FATAL ACUTE HEMOLYSIS FOLLOWING TRIAZOLE THERAPY IN AFRICAN PENGUINS ().

Aspergillosis is a major cause of morbidity and mortality in penguins, with triazole antifungal drugs being commonly used for prophylaxis and treatment. This report describes 15 cases of fatal hemolysis associated with liquid itraconazole and voriconazole formulations administered to African penguins () from four institutions. All penguins underwent stressful events (e.

Oral cinacalcet administration decreases serum ionized calcium and parathyroid hormone concentrations in healthy dogs.

Cinacalcet is an oral calcimimetic that has potential to non-invasively treat primary hyperparathyroidism in dogs (Canis lupis familiaris). There is minimal data assessing its efficacy in dogs. This study aimed to determine whether a single dose of cinacalcet decreases serum ionized calcium (iCa), total calcium (tCa), and parathyroid hormone (PTH) concentrations.

Environmental radon, fracking wells, and lymphoma in dogs.

Background: Multicentric lymphoma (ML) in dogs resembles non-Hodgkin lymphoma (NHL) in humans. Human NHL is associated with multiple environmental exposures, including to radon and volatile organic compounds (VOCs).

Hypothesis/objectives: The objective of this study was to determine whether ML in dogs was associated with environmental radon or proximity to horizontal oil and drilling (fracking), a source of VOC pollution.

Urinary and household chemical exposures in pet dogs with urothelial cell carcinoma.

Urothelial cell carcinoma (UCC) has been linked to environmental chemical exposures in people, but these risk factors are not well understood in dogs with UCC. We hypothesised that household chemical exposures contribute to the risk of UCC in pet dogs. This prospective cross-sectional case-control study included 37 dogs with UCC and 37 unaffected breed-, sex-, and age-matched controls.

Potential mechanism for hyperhomocysteinemia in Greyhound dogs.

Background: Greyhounds have been reported to have hyperhomocysteinemia (HHC), but the underlying mechanisms and clinical implications are unclear.

Hypothesis: Our primary aim was to assess serum concentrations of homocysteine (HCy) and related analytes in Greyhounds and to identify a likely metabolic pathway for HHC. A secondary aim was to determine whether HHC is associated with evidence of oxidative stress.

Genotoxicity from metronidazole detected in vitro, but not in vivo, in healthy dogs in a randomized clinical trial.

Objective: To determine whether metronidazole (MTZ), at recommended therapeutic dosages in dogs, induces peripheral blood cell (PMBC) genotoxicity, using the γ-H2AX assay as a sensitive measure of DNA breaks. The secondary aim was to assess dose-dependent genotoxicity in vitro in dog and cat PBMCs exposed to increasing MTZ concentrations.

Animals: 12 healthy employee- and student-owned dogs and blood samples from 2 other healthy untreated dogs and 2 healthy untreated cats.

Environmental exposures and lymphoma risk: a nested case-control study using the Golden Retriever Lifetime Study cohort.

Lymphoma is the second most common cancer affecting Golden Retrievers and is hypothesized to arise through a complex interaction of genetic and environmental factors. The aim of this nested case-control study was to investigate the association between potential environmental pollutant sources and lymphoma risk among Golden Retrievers participating in the Golden Retriever Lifetime Study. Forty-nine Golden Retrievers with non-cutaneous lymphoma and 98 Golden Retrievers without a history of cancer matched by age, sex and neuter status were selected from the Golden Retriever Lifetime Study cohort.

Incidence of hepatopathies in dogs administered zonisamide orally: A retrospective study of 384 cases.

Background: Acute hepatopathy secondary to administration of zonisamide has been reported in 2 dogs, but overall incidence of hepatopathy is unknown.

Objective: To characterize the incidence of hepatopathy in dogs administered zonisamide PO.

Animals: Three hundred eighty-four dogs administered zonisamide PO.

Risk of bladder cancer and lymphoma in dogs is associated with pollution indices by county of residence.

