Plasma 14C-cholic acid clearance in healthy dogs and dogs with cholestasis or a congenital portosystemic shunt.

The clearance profiles of intravenously injected tracer doses of radioactively labelled cholic acid were investigated in healthy dogs, dogs with a congenital portosystemic shunt and dogs with cholestasis. The rate constants and residual plasma activity were significantly different in the healthy and diseased dogs, but it was not possible to differentiate between the dogs with portosystemic shunting and cholestasis because the results were determined not only by factors involved in plasma bile acid clearance but also by the enterohepatic circulation.

Medical management of recurrent seizures in dogs and cats.

The problem of recurrent seizures is a common and challenging one in veterinary medical practice. The pathophysiology and pharmacologic suppression of focal seizure activity have been studied extensively in basic research settings, yet little is known of the genesis, modulation, and termination of generalized seizures, the most common form of seizures noted to occur in companion animals. Knowledge concerning the pharmacokinetic fate of anticonvulsant drugs currently used in veterinary medicine is adequate, though prospective clinical studies of the efficacy of these drugs in the treatment of various types of seizures are lacking. This study will review the available literature regarding the pharmacology, use, and side effects of anticonvulsant drugs currently available for control of recurrent seizures in companion animals. Alternative anticonvulsant drugs will also be described.

Intrahepatic postsinusoidal venous obstruction in a dog.

Intrahepatic postsinusoidal obstruction, similar to congenital Budd-Chiari syndrome in human patients, was diagnosed in a young Basenji dog. Sonographic, radiographic, and manometric studies were used in antemortem localization of this unusual functional lesion, that was believed to be congenital.

Hematologic values and plasma and tissue folate concentrations in dogs given phenytoin on a long-term basis.

During earlier investigations of the hepatic effects in dogs of long-term administration of phenytoin alone or in combination with primidone, erythrocytic macrocytosis, neutropenia, neutrophilic hypersegmentation, and thrombocytopenia were observed. Such abnormalities were observed most often in dogs given phenytoin and resembled those known to be attributable to folate deficiency in human beings with epilepsy treated with phenytoin. To pursue the theory that these hematologic aberrations were caused by drug-induced folate deficiency, 12 dogs were given a diet specifically formulated to contain a minimally adequate concentration of folate. After 2 weeks, phenytoin was administered daily (400 mg, PO, q 8 h) to 8 of the 12 dogs for 54 weeks. A CBC, bone marrow aspiration biopsy, and measurement of plasma and RBC folate concentrations were done every 3 weeks. Bone marrow aspirates were examined by transmission electron microscopy after 24 and 36 weeks, and at the end of the treatment period. Hepatic folate concentration was also determined in all dogs before and after treatment. Excretion of formiminoglutamic acid, as a marker of folate deficiency, was measured in all dogs at the end of the study. All dogs remained healthy throughout the treatment phase. Consistent abnormalities were not observed in the blood or bone marrow of treated dogs. Plasma and RBC folate concentrations decreased in control and treated dogs as a result of dietary restriction (P less than or equal to 0.02), and remained stable until the end of the study. The RBC folate content decreased further in treated dogs (P less than or equal to 0.02), although the hepatic folate content was similar in control and treated dogs. Treated dogs did not excrete formiminoglutamic acid more rapidly than did control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of a lateral retinacular fascia technique for cranial cruciate ligament rupture in the dog.

A new fascial technique was used to repair artificially induced rupture of the cranial cruciate ligament in 20 dogs. Although technically simple to perform, the procedure resulted in only 12 animals free of lameness. In addition, a drawer sign was present in the stifle of 14 animals 31 days after surgery. Arthritis changes typical of cruciate ligament instability were observed in 16 joints; changes were slight to moderate in 10 joints.

Effects of long-term primidone and phenytoin administration on canine hepatic function and morphology.

