Liver histopathology and liver and serum alanine aminotransferase and alkaline phosphatase activities in epileptic dogs receiving phenobarbital.

Phenobarbital (PB) therapy is frequently associated with elevated serum alanine aminotransferase (ALT) and alkaline phosphatase (AP) activities in dogs without clinical signs of liver disease. The goal of this study was to determine if increased serum ALT and AP activities in clinically healthy PB-treated epileptic dogs are due to hepatic enzyme induction or to subclinical liver injury. Liver biopsies were obtained from 12 PB-treated dogs without clinical signs of liver disease but with elevated serum ALT and/or AP activities or both. Liver biopsies were obtained from eight healthy control dogs not receiving PB. Biopsies were evaluated histopathologically (all dogs) and liver homogenates were assayed for ALT (all dogs) and AP (six treated dogs, all controls) activities. As a positive control, liver cytochrome P4502B, an enzyme known to be induced by PB, was measured by benzyloxyresorufin-O-dealkylase activity and immunoblotting (five treated dogs, all controls). Serum AP isoenzyme analyses were performed. Results showed that ALT and AP activities in liver homogenates were not increased in treated dogs compared with controls, whereas the positive control for induction, CYP2B, was dramatically increased in treated dogs. Histopathological examination of liver biopsies revealed more severe and frequent abnormalities in treated dogs compared to controls, but similar types of abnormalities were found in both groups. Serum AP isoenzyme analyses in treated dogs demonstrated increased corticosteroid-induced and liver isoenzyme activities compared to controls. Results do not support induction of ALT or AP in the liver as the cause of elevated serum activities of these enzymes due to PB.

Changes in serum thyroxine and thyroid-stimulating hormone concentrations in epileptic dogs receiving phenobarbital for one year.

A multicentric prospective study was conducted to monitor the effect of phenobarbital on serum total thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in epileptic dogs. Serum T4 concentrations were determined for 22 epileptic dogs prior to initiation of phenobarbital therapy (time 0), and 3 weeks, 6 months, and 12 months after the start of phenobarbital. Median T4 concentration was significantly lower at 3 weeks and 6 months compared to time 0. Thirty-two percent of dogs had T4 concentrations below the reference range at 6 and 12 months. Nineteen of the 22 dogs had serum TSH concentrations determined at all sampling times. A significant upward trend in median TSH concentration was found. No associations were found between T4 concentration, dose of phenobarbital, or serum phenobarbital concentration. No signs of overt hypothyroidism were evident in dogs with low T4, with one exception. TSH stimulation tests were performed on six of seven dogs with low T4 concentrations at 12 months, and all but one had normal responses. In conclusion, phenobarbital therapy decreased serum T4 concentration but did not appear to cause clinical signs of hypothyroidism. Serum TSH concentrations and TSH stimulation tests suggest that the hypothalamic-pituitary-thyroid axis is functioning appropriately.

Quantitative urinalysis in healthy Beagle puppies from 9 to 27 weeks of age.

UNLABELLED: To evaluate indices of renal function in healthy, growing Beagle puppies from 9 to 27 weeks of age and to determine whether indices change with age during this period. Animals-6 healthy Beagle puppies. PROCEDURE: Urine collections were performed at 2-week intervals in puppies 9 to 27 weeks old. Daily excretion of urinary creatinine, protein, sodium, potassium, chloride, phosphorus, and calcium were determined, as were quantitative urinalyses including endogenous creatinine clearance, urine protein-to-creatinine ratios (UPr/C), and fractional clearances of sodium (FNa), potassium (FK), chloride (FCI), calcium (FCa), and phosphorus (FP). RESULTS: Significant differences among age groups were detected for endogenous creatinine clearance, and daily urinary protein, potassium, calcium, and phosphorus excretion. Significant differences also existed among age groups for UPr/C, FNa, FK, FCI and FP. Age-related effects fit a linear regression model for FNa, UPr/C, daily phosphorus excretion, and daily protein excretion. Quadratic regression models were judged most appropriate for endogenous creatinine clearance, FK, daily chloride excretion, and daily potassium excretion. Endogenous creatinine clearance measurements higher than adult reference ranges were observed from 9 to 21 weeks of age. The FNa, FK, FCI, FCa, and FP were slightly higher than those reported for adult dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Selected results of quantitative urinalyses in healthy 9- to 27-week-old Beagle puppies differ with age and differ from those measured in adult dogs. Diagnostic measurements performed in puppies of this age range should be compared with age-matched results when possible.

