Life course analysis of the impact of mammary cancer and pyometra on age-anchored life expectancy in female Rottweilers: Implications for envisioning ovary conservation as a strategy to promote healthy longevity in pet dogs.

Mammary cancer and pyometra are important health hazards associated with ovary conservation in pet dogs. Early ovariohysterectomy may reduce the incidence of these two diseases, but an estimate of the extent to which the development of mammary cancer or pyometra adversely influences overall longevity is missing. As a first step toward addressing this knowledge gap, the results of a historical cohort study of Rottweilers that lived in North America are reported. Questionnaires completed by owners and veterinarians were used to obtain lifetime health and medical information on 242 female Rottweilers, including years of lifetime ovary exposure, age at death, and cause of death. To determine the extent to which longevity was shortened in females that developed these ovary-associated diseases, age-anchored life expectancy-defined as the median number of remaining years until death for females alive at specified ages during the life course-and years of life lost, a measure of premature mortality, were estimated. Mammary carcinoma was diagnosed in 19 (7.9%) females; median age at diagnosis was 8.5 years; case fatality was 37%. Pyometra was diagnosed in 16 (6.6%) females; median age at diagnosis was 5.4 years; case fatality was 7%. Median lifetime ovary exposure for the study population was 4.3 years. Although risk for developing both diseases increased with longer ovary exposure, longer ovary exposure (≥4.3 years) was also associated with an overall longevity advantage-a 33% decrease in mortality, living 17 months longer than females with shorter ovary exposure (P=0.002). Analysis of age-anchored life expectancy showed that at no time points during the life course was the current or future diagnosis of mammary carcinoma or pyometra associated with shortened survival compared to females who never developed these conditions. This lack of longevity disadvantage is an expected result for diseases with late-onset, moderate (<50%) case fatality (mammary carcinoma) or low (<10%) case fatality (pyometra). These findings fail to support the notion that a strategy, such as elective ovariohysterectomy, implemented to reduce the incidence of mammary carcinoma and pyometra will beneficially impact overall longevity. It follows that future efforts to find and implement effective longevity-promoting interventions should look beyond reducing the incidence of a particular disease to considering trade-offs.

Exceptional longevity in female Rottweiler dogs is not encumbered by investment in reproduction.

To better understand the potential trade-off between female reproductive investment and longevity in an emerging model of human healthspan, we studied pet dogs to determine whether intensity of reproduction (total number of offspring) encumbered the likelihood of exceptional longevity. This hypothesis was tested by collecting and analyzing lifetime medical histories, including complete reproductive histories, for a cohort of canine "centenarians"--exceptionally long-lived Rottweiler dogs that lived more than 30% longer than the breed's average life expectancy. Reproductive intensity (number of litters, total number of pups) and tempo of reproductive effort (age at first reproduction, mean interbirth interval, age at last reproduction) in 78 exceptionally long-lived female Rottweilers (>13 years old) were compared to a cohort of 97 female Rottweilers that had usual longevity (age at death 8.0-10.75 years). We found no evidence that a mother's physiological investment in offspring was associated with disadvantaged longevity. Instead, similar to some studies in women, our data showed an inverted U-shaped trend, suggesting that moderate investment in reproduction may promote longevity. Late reproductive success, a much-studied surrogate of maternal fitness in women, was not a strong predictor of longevity in this canine cohort. Instead, independent of reproductive investment, the duration of lifetime ovary exposure was significantly associated with highly successful aging. Our results from exceptionally long-lived pet dogs provide rationale for further investigative efforts to understand the ovary-sensitive biological factors that promote healthy longevity in women and pet dogs.

Probing the perils of dichotomous binning: how categorizing female dogs as spayed or intact can misinform our assumptions about the lifelong health consequences of ovariohysterectomy.

