Behavioral effects of lead and Toxocara canis in mice.

Adult mice were administered the common parasite Toxocara canis or lead or both. The parasite clearly altered mouse performance on tests of exploration, activity, learning, and motor coordination; behavioral effects in mice receiving lead alone were less general. Consequence of Toxocara administration appeared attenuated in animals receiving both agents. Parasite larvae were found in the central nervous system in all infected mice.

1,2-Dimethylhydrazine-induced nuclear aberrations in A/J and C57BL/6J mouse colonic crypts.

A single exposure to 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8] produces several forms of aberrant nuclei in the crypts of the murine colon. The frequency of nuclear aberrations (NAs) was examined in the distal colonic crypts in DMH-sensitive A/J mice and relatively DMH-resistant C57BL/6J mice before and after a single exposure to DMH. NAs, mitotic figures, and crypt column heights were scored for all animals as a function of time following administration of DMH. In both strains there was a significant increase in the absolute and relative frequency of NAs by 12 hours, with a corresponding drop and subsequent overshoot in the mitotic index by 48 hours after DMH. The temporal changes in crypt column height correlate closely with the temporal changes in frequency of NAs in both strains. The results showed that both inbred strains respond to acute DMH exposure in a similar and parallel fashion over time. It was concluded that the NA index assay is a sensitive method for detecting early DMH exposure. However, this assay does not relate to ultimate outcome after chronic DMH exposure and should not be used as a predictor of eventual neoplastic transformation of colonic mucosa with this carcinogen.

Proliferative characteristics of chronic crypt cells in C57BL/6J and A/J mice as predictors of subsequent tumor formation.

It has been proposed that the number and extent of tumors formed after chronic exposure to dimethylhydrazine (DMH) can be predicted by the indigenous number and distribution of DNA-synthesizing cells in the murine colonic mucosa, and that this sensitivity to DMH is genetically determined. In order to test this hypothesis we studied two genetically distinct inbred strains of mice; the DMH-sensitive A/J (A) mouse, and the relatively DMH-resistant C57BL/6J (B) mouse before and after a single exposure to DMH. The untreated A strain had the longer crypt column [33.2 +/- 0.8 (SD) cells versus 28.8 +/- 0.9 cells], a higher absolute number of labeled cells per crypt column (4.4 +/- 0.6 versus 2.6 +/- 0.9), a greater labeling index (13.4 +/- 1.6% versus 9.1 +/- 2.9%), a wider proliferative compartment, and a greater number and percentage of labeled cells in the middle and upper thirds of the crypt than the untreated B strain. After acute exposure to DMH the A strain lost 14 +/- 3% of their total body weight, while the B strain lost 0.5 +/- 2% total body weight 48 h post-DMH. There was an initial loss of cryptal cells, a drop in the labeling index, and a subsequent increase and overshoot in the number of labeled cells and the labeling index. This pattern of cell loss and recovery over time was parallel in both strains, and thus cannot explain the differences in ultimate tumor formation after chronic exposure to the carcinogen. The data are consistent with the theory that the susceptibility to DMH carcinogenesis can be predicted by the indigenous proliferative characteristics of the murine colonic mucosa. The acute proliferative response to DMH in these strains is similar and parallel; thus ultimate tumor load may depend on long term effects such as the establishment of stable transmissible mutations.

Canine viruses and multiple sclerosis.

Serum and cerebrospinal fluid from multiple sclerosis (MS) patients and control subjects were tested and compared for presence and titer of neutralizing antibody against the most common canine viruses. Canine viruses included canine distemper virus (CDV), canine adenovirus 1 (CAV-1), canine parainfluenza virus (CPIV), canine herpesvirus (CHV), canine coronavirus (CCV), and canine parvovirus (CPV). Neutralizing titers against measles virus (MV) and human adenovirus 8 (HA8) were also tested. Significantly elevated (p less than 0.05) antibody levels in sera from MS patients were found only against MV and CDV, but this depended upon the study population and the method of evaluation. The CDV-neutralizing component in serum could be absorbed on MV-infected cells. Results of this study failed to establish a link between canine viruses and MS.