Effects of phenobarbital treatment on serum thyroxine and thyroid-stimulating hormone concentrations in epileptic dogs.

OBJECTIVE: To determine whether phenobarbital treatment of epileptic dogs alters serum thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations. DESIGN: Cross-sectional study. ANIMALS: 78 epileptic dogs receiving phenobarbital (group 1) and 48 untreated epileptic dogs (group 2). PROCEDURE: Serum biochemical analyses, including T4 and TSH concentrations, were performed for all dogs. Additional in vitro analyses were performed on serum from healthy dogs to determine whether phenobarbital in serum interferes with T4 assays or alters free T4 (fT4) concentrations. RESULTS: Mean serum T4 concentration was significantly lower, and mean serum TSH concentration significantly higher, in dogs in group 1, compared with those in group 2. Thirty-one (40%) dogs in group 1 had serum T4 concentrations less than the reference range, compared with 4 (8%) dogs in group 2. All dogs in group 2 with low serum T4 concentrations had recently had seizure activity. Five (7%) dogs in group 1, but none of the dogs in group 2, had serum TSH concentrations greater than the reference range. Associations were not detected between serum T4 concentration and TSH concentration, age, phenobarbital dosage, duration of treatment, serum phenobarbital concentration, or degree of seizure control. Signs of overt hypothyroidism were not evident in dogs with low T4 concentrations. Addition of phenobarbital in vitro to serum did not affect determination of T4 concentration and only minimally affected fT4 concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Clinicians should be aware of the potential for phenobarbital treatment to decrease serum T4 and increase TSH concentrations and should use caution when interpreting results of thyroid tests in dogs receiving phenobarbital.

The tetrasaccharide L-alpha-D-heptose1-->2-L-alpha-D-heptose1--> 3-L-alpha-D-heptose1-->(3-deoxy-D-manno-octulosonic acid) and phosphate in lipid A define the conserved epitope in Haemophilus lipopolysaccharides recognized by a monoclonal antibody.

A murine monoclonal antibody, MAHI 3 (immunoglobulin G2b), that is broadly reactive with Haemophilus influenzae lipopolysaccharides (LPSs) but nonreactive with all enterobacterial LPSs tested was generated by fusing mouse myeloma cells with spleen cells of BALB/c mice immunized with azide-killed H. influenzae RM.7004. MAHI 3 bound to all H. influenzae, all other human Haemophilus spp., all Bordetella pertussis and Bordetella parapertussis, and all Aeromonas spp. tested but not to any Neisseria or Moraxella catarrhalis strains, as determined by enzyme immunoassay, colony dot immunoblotting, and immunoblotting. In an inhibition enzyme immunoassay, MAHI 3 reacted with all 45 H. influenzae LPSs tested but not with the LPS from the rough mutant I69 Rd-/b+, which has only 3-deoxy-D-manno-octulosonic acid (P) [Kdo(P)] and lipid A. The antibody was not inhibited by H. influenzae lipid A or lipid-free polysaccharide isolated after mild acid hydrolysis. Only native LPSs show positive inhibitory activity, indicating that part of lipid A is involved in the binding of MAHI 3. From the results, it is indicated that the structural element recognized by MAHI 3 is Hep alpha 1-->2Hep alpha 1-->3Hep alpha 1-->Kdo together with part of lipid A, including the phosphate.

Structure of the core oligosaccharide in the lipopolysaccharide isolated from Aeromonas salmonicida ssp. salmonicida.

The core oligosaccharide isolated from the lipopolysaccharide of Aeromonas salmonicida ssp. salmonicida has been investigated by methylation analysis, NMR spectroscopy (13C and 1H), oxidation with periodate and chromium trioxide, and Smith degradation. The following structure is proposed: [Formula: see text]

Relationship between urine ammonium ion excretion and urine anion gap in dogs.