In 2009, we reported findings from the first study evaluating the relationship between canine longevity and number of years of lifetime ovary exposure. All previous studies examining gonadal influences on canine longevity relied upon categorizing females as "intact" or "spayed" based on gonadal status at the time of death. Our study of Rottweilers generated a novel result: Keeping ovaries longer was associated with living longer. This result challenged previous assumptions that spayed females live longer. In the present investigation, we explored a methodological explanation for the apparent contradiction between our results and those of others, so we might better understand the impact that timing of spaying has on longevity. We hypothesized that naming female dogs as "spayed" or "intact" based upon gonadal status at time of death - a method we refer to as dichotomous binning - inadequately represents important biological differences in lifetime ovary exposure among bitches spayed at different ages. This hypothesis predicts that a strong relationship between years of lifetime ovary exposure and longevity in a population could be obscured by categorizing females as spayed or intact. Herein, we provide support for this hypothesis by reanalyzing longevity data from 183 female Rottweilers. In this study population, there was a three-fold increased likelihood of exceptional longevity (living ≥ 13 yr) associated with the longest duration of ovary exposure. However, categorizing females in this population as spayed or intact yielded the spurious, contradictory assertion that spayed females (presumed to have the least ovary exposure) are more likely to reach exceptional longevity than those that are intact. Thus, by ignoring the timing of spaying in each bitch, the inference from these data was distorted. It follows from this new understanding that dichotomous binning-naming females as spayed or intact-is inadequate for representing lifetime ovary exposure, introducing misclassification bias that can generate misleading assumptions regarding the lifelong health consequences of ovariohysterectomy.

The role of angiostatin in the spontaneous bone and prostate cancers of pet dogs.

Angiostatin is a potent inhibitor of angiogenesis generated in cancer-bearing hosts by tumor-derived proteases. Because the naturally occurring bone and prostate cancers of pet dogs provide unique model systems to study factors that regulate cancer progression and tumor dormancy, we investigated the capacity of these tumors to generate angiostatin. We determined that angiostatin fragments are present in urine of dogs with bone cancer. The identity of these fragments was confirmed by comparison of the experimentally determined protein sequence to that of a clone of canine angiostatin. Importantly, these fragments were absent in urine collected from the same dogs after complete surgical removal of the primary tumor. We also demonstrate that canine prostate cancer cells are capable of processing plasminogen to angiostatin in vitro. These findings provide rationale for using spontaneous canine tumor models to isolate endogenous angiogenesis inhibitors and to investigate their therapeutic use against cancer.

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.

Fibrocartilaginous embolic myelopathy in miniature schnauzers.

In large- and giant-breed dogs, fibrocartilaginous embolic myelopathy (FCEM) is a well-recognized syndrome of acute spinal cord infarction caused by embolization of fibrocartilage. The miniature schnauzer is reportedly the most frequently affected small breed, although clinical data from only six miniature schnauzers with FCEM is available in the literature. The purposes of this study were to determine the relative frequency of FCEM compared to other causes of myelopathy in miniature schnauzers, to characterize the clinicopathological features of FCEM in 38 miniature schnauzers, and to directly compare FCEM and intervertebral disk herniation in miniature schnauzers with respect to age at diagnosis; gender; neuroanatomical localization; and progression, asymmetry, and severity of neurological deficits. Fibrocartilaginous embolic myelopathy was the most common cause of myelopathy in miniature schnauzers. Age at diagnosis, asymmetry and severity of neurological deficits, and lack of progression of clinical signs after 24 hours assisted in distinguishing FCEM from intervertebral disk herniation. Fibrocartilaginous embolic myelopathy-related mortality in miniature schnauzers was significantly lower than mortality rates reported for affected large and giant breeds. Only 22% of miniature schnauzers were euthanized because of their disease, although the vast majority of survivors failed to achieve complete neurological recovery.

Prospective study of antibody to human papilloma virus type 16 and risk of cervical, endometrial, and ovarian cancers (United States).

OBJECTIVE: Human papilloma virus (HPV) is frequently detectable in cancers of the cervix, vagina, and vulva, but its role in endometrial and ovarian cancers is less certain. This analysis aimed to examine the association of presence of HPV type 16 (HPV-16) antibodies with subsequent risk of cervical, endometrial, and ovarian cancers. METHODS: In a prospective study enrolling over 15,000 pregnant women, pre-cancer sera from women who developed cervical (n = 83), endometrial (n = 34), and ovarian (n = 35) cancers were compared with sera from 172 control women frequency-matched by age group and race. RESULTS: HPV-16 seropositivity (OR = 2.0, 95% CI 1.0-3.4) was associated with cervical cancer, with the association more prominent for cancers occurring within 10 years of serum sampling (OR = 2.3, 95% CI 1.0-5.3) than cancers occurring later (OR = 1.6, 95% CI 0.75-3.6). Overall, the associations between HPV-16 seropositivity and endometrial (OR = 1.6, 95% CI 0.64-3.8) and ovarian cancers (OR = 1.1, 95% CI 0.43-2.8) were not significant, although the odds ratios for those cancers occurring within 20 years after serum sampling were similar to that for cervical cancer (OR = 2.2 for both). CONCLUSIONS: Our results confirm that HPV-16 infection precedes the development of cervical cancer. Predictability of HPV-16 seropositivity for risk of other female cancers warrants further investigation.

