Lawrence T. Glickman

Mesothelioma in pet dogs associated with exposure of their owners to asbestos

Pet dogs with spontaneous mesothelioma were used to identify environmental exposures that might increase their owners risk of asbestos-related disease. These animals share mans domicile environment, yet do not indulge in activities (e.g., smoking, working) which confound interpretation of epidemiologic studies. Eighteen histologically confirmed canine mesotheliomas were diagnosed at the Veterinary Hospital of the University of Pennsylvania, Philadelphia, from April 1977 to December 1981. Sixteen owners of cases and 32 owners of age, breed, and sex-matched controls were interviewed to determine their occupation and medical history and their dogs medical history, life style, diet, and exposure to asbestos. An asbestos-related occupation or hobby of a household member and use of flea repellents on the dog were significantly associated with mesothelioma. In addition, there was a trend indicating an increased risk of mesothelioma with an urban residence. Lung tissue from three dogs with mesothelioma and one dog with squamous cell carcinoma of the lung had higher levels of chrysotile asbestos fibers than lung tissue from control dogs. These findings indicate that well-designed epidemiological studies of spontaneous tumors in pet animals may provide insight into the role of environmental factors in human cancers and serve as a valuable sentinel model to identify environmental health hazards for humans.

Epidemiologic study of insecticide exposures, obesity, and risk of bladder cancer in household dogs

A case-control study of household dogs was conducted to determine if exposure to sidestream cigarette smoke and chemicals in the home, use of topical insecticides, and obesity are associated with the occurrence of bladder cancer. Information was obtained by interview from owners of 59 dogs with transitional-cell carcinoma of the bladder and 71 age- and breed size-matched control dogs with other chronic diseases or neoplasms. Bladder cancer risk was unrelated to sidestream cigarette smoke and household chemical exposures. Risk was significantly increased by topical insecticide use (OR = 1.6 for 1-2 applications per year and OR = 3.5 for greater than 2 applications per year; chi 2 trend; p = .008). This risk was enhanced in overweight or obese dogs. Further studies of this canine model may facilitate identification of specific carcinogens present in insecticides commonly used on pet animals and in the environment.

Immune-mediated adherence of eosinophils to Toxocara canis infective larvae: the role of excretory-secretory antigens.

Summary The participation of Toxocara canis larval excretory‐secretory antigens in immune‐mediated adherence was determined in vitro. Adsorption of immune sera with excretory‐secretory antigens removed some complement components, removed IgG antibody directed against larval surfaces, and abrogated all adherence observed with untreated immune serum. At least four antigens could be implicated in adherence, by Western blot analysis of adherence mediating sera.

Selective IgA deficiency in the dog

This study documents the occurrence of selective IgA deficiency in the dog. This is a unique spontaneous animal model with clinical and immunologic findings similar to that of selective IgA deficiency in humans, the most common human primary immunodeficiency. The disease in the dog is characterized by chronic, recurrent respiratory infections and dermatitis, low concentrations of serum IgA, normal concentrations of serum IgG and IgM, normal T-cell function as measured by lymphocyte transformation tests, the presence of autoantibodies, and a defect in the maturation or terminal differentiation of IgA B cells into IgA-secreting plasma cells.

Serologic diagnosis of zoonotic pulmonary dirofilariasis

Four symptomatic and four asymptomatic patients with histologically confirmed zoonotic pulmonary dirofilariasis caused by Dirofilaria immitis (dog heartworm) were evaluated serologically. Five patients had diagnostic indirect hemagglutination titers to D. immitis and six had positive findings by enzyme-linked immunosorbent assay. Of the two patients that had nondiagnostic titers by both enzyme-linked immunosorbent assay and indirect hemagglutination, one had an encapsulated necrotic adult worm that appeared to have been dead for some time, and the serum specimen for the second patient had been obtained five months following surgical removal of the granuloma. These findings suggest good sensitivity for these serologic methods in active cases, but declining antibody titers and decreased sensitivity following worm death. In general, cross-reactivity of the enzyme-linked immunosorbent assay with serum from patients with other nonfilarial parasitic infections or neoplasms was not observed.

Zoonotic visceral and ocular larva migrans.

Infection of children with the larval stage of the dog roundworm Toxocara canis usually produces few, if any, clinical signs. In some children, however, the disease may be severe, with permanent ocular or neurologic sequelae. Because the prevalence of infection may exceed 10 per cent in some population subgroups, it is important to understand the modes of transmission and risk factors for infection. The clinical presentations of toxocariasis as well as recommendations for their prevention are described.

