Procarbazine as adjunctive therapy for treatment of dogs with presumptive antemortem diagnosis of granulomatous meningoencephalomyelitis: 21 cases (1998-2004)

BACKGROUND: Granulomatous meningoencephalomyelitis (GME) is an idiopathic inflammatory disease of the central nervous system. Remission often is short-lived in dogs treated with glucocorticoids. Procarbazine is T cell-specific and crosses the blood-brain barrier. HYPOTHESIS: Dogs with presumptive antemortem diagnosis of GME given procarbazine as adjunctive therapy to prednisone will have improved long-term outcome compared with dogs given no treatment or glucocorticoids alone. ANIMALS: Two groups were studied: (1) Dogs with presumptive antemortem diagnosis of GME treated with procarbazine and prednisone (n = 21); (2) Dogs that had a histologic diagnosis of GME at postmortem examination and received no treatment (n = 11). METHODS: Dogs with presumptive GME treated with procarbazine were identified retrospectively from medical records of 2 veterinary referral hospitals. Selection criteria required all dogs have a neurologic examination, blood work, cerebrospinal fluid analysis, and brain imaging (MRI or CT). RESULTS: Median survival time for all dogs studied was 5.0 months. Median survival time for dogs treated with procarbazine was 14.0 months and for untreated dogs, 0.73 months. Treatment with procarbazine was significantly correlated with survival time (P < .001). Procarbazine was the only independent predictor of survival. Prednisone was reduced in dosage or discontinued in 17 dogs. Adverse reactions to procarbazine therapy included myelosuppression in 7 dogs and hemorrhagic gastroenteritis in 3 dogs. CONCLUSION: These data suggest that procarbazine treatment of presumptive GME may result in greater improved long-term outcome than has been previously reported for glucocorticoid treatment alone and may complement other immunomodulatory therapies. Procarbazine-treated dogs must be monitored for adverse reactions.     

Spatial clustering of swine influenza in Ontario on the basis of herd-level disease status with different misclassification errors

This approach maximizes sensitivity of serology-based monitoring systems by considering spatial clustering of herds classified as false positive by herd testing, allowing outbreaks to be detected in an early phase. The primary objective of this study was to determine whether swine herds infected with influenza viruses cluster in space, and if so, where they cluster. The secondary objective was to investigate the combining of a multivariate spatial scan statistic with herd test results to maximize the sensitivity of the surveillance system for swine influenza. We tested for spatial clustering of swine influenza using the Cuzick–Edwards test as a global test. The location of the most likely spatial clusters of cases for each subtype and strain in a sample of 65 sow and 72 finisher herds in 2001 (Ontario, Canada), and 76 sow herds in 2003 (Ontario, Canada) was determined by a spatial scan statistic in a purely spatial Bernoulli model based on single and multiple datasets.

A case herd was defined by true herd-disease status for sow or finisher herds tested for H1N1, and by apparent herd-disease status for sow herds tested for two H3N2 strains (A/Swine/Colorado/1/77 (Sw/Col/77) and A/Swine/Texas/4199-2/98 (Sw/Tex/98)). In sow herds, there was no statistically significant clustering of H1N1 influenza after adjustment for pig-farm density. Similarly, spatial clustering was not found in finisher herds. In contrast, clustering of H3N2 Sw/Col/77 (prevalence ratio = 12.5) and H3N2 Sw/Tex/98 (prevalence ratio = 15) was identified in an area close to a region with documented isolation of avian influenza isolates from pigs.

For the H1N1 subtype tested by ELISA, we used an approach that minimized overall misclassification at the herd level. This could be more applicable for detecting clusters of positive farms when herd prevalence is moderate to high than when herd prevalence is low. For the H3N2 strains we used an approach that maximized herd-level sensitivity by minimizing the herd cut-off. This is useful in situations where prevalence of the pathogen is low. The results of applying a multivariate spatial scan statistic approach, led us to generate the hypothesis that an unknown variant of influenza of avian origin was circulating in swine herds close to an area where avian strains had previously been isolated from swine. Maximizing herd sensitivity and linking it with the spatial information can be of use for monitoring of pathogens that exhibit the potential for rapid antigenic change, which, consequently, might then lead to diminished cross-reactivity of routinely used assays and lower test sensitivity for the newly emerged variants. Veterinary authorities might incorporate this approach into animal disease surveillance programs that either substantiate freedom from disease, or are aimed at detecting early incursion of a pathogen, such as influenza virus, or both.     