Acidemia stimulates renal ammonia production and excretion. This adaptive response allows increased H+ secretion and generation of new bicarbonate. To determine whether a relationship existed between urine ammonium (NH4+) concentration and excretion and urine anion gap (Na+ + K(+)- Cl-), ammonium chloride (NH4Cl) was administered per OS for 5 days to induce systemic acidemia in 12 healthy Beagles. During NH4Cl administration, a strong, statistically significant (P less than 0.0001) relationship was apparent between urine NH4+ concentration measured in millimoles per liter and urine anion gap. Regression equation: urine [NH4+] = 8.2 - 0.416 x urine anion gap; r = -0.897. A statistically significant (P = 0.0001) relationship existed between urine NH4+ excretion measured in millimoles per kilogram of body weight per day and urine anion gap. Regression equation: urine NH4+ excretion = 0.74 - 0.38 x urine anion gap; r = -0.768. As urine NH4+ concentration or excretion increased, urine anion gap became more negative. Before NH4Cl administration (no systemic acidemia), a weak, but statistically significant (P = 0.015) relationship was observed between urine NH4+ concentration and urine anion gap. Regression equation: urine [NH4+] = 65.2 - 0.141 x urine anion gap; r = -0.41. However, a relationship was not evident between urine NH4+ excretion and urine anion gap before NH4Cl administration. Hence, urine anion gap is a reliable index of urine NH4+ concentration and excretion only in dogs with metabolic acidosis. In human beings with distal renal tubular acidosis, NH4+ excretion is inappropriately low and results in a positive urine anion gap.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical treatment of a congenital bronchoesophageal fistula in a dog.

A 1-year-old male Cairn Terrier was evaluated for chronic coughing that was aggravated by eating or drinking. Radiography revealed an esophageal diverticulum, regional megaesophagus, and focal interstitial densities in the right caudal and middle lung lobes. Using fluoroscopy and contrast radiography, contrast material was seen to accumulate in the diverticulum and to reflux into the right middle, caudal, and accessory bronchi. Radiographic diagnosis was bronchoesophageal fistula. Via right eighth intercostal space thoracotomy, the abnormal connection between esophagus and caudal lobe of the right lung was identified, the lobe was resected, and the esophagus was closed. Histologic examination of the connecting tissue revealed a lining of stratified epithelium, with the superficial layer being predominantly ciliated columnar epithelium. Several findings led to the conclusion that the fistula was a congenital lesion, arising from aberrant formation of the respiratory tract from the embryologic digestive tract. Histologic examination revealed smooth muscle and lack of inflammation in tissue surrounding the fistula, which are criteria for identifying congenital bronchoesophageal fistula in human patients. The dog was young and did not have a history of esophageal foreign bodies. Postoperative complications were not encountered, and 9 months later, the dog was reported to be eating dry dog food without coughing. Congenital and acquired bronchoesophageal fistulas in dogs are reported infrequently. Furthermore, 2 of 12 previously reported bronchoesophageal fistulas in dogs, one of which was considered congenital, developed in Cairn Terriers.

Effect of enrofloxacin on digoxin clearance and steady-state serum concentrations in dogs.

The effect of enrofloxacin on the oral clearance and steady-state concentrations of digoxin in serum was evaluated in dogs. Digoxin was administered orally to six healthy adult Beagle dogs following a multiple-dose regimen of 0.0625 mg every 12 h for 23 days. From days 14 to 23 enrofloxacin was administered orally at a dosage of 2.5 mg/kg every 12 h, with subjects receiving enrofloxacin 2 h prior to digoxin. Trough serum concentrations of digoxin were measured using an immunoassay technique. On days 13 and 22, dogs were catheterized for multiple blood sample collection during the 12 h digoxin dosing interval and serum samples were analyzed for digoxin concentrations. In general, steady-state digoxin concentrations in trough serum were not significantly different during enrofloxacin treatment than before enrofloxacin administration. Similarly, digoxin oral clearance was not significantly different between pre-enrofloxacin and digoxin + enrofloxacin periods. We conclude that enrofloxacin is unlikely to have a significant impact on digoxin disposition in dogs.