Primidone, phenytoin, or phenytoin and primidone in combination were given to healthy Beagle dogs for 6 months. Serum biochemical changes in dogs given primidone alone or phenytoin and primidone in combination for the entire 6-month test period included increased activities of alanine aminotransferase, alkaline phosphatase (AP), and gamma-glutamyltransferase, and decreased concentrations of albumin and cholesterol. Changes in dogs given phenytoin alone were limited to increased AP activity and decreased albumin concentration. Sulfobromophthalein excretion and conjugated bile acid concentration were within normal limits. All dogs given primidone alone or phenytoin alone remained clinically healthy throughout the treatment period. Three of 8 dogs given both drugs in combination became clinically ill after 9, 14, and 15 weeks of treatment, and were euthanatized. Two of the dogs developed clinical jaundice. In addition to the serum biochemical abnormalities observed in clinically healthy dogs, these dogs developed hyperbilirubinemia, delayed sulfobromophthalein excretion, and increased conjugated bile acid concentrations. Histologic examination of the liver showed intracanalicular casts of bile pigment typical of intrahepatic cholestasis in all 3 dogs. Histologic findings characteristic of treated dogs included hepatocellular hypertrophy attributable to hyperplasia of the smooth endoplasmic reticulum. Single-cell necrosis and multifocal lipidosis were observed in individuals of all treatment groups. Electron microscopy of the liver showed dilated bile canaliculi and damaged sinusoidal epithelium in dogs given both drugs. The elevated serum AP activity, associated with anticonvulsant drug therapy, was found to be exclusively the liver isoenzyme by cellulose acetate electrophoresis. The hepatic AP was localized to primarily the canalicular membranes by enzyme histochemistry. There was a statistically significant positive correlation between the AP activities of liver and serum. The results of this study indicate that long-term administration of anticonvulsant drugs to dogs is associated with clinical, serum biochemical, and histologic evidence of hepatic dysfunction. High drug dosage contributed most to abnormal serum biochemical test results, and combining phenytoin with primidone was responsible for more severe electron microscopic lesions of the liver of surviving dogs and for the death of 3 dogs.

Characterization of iron status in young dogs with portosystemic shunt.

Microcytosis is a common laboratory finding in dogs with congenital portosystemic shunt (PSS), although its pathogenesis is not yet understood. Because the most common cause of microcytosis in dogs is absolute or relative iron deficiency, iron status was evaluated in 12 young dogs with PSS. Complete blood counting was done before surgical correction in all dogs, and in 5 dogs after surgery, by use of an automated hematology analyzer. Serum iron concentration and total iron-binding capacity (TIBC) were determined coulometrically, and percentage of transferrin saturation was calculated. Erythrocyte protoporphyrin content was quantified by use of front-face fluorometry. Serum ferritin concentration was measured by use of ELISA. Serum ceruloplasmin content was determined colorimetrically (with p-phenylenediamine dihydrochloride as substrate) as an indirect indicator of subclinical inflammation, which may result in impaired iron utilization. Special stains were applied to liver (10 dogs; Gomori's) and bone marrow aspiration biopsy (7 dogs; Prussian blue) specimens for qualitative assessment of tissue iron content. Nonpaired Student's t-tests were used to compare serum iron concentration, TIBC, percentage of transferrin saturation, and erythrocyte protoporphyrin, ferritin, and ceruloplasmin concentrations in dogs with PSS with those in clinically normal dogs. All dogs had microcytosis before surgery; microcytosis resolved in 3 dogs after surgical correction. Serum iron concentration and TIBC were significantly lower in PSS-affected dogs than in clinically normal dogs. Erythrocyte protoporphyrin, ferritin, and ceruloplasmin concentrations in PSS-affected dogs were not significantly different from those in health dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of sulfobromophthalein and indocyanine green clearances in the dog.

Sulfobromophthalein (BSP) and indocyanine green (ICG) were given in single-dose IV injections to dogs and plasma disappearances were measured. The BSP was given at a dose of 5 mg/kg of body weight, and ICG was given at doses of 1.0 and 1.5 mg/kg. The half-life for BSP was 4.2 +/- 0.8 minutes, and for ICG at the 1.0 mg/kg dose, 9.0 +/- 2.0 minutes, and at the 1.5 mg/kg dose, 8.4 +/- 1.9 minutes. The disappearance rate (percentage per minute) for BSP was 17.0 +/- 3.2, and for ICG at the small dose level, 8.1 +/- 1.7, and at the large dose level, 8.7 +/- 2.2. The clearances (ml/min/kg) for BSP were 15.4 +/- 6.2 and for ICG at the small dose level, 3.7 +/- 0.7, and at the large dose level, 3.9 +/- 0.7. The 30-minute percentage retentions for BSP were 1.9 +/- 1.1 and for ICG at the small dose level, 14.7 +/- 5.0, and for ICG at the large dose level, 11.4 +/- 3.0. All of the differences between BSP and ICG means for these values measured were statistically significant (P less than 0.01). There were no significant differences between sexes or between the ICG doses for any of the values (P greater than 0.05).