Prostaglandin E2 concentrations in naturally occurring canine cancer.

The purpose of this study was to determine the PGE2 concentration in naturally-occurring cancer in pet dogs and in canine cancer cell lines in order to identify specific types of canine cancer with high PGE2 production which could serve as preclinical models to evaluate anticancer strategies targeting PGE2. PGE2 concentrations were measured by enzyme immunoassay in canine melanoma, soft tissue sarcoma, transitional cell carcinoma, osteosarcoma, and prostatic carcinoma cell lines; in 80 canine tumor tissue samples including oral melanoma (MEL), oral squamous cell carcinoma (SCC), transitional cell carcinoma of the urinary bladder (TCC), lymphoma (LSA), mammary carcinoma (MCA), osteosarcoma (OSA), prostatic carcinoma (PCA); and in corresponding normal organ tissues. High concentrations of PGE(2)(range 400-3300 pg/10(4)cells) were present in cell culture medium from the transitional cell carcinoma, prostatic carcinoma, and osteosarcoma cell lines. PGE2 concentrations in tumor tissues were elevated (tumor PGE2 concentration>mean+2X sd PGE(2)concentration of normal organ tissue) in 21/22 TCC, 5/6 PCA, 7/10 SCC, 5/10 MEL, 3/8 MCA, 4/15 OSA, and 0/9 LSA. Results of this study will help guide future investigations of anticancer therapies that target cyclooxygenase and PGE2.

Clinical and pathologic aspects of spontaneous canine prostate carcinoma: a retrospective analysis of 76 cases.

BACKGROUND: Pet dogs and men share a vulnerability for the development of prostate carcinoma. The purpose of this study was to further characterize the clinical and pathologic features of spontaneous canine prostate carcinoma. METHODS: A multiinstitutional, retrospective study was conducted using 76 dogs with prostate carcinoma that underwent postmortem evaluation. For each case, clinical and pathologic data were tabulated and hematoxylin/eosin-stained tissue sections from the primary tumor and metastatic lesions were evaluated. Prostatic carcinomas were subclassified based upon the presence of glandular, urothelial, squamoid, or sarcomatoid differentiation. We focused our analysis on dogs that differed with respect to morphologic features of the primary tumor, lifetime duration of testicular hormone exposure, and presence of skeletal metastases. RESULTS: The vast majority of canine prostate carcinomas affected elderly sexually intact dogs or dogs that underwent surgical castration after sexual maturity. Adenocarcinoma was the most frequent histologic type, although more than half of canine prostate carcinomas exhibited intratumoral heterogeneity. In many cases, primary tumors showed mixed morphology, characterized by two or more types of differentiation. Duration of testicular hormone exposure was significantly different between dogs with adenocarcinoma and dogs with mixed morphology tumor, but did not appear to influence the frequency or pattern of metastases. Overall, gross metastases were present in 80% of dogs with prostate carcinoma. Skeletal metastases were present in 22% of cases, and the predominantly axial skeletal distribution of these lesions was similar to that reported in men with prostate carcinoma. Young dogs were at highest risk for development of skeletal metastases. CONCLUSIONS: This study provides a more complete characterization of spontaneous prostate carcinoma of dogs in terms of morphologic heterogeneity, skeletal metastases, and the influence of testicular hormones. Prostate carcinoma in pet dogs provides an immunocompetent, autochthonous tumor system that mimics certain aspects of human prostate cancer. This spontaneous model may contribute to our understanding of the factors that regulate carcinogenesis within the aged prostate, and to the development of chemoprevention strategies or bone-targeted therapies.

Life expectancy, antagonistic pleiotropy, and the testis of dogs and men.