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.

Intrathecal dextrose to prevent seizures after metrizamide myelography in dogs.

Seizures are possible complications of metrizamide myelography. The protective effect (as measured by reduction in seizure incidence) of dextrose in solution with metrizamide was studied by conducting a double-blind trail. Fourteen dogs each had two myelograms at five- to 16-day intervals in a crossover study, while ten additional dogs each had a single myelogram. Metrizamide alone and metrizamide in dextrose were used for the myelograms. No significant protective effect of dextrose was found.

Nematode intestinal parasites of children in rural Guinea, Africa: prevalence and relationship to geophagia.

BACKGROUND: Intestinal parasitism is common among children in developing countries, but the risk factors for infection are not well characterized. METHODS: A stool examination was performed on 286 randomly selected children aged 1-18 years from three rural villages in Guinea, Africa. Information collected by questionnaire was used to examine the relationship between geophagia and infection with intestinal nematodes acquired by ingestion versus skin penetration. RESULTS: Fifty-three per cent of children were infected by at least one type of soil-transmitted nematode. Geophagia was reported by parents to occur in 57%, 53%, and 43%, of children ages 1-5, 6-10, and 11-18 years, respectively. The pattern of geophagia by age and gender of the children more closely resembled the infection pattern for the two orally acquired and soil-transmitted nematodes (Ascaris lumbricoides, Trichuris trichiura) than it did the infection pattern for the two soil-transmitted nematodes that infect by skin penetration (hookworm, Strongyloides stercoralis). CONCLUSIONS: These findings demonstrate that geophagia is an important risk factor for orally acquired nematode infections in African children. Education regarding geophagia prevention should be an integral component of any soil-transmitted parasite control programme.

PIP: Intestinal parasites are routinely found among children in developing countries, but the risk factors of such infection are poorly characterized. The stools of 286 randomly selected children aged 1-18 years from 3 rural villages in Guinea were examined. Data collected via questionnaire were then analyzed to assess the relationship between geophagia, the regular ingestion of soil, and infection with intestinal nematodes acquired through ingestion rather than through skin penetration. 53% of children were infected with at least 1 type of soil-transmitted nematode, and geophagia was reported by parents to occur in 57%, 53%, and 43% of children aged 1-5, 6-10, and 11-18 years, respectively. The pattern of geophagia by age and gender of the children more closely resembled the infection pattern for the 2 orally acquired and soil-transmitted nematodes Ascaris lumbricoides and Trichuris trichiura than it did the infection pattern for the 2 soil-transmitted nematodes which infect by penetrating the skin, hookworm and Strongyloides stercoralis. Geophagia is therefore an important risk factor for orally acquired nematode infections among African children, and education on geophagia prevention should be an integral component of all soil-transmitted parasite control programs.

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.

Comparative longevity of pet dogs and humans: implications for gerontology research.

The effect of breed and body weight on longevity in the pet dog was analyzed, and a method was developed to standardize the chronological age of dogs in terms of physiological time, using human year equivalents. Mortality data from 23,535 pet dogs were obtained from a computerized data base of North American veterinary teaching hospitals, and the median age at death was determined for pure and mixed breed dogs of different body weight. Body size in the dog was inversely related to longevity. Within each body weight category, the median age at death was lower for pure breed dogs compared with mixed breed dogs. The difference between the standardized physiological ages of mixed breed dogs of the same chronological age in the smallest and largest body weight categories varied from 8 to > 15 years, and between large and small pure breed dogs, the disparity was even greater. Laboratory research to explore the biological basis for these breed and body weight specific differences in life span among dogs may provide additional clues to genetic factors influencing senescence.

Zoonotic roundworm infections.

