Time-course study of the immunotoxic effects of the anticancer drug chlorambucil in the rat.

In 2005, the International conference on harmonization (ICH) recommended that all new human pharmaceuticals be tested for unintended immunomodulatory potential via a tiered approach. Included in this approach is a semiquantitative description of changes in the separate compartments of lymphoid tissue (also called enhanced histopathology). Chlorambucil was administered to Hanover Wistar rats at regular time points, followed by a treatment-free (recovery) period. Groups of treated and control animals were sacrificed regularly during both the treatment and recovery periods. Selected tissues were removed, weighed fresh and fixed in formalin, processed, and stained with hematoxylin and eosin. Blood samples and bone marrow smears were also obtained. With the use of enhanced histopathology, a description of the changes in lymphoid tissues and bone marrow was used as a means of assessing the susceptibility, and recovery, of the different lymphoid cell populations over time. A correlation with organ weights, flow cytometry data, and bone marrow cytology was achieved. The administration of chlorambucil in the Hanover Wistar rat provided a useful tool to examine the rate and sequence of changes in the lymphoid organs and bone marrow during treatment with, and the recovery from the effects of, a potent immunosuppressive agent.

Evaluation of coagulation markers in the plasma of healthy cats and cats with asymptomatic hypertrophic cardiomyopathy.

BACKGROUND: Thrombosis and arterial thromboembolism are frequent complications of feline cardiomyopathy, especially when associated with left atrial enlargement. Markers of activated coagulation may be used to evaluate the coagulation status of cats with hypertrophic cardiomyopathy (HCM) in relation to left atrial size. OBJECTIVES: The objective of this study was to compare plasma concentrations of thrombin-antithrombin complex (TAT), D-dimer, and fibrin degradation products (FDP) between clinically healthy cats and cats with HCM. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and antithrombin activity were also compared and the association between left atrial (LA) size and coagulation results in cats with HCM was evaluated. METHODS: Blood samples from 19 clinically healthy cats and 20 cats with HCM were obtained. All cats with HCM were asymptomatic and had no signs of heart failure. LA diameter and LA to proximal aortic (Ao) diameter ratio (LA:Ao) were determined by echocardiography. RESULTS: Reference intervals for D-dimer and TAT concentrations in plasma of healthy cats were established as 0.09-0.32 microg/mL and 2.0-20.0 microg/L, respectively. TAT, D-dimer, and FDP concentrations were increased in 5, 3, and 2 cats with HCM, respectively. TAT and D-dimer concentrations, and PT and aPTT were not significantly different between groups. Antithrombin activity was significantly decreased in cats with HCM (P=.03) despite marked range overlap. LA and LA:Ao were not correlated with coagulation results. CONCLUSIONS: Laboratory evidence of hypercoagulability was found in 45% of cats with HCM. Left atrial size was not associated with laboratory evidence of hypercoagulability. Association between coagulation markers and risk of thrombosis has yet to be evaluated in cats with HCM.

Evaluation of variation in serum globulin concentrations in dairy cattle.

BACKGROUND: Several factors may influence the concentration of serum globulins in healthy cows and thereby affect clinical interpretation; however, few studies have addressed sources of variation in globulin values. OBJECTIVES: The purpose of this study was to compare colorimetry-based total serum globulin values with electrophoretically-determined serum globulin fractions and with IgG concentration, and to evaluate diurnal and long-term physiological variation and the effects of lactation and venipuncture site on serum globulin concentrations in Holstein dairy cattle. METHODS: Serum total globulin and albumin concentrations were analyzed by colorimetry and electrophoresis in 86 lactating cows; IgG concentrations were determined by radial immunodiffusion in 41 dry and 34 lactating cows. Serum globulins were analyzed hourly for 24 hours in 8 lactating cows and weekly for 15 weeks in 6 additional cows. Globulin concentrations were compared in samples obtained from jugular and coccygeal venipuncture sites in 4 cows. Results were analyzed using parametric statistical tests. RESULTS: Colorimetry-based total serum globulin concentrations correlated well with gamma-globulin fractions (r2 = 0.87) and IgG concentrations (r2 = 0.91). Diurnal variation of total serum globulins concentration was significant (P =.01); however, globulins did not vary significantly over a 15-week period. Mean serum globulins concentration in samples obtained from the jugular vein was 2.35 g/L higher than that in samples obtained by coccygeal venipuncture (P <.0001). CONCLUSIONS: The colorimetric method used widely in routine laboratory analyses remains a useful test for globulins determination in dairy cattle. However, time of sampling and venipuncture site should be considered in the interpretation of serum globulins on serial or interindividual specimens.

Parasitemia in a neonatal bison calf.

A 3-day old female bison calf (Bison bison) was presented in lateral recumbency to the Université de Montréal Veterinary Teaching Hospital. The animal was severely depressed and dehydrated (10%) and died a few hours after admission. Prior to death, blood samples were obtained for CBC, clinical chemistry, and serology tests. Abnormal CBC findings included thrombocytopenia, lymphocytosis, mild monocytosis, and a toxic left shift. Abnormal serum clinical chemistry findings included marked azotemia, hyperphosphatemia, hypernatremia, hyperalbuminemia, hypoglobulinemia, and low gamma-glutamyltransferase activity. Serologic test results for bovine leukosis virus and bovine viral diarrhea virus were negative. Blood smear examination revealed numerous elongated organisms that were tapered at both ends and characterized by an undulating membrane and a long flagellum. The organisms ranged in length from 35 to 40 micro meter, excluding the flagellum, and were identified as Trypanosoma theileri. Postmortem examination revealed that the animal suffered from concurrent mycotic abomasitis and colisepticemia.