BACKGROUND: Prostate cancer and benign prostatic hyperplasia are important age-related prostatic diseases that are under the influence of testicular hormones. However, the disparity between male and female life expectancy within the human population cannot be explained solely by the prevalence of prostatic disease-related mortality. The purpose of this paper is to explore the possibility that the testis exerts a detrimental effect on life span. METHODS: First, we review previously published and unpublished data on the influence of the testis on the life span of dogs and men. Aging in pet dogs and men is then discussed in terms of evolutionary theory, emphasizing the significance of a prolonged postreproductive life span and possible consequences of late-acting deleterious genes in these two species. Finally, we present preliminary data that orchiectomy can reduce DNA damage within the brain of elderly male dogs. RESULTS AND CONCLUSIONS Taken together, these observations raise the intriguing possibility that interventions to antagonize the testis might have much broader therapeutic applications that will extend well beyond the treatment of prostate cancer.

HTLV type I/II in British Columbia Amerindians: a seroprevalence study and sequence characterization of an HTLV type IIa isolate.

It has been established that the human T cell lymphotropic viruses type I and II (HTLV-I and HTLV-II) are both present in some indigenous peoples of the Americas. While HTLV-I has been identified in coastal British Columbia Indians (BCIs), HTLV-II has not been previously reported in the BCIs or other Canadian Amerindians. The prevalence of HTLV-I and HTLV-II in these populations has not been extensively studied. In this article, we examine a group of BCIs from Vancouver Island who belong to the Nuu-Chah-Nulth and are known to have an increased incidence of rheumatic disease. In 494 serum samples from this tribe, the levels of prevalence of HTLV-I and HTLV-II were 2.8 and 1.6%, respectively. No association could be made between arthropathy and HTLV-I infection. In addition, we characterized an HTLV-II isolate of a BCI from the coastal mainland of British Columbia and with a history of intravenous drug abuse. This case represents the first molecular characterization of a Canadian Amerindian HTLV-II isolate: a subtype IIa virus with phylogenetic affinity for intravenous drug user isolates and containing an extended form of the Tax protein. These results are consistent either with this strain having been sampled from a polymorphic ancestral pool of HTLV-II that gave rise to the current epidemic spread of this virus by intravenous drug use and sexual transmission, or with its being "back-transmitted" into the BC Amerindian population in association with intravenous drug use.

5' Nuclease assays for the loci CCR5-+/Delta32, CCR2-V64I, and SDF1-G801A related to pathogenesis of AIDS.

BACKGROUND: Variations within the human genome play important roles in human disease. To study variations related to susceptibility to AIDS, we have developed 5' nuclease assays that eliminate post-PCR molecular biology steps. METHODS: TaqMan assays based on the 5' nuclease activity of Taq polymerase and fluorescent resonance energy transfer were developed to score alleles at the biallelic loci CCR5-+/Delta32, CCR2-V64I and SDF1-G801A. For each assay, 72 samples were analyzed. Data collection and analysis were performed on the Prism 7700 Sequence Detection System. For comparison with gel electrophoresis methods, each locus was also scored on a subset of 24 samples, using restriction enzymes or single-strand conformational polymorphism (SSCP). RESULTS: Clear allelic discrimination was obtained on each of the 72 samples for all three TaqMan assays. The TaqMan scores for the subset of 24 samples were concordant with the restriction enzyme and SSCP scores. CONCLUSIONS: Because of its simplicity, speed, and potential for automation and miniaturization, TaqMan is an excellent candidate for investigation of genetic variation in clinical, research, and forensic settings.

Reoperative neurosurgery in dogs with thoracolumbar disc disease.

