The results of clinical and pulmonary functional evaluation of 24 cats with bronchopulmonary disease and 15 healthy cats are presented. Affected cats had historical evidence of excessive reflexes (coughing, sneezing); physical evidence of airway secretions (crackles), obstruction (wheezing), and increased tracheal sensitivity; radiographic evidence of bronchial and interstitial lung disease; and cytological evidence of airway inflammation or mucous secretions. Bacterial isolates from healthy and affected cats were predominantly Gram-negative rods, indicating that bronchi of cats are not always sterile and that normal flora should be considered in interpreting cultures from cats with suspected bronchopulmonary disease. Cats were grouped according t o relative disease severity based on scored historical, physical, and radiographic abnormalities. The mean (? standard deviation) baseline lung resistance measurement in healthy cats was 28.9 cm H,O/L/s (?6.2 cm H,O/L/s), whereas in mildly, ronchopulmonary disease in the cat represents a group B of poorly understood airway and alveolar space disorder^.'.^ Clinical signs are thought to be due, in part, to underlying airway obstruction. Factors contributing to the development of airway obstruction presumably include development of airway inflammation and mucosal edema, development of airway smooth muscle hypertrophy and constriction, and excessive production or retention of pulmonary secretions. Actual measurements of pulmonary function in cats with bronchopulmonary disease have not been available previously. We obtained pulmonary functional measurements from cats with naturally occurring disease and from clinically healthy cats in an attempt to better assess the presence and degree of airway obstruction in affected cats. Healthy cats were defined as subjects with no known historical or physical findings indicating respiratory disease. A complete clinical database (including historical, physical, and radiographic assessments) was obtained for all cats and also was used to quantify the relative clinical severity of respiratory disease. Measurements of baseline lung resistance (RL) and dynamic lung compliance (Cdyn) were obtained, and airway cytological and microbial culture data were collected. Whenever possible, evaluation also included IV administration of a bronchodilator (BD) to assess reversibility of the airway obstruction, or alternatively, an aerosolized bronchoprovocative challenge to assess the ease with which airway obstruction could be induced (ie, the degree of airway responsiveness [AR] present). Materials and Methods CatsTwenty-four cats with naturally occurring bronchopulmonary disease and 15 clinically healthy cats were evaluated in a cross-sectional study conducted over a 1-year period. The cats with bronchopulmonary disease included 21 cats presented or referred to the University of Illinois Veterinary Medicine Teaching Hospital (UIVMTH) for a variety of clinical signs suggestive of lower respiratory disease. One

Co-incident with the introduction of polybrominated diphenyl ethers (PBDEs) into household materials nearly 30 years ago, feline hyperthyroidism (FH) has increased dramatically. Risk of developing FH is associated with indoor living and consumption of canned catfood. We hypothesized that increases in FH were, in part, related to increased PBDE exposure, with key routes of exposure being diet and ingestion of house dust. This study was designed to determine whether body burdens of PBDEs in hyperthyroid (HT) cats were greater than that of young or sick non-HT cats. Serum samples and clinical information were collected from 23 cats. Serum and dry and canned cat food were analyzed for PBDEs. A spectrum of BDE congeners was detected in all cats, with BDE-47, 99, 207, and 209 predominating. Mean +/- standard error (and median) cumulative sigma PBDE serum concentrations of young, old non-HT, and HT cats were 4.3 +/- 1.5 (3.5), 10.5 +/- 3.5 (5.9), and 12.7 +/- 3.9 (6.2) ng/mL, respectively. Due to high variability within each group, no association was detected between HT cats and sigma PBDE levels. Indicative of age- or disease-dependent changes in PBDE metabolism, BDE-47/99 ratios were inversely correlated with age, and 47/99 and 100/ 99 ratios in HT cats were significantly lower than those in the other cats. Overall, sigma PBDE levels in cats were 20- to 100-fold greater than median levels in U.S. adults. Our results support the hypothesis that cats are highly exposed to PBDEs; hence, pet cats may serve as sentinels to better assess human exposure and adverse health outcomes related to low-level but chronic PBDE exposure.