The larval stage of several animal parasites can infect humans and produce severe disease. Visceral and ocular larval migrans caused by the common dog roundworm, Toxocara canis, are two well-recognized clinical syndromes. With the wider availability of serodiagnostic tests for toxocaral infection, other syndromes characterized by neuropsychologic deficits, epilepsy, asthma, abdominal distress, and chronic allergy have been described. Treatment with corticosteroids in conjunction with anthelminthic drugs may be life- or sight-saving. Recognition of the risk factors for infection is key to prevention, reinfection, and more serious illness.

Clinical, serologic, and epidemiologic characteristics of ocular toxocariasis.

The clinical, serologic, and epidemiologic characteristics of 17 cases of ocular toxocariasis (OT) were studied and compared with those of a control group of 15 cases of other ocular diseases whose differential diagnosis included retinoblastoma. The prevalence and mean titers of Toxocara antibody detected by enzyme-linked immunosorbent assay were greater (P less than 0.005) for patients with OT than for the control group, but not all clinically diagnosed OT cases had detectable antibody. The prevalence of pica was significantly greater in cases than in controls (P less than 0.05). Almost all case and control patients had a history of exposure to pet dogs and cats, but recent exposure to puppies (less than 3 months old) was significantly associated with Toxocara infection in this study group.

Pica patterns, toxocariasis, and elevated blood lead in children.

Blood samples were obtained during a lead screening program from 100 children aged 1-6 years in Allegheny County, Pennsylvania, to determine whether there was any association between specific forms of pica and infection with Toxocara canis, the principal cause of visceral larva migrans in the United States, or elevated blood lead levels. Significant associations were found between: 1) feces, soil, or grass pica and Toxocara infection; 2) paint or plaster pica and elevated blood lead; and 3) dog ownership and Toxocara infection. These findings suggest that an accurate pica history may be useful in identifying potential health problems in children.

Cisplatin versus cisplatin combined with piroxicam in a canine model of human invasive urinary bladder cancer.

PURPOSE: More than 12,000 people are expected to die from invasive transitional cell carcinoma (TCC) of the urinary bladder each year in the United States, indicating that more effective therapy is needed. Drugs inhibiting cyclooxygenase (cox) have recently been found to have chemopreventive and antitumor activity and may potentiate the effects of chemotherapy. The purpose of this study was to determine whether cisplatin combined with the cox-inhibitor piroxicam would induce remission more frequently than cisplatin alone in a relevant animal model of human invasive TCC. METHODS: Pet dogs with naturally occurring, histopathologically confirmed, measurable TCC of the urinary bladder were randomized to receive cisplatin (60 mg/m2 i.v. every 21 days) or cisplatin (same dosage) combined with piroxicam (0.3 mg/kg orally every 24 h). Complete staging was performed prior to and at 6-week intervals during therapy. RESULTS: After eight dogs had been evaluated in each treatment group, a significant difference in remission rate was noted (Fisher's Exact test, P < 0.004). Tumor responses in the cisplatin/piroxicam group included two complete remissions (CR), four partial remissions (PR), two stable disease (SD), and no progressive disease (PD). Tumor responses to cisplatin alone in eight dogs were no CR, no PR, four SD, and four PD. Six additional dogs were treated with cisplatin/piroxicam, and in total 10 of 14 dogs had remission (two CR, eight PR). Renal toxicity of cisplatin/ piroxicam was frequent and dose limiting. CONCLUSIONS: Cisplatin/piroxicam induced remission more frequently than cisplatin alone in a canine model of human invasive TCC. Strategies to reduce renal toxicity need to be developed prior to evaluation of cisplatin/piroxicam in humans or general use of this treatment in pet dogs.

Naturally-occurring canine transitional cell carcinoma of the urinary bladder A relevant model of human invasive bladder cancer.