Human urothelial cell carcinoma (UCC) and non-Hodgkin lymphoma are considered environmental cancers in people, but less is known about environment risk for UCC and lymphoma in dogs. The objective of this study was to determine whether dogs with these cancers, compared to unaffected control dogs, live in counties with higher tap water contaminants or higher levels of air pollution as measured by the Environmental Protection Agency (EPA) and by National Air Toxics Assessment chemical exposure risk estimates. Dogs with available home addresses from two previously published case-control populations were included: 66 dogs with UCC and 70 unaffected controls; and 56 boxer dogs with lymphoma and 84 unaffected boxer controls.

Environmental chemical exposures in the urine of dogs and people sharing the same households.

Introduction: Urothelial carcinoma (UCC) develops in both humans and dogs and tracks to regions of high industrial activity. We hypothesize that dogs with UCC may act as sentinels for human urothelial carcinogen exposures. The aim of this pilot study was to determine whether healthy people and dogs in the same households share urinary exposures to potentially mutagenic chemical carcinogens.

Plasma and urinary F-isoprostane markers of oxidative stress are increased in cats with early (stage 1) chronic kidney disease.

Objectives: Oxidative stress contributes to chronic kidney disease (CKD) progression in humans and rodent models; F-isoprostanes (F-IsoPs) are established biomarkers of oxidative stress. Our primary aim was to evaluate plasma F-IsoPs in cats with International Renal Interest Society stage 1 and 2 CKD, compared with healthy cats, and to determine whether plasma and urinary F-IsoPs are equivalent biomarkers. The secondary aim was to assess whether consumption of a renal diet enriched in omega-3 fatty acids led to improvements in plasma and urinary F-IsoPs.

Biochemical, functional, and histopathologic characterization of lomustine-induced liver injury in dogs.

Objective: To characterize the biochemical, functional, and histopathologic changes associated with lomustine-induced liver injury in dogs.

Animals: I0 healthy purpose-bred sexually intact female hounds.

Procedures: Dogs were randomly assigned to receive lomustine (approx 75 mg/m, PO, q 21 d for 5 doses) alone (n = 5) or with prednisone (approx 1.

Genetic and environmental risk for lymphoma in boxer dogs.

Background: Non-Hodgkin lymphoma in humans is associated with environmental chemical exposures, and risk is enhanced by genetic variants in glutathione S-transferases (GST) enzymes.

Objective: We hypothesized that boxer dogs, a breed at risk for lymphoma, would have a higher prevalence of GST variants with predicted low activity, and greater accumulated DNA damage, compared to other breeds. We also hypothesized that lymphoma in boxers would be associated with specific environmental exposures and a higher prevalence of canine GST variants.

Glutathione S-transferase theta genotypes and environmental exposures in the risk of canine transitional cell carcinoma.

Introduction: Transitional cell carcinoma (TCC) in humans is associated with environmental exposures and variants in glutathione S-transferase (GST) genes. Scottish Terriers have a high breed risk for TCC, but the relationship between genetic and environmental risk in dogs is not fully understood.

Hypotheses: Scottish Terriers have a higher frequency of GST-theta variants compared to lower risk breeds.

Prospective crossover clinical trial comparing transdermal with oral phenobarbital administration in epileptic cats.

Objectives: The aim of this study was to compare serum phenobarbital concentrations, adverse events and client satisfaction during 14 weeks of transdermal vs oral phenobarbital administration to epileptic cats.

Methods: This was a prospective, fixed-order, crossover pilot study. Nine client-owned cats with presumptive or diagnosed idiopathic epilepsy were enrolled.

RNA expression profiling in sulfamethoxazole-treated patients with a range of in vitro lymphocyte cytotoxicity phenotypes.

The lymphocyte toxicity assay (LTA) is a proposed surrogate marker of sulfonamide antibiotic hypersensitivity. In the LTA, peripheral blood mononuclear cells (PBMCs) undergo apoptosis more readily in hypersensitive versus tolerant patients when exposed to drug-hydroxylamine metabolites in vitro. The purpose of this study was to identify key gene transcripts associated with increased cytotoxicity from sulfamethoxazole-hydroxylamine in human PBMCs in the LTA.