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High-dose manganese exposure is associated with parkinsonism. Because manganese is paramagnetic, its relative distribution within the brain can be examined using magnetic resonance imaging (MRI). Herein, we present the first comprehensive study to use MRI, pallidal index (PI), and T(1) relaxation rate (R1) in concert with chemical analysis to establish a direct association between MRI changes and pallidal manganese concentration in rhesus monkeys following subchronic inhalation of manganese sulfate (MnSO(4)). Monkeys exposed to MnSO(4) at > or = 0.06 mg Mn/m(3) developed increased manganese concentrations in the globus pallidus, putamen, olfactory epithelium, olfactory bulb, and cerebellum. Manganese concentrations within the olfactory system of the MnSO(4)-exposed monkeys demonstrated a decreasing rostral-caudal concentration gradient, a finding consistent with olfactory transport of inhaled manganese. Marked MRI signal hyperintensities were seen within the olfactory bulb and the globus pallidus; however, comparable changes could not be discerned in the intervening tissue. The R1 and PI were correlated with the pallidal manganese concentration. However, increases in white matter manganese concentrations in MnSO(4)-exposed monkeys confounded the PI measurement and may lead to underestimation of pallidal manganese accumulation. Our results indicate that the R1 can be used to estimate regional brain manganese concentrations and may be a reliable biomarker of occupational manganese exposure. To our knowledge, this study is the first to provide evidence of direct olfactory transport of an inhaled metal in a nonhuman primate. Pallidal delivery of manganese, however, likely arises primarily from systemic delivery and not directly from olfactory transport.

Epidemiologic reports by C.A. Pope III et. al. demonstrated that in the Utah Valley, closure of an open-hearth steel mill over the winter of 1987 was associated with reductions in respiratory disease and related hospital admissions in valley residents. To better examine the relationship between plant-associated changes in ambient particulate matter (PM) and respiratory health effects, we obtained total suspended particulate filters originally collected near the steel mill during the winter of 1986 (before closure), 1987 (during closure), and 1988 (after plant reopening). PM subcomponents were water-extracted from these filters and Sprague-Dawley rats were intratracheally instilled with equivalent masses of extract. Data indicated that 24 hr later, rats exposed to 1986 or 1988 extracts developed significant pulmonary injury and neutrophilic inflammation. Additionally, 50% of rats exposed to 1986 or 1988 extracts had increased airway responsiveness to acetylcholine, compared to 17 and 25% of rats exposed to saline or the 1987 extract, respectively. By 96 hr, these effects were largely resolved except for increases in lung lavage fluid neutrophils and lymphocytes in 1986 extract-exposed rats. Analogous effects were observed with lung histologic assessment. Extract analysis using inductively coupled plasma-mass spectroscopy demonstrated in all three extracts nearly 70% of the mass appeared to be sodium-based salts derived from the glass filter matrix. Interestingly, relative to the 1987 extract, the 1986/1988 extracts contained more sulfate, cationic salts (i.e., calcium, potassium, magnesium), and certain metals (i.e., copper, zinc, iron, lead, strontium, arsenic, manganese, nickel). Although total metal content was (3/4) 1% of the extracts by mass, the greater quantity detected in the 1986 and 1988 extracts suggests metals may be important determinants of the pulmonary toxicity observed. In conclusion, the pulmonary effects induced by exposure of rats to water-based extracts of local ambient PM filters were in good accord with the cross-sectional epidemiologic reports of adverse respiratory health effects in Utah Valley residents.

Records from 20 animals (13 dogs, seven cats) with Candida spp. urinary tract infections were reviewed. Six Candida spp. were isolated; Candida albicans was the most common isolate. Concurrent diseases or nonantifungal drugs administered within 1 month of isolation included antibiotics (n=16), corticosteroids (n=6), diabetes mellitus (n=4), nonurogenital neoplasia (n=3), and noncandidal urogenital disease (n=14). All animals had sources of local or systemic immune compromise that likely predisposed to infection. Of five animals with resolution of infection, three did not receive specific antifungal treatment. The authors conclude that correction of predisposing conditions is likely critical for management of Candida spp. urinary tract infection.

