Acute basophilic leukaemia in a three-month-old calf

A three-month-old female Holstein–Friesian calf was presented with acute tetraparesis. After neurological examination a multifocal lesion in the central nervous system was suspected with the most pronounced lesions between the third thoracic and the third lumbar vertebrae. Haematological examination revealed moderate anaemia as well as severe thrombocytopenia, neutropenia and leucocytosis. A blood smear and bone marrow aspirate exhibited predominantly blasts with basophilic granulation leading to a diagnosis of acute (myeloid) leukaemia with involvement of the basophilic lineage or an acute basophilic leukaemia. Magnetic resonance imaging revealed spinal cord compression; at necropsy, extensive localised haemorrhages extending into the thoracic vertebral canal were found. Histopathology revealed a large population of blast cells in several tissues including the meninges. Due to multifocal detection of neoplastic cells in the vascular system, neoplasia of the haematopoietic system was assumed in agreement with haematological findings. Signs of paresis could be explained by intramedullary spinal cord haemorrhage and myeloid infiltrations of meningeal vessels. In conclusion, despite its rarity, acute myeloid leukaemia with involvement of the basophilic lineage may be considered in diagnosing calves with progressive deteriorating general condition, paresis, leucocytosis with moderate basophilic differentiation or haemorrhagic disorders.     

Pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid in horses

OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid (EACA), including the effects of EACA on coagulation and fibrinolysis in healthy horses. ANIMALS: 6 adult horses. PROCEDURES: Each horse received 3.5 mg of EACA/kg/min for 20 minutes, i.v. Plasma EACA concentration was measured before (time 0), during, and after infusion. Coagulation variables and plasma alpha(2)-antiplasmin activity were evaluated at time 0 and 4 hours after infusion; viscoelastic properties of clot formation were assessed at time 0 and 0.5, 1, and 4 hours after infusion. Plasma concentration versus time data were evaluated by use of a pharmacokinetic analysis computer program. RESULTS: Drug disposition was best described by a 2-compartment model with a rapid distribution phase, an elimination half-life of 2.3 hours, and mean residence time of 2.5 +/- 0.5 hours. Peak plasma EACA concentration was 462.9 +/- 70.1 microg/mL; after the end of the infusion, EACA concentration remained greater than the proposed therapeutic concentration (130 microg/mL) for 1 hour. Compared with findings at 0 minutes, EACA administration resulted in no significant change in plasma alpha(2)-antiplasmin activity at 1 or 4 hours after infusion. Thirty minutes after infusion, platelet function was significantly different from that at time 0 and 1 and 4 hours after infusion. The continuous rate infusion that would maintain proposed therapeutic plasma concentrations of EACA was predicted (ie, 3.5 mg/kg/min for 15 minutes, then 0.25 mg/kg/min). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that EACA has potential clinical use in horses for which improved clot maintenance is desired.     

Macrogeographic population structure in a parasitic nematode with avian hosts

Much remains to be discovered about the population genetic structure of parasites, despite the importance of such knowledge to understanding the processes involved in the spread of drug resistance through populations. Here we present a study of population genetic diversity in Trichostrongylus tenuis, an avian parasitic nematode infecting both poultry and game birds, where anthelmintic use is common. We examined diversity of nicotinamide dehydrogenase subunit 4 (nad4) mtDNA sequences within and between seven locations: five in the UK (red grouse hosts), one in Iceland (domestic goose) and one in Norway (willow grouse). Within-UK comparisons showed high nucleotide diversity (pi=0.015, n=23) but no structure between locations (Phi(ST)=0.022, P=0.27), with over 97% of variation distributed within-hosts. The highest diversity was found in Iceland (pi=0.043, n=4), and the lowest in Norway (pi=0.003, n=4). Differentiation between countries was considerable (Phi(CT)=0.44, P<0.05), in spite of the potential mixing effects of gene flow via migrating wild hosts and the poultry trade. However, significant pairwise F(ST) values were found only between Norway and the other locations. Phylogenetic analysis provided statistical support for a separate clade for Norwegian samples only, with unresolved diversity leading to a star-shaped relationship between Icelandic and UK haplotypes. These results suggest that Norwegian T. tenuis are isolated, but that there is some connectivity between UK and Icelandic populations. Although anthelmintic resistance has not yet been reported for T. tenuis, the population structure is such that emerging resistance has the potential to spread by gene flow over a large geographic scale.     

Phytoestrogens alter cortisol and androstenedione secretion by porcine adrenocortical cells

The effect of plant-derived, nonsteroidal estrogens (genistein, daidzein and biochanin A) on cortisol and androstenedione secretion by porcine adrenocortical cells was examined. Adrenals were harvested from locally slaughtered mature gilts on days 5-9 of the oestrous cycle. Adrenocortical cells were incubated with or without genistein, daidzein, biochanin A (0.5, 5, 10 or 50 microM), oestradiol (10, 50, 100 or 500 pg/mL) and ACTH (5 nM--positive control). All incubations were performed for 8 h (95% air and 5% CO2, 37 degrees C). ACTH increased cortisol and androstenedione secretion. Genistein, daidzein and biochanin A suppressed cortisol output, whereas androstenedione secretion was enhanced by these phytoestrogens. In contrast, oestradiol did not alter steroid secretion by porcine adrenocortical cells, which may suggest that phytoestrogens have a non-oestrogenic mechanism of action. Therefore, phytoestrogens present in commercial forage may influence adrenocortical function in pigs by decreasing cortisol and increasing androstenedione secretion.     