Invasive bladder cancer results in over 10,000 deaths yearly in the United States alone. More effective therapy for invasive bladder cancer is clearly needed. As new cellular and molecular targets for therapy are identified, relevant animal models are needed to test new therapeutic strategies aimed at these targets prior to human clinical trials. The purpose of this review is to characterize spontaneous invasive transitional cell carcinoma of the urinary bladder (TCC) in dogs, to summarize the similarities and differences between canine and human invasive TCC, and to describe how canine TCC could serve as a relevant model of human invasive bladder cancer. Information was summarized from 102 dogs with TCC evaluated and treated at the Purdue University Veterinary Teaching Hospital, from a review of the Veterinary Medical Data Base, and from reports in the literature. Canine TCC was found to be very similar to human invasive bladder cancer in histopathologic characteristics, molecular features, biological behavior including metastasis, response to medical therapy, and prognosis. Differences between canine and human TCC were few, but included gender predilection with a male:female ratio of 2.8:1 in humans versus a male:female ratio of 0.5:1 in dogs. The location of the TCC within the bladder also differed: Most canine TCC was trigonal in location, whereas more than 50% of human TCC was in the lateral and posterior walls of the bladder. Considering the great similarity between invasive bladder cancer in humans and dogs, spontaneous canine TCC can be considered a relevant animal model of human invasive bladder cancer.

Serum and vitreous Toxocara antibody in nematode endophthalmitis.

Five patients had a clinical diagnosis of nematode endophthalmitis and had both a serum and vitreous titer for Toxocara antibody. All five patients had a vitreous titer that was equal to or greater than the serum titer. Serum and vitreous obtained from ten other patients who had no evidence of endophthalmitis did not show this correlation. This study provides the clinician with a further understanding of the meaning of a positive enzyme-linked immunosorbent assay titer as well as an additional area for analysis in selected patients with ocular inflammation.

Epidemiological characteristics and clinical findings in patients with serologically proven toxocariasis.

The enzyme-linked immunosorbent assay (ELISA) using Toxocara canis larva-specific antigens was used to confirm a presumptive clinical diagnosis of visceral larva migrans in patients whose serum specimens were submitted to the Center for Disease Control. The clinical and epidemiological characteristics of patients with diagnostic ELISA titres (greater than or equal to log2 5) were compared with patients who had less or no detectable antibody. The typical patient with serologically confirmed toxocaral visceral larva migrans was about five years of age and resided in the southern half of the USA. Clinical findings were likely to include leucocytosis, eosinophilia, an increased anti-A or anti-B isohaemagglutinin titre, and an elevated serum IgG level. Pica, as ascertained by a physician questionnaire, was not a consistent finding and both sexes were nearly equally represented.

Reduction in DNA damage in brain and peripheral blood lymphocytes of elderly dogs after treatment with dehydroepiandrosterone (DHEA).

Steady state levels of DNA damage are substantial in vertebrate animals as a consequence of exposure to endogenous and environmental mutagens. DNA damage may contribute to organismal senescence and an increased risk for specific age-related diseases. In this study, we determined if treatment with the neuroactive adrenal steroid, dehydroepiandrosterone (DHEA), which exhibits antioxidant and anticarcinogenic properties in rodents, would reduce DNA damage in the brain and peripheral blood lymphocytes (PBLs) of elderly dogs. Elderly male dogs, physiologically equivalent to 59-69-year-old men, were randomly assigned to receive no treatment (n=9 dogs) or DHEA at 100mg/kg PO daily (n=8 dogs). Extent of DNA damage in brain cells and PBLs was measured using alkaline comet assay. The effect of DHEA treatment on the susceptibility of PBLs to H(2)O(2)-induced DNA damage was also measured. We found that elderly male dogs receiving daily DHEA treatment for 7 months had significantly less DNA damage detectable in their brain compared to age-matched control dogs. After 7 months treatment, DHEA-treated dogs also had a significant reduction in DNA damage in PBLs compared to pre-treatment levels. We also found that PBLs of dogs treated with DHEA were more resistant to H(2)O(2)-induced DNA damage than PBLs of untreated dogs. Our results did not show that basal DNA damage in PBLs was strongly correlated with DNA damage within the brain. The results of this study suggest that DHEA supplementation can significantly reduce steady state levels of DNA damage in the mammalian brain. Further evaluation of DHEA as a neuroactive agent and its effects on DNA damage and gene expression in other tissues and species is warranted.

