Adrenomedullin (AM) and adrenomedullin binding protein (AM-BP) in the bovine mammary gland and milk: Effects of stage of lactation and experimental intramammary E. coli infection

Adrenomedullin (AM) has been characterized as an endogenous tissue survival factor and modulator of many inflammatory processes. Because of the increased susceptibility of the mammary gland to infection during the time surrounding parturition in the cow, we investigated how milk and tissue content of AM and its binding protein (AM-BP) might be affected by the stage of lactation and the udder health status. Milk and mammary biopsy samples were obtained from Holstein cows 21 days prior to and at various times after calving to represent the dry period and early and mid-stages of lactation. Additional cows received an intramammary challenge with Escherichia coli for immunohistochemical characterization of AM and AM-BP. Milk AM concentrations were relatively constant across the stages of lactation while AM-BP increased two-fold (P<0.04) between early and mid-lactation. Milk AM (P<0.04) and AM-BP (P<0.03) increased as somatic cell counts (SCCs) increased within a given stage of lactation. Tissue content of both (AM and AM-BP) were significantly affected by stage of lactation, lowest in the dry period and progressively increasing to peak at mid-lactation as well as increasing in association with higher levels of SCCs. Following E. coli challenge, AM increased in epithelial cells surrounding mammary alveoli presenting high levels of SCCs. The data suggest that AM and AM-BP are cooperatively regulated in the mammary gland during lactation; changes in localized tissue AM and AM-BP content reflect a dynamic regulation of these tissue factors in the bovine mammary gland consistent with their protective effects within inflamed tissue.     

Bradyarrhythmia in an anaesthetised, elderly, hypertensive cat

A 14-year-old neutered male domestic shorthaired cat was presented to the University Veterinary Centre Sydney for evaluation and treatment of dental disease. This cat developed an unusual bradyarrhythmia under anaesthesia. The possible causes and treatment of the dysrythmia are discussed.     

Adjuvant immunotherapy of feline fibrosarcoma with recombinant feline interferon-omega

BACKGROUND: Recombinant feline interferon-omega (rFeIFN-omega) was tested as a treatment option for cats with fibrosarcoma to assess safety and feasibility. HYPOTHESIS: Treatment with rFeIFN-omega in cats with fibrosarcoma is safe and feasible. ANIMALS: Twenty domestic cats. METHODS: In an open-labeled uncontrolled clinical trial 12 injections of 1 x 10(6) U/kg rFeIFN-omega were administered over a 5-week period: the 1st through 4th injections were given intratumorally, and the 5th through 12th injections were administered subcutaneously at the tumor excision site. Wide surgical excision of the tumors was carried out after the 4th injection and before the 5th injection of rFeIFN-omega. A Common Terminology Criteria for Adverse Events (CTCAE) analysis was conducted. Flow cytometry of fibrosarcoma cells after incubation with rFeIFN-omega and recombinant feline interferon-gamma was performed to assess the biological effect of rFeIFN-omega. RESULTS: Changes in blood cell count, increases in serum aspartate-amino-transferase activity, serum bilirubin concentration, serum creatinine and serum electrolyte concentrations, weight loss, anorexia, increased body temperature, and reduced general condition were observed but were mostly minor (grade 1 and 2) and self limiting. Eosinophilia (P = .025), neutropenia (P = .021), and weight loss (P < .001) were statistically correlated with rFeIFN-omega-treatment (analysis of parameters before treatment and after 3 injections of rFeIFN-omega). Flow cytometry of 5 unrelated feline fibrosarcoma cell lines showed increased expression of major histocompatibility complex (MHC) class I molecules (P = .026) in response to in vitro incubation with rFeIFN-omega, whereas expression of MHC class II molecules was not affected significantly. CONCLUSIONS AND CLINICAL IMPORTANCE: RFeIFN-omega for the treatment of feline fibrosarcoma is safe, well tolerated, and can be easily performed in practice. To assess the efficacy of the treatment, it should be tested in a placebo-controlled trial.     

High-resolution ultrasonography of xenografted domestic cat ovarian cortex

Transplantation of ovarian tissue has high potential for female gamete conservation. However, optimal timing of oocyte recovery for in vitro maturation and fertilization is still critical. Therefore the aim of the present study was to use high-resolution transcutaneous ultrasonography to monitor follicular development within xenografted ovarian tissue. Ovarian cortex fragments (n=44) from domestic cats were transplanted into athymic nude rats (n=12). Graft development in the animals was assessed weekly by high frequency ultrasound (10-22 MHz) under two different FSH regimes. Blood collection for serum estradiol determination and vaginal smears were performed simultaneously. The xenografts were removed at different time points according to the ultrasound findings. The survival rate of the transplants 4 weeks after surgery was 54.5% and antral follicular growth was observed within 10 grafts from 5 different hosts (8.6 +/- 6.43 follicles per graft). Early follicle antrums could be detected from 0.4 mm onwards. The growth rate of the antral cavity was calculated from weekly measurements (0.56 +/- 0.44 mm per week). Although vaginal cells and estradiol levels followed a cyclic pattern, no correlation was found between follicular diameter, estradiol and keratinized vaginal cells. We recovered 5, 1 and 4 cumulus oocyte complexes from three different individuals during weeks 19, 21, and 23 respectively. Extrusion of a polar body (1 oocyte) and germinal vesicle break down (7 oocytes) indicated progression of maturation after in vitro culture. We conclude that ultrasonography und provided a reliable method to examine xenograft survival and follicular development within the grafts. Furthermore, this technique is suitable for assessment of the efficiency of hormonal treatment and narrowing of the optimal time frame for oocyte retrieval. To our knowledge, this is the first report of the in vivo development of early antral follicles in mammalian species.     

