J. Catharine Scott-Moncrieff

Plasma and cerebrospinal fluid pharmacokinetics of cytosine arabinoside in dogs

SummaryCytosine arabinoside (ara-C) is a component of many protocols for the treatment of CNS (central nervous system) leukemia and lymphoma in humans and dogs. It is also used for the prophylaxis of CNS metastasis in acute lymphoblastic leukemia. Although ara-C enters the cerebrospinal fluid (CSF) of human cancer patients after i.v. administration, it is unclear whether a similar CNS distribution occurs in humans whose blood-brain barrier has not been compromised by invasive disease. No information on the penetration of ara-C into the CSF in dogs is available. We studied the plasma and CSF pharmacokinetics of 600 mg/m2 ara-C in ten healthy male dogs after its administration as a rapid i.v. bolus (six dogs) or as a 12-h i.v. infusion (four dogs). Ara-C concentration in blood and CSF samples was determined by high-performance liquid chromatography (HPLC). After an i.v. bolus of ara-C, the mean plasma distribution half-life was 7.1±4.5 min and the mean elimination half-life was 69±28 min. The mean plasma clearance was 227±125 ml min−1 m−2. The peak concentration of ara-C in the CSF was 29±11 μm, which occurred at 57±13 min after the ara-C bolus. The CSF elimination half-life was 113±26 min. During a 12-h infusion of ara-C (50 mg m−2 h−1), the plasma steady-state concentration was 14.1±4.2 μm, the CSF steady-state concentration was 8.3±1.1 μm, and the CSF: plasma ratio was 0.62±0.14. The plasma eleimination half-life was 64±19 min and the plasma clearance was 214±69 ml min−1 m−2. The CSF elimination half-life was 165±28 min. No clinically significant toxicity was observed over a 21-day period following drug administration in either of the treatment groups. Our data indicate that ara-C crosses the blood-brain barrier in normal dogs and that i.v. administration of this drug has potential as a treatment modality for neoplasia involving the CNS.

Effect of a Single Plasma Transfusion on Thromboembolism in 13 Dogs With Primary Immune-Mediated Hemolytic Anemia

Thirteen dogs with primary immune-mediated hemolytic anemia received fresh-frozen plasma within 12 hours of admission, in addition to unfractionated heparin and other therapies, such as prednisone, azathioprine, and packed red blood cell transfusion. Antithrombin activity was quantified prior to transfusion and at 30 minutes and 48 hours after transfusion. Plasma antithrombin activity did not change significantly after a single plasma transfusion. There were no deaths in the first 48 hours of treatment. Thromboembolism was identified at necropsy in six of 10 dogs that died within 12 months of admission. There was no significant difference in the incidence of thromboembolism between the current treatment group and a historical control group.

Feline Hyperthyroidism: Potential Relationship with Iodine Supplement Requirements of Commercial Cat Foods

Article rationale Since the late 1970s, there has been a significant increase in the prevalence of feline hyperthyroidism (FH). It is now recognized worldwide as the most common endocrinopathy of older cats, resembling toxic nodular goiter of older humans in iodine-deficient areas. The purpose of this article is to identify the potential for iodine concentrations in the diet to contribute to the etiology of FH. Historical context Iodine concentrations of commercial cat foods vary widely. A review of historical iodine recommendations revealed that the units of iodine supplementation changed in the 1970s. Given this change, foods minimally supplemented since the late 1970s would have been iodine deficient for most cats. Practical relevance Iodine supplementation of commercial cat foods should be evaluated in the light of the iodine recommendations revised in 2006. Foods may remain deficient in iodine if supplemented at the minimum recommended concentration, possibly contributing to the development of FH.

Insulin resistance in cats.

Insulin resistance is defined as decreased sensitivity to insulin. Insulin resistance is an important component of the pathogenesis of type 2 diabetes mellitus (DM), and resolution of peripheral insulin resistance in cats with type 2 DM together with good glycemic control may result in diabetic remission. In insulin-dependent diabetic cats, insulin resistance is manifested clinically as an inadequate response to an appropriate pharmacologic dose of insulin. This article focuses on the clinical problem of insulin resistance in insulin-dependent diabetic cats.

A prospective study of unfractionated heparin therapy in dogs with primary immune-mediated hemolytic anemia.

Unfractionated heparin therapy was initiated at a standard dosage of 300 IU/kg subcutaneously q 6 hours to 18 dogs with immune-mediated hemolytic anemia. Heparins prolongation of activated partial thromboplastin time and change in factor Xa inhibition (anti-Xa activity) were serially monitored during the first 40 hours of therapy. During the initial 40 hours, only eight of 18 dogs had attained anti-Xa activities of > or =0.35 U/mL. No dogs had clinical signs of hemorrhage. Fifteen dogs survived to discharge; 11 dogs were alive at 1 year, and thrombosis was identified in three of six nonsurvivors that were necropsied.