Comparison of sulfobromophthalein and indocyanine green clearances in the cat.

Plasma disappearances of sulfobromophthalein (BSP) and indocyanine green (ICG) given in single-dose IV injections to cats were measured. The BSP was given at a dose of 5 mg/kg of body weight; ICG was given at a dose of 1.5 mg/kg of body weight. The half-life, disappearance rate (percent per minute) and clearance (ml/min/kg) were determined during the initial phase of plasma dye elimination. The half-life for BSP was 2.2 +/- 0.7 minutes, and for ICG, 3.8 +/- 0.9 minutes. The disappearance rate for BSP was 34.7 +/- 10.1, and for ICG, 19.2 +/- 4.5. The clearance for BSP was 26.3 +/- 23.1 and for ICG, 8.6 +/- 4.1. The 30-minute percentage retention for BSP was 0.6 +/- 0.8% and for ICG, 7.3 +/- 2.9%. In the cat, ICG was cleared from the plasma less rapidly than BSP. There were no significant differences between males and females for these values. For both BSP and ICG, a significantly shorter half-life, faster disappearance rate, and lower 30-minute percentage retention were observed in the cat, compared with values observed in the dog given similar dye dosages. Clearance curves for BSP and ICG in the cat were similar to those in the dog, indicating that the 2 species may have similar volumes of dye distribution and excretory mechanisms. The results of the present study indicate that the 30-minute plasma level following a 5 mg/kg dose of BSP in normal cats is often too low for measurement, whereas the 30-minute plasma concentration of ICG following a 1.5 mg/kg dose is adequate. For the 30-minute dye retention test in the cat, ICG may be a preferred diagnostic agent.

Radioimmunoassay of conjugated bile acids in canine and feline sera.

A solid-phase radioimmunoassay for the measurement of total conjugated bile acids was validated for use in dogs and cats. The method used an 125I-labeled iodoglycocholate tracer and polypropylene assay tubes coated with rabbit antiserum against the major conjugated bile acids. Standard solutions of sodium taurocholate provided with the kit and serial dilutions of canine and feline sera containing low, medium, and high endogenous bile acid concentrations inhibited binding of the [125I]iodoglycocholate tracer to the antibody in a parallel manner; this inhibition indicated specificity of the assay for bile acids in the serum of dogs and cats. Increased serum bile acid concentrations in animals with liver disease confirmed the biologic specificity of the assay in dogs and cats. Accuracy was shown by quantitative recovery of purified sodium taurocholate from canine and feline sera. Intra-assay precision was 7.2% to 17.3% for dogs and 8.5% to 18.5% for cats. Interassay precision was 4.8% to 17.2% for dogs and 3.5% to 11.2% for cats. The sensitivity of the assay in dogs and cats was 0.4 mumol/L. Solid-phase radioimmunoassay is a valid method for the direct measurement of total conjugated bile acids in the dog and cat, and is of value in the diagnosis of hepatobiliary disease in these species.

Iatrogenic copper deficiency associated with long-term copper chelation for treatment of copper storage disease in a Bedlington Terrier.

A 9-year-old Bedlington Terrier was evaluated because of weight loss, inappetence, and hematemesis. Copper storage disease had been diagnosed previously on the basis of high hepatic copper concentration. Treatment had included dietary copper restriction and administration of trientine for chelation of copper. A CBC revealed microcytic hypochromic anemia. High serum activities of liver enzymes, high bile acid concentrations, and low BUN and albumin concentrations were detected. Vomiting resolved temporarily with treatment, but the clinicopathologic abnormalities persisted. Results of transcolonic portal scintigraphy suggested an abnormal shunt fraction. Results of liver biopsy and copper quantification revealed glycogen accumulation and extremely low hepatic copper concentration. Serum and hair copper concentrations were also low. Chelation and dietary copper restriction were tapered and discontinued. Clinical signs and all clinicopathologic abnormalities improved during a period of several months.