Analysis of Toxocara canis larval excretory-secretory antigens: physicochemical characterization and antibody recognition.

Toxocara canis larval excretory-secretory antigens (TEX) were resolved by gradient pore polyacrylamide gel electrophoresis and analyzed using silver, periodic acid-Schiff, and immunoperoxidase stains. At least 15 bands between 29 and 94 kilodaltons (kDa) were detected by silver stain, all of which were recognized by antibodies in serum of a patient with visceral larva migrans. Immunoperoxidase stain detected an additional band at 92 kDa and 4-6 others above 200 kDa. Periodic acid-Schiff stain also detected the high molecular weight components, but did not detect constituents of approximately 53 and 57 kDa. Immunoperoxidase stain using antibody from the vitreous fluid of an ocular larva migrans patient detected 2 TEX components, approximately 76 and 80 kDa. Antigens were compared with respect to batch of larvae and age of larvae in culture. Qualitative differences that correlated with batch were found in the number of constituents above 200 kDa, and in 1 component of 78 kDa. Qualitative differences were noted in many minor components, some of which appeared to correlate with age of larvae in culture. Major TEX constituents were recognized consistently by antibody, regardless of batch or age of larvae. Total protein production per larva was approximately 8 ng/day, and was consistent over time. There was no evidence of neutral proteases in TEX.

Asymptomatic Toxocariasis in Children A Prospective Study and Treatment Trial

Screening of 153 Hispanic children attending a Hospital-based primary care clinic revealed a 16 percent prevalence of Toxocara canis infection. Infections were found in other household occupants for half of these children. Follow-up of 20 children (for periods of up to 7 years) with asymptomatic T. canis infection failed to demonstrate any clinical sequelae. However, longer periods would be necessary to entirely discount the possibility of latent ocular disease. Treatment with thiabendazole did not appear to alter the course of the infection in a controlled 1-year evaluation as measured by eosinophil counts and specific T. canis antibody titers.

Evaluation of the risk of endocarditis and other cardiovascular events on the basis of the severity of periodontal disease in dogs

OBJECTIVE To test the hypothesis that increased severity of periodontal disease in dogs is associated with an increased risk of cardiovascular-related events, such as endocarditis and cardiomyopathy, as well as markers of inflammation. DESIGN Historical cohort observational study. SAMPLE POPULATION 59,296 dogs with a history of periodontal disease (periodontal cohort), of which 23,043 had stage 1 disease, 20,732 had stage 2 disease, and 15,521 had stage 3 disease; and an age-matched comparison group of 59,296 dogs with no history of periodontal disease (nonperiodontal cohort). PROCEDURES Cox proportional hazard regression models were used to estimate the risk of cardiovascular-related diagnoses and examination findings in dogs as a function of the stage of periodontal disease (1, 2, or 3 or no periodontal disease) over time while controlling for the effect of potential confounding factors. RESULTS Significant associations were detected between the severity of periodontal disease and the subsequent risk of cardiovascular-related conditions, such as endocarditis and cardiomyopathy, but not between the severity of periodontal disease and the risk of a variety of other common noncardiovascular-related conditions. CONCLUSIONS AND CLINICAL RELEVANCE The findings of this observational study, similar to epidemiologic studies in humans, suggested that periodontal disease was associated with cardiovascular-related conditions, such as endocarditis and cardiomyopathy. Chronic inflammation is probably an important mechanism connecting bacterial flora in the oral cavity of dogs with systemic disease. Canine health may be improved if veterinarians and pet owners place a higher priority on routine dental care.

Serodiagnosis of ocular toxocariasis: a comparison of two antigens.

This study was designed to compare the sensitivity and specificity of enzyme linked immunosorbent assay (ELISA) for the serodiagnosis of ocular toxocariasis using Toxocara canis embryonated egg antigen (TEE) and toxocara excretory-secretory or exoantigen (TEX) produced in vitro. TEE and TEX ELISA were comparably sensitive, but TEX ELISA was better able to discriminate between serum samples from patients with ocular toxocariasis and those from patients with retinoblastoma. In addition, preabsorption of sera with Ascaris suum embryonated egg antigen seemed to be essential to prevent false positive results with TEE ELISA but was not so critical for TEX-ELISA. Further studies are still required to standardise TEX for serodiagnosis.