Association between frontal-sinus size and syringohydromyelia in small-breed dogs

OBJECTIVE: To determine whether frontal-sinus size is associated with syringohydromyelia. SAMPLE POPULATION: Medical records and magnetic resonance images of 62 small-breed dogs. PROCEDURES: Medical records and magnetic resonance images were reviewed retrospectively for evaluation of frontal-sinus size and syringohydromyelia. A Yates-corrected 2-tailed chi2 test was used to determine whether an association existed between absent or miniscule frontal sinuses and syringohydromyelia. The strength of the association was evaluated by means of prevalence and odds ratios. RESULTS: Absent or miniscule air-filled frontal sinuses were detected in 28 of 62 (45%) dogs, and syringohydromyelia was detected in 12 of 62 (19%) dogs. Syringohydromyelia was detected in 10 of 28 dogs with absent or miniscule frontal sinuses (prevalence, 36%; 95% confidence interval, 16% to 55%) and in 2 of 34 dogs with larger frontal sinuses (prevalence, 6%; confidence interval, 0% to 15%). The probability of detecting syringohydromyelia in dogs with absent or miniscule air-filled frontal sinuses was significantly greater than the probability of detecting it in dogs with larger frontal sinuses. The prevalence ratio was 6.1, and the odds ratio was 8.9. CONCLUSIONS AND CLINICAL RELEVANCE: An association between frontal-sinus size and syringohydromyelia was identified in small-breed dogs, suggesting that the pathogenesis of syringohydromyelia in some instances may involve abnormal development of the entire or supratentorial part of the cranium, as opposed to being limited to the infratentorial part.     

Biomarkers in the assessment of acute and chronic kidney diseases in the dog and cat

In both human and veterinary medicine, diagnosing and staging renal disease can be difficult. Measurement of glomerular filtration rate is considered the gold standard for assessing renal function but methods for its assessment can be technically challenging and impractical. The main parameters used to diagnose acute and chronic kidney disease include circulating creatinine and urea concentrations, and urine‐specific gravity. However, these parameters can be insensitive. Therefore, there is a need for better methods to diagnose and monitor patients with renal disease. The use of renal biomarkers is increasing in human and veterinary medicine for the diagnosis and monitoring of acute and chronic kidney diseases. An ideal biomarker would identify site and severity of injury, and correlate with renal function, among other qualities. This article will review the advantages and limitations of renal biomarkers that have been used in dogs and cats, as well as some markers used in humans that may be adapted for veterinary use. In the future, measuring a combination of biomarkers will likely be a useful approach in the diagnosis of kidney disorders.     

The association between submission counts to a veterinary diagnostic laboratory and the economic and disease challenges of the Ontario swine industry from 1998 to 2009

An intuitive assumption is to believe that the number of submissions made to a veterinary diagnostic laboratory is dictated by the financial state of the industries using the laboratory. However, no research is available to document how the economics of a food animal industry affects laboratory submissions and therefore disease monitoring and surveillance efforts. The objective of this study was to determine if economic indices associated with the Ontario swine industry can account for the variability seen in these submissions. Retrospective swine submissions made to the Animal Health Laboratory at the University of Guelph, Guelph, Ontario from January 1998 to July 2009 were compiled. The following economic, demographic, and health variables impacting Ontario swine production were selected for analysis: auction price, lean-hog futures, currency exchange rate, price of corn, an outbreak of porcine circovirus type-2 associated diseases (PCVAD), government incentive program, number of farms in province, and average farm size. All independent variables identified by unconditional associations to have a significance of P≤0.2 with the outcome of monthly submission count were included in a multivariable negative binomial model. A final model was identified by a backwards elimination procedure. A total of 30,432 swine submissions were recorded. The mean frequency of monthly submissions over 139months was 212.9 (SD=56.0). After controlling for farm size, the number of pigs in Ontario, higher submission counts were associated with a weaker CAD$ versus US$, higher auction prices, and a PCVAD outbreak (P<0.001). The results suggest that both economic volatility and disease outbreaks in the Ontario swine industry drive submissions to the laboratory. In conclusion, lab submissions are a useful source of animal health data for disease surveillance; however, surveillance activities should also monitor the economics of the industry.     

Ovulation,Pregnancy Rate and Early Embryonic Development in Vernal Transitional Mares Treated with Equine‐ or Porcine‐FSH

The objective of this study was to compare the efficacy of purified equine‐ and porcine‐FSH treatment regimes in mares in early vernal transition. Mares (n = 22) kept under ambient light were examined ultrasonographically per‐rectum, starting January 30th. They were assigned to one of two treatment groups using a sequential alternating treatment design when a follicle ≥ 25 mm was detected. In the eFSH group, mares were treated twice daily with equine‐FSH, and in the pFSH group mares were treated twice daily with porcine‐FSH; treatments were continued until follicle(s) ≥ 35 mm, and 24 h later hCG was administered. Oestrous mares were inseminated with fresh semen and examined for pregnancy on days 11–20 post‐ovulation. In the eFSH group, 11/11 (100%) mares developed follicle(s) ≥ 35 mm, 8/11 (73%) ovulated and 6/8 (75%) conceived. In the pFSH group, 5/11 (45%) developed follicle(s) ≥ 35 mm, 4/11 (36%) ovulated and 3/4 (75%) conceived. Treatment with eFSH resulted in a greater ovarian stimulation; higher number of pre‐ovulatory‐sized follicles, higher number of ovulations and higher number of embryos (p < 0.05). Following ovulation, serum progesterone concentrations were correlated with the number of CLs and supported early embryonic development; maternal recognition of pregnancy occurred in all pregnant mares. We concluded that eFSH can be used to effectively induce follicular growth and ovulation in vernal transitional mares; however, if bred, diagnosis and management of twins’ pregnancies would be required prior to day 16 because of the increased risk of multiple embryos per pregnancy. Conversely, the current pFSH treatment regime cannot be recommended.     