OBJECTIVE: To characterize the subset of dogs in our neurosurgical practice that underwent spinal surgery for thoracolumbar (TL) disc herniation and subsequently underwent additional decompressive TL surgery. STUDY DESIGN: A retrospective case series. SAMPLE POPULATION: Thirty dogs that underwent reoperation for TL disc herniation. A comparison group of Dachshunds that underwent only one decompressive TL disc surgery was also studied. METHODS: Dogs that underwent reoperation were divided into two groups based on the interval between their first and second surgery. The early reoperation group included those dogs having a second surgery less than 4 weeks after the initial operation. The late reoperation group included those dogs having a second surgery more than 4 weeks after the initial operation. For each Dachshund in the late reoperation group, two Dachshunds that underwent only one decompressive TL disc surgery were selected and formed the comparison group. Dogs in the comparison group were matched with reoperated cases based on the severity of preoperative neurologic deficit and site of disc herniation. These two groups were compared to determine: (1) if age and body weight were risk factors for reoperation, and (2) if dogs had a poorer functional outcome after their second decompressive surgery than did those in the comparison group after their first (and only) decompressive surgery. RESULTS: A total of 30 of 467 (6.4%) dogs that underwent decompressive TL disc surgery were reoperated. In the early reoperative cases (n = 5 dogs), the inciting cause in all cases was residual compression from disc material at the site of the initial surgery. In the late reoperation group, 22 of 25 (88%) cases had a second disc herniation at a site distinct from the initial lesion. Dachshunds had a significantly higher risk for late reoperation (odds ratio and 95% CI = 3.67, 1.46 to 10.03); other small and medium-sized breeds (<20 kg) were underrepresented. Age and body weight were not significant predictors for reoperation. A total of 21 of 23 (91%) dogs had functional recovery after late reoperation. Complete sensorimotor loss was a significant negative predictor of functional recovery in the late reoperative cases (P = .01). Likelihood of functional recovery in dogs after their second decompressive surgery was identical to the functional recovery of dogs in the comparison group. CONCLUSIONS AND CLINICAL RELEVANCE: Our results show that a second disc herniation occurring at a site distinct from the initial lesion is the most common cause for reoperation and that Dachshunds have a significantly greater risk than other breeds.

An apparent case of human T-cell lymphotropic virus type II (HTLV-II)-associated neurological disease: a clinical, molecular, and phylogenetic characterisation.

Several studies have reported an association between HTLV-II and a neurological condition which has come to be called HTLV-II-associated myelopathy and is similar, in some cases, to HTLV-I-associated myelopathy. To further explore the establishment of an etiological link between this virus and neurological disease, we determined the HTLV status of three individuals, one of which presented with symptoms of progressive ataxia. Since the patient with neurological disease and her husband were HTLV-II positive, we had the potential to study one of few cases of an HTLV-II-associated neurological disorder, and the first case in Canada. However, although the individual with the neurological disease was HTLV-II positive, we discovered that her brother, who displays the same clinical symptoms, was not positive for either HTLV-II or HTLV-I. Thus, disease association with HTLV-II became unsupportable. We present here, nevertheless, the first sequence and phylogenetic analysis of an HTLV-II isolate in Canada. This study suggests that cases of HTLV-II and neurological disease must be carefully investigated before any etiological conclusions can be made.

Overexpression of the EphA2 tyrosine kinase in prostate cancer.

BACKGROUND: Molecules that are highly expressed by human prostate cancers may serve as therapeutically relevant targets or tumor markers. Tyrosine kinases are frequently overexpressed in metastatic tumor cells and this prompted us to screen for tyrosine kinases that are overexpressed in prostate cancer cells. METHODS: Expression levels of the EphA2 receptor tyrosine kinase were determined by Western blot analysis in canine and human prostate cancer cell lines and in immortalized and transformed variants of 267B1 prostatic epithelial cells. EphA2 levels in benign human prostate and prostate cancers were also determined in formalin-fixed, paraffin-embedded tissues using immunohistochemical staining. RESULTS: Metastatic prostate cancer cells overexpressed EphA2 by 10-100 fold as compared with non-invasive prostatic epithelial cells. EphA2 immunoreactivity in vivo was also significantly greater in human prostate cancers as compared with benign prostate epithelium. CONCLUSIONS: The EphA2 receptor tyrosine kinase is differentially expressed in human and canine prostate cancer cell lines and overexpressed in human prostate cancers as compared with benign prostate tissues. Metastasis-derived canine prostate carcinoma cell lines overexpress EphA2 and may provide pre-clinical models to further evaluate the role of EphA2 in prostate carcinogenesis. Further investigations are needed to determine the utility of EphA2 as a tumor marker and a novel target in human prostate cancer.

Imaging of spontaneous canine mammary tumors using fluorescent contrast agents.