Doxorubicin and BAY 12-9566 for the treatment of osteosarcoma in dogs: a randomized, double-blind, placebo-controlled study

BACKGROUND: This study was designed to assess the efficacy of a matrix metalloproteinase inhibitor in prolonging posttreatment survival for dogs with appendicular osteosarcoma after treatment with amputation and doxorubicin chemotherapy. HYPOTHESIS: Survival will be prolonged in dogs receiving BAY 12-9566. ANIMALS: The study included 303 dogs with appendicular osteosarcoma. METHODS: Dogs were treated with doxorubicin (30 mg/m2) every 2 weeks for 5 treatments starting 2 weeks after amputation. Dogs were randomly allocated to receive a novel nonpeptidic biphenyl inhibitor of matrix metalloproteinases (MMPs, BAY 12-9566; 4-[4-4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) or placebo after doxorubicin chemotherapy. RESULTS: Median survival for all 303 dogs was 8 months; and 1-year, 2-year, and 3-year survival rates were 35%, 17%, and 9%, respectively. Treatment with BAY 12-9566 did not influence survival. Multivariate analysis revealed that increasing age (P = .004), increasing weight (P = .006), high serum alkaline phosphatase (ALP) (P = .012) and high bone ALP (P < .001) were independently associated with shorter median survival times. Additional analyses on available data indicated that as the number of mitotic figures in the biopsy increased (P = .013), and as plasma active MMP-2 concentrations increased (P = .027), the risk of dying increased. CONCLUSIONS AND CLINICAL IMPORTANCE: Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.     

Evaluation of a novel tumor vaccine in dogs with hemangiosarcoma

BACKGROUND: Hemangiosarcoma (HSA) is a highly metastatic and often rapidly fatal tumor of dogs. At present, adjuvant chemotherapy is the only proven effective treatment for dogs with HSA, though the benefits from chemotherapy are modest. Administration of immunotherapy together with chemotherapy has also been reported to improve survival in dogs with HSA. Therefore, we evaluated safety and immunologic responses to a novel tumor vaccine administered together with doxorubicin chemotherapy in dogs with different stages of HSA. HYPOTHESIS: That tumor vaccination could be safely and effectively combined with doxorubicin chemotherapy for treatment of dogs with HSA. ANIMALS: Twenty-eight dogs with various stages of HSA were enrolled in the study. METHODS: The HSA vaccine was prepared with lysates of allogeneic canine HSA cell lines mixed with an adjuvant composed of liposome-DNA complexes. Dogs received a series of 8 immunizations administered over a 22-week period, and most also received chemotherapy. Clinical adverse effects were noted, immune responses were measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry, and survival times were calculated. RESULTS: The most common adverse effects observed in vaccinated dogs also treated with doxorubicin chemotherapy were diarrhea and anorexia. Vaccinated dogs were found to mount strong humoral immune responses against a control antigen and, most dogs also mounted antibody responses against canine HSA cells. Thirteen dogs with stage II splenic HSA that received the tumor vaccine plus doxorubicin chemotherapy had an overall median survival time of 182 days. CONCLUSIONS: We conclude that an allogeneic tumor lysate vaccine is safe in dogs with HSA and can elicit humoral immune responses in dogs that are receiving concurrent doxorubicin chemotherapy.     

Effects on Pasting Viscosity of Starch and Flour from Different Operating Conditions for the Rapid Visco Analyser

Three wheat flours, three wheat starches, a regular maize starch and a waxy maize starch were subjected to a number of different RVA profiles. Five different initial temperatures were used, 40, 50, 55, 60, and 65°C, with different initial holding times (0–3 min), heating times (2fl–10 min), holding times at 95°C (0–6 min), cooling times (2–6 min), and final hold times (0–10 min) being applied. A range of final temperatures of 30–60°C was also utilized. Significant variations in viscosity were observed with these conditions, particularly in wheat starch and flour. The most important parameters causing these variations were the initial temperature, the heating rate, and the final holding time. Short initial holding times also resulted in a wider spread of values for peak viscosity although there was little effect on the mean value and no significant effect on the holding strength or final viscosity. The final temperature was also important in that lower temperatures gave more viscous gels. Provided that the desired cooling rate could be achieved, varying the cooling time had no effect on the peak or trough viscosities and only a very minor effect on the final viscosity. If final temperatures of 40°C or lower are to be used, the cooling conditions and final hold time would need to be adjusted so that maximum viscosity could be achieved. A proposal for a standard Rapid Visco Analyser (RVA) procedure is: at least 1 min at 50°C, heat to 95°C over 4 min, hold at 95°C for 4 min, cool to 50°C in 3 min, and hold at 50°C for 4 min. These conditions should minimize variation within samples and should allow a better comparison between samples.     

The impact of climate on radial growth and nut production of Persian walnut (<Emphasis Type="Italic">Juglans regia</Emphasis> L.) in Southern Kyrgyzstan

This dendroecological study used time series of climate and radial growth and nut production of Juglans regia to investigate the relationships between these parameters. More than 200 trees growing at sites of different altitude, aspect, inclination and human impact intensity were sampled in walnut-fruit forests of the Jalal Abad region in Southern Kyrgyzstan. Tree rings were dated and ring widths measured. Wide and narrow tree rings, so called positive and negative pointer years, could be explained by climatic events. The mean annual increment differed significantly in different regions and altitudes. The highest values could be found in plantations and at higher altitudes (1,700–2,000 m a.s.l.). Analysing the relationships between nut crop yields and annual increment, we found a significantly positive correlation between nut crop of the current year (x) and ring width of the previous year (x − 1). This relationship is influenced by climatic conditions, and may change in the future if climatic conditions in the region will change. Our study shows that Persian walnut (Juglans regia L.) of South Kyrgyzstan can be used in dendrochronological studies, and illustrates the influence of site conditions and management practices on radial growth of this tree species.