Pharmacokinetic and Phase I Evaluation of Carboplatin in Dogs

Thirty dogs with spontaneously occurring malignant neoplasms were treated monthly with carboplatin (CBDCA) given as a 30-minute intravenous infusion in a dose escalation study. Twenty-eight dogs were considered evaluable for toxicity. The maximally tolerated dose of CBDCA was conceptually defined as that dose, determined by logistic regression analyses of toxicity data, resulting in a 50% incidence of moderate toxicity (MOD₅₀) or a 5% incidence of severe toxicity (SEV₅). Each designated maximally tolerated dose was calculated for the first course of treatment only and for the first and second courses of treatment combined to estimate cumulative drug toxicity. The MOD₅₀ and SEV₅ for the first treatment course were 340 and 278 mg/M², respectively. MOD₅₀ and SEV₅ values for the first plus second treatment courses were 327 and 231 mg/M², respectively. The nadir of neutrophil and platelet counts occurred approximately 14 days after treatment. The mean neutrophil and platelet values for all dogs experiencing myelosuppression during the first two treatment courses were 1541/μL and 62,600/μL, respectively. Nonparametric pharmacokinetic analysis of plasma CBDCA values suggested that half-life (T_1/2), area-under-the-curve and total body clearance (CL_b) were not dose dependent. Volume of distribution (VD_ss) significantly increased with dose only between 100 and 150 mg/M², not between 150 and 300 mg/M². Dose-independent serum CBDCA pharmacokinetic disposition indicates that detailed investigation of tissue CBDCA distribution would be warranted and may identify novel dosing strategies that could improve the therapeutic index of CBDCA by minimizing toxicity. (Journal of Veterinary Internal Medicine 1993; 7:235–240. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

Differentiation and transplantation antigens on the surface of mononuclear cells of cattle, horses and dogs

The determination of differentiation and transplantation antigens will be of growing importance in immune diagnosis for individual animals as well as for breeding purposes in populations. Differentiation antigens characterize subsets of cell populations and indicate their functional capacity while transplantation antigens represent markers of individuals of a species. Occurrence and significance of these antigenic systems are briefly reviewed.     

Sentinel practice-based survey of the management and health of horses in northern Britain.

Details of the management, feeding, level of activity and routine health care of horses in Scotland and the five northernmost counties in England were recorded through a stratified random sample of horse owners who had responded to a previous survey. Sixty-eight per cent of the horses were kept where their owners resided, and 32 per cent were kept away from the owner's home. More than 99 per cent were turned out to grazing for at least part of the year and 81 per cent were stabled for at least part of the time, most commonly bedded on straw (50 per cent) or shavings (34 per cent). Hay was fed to 87 per cent, sugar beet pulp to 64 per cent and commercially prepared concentrate mixes to 60 per cent of the horses. Hacking was the most popular activity (52 per cent of horses) followed by riding/pony club events (28 per cent) and showing (21 per cent). The majority of the horses were involved in more than one activity. There were an estimated 0.88 veterinary visits per horse per year and 29 per cent of the horses were reported to suffer from at least one permanent or recurrent health disorder. The median annual numbers of administrations of vaccines (influenza and tetanus) and anthelmintics were one and seven respectively per horse, and each horse was shod a median seven times. There were significant differences in the management of horses kept in different types of premises and in areas of different human population density.     

Selectivity estimates for Amblygaster sirm (Clupeidae) in the small-meshed gill net fishery on the west coast of Sri Lanka

Selectivity of Amblygaster sirm by gill nets of seven mesh sizes ranging from 2.3 to 3.8 cm stretched mesh was studied for a period of 12 months in the coastal waters off Negombo on the west coast of Sri Lanka. The size range of fish caught was 9.0–22.0 cm. Selection by mesh sizes smaller than 3.0 cm was towards the lower end of the selection curve.

Estimated values for selection factors ranged from 5.11 to 6.03 and those for optimum selection lengths varied from 12.9 to 19.7 cm. The highest selection factor was observed for 2.9 cm mesh, probably due to wedging of larger individuals in this mesh.     

Interferon in sheep]

There is only limited information on sheep interferon available. Recent publications have reported on: 1. an interferon (IFN) alpha subtype, which is secreted by the fetal trophectoderm into the lumen of the uterus between the 10th and 21st day of gestation. It was therefore named ovine trophoblast protein (oTP-1), and is responsible for signalling pregnancy to the ewe via high affinity receptors in the endometrium. It is thought that oTP-1 acts by directly influencing prostaglandin metabolism. 2. the role of lentivirus-induced interferon (LV-IFN) in the pathogenesis of Maedi/Visna. The results indicate that LV-IFN limits viral replication and therefore contributes to virus persistence and is also responsible for a chronic inflammatory process. 3. the mitogen- or antigen-dependent induction of ovine interferon gamma (IFN gamma) and its characterization.     

Controversial issues in drug treatment during cardiopulmonary resuscitation.

The goal of advanced life support in CPR must be to restore and maintain respiratory and hemodynamic effectiveness, and to correct the underlying dysrhythmia. Optimal basic life-support techniques must be continued to meet these goals. Many drugs have been suggested in the treatment of cardiac arrest, but unfortunately, drug effects are inconsistent and resuscitation rates remain low. Epinephrine, atropine, lidocaine, bretylium, and naloxone remain important drugs for consideration in CPR in most animals with cardiac arrest. The best chance of survival remains in early recognition of animals susceptible to arrest and in treatment of the underlying cause.     

Differential effects of heparin on NO and tumor necrosis factor-alpha production in bovine blood mononuclear cells stimulated with Salmonella typhimurium lipopolisaccharide.

We investigated the influence of heparin, one of the extracellular matrix (ECM) components, on nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production by bovine peripheral blood mononuclear cells (PBMC) and monocytes left to adhere for 2 (freshly adherent monocytes) and 48 h (resting monocytes), activated with Salmonella typhimurium lipopolysaccharide (LPS). After 24-h stimulation with LPS, heparin (100 microg/ml) increased (by about 40%) NO production by peripheral blood mononuclear cells and by freshly adherent monocytes. However, it did not change NO synthesis by the resting monocytes. Unlike its influence on NO level, heparin diminished TNF-alpha production by PBMC and monocytes stimulated with LPS. Microscopical examination of PBMC stained with biotin-labeled heparin, showed that both lymphocytes and monocytes were able to bind this glycosaminoglycan. We suggest that heparin, as a component of ECM, modulates the early response of monocytes to exogenous stimuli.