Transplacental Transfer of Iron in the Water Buffalo (Bubalus bubalis): Uteroferrin and Erythrophagocytosis

The objectives of this investigation were to understand transplacental transport of iron by secreted uteroferrin (UF) and haemophagous areas of water buffalo placenta and clarify the role(s) of blood extravasation at the placental‐maternal interface. Placentomes and interplacentomal region of 51 placentae at various stages of gestation were fixed, processed for light and transmission electron microscopy, histochemistry and immunohistochemistry. Haemophagous areas were present in placentomes collected between 4 and 10 months of pregnancy. Perl’s reaction for ferric iron was negative in placentomes, but positive in endometrial glands. Positive staining for UF indicated areas in which it was being taken up by phagocytosis and/or fluid phase pinocytosis in areolae of the interplacentomal mesenchyme, with little staining in endometrial stroma. Imunohistochemistry detected UF in trophectoderm of haemophagous regions of placentomes and in other parts of the foetal villous tree, but the strongest immunostaining was in the epithelial cells and lumen of uterine glands. Ultrastructural analyses indicated that erythrophagocytosis was occurring and that erythrocytes were present inside cells of the chorion that also contained endocytic vesicles and caveolae. Results of this study indicate that both the haemophagous areas of placentomes and the areolae at the interface between chorion and endometrial glands are important sites for iron transfer from mother to foetal‐placental tissues in buffalo throughout pregnancy.     

Persistent,symptomless, systemic,and seed-borne infection of lettuce by <Emphasis Type="Italic">Botrytis cinerea</Emphasis>

Experiments are presented which show that Botrytis cinerea, the cause of grey mould disease, is often present in symptomless lettuce plants as a systemic, endophytic, infection which may arise from seed. The fungus was isolated on selective media from surface-sterilised sections of roots, stem pieces and leaf discs from symptomless plants grown in a conventional glasshouse and in a spore-free air-flow provided by an isolation propagator. The presence of B. cinerea was confirmed by immuno-labelling the tissues with the Botrytis-specific monoclonal antibody BC-12.CA4. As plants grew, infection spread from the roots to stems and leaves. Surface-sterilisation of seeds reduced the number of infected symptomless plants. Artificial infection of seedlings with dry conidia increased the rate of infection in some experiments. Selected isolates were genetically finger-printed using microsatellite loci. This confirmed systemic spread of the inoculating isolates but showed that other isolates were also present and that single plants hosted multiple isolates. This shows that B. cinerea commonly grows in lettuce plants as an endophyte, as has already been shown for Primula. If true for other hosts, the endophytic phase may be as important a component of the species population as the aggressive necrotrophic phase.     

The effect of select seminal plasma proteins on endometrial mRNA cytokine expression in mares susceptible to persistent mating‐induced endometritis

In the horse, breeding induces a transient endometrial inflammation. A subset of mares are unable to resolve this inflammation, and they are considered susceptible to persistent mating‐induced endometritis PMIE Select seminal plasma proteins cysteine‐rich secretory protein‐3 (CRISP‐3) and lactoferrin have been shown to affect the innate immune response to sperm in vitro. The objective of this study was to determine whether the addition of CRISP‐3 and lactoferrin at the time of insemination had an effect on the mRNA expression of endometrial cytokines in susceptible mares after breeding. Six mares classified as susceptible to PMIE were inseminated during four consecutive oestrous cycles with treatments in randomized order of: 1 mg/ml CRISP‐3, 150 μg/ml lactoferrin, seminal plasma (positive control) or lactated Ringer's solution (LRS; negative control) to a total volume of 10 ml combined with 1 × 10⁹ spermatozoa pooled from two stallions. Six hours after treatment, an endometrial biopsy was obtained for qPCR analysis of selected genes associated with inflammation (pro‐inflammatory cytokines interleukin (IL)‐1β, IL‐8, tumour necrosis factor (TNF)‐α, interferon (INF)‐γ, anti‐inflammatory cytokines IL‐1RN and IL‐10, and inflammatory‐modulating cytokine IL‐6). Seminal plasma treatment increased the mRNA expression of IL‐1β (p = .019) and IL‐8 (p = .0068), while suppressing the mRNA expression of TNF (p = .0013). Lactoferrin also suppressed the mRNA expression of TNF (p = .0013). In conclusion, exogenous lactoferrin may be considered as one modulator of the complex series of events resulting in the poorly regulated pro‐inflammatory response seen in susceptible mares.