Evaluation of potential serum biomarkers of hepatic fibrosis and necroinflammatory activity in dogs with liver disease.

Background: Serum interleukin 6 (IL-6), chemokine ligand 2 (CCL2), C-reactive protein (CRP), and the ratio of aspartate transaminase to alanine transaminase (AST:ALT) have been correlated with fibrosis and necroinflammatory activity in humans with various hepatopathies.

Hypothesis/objectives: To determine whether increases in serum IL-6, CCL2, CRP, or AST:ALT were associated with moderate to severe fibrosis or necroinflammatory activity in dogs with various hepatopathies.

Animals: Forty-four client-owned dogs with clinical evidence of liver disease and 10 healthy purpose-bred dogs, all undergoing liver biopsies by laparoscopy or laparotomy.

Hepatic expression profiles in retroviral infection: relevance to drug hypersensitivity risk.

HIV-infected patients show a markedly increased risk of delayed hypersensitivity (HS) reactions to potentiated sulfonamide antibiotics (trimethoprim/sulfamethoxazole or TMP/SMX). Some studies have suggested altered SMX biotransformation in HIV infection, but hepatic biotransformation pathways have not been evaluated directly. Systemic lupus erythematosus (SLE) is another chronic inflammatory disease with a higher incidence of sulfonamide HS, but it is unclear whether retroviral infection and SLE share risk factors for drug HS.

Immunogenicity of trimethoprim/sulfamethoxazole in a macaque model of HIV infection.

Background: Sulfonamide hypersensitivity has a high incidence in HIV infection and correlates with low CD4+ counts, but the mechanisms are not understood. The aims of this study were to determine whether trimethoprim/sulfamethoxazole (TMP/SMX) led to SMX adduct formation, immunogenicity, or signs of drug hypersensitivity in SIV-infected rhesus macaques, and whether differences in antioxidants, pro-inflammatory mediators, or SMX disposition were predictive of drug immunogenicity.

Methods: Nine macaques chronically infected with SIVmac239 and 7 non-infected controls were studied.

Genome-Wide Association Study in Immunocompetent Patients with Delayed Hypersensitivity to Sulfonamide Antimicrobials.

Background: Hypersensitivity (HS) reactions to sulfonamide antibiotics occur uncommonly, but with potentially severe clinical manifestations. A familial predisposition to sulfonamide HS is suspected, but robust predictive genetic risk factors have yet to be identified. Strongly linked genetic polymorphisms have been used clinically as screening tests for other HS reactions prior to administration of high-risk drugs.

Transient cold agglutinins associated with Mycoplasma cynos pneumonia in a dog.

This report details a case of reversible cold agglutinins in a dog with Mycoplasma cynos pneumonia. An 11-month-old female spayed Rhodesian Ridgeback was presented for lethargy and cough. Thoracic radiographs revealed an alveolar pattern present bilaterally in the cranioventral lung lobes.

Report from the National Institute of Allergy and Infectious Diseases workshop on drug allergy.

Allergic reactions to drugs are a serious public health concern. In 2013, the Division of Allergy, Immunology, and Transplantation of the National Institute of Allergy and Infectious Diseases sponsored a workshop on drug allergy. International experts in the field of drug allergy with backgrounds in allergy, immunology, infectious diseases, dermatology, clinical pharmacology, and pharmacogenomics discussed the current state of drug allergy research.

Polymorphisms in the carcinogen detoxification genes CYB5A and CYB5R3 and breast cancer risk in African American women.

Purpose: Cytochrome b 5 (encoded by CYB5A) and NADH cytochrome b 5 reductase (encoded by CYB5R3) detoxify aromatic and heterocyclic amine mammary carcinogens found in cigarette smoke. We hypothesized that CYB5A and CYB5R3 polymorphisms would be associated with breast cancer risk in women.

Methods: We characterized the prevalence of 18 CYB5A and CYB5R3 variants in genomic DNA from African American (AfrAm) and Caucasian (Cauc) women from the Carolina Breast Cancer Study population (1,946 cases and 1,747 controls) and determined their associations with breast cancer risk, with effect modification by smoking.