Urine-blood carbon dioxide tension gradient in healthy dogs.

The urine-blood carbon dioxide tension (PCO2) gradient was measured in 10 healthy mature Beagles after alkalinization of the urine by administration of sodium bicarbonate. The mean (+/- SD) urine-blood PCO2 gradient was 65.92 +/- 14.42 mm of Hg, with range of 38.2 to 82.2 mm of Hg. Mean urine PCO2 was 110.21 +/- 14.19 mm of Hg, with range of 84.1 to 127.3 mm of Hg. Because urine-blood PCO 2 gradient less than 30.0 mm of Hg or urine PCO2 less than 55 mm of Hg in people is diagnostic for a defect in distal nephron acidification, similar values might be applicable to diseases in dogs.

Acute response of urine pH following ammonium chloride administration to dogs.

To test the acidifying ability of the distal portion of the nephrons in healthy dogs, 0.2 g of NH4Cl/kg of body weight was given PO. Samples for venous blood gas analysis and urine pH were taken hourly for 6 hours. Systemic acidemia developed, as evidenced by a statistically significant (P less than 0.05) decrease in blood pH 1 hour after NH4Cl administration. Four hours after administration, mean urine pH decreased to a low of 5.16 +/- 0.1 and was less than 5.5 3 hours after administration. Changes in urine pH 2 hours after administration were statistically significant (P less than 0.05). In human beings, NH4Cl loading is used to detect patients with distal renal tubular acidosis (defective hydrogen ion secretion by the distal nephrons) and normal acid/base values. Distal renal tubular acidosis is diagnosed if urine pH fails to decrease to less than 5.5 after NH4Cl administration. On the basis of the findings of this study, a similar value would be valid for dogs.

Synthesis of glycoconjugates derived from various lipopolysaccharides of the Vibrionaceae family.

Conjugation of simple ketoses (such as 3-deoxy-D-manno-2-octulosonic acid and N-acetylneuraminic acid) and of various O-specific polysaccharides (from Aeromonas hydrophila and Aeromonas salmonicida) to the bifunctional spacer 1,6-hexanediamine, was achieved by reductive amination. The saccharide--1-(6-amino)-hexane alkyamines obtained were converted into the corresponding isothiocyanate derivatives and coupled to the free epsilon-amino group of lysine residues of the protein carrier bovine serum albumin. In similar manner, the aldehyde group introduced by selective periodate oxidation into the partially O-deacylated lipopolysaccharide of Vibrio anguillarum was conjugated to 1,6-hexanediamine, converted into the corresponding isothiocyanate and covalently attached to bovine serum albumin.

Self-sterilization of the electrosurgery electrode.

Sterilization of the electrode used in electrosurgery has been assumed to occur at the instant of contact of the energized electrode tip to a grounded source. This study evaluated whether the time of electrode activation or the amount of energy delivered is important in the self-sterilization process. Standard bacteriologic culturing techniques were employed to assess sterility of the electrode tip following activation. Total time of application of the current and the energy used were recorded on audiotape and later tabulated. The data indicate that the time of energizing and the energy units used are critical in the sterilization of the electrode tip. These results confirm that self-sterilization of the electrosurgery electrode tip occurs, but full confidence is not realized with the time intervals commonly employed in clinical practice. The electrode tip must be considered a potential source of bacterial contamination of electrosurgically managed dental procedures.

Gastrinoma (Zollinger-Ellison Syndrome) in the Dog and cat.

Tumors of gastrin-secreting cells (gastrinomas) result in a characteristic clinical syndrome of hypergastrinemia, which leads to gastric acid hypersecretion with subsequent severe gastrointestinal ulceration. The most common clinical signs are inappetance/anorexia, lethargy, weight loss, vomiting, diarrhea, and hypoalbuminemia. Hypergastrinemia is also seen in other disorders and caution should be used in utilizing fasting serum gastrin concentrations as the sole diagnostic criterion.