Clinical hypothyroidism associated with trimethoprim-sulfadiazine administration in a dog.

Treatment of a 9-year-old spayed female mixed-breed dog with trimethoprim-sulfadiazine for a prolonged period resulted in clinical signs of hypothyroidism, and results of thyroid gland function tests were indistinguishable from those associated with endogenous hypothyroidism. Drug-induced hypothyroidism was diagnosed on the basis of history, normal thyroid uptake of sodium pertechnetate, and complete recovery of thyroid gland function after administration of trimethoprim-sulfadiazine was discontinued.

A modified laparoscopic approach for liver biopsy in dogs.

A modified laparoscopic technique for liver biopsy in dogs was developed, using an otoscope to observe the liver and to guide the biopsy needle. The procedure was used to obtain liver biopsy specimens from 7 control dogs and 22 treated dogs during studies of the hepatic effects of long-term anticonvulsant drug therapy. In addition, biopsy specimens were obtained from 10 clinical patients with diffuse liver disease. Diagnostic liver specimens were obtained from all dogs with minimal complications. The procedure used basic principles of needle biopsy technique under visual control. It enabled the operator to observe the liver, select a biopsy site, and obtain diagnostic samples quickly, with considerably less expense than by use of fiberoptic laparoscopy. The results of this study indicate that the modified laparoscopic approach is a safe, practical method for liver biopsy in dogs.

Idiopathic noncirrhotic portal hypertension in dogs: 33 cases (1982-1998).

OBJECTIVE: To describe clinical signs, diagnostic findings, and outcome in dogs with idiopathic intrahepatic portal hypertension. DESIGN: Retrospective study. ANIMALS: 33 dogs. PROCEDURE: Medical records of dogs with portal hypertension of intra-abdominal origin were reviewed. Dogs with intra-abdominal portal hypertension of vascular causes or with hepatic histopathologic changes consistent with severe diffuse hepatobiliary disease were excluded. History and results of physical examination, clinicopathologic tests, diagnostic imaging studies, histologic examination, and treatment were summarized. Outcome was determined in 26 dogs. RESULTS: Dogs were referred most often because of ascites, intermittent vomiting or diarrhea, and polydipsia of several months' duration. Microcytosis, high serum alkaline phosphatase and alanine transaminase activities, hepatic dysfunction, urine specific gravity < or = 1.021, and abdominal transudate were the predominant clinicopathologic features. Microhepatia, abdominal effusion, and multiple anomalous venous anastomoses were the major findings of diagnostic imaging. Hepatic histopathologic changes were consistent with idiopathic noncirrhotic portal hypertension and were indistinguishable from those of dogs with surgically created portocaval anastomosis. Outcome was determined for 19 dogs released from hospital; 13 dogs remained healthy with mostly palliative treatment for periods of 5 months to 9 years. CONCLUSIONS AND CLINICAL RELEVANCE: The clinical signs, clinicopathologic test results, portal pressure, and gross appearance of the liver of dogs with idiopathic noncirrhotic portal hypertension may be identical to those of dogs with cirrhosis; therefore liver biopsy is crucial. Because the prognosis for idiopathic noncirrhotic portal hypertension is generally favorable, owners of affected dogs should be discouraged from choosing euthanasia.

Spur cell anemia in a dog.

Marked spiculation of red blood cells was observed in a young dog with severe hepatic disease. The resulting anemia was similar to spur cell anemia associated with hepatocellular disease in man. Though the exact cause of spur cell formation is not known, abnormalities in serum lipids and red cell membrane lipids are likely involved. A peculiar pattern of serum lipoproteins may have been involved in formation of this dog's spur cells.

Hepatic cirrhosis associated with long-term anticonvulsant drug therapy in dogs.

Advanced chronic hepatic disease was observed in 5 dogs that had received anticonvulsant drug therapy for 2 to 3 years. Clinical signs included anorexia, weakness, and restlessness, and 2 dogs also had ascites. There were remarkable increases in the serum activities of alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase. The total serum bile acid concentration was high in 3 of 4 dogs that were tested. Sulfobromophthalein excretion was delayed in all dogs. Histologic examination of liver specimens from 4 of the dogs demonstrated macronodular or micronodular cirrhosis.