Thyroid disorders in the geriatric veterinary patient.

The effects of age, concurrent illness, and administered medications complicate diagnosis of thyroid dysfunction in geriatric patients. Interpretation of thyroid hormone testing should take these factors into account. The most common thyroid disorder in dogs is acquired hypothyroidism. Therapeutic monitoring should be utilized for monitoring treatment of canine hypothyroidism. The most common thyroid disorder in cats is benign hyperthyroidism. Diagnosis is most often complicated by the presence of concurrent illness. Treatment should be individualized based on individual case characteristics and presence of concurrent illness. Some older cats have a palpable goiter months to years before development of clinical signs of hyperthyroidism.

Cyclic estrous-like behavior in a spayed cat associated with excessive sex-hormone production by an adrenocortical carcinoma

A 15-year-old, spayed female domestic shorthair cat was evaluated for 1-year duration of cyclic intermittent estrous behavior. Diagnostic testing performed before referral, including baseline progesterone concentration, human chorionic gonadotropin (hCG) hormone stimulation test and surgical exploratory laparotomy, had remained inconclusive for a remnant ovary. Evaluation of sex hormones before and after adrenocorticotropic hormone (ACTH) administration revealed increased basal concentrations of androstenedione, estradiol, progesterone, and 17α−hydroxyprogesterone and normal ACTH-stimulated hormone concentrations. Enlargement of the right adrenal gland was identified by abdominal ultrasound. The cat underwent an adrenalectomy and histopathology of the excised adrenal gland was consistent with an adrenocortical carcinoma. Clinical signs resolved immediately following surgery, and most hormone concentrations declined to within or below the reference interval (RI) by 2 months after surgery.

Characteristics of commercially manufactured and compounded protamine zinc insulin

OBJECTIVE To evaluate and compare characteristics of a commercially manufactured protamine zinc insulin (PZI) product and PZI products obtained from various compounding pharmacies. DESIGN Evaluation study. SAMPLE 112 vials of PZI (16 vials of the commercially manufactured product and 8 vials from each of 12 compounding pharmacies) purchased over an 8-month period. PROCEDURES Validated methods were used to analyze 2 vials of each product at 4 time points. Appearance, endotoxin concentration, crystal size, insulin concentration in the supernatant, pH, total insulin and zinc concentrations, and species of insulin origin were evaluated. RESULTS All 16 vials of commercially manufactured PZI met United States Pharmacopeia (USP) specifications. Of 96 vials of compounded PZI, 1 (1 %) contained a concentration of endotoxin > 32 endotoxin U/mL, 23 (24%) had concentrations of insulin in the supernatant > 1.0 U/mL, and 45 (47%) had pH values < 7.1 or > 7.4; all of these values were outside of specifications. Several vials of compounded PZI (52/96 [54%]) did not meet specifications for zinc concentration (0.06 to 0.1 mg/mL for 40 U of insulin/mL, 0.075 to 0.12 mg/mL for 50 U of insulin/mL, and 0.15 to 0.25 mg/mL for 100 U of insulin/mL), and total insulin concentration in 36 [38%] vials was < 90% of the labeled concentration. CONCLUSIONS AND CLINICAL RELEVANCE Only 1 of 12 compounded PZI products met all USP specifications in all vials tested. Use of compounded PZI insulin products could potentially lead to serious problems with glycemic control in veterinary patients.

Interleukin-6 activity in dogs with juvenile polyarteritis syndrome: effect of corticosteroids.

Juvenile polyarteritis syndrome (JPS) is an idiopathic febrile disease in dogs. Elevated serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) have been reported in human patients with vasculitis. We investigated whether these cytokines are also elevated in serum of dogs with JPS using sensitive bioassays. Increased levels of IL-6 activity were detected in the serum of 12 acutely ill dogs, whereas the IL-6 activity decreased to low or undetectable levels during convalescence. Treatment of 5 acute JPS dogs with prednisone resulted in a rapid clinical improvement accompanied by a decrease of IL-6 activity. Withdrawal of prednisone treatment caused reappearance of clinical symptoms and high serum IL-6 activity within a few days. TNF activity could not be detected in the samples of normal dogs, convalescent JPS, or acute JPS dogs. These studies support a role for IL-6 in the pathogenesis of JPS.

Primary esophageal squamous cell carcinoma in a cat.

Primary esophageal squamous cell carcinoma causing stricture was diagnosed in a cat via endoscopy and computed tomography. Difficulty in making this diagnosis via endoscopic biopsy alone is described. Although balloon dilatation was unsuccessful, supportive care via gastrostomy tube feeding and administration of piroxicam successfully allowed a 16-week survival from the time of presentation and a 4-week survival from the onset of treatment with piroxicam.