Interstitial lung diseases are a heterogeneous group of disorders with a variety of causes. In veterinary medicine, such lung diseases with a prominent fibrotic component of unknown etiology are often called idiopathic pulmonary fibrosis (IPF). In human medicine, this term is reserved for a distinct disease entity with specific histologic findings labeled as usual interstitial pneumonia (UIP). We identified 23 cats displaying histologic criteria of UIP The purpose of this retrospective study is to describe the presentation and response to therapy of these cats to better define this disease entity. All but 2 cats were middle aged to older (median 8.7 years), with no apparent sex or breed predisposition. Complaints included respiratory distress (n = 18) and cough (13). Duration of signs was less than 6 months in 17 cats. Physical-examination abnormalities included tachypnea, inspiratory or mixed inspiratory and expiratory effort, and adventitial lung sounds. No consistent hematologic or biochemical abnormalities, parasites, or positive serologic results for feline retroviruses, heartworms, or toxoplasmosis were present. Radiographic changes included dense patchy or diffuse interstitial, bronchiolar, and alveolar infiltrates. Analysis of bronchial lavage fluid revealed mild neutrophilic inflammation (n = 6) with no consistent pathogen growth. Clinical condition of 5 cats worsened after lavage. Coincident pulmonary neoplasia was identified in 6 cats. Response to therapy (corticosteroids, antibiotics, bronchodilators, and diuretics) was poor, and most cats died within days to months. Cats with histologic changes compatible with UIP had signs that mimicked many of the clinical findings of human IPF, and treatment response was similarly unrewarding.

BackgroundEmissions from a large peat fire in North Carolina in 2008 were associated with increased hospital admissions for asthma and the rate of heart failure in the exposed population. Peat fires often produce larger amounts of smoke and last longer than forest fires, however few studies have reported on their toxicity. Moreover, reliable alternatives to traditional animal toxicity testing are needed to reduce the number of animals required for hazard identification and risk assessments.MethodsSize-fractionated particulate matter (PM; ultrafine, fine, and coarse) were obtained from the peat fire while smoldering (ENCF-1) or when nearly extinguished (ENCF-4). Extracted samples were analyzed for chemical constituents and endotoxin content. Female CD-1 mice were exposed via oropharyngeal aspiration to 100 μg/mouse, and assessed for relative changes in lung and systemic markers of injury and inflammation. At 24 h post-exposure, hearts were removed for ex vivo functional assessments and ischemic challenge. Lastly, 8 mm diameter lung slices from CD-1 mice were exposed (11 μg) ± co-treatment of PM with polymyxin B (PMB), an endotoxin-binding compound.ResultsOn an equi-mass basis, coarse ENCF-1 PM had the highest endotoxin content and elicited the greatest pro-inflammatory responses in the mice including: increases in bronchoalveolar lavage fluid protein, cytokines (IL-6, TNF-α, and MIP-2), neutrophils and intracellular reactive oxygen species (ROS) production. Exposure to fine or ultrafine particles from either period failed to elicit significant lung or systemic effects. In contrast, mice exposed to ENCF-1 ultrafine PM developed significantly decreased cardiac function and greater post-ischemia-associated myocardial infarction. Finally, similar exposures to mouse lung slices induced comparable patterns of cytokine production; and these responses were significantly attenuated by PMB.ConclusionsThe findings suggest that exposure to coarse PM collected during a peat fire causes greater lung inflammation in association with endotoxin and ROS, whereas the ultrafine PM preferentially affected cardiac responses. In addition, lung tissue slices were shown to be a predictive, alternative assay to assess pro-inflammatory effects of PM of differing size and composition. Importantly, these toxicological findings were consistent with the cardiopulmonary health effects noted in epidemiologic reports from exposed populations.