Factors associated with variation in Neospora caninum bulk-milk S/P ratios in initially bulk-milk negative testing Dutch dairy herds

We conducted a study on 81 initially bulk-milk ELISA negative dairy herds taken from a random sample of Dutch dairy herds to evaluate variation in bulk-milk S/P ratios and to study reasons for bulk-milk conversion. These herds were repeatedly (3-month intervals) tested between April 2004 and August 2005 and serostatus of all animals had previously been established as negative (N), low-positive (LP) or high-positive (HP). Of these herds, herd- and test-related factors associated with variation in sample over positive (S/P) ratios were analysed using a multivariable linear-mixed model with ‘herd’ as random effect. In addition, changes of animal serostatus in converting herds were described. S/P ratios were calculated as the optical density of the bulk-milk sample minus the optical density of the negative serum control divided by the difference in optical density between the positive and negative serum control.

Sixteen bulk-milk conversions in 12 dairy herds were seen with few indications of serological conversion in lactating cattle except for one herd in which recrudescence of infection appeared likely in nine cows. The effect of HP serostatus on bulk-milk S/P ratio was 2–3 times stronger compared with LP serostatus. In addition, bulk-milk S/P-ratio increased when the proportion of HP animals between 1 and 60 days in milk increased and decreased when the average milk-production level of the herd increased. Besides these herd-related factors, the use of different ELISA-testkits between test rounds had a significant effect on the S/P-ratio in bulk-milk samples.     

Rapid brain MRI protocols result in comparable differential diagnoses versus a full brain protocol in most canine and feline cases

Evaluation of brain disease in veterinary patients uses a wide variety of MRI sequences. A shortened protocol that maintains consistency of interpretation would reduce radiologist reporting time, patient anesthetic time, and client cost. The aims of this retrospective, methods comparison, observer agreement study were to evaluate whether abbreviated MRI protocols alter differential diagnoses and recommendations compared to our institution's standard protocol; evaluate interobserver agreement on standard brain MRIs; and assess whether differential diagnoses change after postcontrast images. Normal and pathologic canine and feline brain MRIs were retrieved from hospital archives. Three protocols were created from each: a 5-sequence noncontrast enhanced Fast Brain Protocol 1 (FBP1); a 6-sequence contrast-enhanced Fast Brain Protocol 2 (FBP2); and an 11-sequence standard brain protocol (SBP). Three blinded veterinary radiologists interpreted FBP images for 98 cases (1 reader/case) and SBP images for 20 cases (3 readers/case). A fourth observer compared these interpretations to the original MRI reports (OMR). Overall agreement between FBPs and OMR was good (k = 0.75) and comparable to interobserver agreement for multiple reviews of SBP cases. Postcontrast images substantially altered conclusions in 17/97 cases (17.5%), as well as improved interobserver agreement compared to noncontrast studies. The conclusions reached with shortened brain protocols were comparable to those of a full brain study. The findings supported the use of a 6-sequence brain MRI protocol (sagittal T2-weighted [T2w] TSE; transverse T2w turbo spin echo fluid-attenuated inversion recovery, T2*-weighted gradient recalled echo, T1-weighted spin echo, and diffusion weighted imaging/apparent diffusion coefficient; and postcontrast transverse T1-weighted spin echo) for dogs and cats with suspected intracranial disease.     

Intracranial medulloblastoma as the cause of progressive ataxia in a 6-month-old draft horse cross gelding

We describe the unique clinical presentation of a central nervous system neoplasm in a 6-month-old draft horse cross gelding. Based on the neurologic examination at admission, neurolocalization was most consistent with a mildly asymmetric cervical, multifocal, or diffuse myelopathy. Mild vestibular involvement also was considered, but no cranial nerve deficits were observed. The gelding was negative for Sarcocystis neurona or Neospora hughesi based on paired serum and cerebrospinal fluid (CSF) samples analyzed, with no evidence of cervical compression based on contrast myelography. The horse was euthanized because of progression of clinical signs. At necropsy, a mass was identified associated with the cerebellum, and histopathology was consistent with medulloblastoma, which has not been reported previously in the horse.     

Onchocerca sp. in an imported Zangersheide gelding causing suspensory ligament desmitis

A 5-year-old imported Zangersheide gelding was evaluated for SC swellings over both forelimbs and lameness localized to the distal metacarpus. Ultrasound examination of the SC masses was compatible with verminous granulomas. Linear hyperechoic foci were present within the suspensory ligament branches of both forelimbs, suggestive of ligamentous parasitic infiltrates. A diagnosis of onchocerciasis was confirmed on biopsy of a SC mass. The gelding was treated with ivermectin and a tapering course of PO dexamethasone but was eventually euthanized. Necropsy confirmed the presence of SC eosinophilic granulomas and degenerative suspensory ligament desmitis, both with intralesional nematodes. Given the location and appearance of the nematode, a diagnosis of Onchocerca sp., most likely O. reticulata, was made. Onchocerciasis should be included as a differential diagnosis for multifocal suspensory ligament desmitis with these sonographic characteristics when paired with SC masses in imported European Warmbloods.