema values in accordance with the Committee International d'Eclairage (CIE)-Lab color system. RESULTS: Repeatability was high for both techniques. Within-dog variation was lower than between-dog variation. Between-dog variation was high for both groups of dogs. Interregional variation was significant in German Shepherd Dogs and mixed-breed dogs. Erythema values revealed symmetry between the right and left lateral aspects of the thorax and loin and groin areas. CONCLUSIONS AND CLINICAL RELEVANCE: Precise objective methods are available for skin erythema quantification. Chromametric and photographic erythema values had a high within-dog reproducibility. Between-dog variability was high for German Shepherd Dogs and mixed-breed dogs as was regional variation, indicating differences in color among dogs.     

The effects of gel pad thickness on the evaluation of skin structures using ultrasonography in normal dogs

Gel pads are commonly used in skin ultrasonography; however, the effects of their thickness are unknown. This study investigated the effects of pad thickness on measurements of skin thickness in 10 beagle dogs. Sonograms to measure neck skin thickness were captured without pads and using pads with thicknesses of 3, 5, 10, and 20 mm. Without pads, acoustic shading was observed due to air bubbles in the coupling gel. With 20-mm pads, echogenic artifacts were observed on the skin surface. Entry echo with 20-mm pads was significantly higher than with 3-mm pads. This suggests that visibility of the skin structure could be affected when a gel pad is not used or when a thick gel pad is selected.     

Telomerase activity in clinically normal dogs and dogs with malignant lymphoma

OBJECTIVES: To determine whether telomerase activity was present in lymph nodes, buffy coat, and serum samples from dogs with malignant lymphoma (ML) and in liver, lymph node, buffy coat, and serum samples from clinically normal dogs SAMPLE POPULATION: Tissue specimens and blood samples were obtained from 11 clinically normal adult dogs (age range, 1 to 4 years) and 14 client-owned dogs with ML. PROCEDURE: The telomere repeat amplification protocol assay was used to quantify telomerase activity in the tissues from clinically normal dogs and dogs with ML. RESULTS: Of 11 clinically normal dogs, 8 had lymph node samples, 5 had liver samples, and 1 had buffy coat samples with detectable telomerase activity. None of the serum samples from the clinically normal dogs had detectable telomerase activity. Of 14 dogs with ML, 9 had lymph node samples, 3 had buffy coat samples, and 1 had serum samples with measurable telomerase activity. CONCLUSIONS AND CLINICAL RELEVANCE: Telomerase activity was not specific to tumor cells and overlapped with that found in cells from clinically normal dogs. Telomerase activity in neoplastic lymph nodes was not substantially different from that found in lymph nodes from clinically normal dogs. The determination of telomerase activity cannot be used as a sole diagnostic test for cancer. Therapeutic modalities directed toward the telomerase enzyme may not be feasible in dogs, because somatic tissues from clinically normal dogs possess variable amounts of telomerase activity.     

Computed tomographic osteoabsorptiometry of the elbow joint in clinically normal dogs

OBJECTIVE: To evaluate subchondral bone density patterns in elbow joints of clinically normal dogs by use of computed tomographic (CT) osteoabsorptiometry. SAMPLE POPULATION: 20 cadaver forelimbs from 10 clinically normal dogs. PROCEDURE: Each elbow joint was imaged in parasagittal and transverse planes of 1.5-mm thickness. Slice data were converted to dipotassium phosphate equivalent density (PPED) values. Sagittal, parasagittal, and transverse medial coronoid process topographic maps were constructed. Defined zones were created for each of the 3 CT planes, and confluence and peak PPED values were determined. RESULTS: The lowest PPED value was 340 mg/ml (articular and subchondral confluence), and the highest was 1780 mg/ml (peak subchondral density). Detectable effects of joint laterality were not found in the confluence or peak PPED measurements or in the peak-to-confluence PPED ratio for all 3 CT planes. Significant differences were found among zones in all 3 planes for confluence and peak PPED measurements and between sagittal and transverse planes for peak-to-confluence PPED ratios. Subjectively, the pattern of density distribution among dogs was fairly consistent for the sagittal and parasagittal slices. Three specific patterns of density distribution were apparent on the transverse topographic maps of the medial coronoid process that corresponded to conformational differences. CONCLUSIONS AND CLINICAL RELEVANCE: The use of CT osteoabsorptiometry provides a repeatable technique that can be used to noninvasively examine bone density and the effects of stress acting on joints in vivo. Variability in density values for any of the CT planes was not identified among clinically normal dogs.     

Osmotic fragility of erythrocytes in clinically normal dogs and dogs infected with parasites

The osmotic fragility of the erythrocytes was measured in blood samples collected from randomly selected healthy and infected dogs at a dogs' rescue shelter. The dogs were classified into six groups on the basis of the final diagnoses from clinical, post mortem and laboratory findings. The minimum (less than 5 per cent) and maximum (more than 90 per cent) haemolysis of the erythrocytes of the clinically normal dogs (group 1), occurred in 0·60 per cent and 0·30 per cent solutions of sodium chloride (NaCI). For the non-anaemic hookworm-infected dogs (group 2a) the respective values were 0·8 per cent and 0·4 per cent NaCl, and for the anaemic hookworm-infected dogs (group 2b) they were 0·85 per cent and 0·5 per cent NaCl, respectively. The erythrocytes from dogs with Babesia canis (group 3), concurrent hookworm and B canis (group 4) and Ehrlichia canis infections (group 5) had minimum haemolysis in 0·75 per cent NaCl and maximum haemolysis at between 0·20 per cent and 0·35 per cent NaCI solutions. The derivative fragiligrams for groups 2a, 2b, 3 and 4 were shifted to the left, whereas the fragiligram for group 5 was similar to that for the clinically normal dogs (group 1). The left shift for the hookworm-infected dogs was due to the increased osmotic fragility of a minor sub-population of the erythrocytes, but for the dogs, infected with B canis major sub-populations of the erythrocytes had an increased osmotic fragility.     