We present near-infrared frequency-domain photon migration imaging for the lifetime sensitive detection and localization of exogenous fluorescent contrast agents within tissue-simulating phantoms and actual tissues. We employ intensity-modulated excitation light that is expanded and delivered to the surface of a tissue or tissue-simulating phantom. The intensity-modulated fluorescence generated from within the volume propagates to the surface and is collected using a gain-modulated image-intensified charge-coupled device camera. From the spatial values of modulation amplitude and phase of the detected fluorescent light, micromolar volumes of diethylthiatricarbocyanine iodide (tau = 1.17 ns) and indocyanine green (ICG) (tau = 0.58 ns) embedded 1.0 cm deep in a tissue phantom are localized and discriminated on the basis of their lifetime differences. To demonstrate the utility of frequency-domain fluorescent measurements for imaging disease, we image the fluorescence emitted from the surface of in vivo and ex vivo canine mammary gland tissues containing lesions with preferential uptake of ICG. Pathology confirms the ability to detect spontaneous mammary tumors and regional lymph nodes amidst normal mammary tissue and fat as deep as 1.5 cm from the tissue surface.

Functional outcome in dogs after surgical treatment of caudal lumbar intervertebral disk herniation.

Caudal lumbar disk herniations (i.e., third lumbar [L3] to seventh lumbar [L7] intervertebral spaces) represent approximately 15% of surgically treated thoracolumbar disk herniations in dogs. A retrospective case-control study was conducted to determine the postoperative outcome of this subset of dogs in the authors' neurosurgical practice. Medical records (1985 through 1996) were reviewed for dogs with caudal lumbar disk herniation confirmed at surgery. Thirty-six cases were identified. For each case, two dogs that underwent surgical treatment for upper motor neuron thoracolumbar disk herniation (tenth thoracic [T10] to L3 intervertebral spaces) were selected as controls. Probabilities of functional recovery for cases and controls were 81% and 85%, respectively (p value of 0.49). In dogs with caudal lumbar disk herniation, complete sensorimotor loss was the only significant predictor of functional recovery (p value of 0.005). Disk herniations that occur at the thoracolumbar junction and those that occur in the caudal lumbar region should not be considered to be different in terms of surgical treatment and postoperative outcome. The lower motor neuron signs that often accompany caudal lumbar disk herniation reflect the site of spinal cord injury and do not necessarily predict a poor prognosis.

High-grade prostatic intraepithelial neoplasia in dogs.

The dog is the only nonhuman species in which high-grade intraepithelial neoplasia (HGPIN) and invasive carcinoma spontaneously occur. Our work was the first to describe HGPIN in the dog prostate. Canine HGPIN bears remarkable morphologic similarity to its human counterpart. There is also striking similarity between canine and human HGPIN with respect to basal layer disruption, proliferative index, and microvessel density. For each of these parameters, HGPIN is intermediate between benign epithelium and invasive carcinoma, strengthening the hypothesis that HGPIN is an intermediate step on the road to prostate cancer. In another study, we showed that HGPIN is present in the majority (55%) of elderly sexually intact pet dogs without clinical evidence of prostate cancer. These data suggest that the early events of prostate carcinogenesis may occur with high frequency within the prostates of pet dogs sharing the same environment as humans. We are currently conducting a large-scale autopsy-epidemiological study to further characterize the epidemiology of HGPIN and invasive carcinoma in pet dogs. We are also testing the potential utility of pet dogs for the rapid, cost-effective in vivo screening of chemopreventive agents by using the prevalence and extent of HGPIN in the dog prostate as a surrogate endpoint biomarker.

Cervical vertebral fractures in 56 dogs: a retrospective study.

The clinicopathological features of cervical fractures in 56 dogs were reviewed. "Hit by car" (HBC) was the most common inciting cause, and the axis and atlas were the vertebrae most frequently affected. Surgical treatment was associated with high (36%) perioperative mortality. However, all dogs that survived the perioperative period achieved functional recovery. Functional recovery was achieved in 25 (89%) of 28 nonsurgically treated dogs with adequate follow-up. Overall, severity of neurological deficits (nonambulatory status) and prolonged interval (five days or longer) from trauma to referral were associated with poorer outcome. Nonsurgical treatment is a viable therapeutic approach for many dogs with cervical fractures. Early neck immobilization and prompt referral are recommended, because delay in referral decreases the likelihood of functional recovery.