Immune response of neonatal specific pathogen-free cats to experimental infection with Bartonella henselae.

The purpose of this study was to determine whether neonatal cats develop and maintain a persistent bacteremia for longer than do adult cats with a normal mature immune system, and whether neonatal cats are susceptible to infection with Bartonella henselae by oral inoculation. Neonatal specific pathogen-free (SPF) cats were inoculated with B. henselae intradermally (n = 4) or orally (n = 5) or with 0.9% NaCl (n = 2). Blood was collected periodically through 16 weeks post-inoculation (PI) for serology, bacteriology and complete blood count. Cats inoculated orally or intradermally at 3-5 days of age were bacteremic through 12-16 weeks PI, similar to what is documented for adult cats inoculated intradermally or intravenously. One cat inoculated at age 2 weeks was bacteremic through 10 weeks PI; the other was not bacteremic. Intradermally inoculated neonatal cats produced serum IgG antibodies to B. henselae but orally inoculated neonatal cats did not. Infected cats with and without serum IgG antibodies to B. henselae became blood-culture negative simultaneously, suggesting that IgG is not required to clear bacteremia.

Evidence of reproductive failure and lack of perinatal transmission of Bartonella henselae in experimentally infected cats.

Five female specific pathogen-free (SPF) cats inoculated intradermally with B. henselae and bacteremic for 4 weeks, and one cat inoculated with 0.9% NaCl, were bred with uninfected SPF male cats. The uninfected female became pregnant with one breeding, while three infected cats became pregnant 1-12 weeks later, after repeated breedings. Two infected females either did not become pregnant or maintain pregnancies despite repeated breedings. Infected cats produced anti-B. henselae IgM and IgG antibodies. Fetuses and kittens of infected cats were not infected and did not produce anti-B. henselae antibodies. Male cats bred with infected females did not become infected or seroconvert. Maternal anti-B. henselae IgG antibodies detected in sera of kittens 2 weeks post-partum were no longer detectable 10 weeks post-partum. These findings suggest that B. henselae causes reproductive failure in female cats, but is not transmitted transplacentally, in colostrum or milk, or venereally. Infected cats immunosuppressed with methylprednisolone acetate after their kittens were weaned had no detectable bacteria in tissues, suggesting that they were no longer infected.

Streptococcus suis infection in swine: a retrospective study of 256 cases. Part I. Epidemiologic factors and antibiotic susceptibility patterns.

A retrospective study of 256 cases of naturally acquired Streptococcus suis infections in swine submitted to the Indiana Animal Disease Diagnostic Laboratory from 1985 to 1989 was performed to determine the epidemiologic factors and antibiotic susceptibility patterns associated with S. suis serotypes 1-8 and 1/2. A standardized computer form was used to record the history, signalment, and clinical signs obtained from the records of selected cases and the microscopic lesions identified after review of the histopathology slides for each case. A computer statistics package (SAS) was used to evaluate the data. Although the number of recovered S. suis isolates increased in the fall and winter months, most serotypes were readily isolated throughout the year; only serotypes 1, 4, 7, and 1/2 increased in frequency of isolation in the fall, winter, and spring months. The majority (61.1%) of infected pigs in this study were < 12 weeks of age. More than 75% of pigs infected with serotypes 1, 6, 7, and 1/2 were < 12 weeks of age. There was extensive overlap in the age distributions for pigs with each serotype, and statistically significant differences for most serotypes were not observed. Fifty percent of pigs infected with S. suis serotypes 1 and 1/2 were 3-10 weeks of age, 50% of pigs infected with serotype 2 were 6-14 weeks of age, and 50% of pigs infected with serotypes 3, 4, 5, 7, and 8 were 2-16 weeks of age. Isolates of S. suis were not uniformly susceptible to penicillin, and a large percentage of isolates were resistant to many antibiotics in common usage.(ABSTRACT TRUNCATED AT 250 WORDS)