Compromised hepatic function in dogs treated with anticonvulsant drugs.

Hepatic function tests were performed on 48 dogs that had been given primidone, phenytoin, or a combination of anticonvulsant drugs for 6 months or longer. Except for histories of seizures, 44 of the dogs were healthy at the time the tests were performed. Abnormal test results were observed most frequently in dogs given only primidone and in dogs given combinations of anticonvulsant drugs. The test results that were abnormal most often were those for alanine transaminase and alkaline phosphatase activities, and sulfobromophthalein excretion. The dosage of anticonvulsant drug was found to modify certain test results. Statistically significant positive correlations were found between the dosage of primidone and serum alanine transaminase activity and between the dosage of phenytoin and serum alkaline phosphatase activity. Four of the dogs were examined because of signs of weakness and anorexia and 2 also had ascites. Three of the 4 dogs were euthanatized 2 to 49 days after admission with clinical signs compatible with hepatic failure, and cirrhosis of the liver was confirmed at necropsy. The fourth dog died at home and was not necropsied. Four of the remaining 44 dogs that apparently were healthy at the time of examination had abnormalities in hepatic biochemical test results that were comparable with those in the 4 dogs with clinical illness. We concluded that, although results of hepatic biochemical tests frequently may be abnormal in dogs given anticonvulsant drugs long-term, severe hepatic injury is observed less often.(ABSTRACT TRUNCATED AT 250 WORDS)

Idiopathic pleural effusion and pulmonary thromboembolism in a dog with autoimmune hemolytic anemia.

Pleural effusion and pulmonary thromboembolism were diagnosed in a dog with autoimmune hemolytic anemia. Clinical signs of tachypnea, then dyspnea in association with pleural effusion, developed after 10 days of immunosuppressive corticosteroid therapy (greater than 2 mg/kg of body weight/d, PO). The diagnosis of pulmonary thromboembolism was made tentatively on the basis of results of a radionuclide lung perfusion scan and was confirmed by exploratory thoracotomy and lung biopsy. Tachypnea and pleural effusion gradually resolved without specific treatment, and additional episodes of anemia or dyspnea have not been observed. The pathogenesis of these findings was suspected to be related to corticosteroid-induced thrombotic tendencies, persistent thrombocytosis (greater than 800,000 cells/microliters), and vascular injury caused by repeated jugular venous catheterization. Pulmonary thromboembolism should be considered in dogs that develop clinical signs of tachypnea and/or pleural effusion during administration of immunosuppressive dosages of corticosteroids.

Cryptosporidiosis in a feline leukemia virus-positive cat.

A 4-year-old FeLV-positive cat with a 1-year history of intermittent diarrhea and subsequent anorexia, depression, and weight loss had enteric cryptosporidiosis at necropsy. Cryptosporidium sp is an important cause of gastroenteritis and diarrhea in various species, including human beings with acquired immunodeficiency syndrome. A major determinant of the severity of the disease caused by Cryptosporidium sp is the immunologic status of the affected animal. Cryptosporidiosis should be included in the differential diagnosis of protracted diarrhea in FeLV-positive cats. Because cryptosporidiosis now is recognized as a zoonosis, cats with this disease should be considered a potential source of human infection.

Tethered spinal cord and an intradural lipoma associated with a meningocele in a Manx-type cat.

An 8-month-old neutered male Manx-type cat was evaluated because of clear fluid that had been draining from a skin mass dorsocaudal to the sacrum for 1 week. Neurologically, the cat had poor postural reactions and poor withdrawal reflexes in the hind limbs. Ultrasonography of the dorsal sacral area revealed a 3-cm-long hypoechoic tract extending from the skin mass cranioventrally to the area of the sacrum. The tract appeared to contain a circular mass. Results of myelography and computed tomography helped to confirm the diagnosis of a meningocutaneous tract containing a mass. Surgical exploration was performed and the tract was excised. Histologic changes were similar to those in human beings with tethered spinal cord syndrome and an intradural lumbosacral lipoma. Surgery was indicated in this cat to prevent progression of neurologic signs associated with tethered cord syndrome and to prevent problems associated with loss of CSF through a fistulated meningocele.