Treatment of clinically normal and cystinuric dogs with 2-mercaptopropionylglycine

In a pharmacokinetic and tolerance study, 2 healthy Beagles were given 13.2 to 39.5 mg of 2-mercaptopropionylglycine (2-MPG)/kg of body weight orally once daily in increasing doses for 3 weeks. A third dog was given 10 mg of 2-MPG/kg of body weight, IV. The drug was well tolerated. After these initial studies, 15 cystinuric dogs were treated with 2-MPG orally once daily for 5 to 45 months and with sodium bicarbonate for urine alkalinization and fluid diuresis. Pharmacokinetic studies were done in 7 dogs on the third day of oral treatment with 2-MPG. After oral administration of 15.6 to 31.3 of 2-MPG/kg of body weight, maximal serum/plasma concentrations were from 28.6 to 76.3/mumol/L after 1 to 3 hours in 6 cystinuric dogs. The mean urinary excretion was 22% (range, 0.3 to 58.9%) of the dose. Ten of 15 cystinuric dogs had no re-formation of uroliths. Of 4 dogs with uroliths at the beginning of treatment, 3 had total urolith dissolution on continuous treatment. During treatment, further growth of the uroliths was inhibited in one dog, and in another dog with re-formed uroliths, they dissolved. We concluded that 2-MPG is well tolerated and promising for treatment of cystinuric dogs, but the pharmacokinetic studies should be expanded to include different dosage regimens, and results of long-term treatment should be evaluated. Our recommendations for treatment of dogs with cystine uroliths include surgical intervention if the dog has urethral obstruction or has dysuria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nuclear scintigraphic assessment of liver size in clinically normal dogs

Measurement of liver size was made on nuclear scintigraphic images obtained from 16 clinically normal, anesthetized dogs in ventral, dorsal, right and left lateral, and left dorsal oblique positions after administration of technetium 99m-sulfur colloid. Linear measurements of liver length and width were made from each scintiscan, and liver surface area was determined by setting a region of interest manually and by use of a computer count of pixels above a minimal intensity (threshold method). All linear measurements had a statistically significant (P less than 0.05) correlation with liver and body weight, with the exception of the measurements of liver width made on dogs in dorsal and left lateral dorsal oblique positions. The highest correlation (r = 0.89) between the scintigraphic measurements and liver weight was the multiplication of measurements of liver width and length from the right lateral view. Although all area determinations were significantly (P less than 0.05) correlated with liver and body weight, for most views, the manual method of determining the region of interest had a slightly better correlation with the liver weight than did the threshold method.     

Quantitative noninvasive assessment of liver size in clinically normal dogs

Measurements of liver size were made from radiographs of 16 clinically normal anesthetized dogs. Two measurements were made from each of 3 views: right and left lateral and ventrodorsal. Each measurement was correlated with liver weight and volume. Liver weight and volume were also correlated with both measurements from the same radiograph multiplied together. All measurements, with the exception of ventrodorsal depth, correlated significantly (P less than 0.05) with liver weight and volume. The multiplication of the 2 measurements made from the right lateral radiograph correlated most highly with liver weight. These data were then compared with those from similar studies involving liver measurements obtained from nuclear scintigraphic and ultrasonographic scans on the same dogs. The radiographic measurements made from the right lateral view had the highest correlation with liver weight, followed by the nuclear scintigraphic measurements made from the same position.     

Effect of mitotane on pituitary corticotrophs in clinically normal dogs

OBJECTIVE: To evaluate the effects of mitotane administration on the function and morphology of pituitary corticotrophs in clinically normal dogs. ANIMALS: 12 clinically normal adult Beagles. PROCEDURES: Dogs were randomly assigned to the control group or the mitotane treatment group. In mitotane treatment group dogs, mitotane was administered for 1 month. In both groups, ACTH stimulation testing and corticotrophin-releasing hormone (CRH) stimulation testing were performed. Magnetic resonance imaging (MRI) of the pituitary gland and brain was performed in mitotane treatment group dogs before and after administration of mitotane. After CRH stimulation testing and MRI, dogs were euthanatized and the pituitary gland and adrenal glands were excised for gross and histologic examination. RESULTS: ACTH concentrations in mitotane treatment group dogs were significantly higher than in the control group dogs following CRH stimulation. Magnetic resonance imaging revealed that pituitary glands were significantly larger in treatment group dogs after administration of mitotane, compared with before administration. On gross and histologic examinations, the adrenal cortex was markedly atrophied. Immunohistochemistry revealed hypertrophy of corticotrophs in pituitary glands of mitotane treatment group dogs. CONCLUSIONS AND CLINICAL RELEVANCE: These findings indicate that inhibition of the adrenal cortex by continuous administration of mitotane leads to functional amplification and morphologic enhancement of corticotrophs in clinically normal dogs. In instances of corticotroph adenoma, hypertrophy of individual corticotrophs induced by mitotane may greatly facilitate enlargement of the pituitary gland and increases in ACTH secretion.