Cancer clinical trials: development and implementation.

Although much of the current standard of care in veterinary oncology is based on retrospective studies or transference from the human literature, a new era of clinical trial awareness brought on by new consortia and cooperative investigative groups is beginning to change this limitation. The use of controlled, randomized, blind multicenter trials testing new cytotoxics and cytostatic agents is now becoming the norm rather than the exception. Ultimately, advanced clinical trial design applied to companion animal populations should advance veterinary-based practice and inform future human clinical trials that may follow.     

An evaluation of mycophage therapy, chemotherapy and vaccination for control of Mycobacterium avium subsp. paratuberculosis infection

The control of ovine Johne's disease (OJD) is important for domestic trade, the viability of farming units and possibly also for public health. Current strategies in Australia have included quarantine and pasture spelling to decrease prevalence and shedding rates and reduce numbers of Mycobacterium paratuberculosis (Mptb) ingested by susceptible sheep. However, alternative procedures are needed and vaccination with Gudair has recently commenced. This review examines prospects for the control of OJD by chemotherapy, vaccination and mycophages. Current chemotherapeutic regimes for treatment of M. paratuberculosis in ruminants are prohibitively expensive and of dubious efficacy, and apart from environmental concerns, mycophage therapy lacks a track record of success against intracellular bacteria. There is substantial evidence that live and killed mycobacterial vaccines reduce the incidence of clinical disease and shedding rates in OJD. An appraisal of recent experimental results suggests that neonatal vaccination with a defined dose of M. paratuberculosis offers the best prospects for the induction of protective Th1-type immunity.     

Effects of extracorporeal shock wave therapy and radial pressure wave therapy on elasticity and microstructure of equine cortical bone

OBJECTIVE: To measure changes in the modulus of elasticity (E) and describe histologic findings after extracorporeal shock wave therapy and radial pressure wave therapy on equine cortical bone specimens. SAMPLE POPULATION: 16 bone specimens from the proximodorsal cortex of an equine third metacarpal or metatarsal bone. PROCEDURE: Baseline E was determined by the density (p) and unidirectional ultrasound transmission velocity (C) of each specimen according to the equation E = pC2. Eight specimens were treated with 500 pulses of 0.15 mJ/mm2 of extracorporeal shock wave therapy, and 8 specimens were treated with 500 pulses of 0.16 mJ/mm2of radial pressure wave therapy. After treatment, C was determined again. Four treatment sessions resulted in 2,000 pulses and 5 C measurements. The p of each sample was measured again. Mean post-treatment E was calculated for each group. Nondecalcified sections of all specimens were stained with toluidine blue or basic fuchsin for histologic evaluation. RESULTS: Overall treatment group effect was not significant for C or E. Final E was not different from baseline values for extracorporeal shock wave therapy and radial pressure wave therapy. No histologic changes could be attributed to either treatment modality. CONCLUSIONS AND CLINICAL RELEVANCE: Extracorporeal shock wave therapy and radial pressure wave therapy did not affect the material properties of equine bone at the energy and pulse values used in this study.     

Age-related alterations to immune parameters in Labrador retriever dogs

In order to assess age-related changes in the immune status of Labrador retriever dogs, leukocyte phenotypes, lymphocyte proliferative capacity, and serum antibody levels were measured in four cohorts of dogs, ranging from 2 to 10 years of age. Absolute numbers of white blood cells, lymphocytes, monocytes, granulocytes, and CD3+, CD4+, CD8+ and CD21+ lymphocytes significantly decreased with increasing age. Relative percentages of lymphocytes and CD4 cells were significantly decreased, and relative percentages of granulocytes and CD8 cells significantly increased, with age. The CD4:CD8 ratio showed a significant age-related decrease. Proliferative responses of T-cells to mitogens in whole-blood cultures either increased (Concanavalin A) or remained the same (phytohemagglutinin) with age when data was normalised to allow for differences in responding cell number. Similarly, normalised data of proliferative response to anti-CD3 stimulation together with phorbol 12-myristate 13-acetate showed an age-related increase. Serum levels of total IgA significantly increased with age whereas total IgG levels remained unchanged. These observations illustrate a significant change to a number of immune parameters with age. However, further work is required to determine whether the differences reported here are sufficient to cause overt or functional immune senescence in Labrador retriever dogs.     

Activin A: from sometime reproductive factor to genuine cytokine

The growth factor, activin A, was initially characterized as a putative reproductive hormone but is now known to have many other divergent roles. One of these is during inflammation. Following intravenous injection of bacterial lipopolysaccharide (LPS) into sheep, activin A is released extremely rapidly into the circulation. The release of activin A appears to be independent of fever, prostaglandins or other key proinflammatory cytokines such as TNF-alpha or IL-1beta. While the precise roles and function of this factor in inflammation are yet to be elucidated, the activin response occurs in other mammalian species besides the sheep and elevated activin has been documented for a number of clinical inflammatory conditions. Activin A therefore seems to be part of the regulatory component of the innate immune response.     

Heat Dosage and Oviposition Depth Influence Egg Mortality of Two Common Rangeland Grasshopper Species

Rangeland fire is a common naturally occurring event and management tool, with the amount and structure of biomass controlling transfer of heat belowground. Temperatures that grasshopper eggs are exposed to during rangeland fires are mediated by species-specific oviposition traits. This experiment examined egg mortality in two slant-faced grasshopper species with differing oviposition traits, namely Aulocara elliotti (Thomas) and Opeia obscura (Thomas). We hypothesized that A. elliotti egg mortality would increase with fire intensity because the shallow egg location below the soil surface would result in exposure to higher temperatures, and that the deeper O. obscura eggs would not be affected by fire intensity. Fire intensity did not significantly affect the mortality of O. obscura eggs, with very low mortality in all treatments. Fire intensity significantly affected mortality of A. elliotti eggs, which are laid in shallow egg pods with the midpoint of the egg clutch at a depth of ～ 0.825 cm. Aulocara elliotti egg mortality increased with higher levels of heat application, with 79% egg mortality in the 4 500 kg · ha^?1 heat treatment. Heat effects on A. elliotti egg mortality were similar to those previously observed for another shallow-egg-laying species. Limited research has examined if rangeland fires reduce population densities of specific economically important grasshopper species. The results from this experiment indicate that grasshopper species with the midpoint of the egg pod less than 1 cm below the surface are likely in general to be vulnerable to fire-induced egg mortality during rangeland fires.     

In-vitro comparison of 3 knotting techniques for lateral fabellotibial suture stabilization

This study evaluated the biomechanical characteristics of a single self-locking knot (sSLK) and a double self-locking knot (dSLK) compared with the square knot (SQ) for stabilization of cranial cruciate ligament rupture. Each knot underwent monotonic tensile and cyclical loading. Starting tension, elongation, stiffness, and load to failure were all evaluated. A value of P < 0.05 was considered significant. Starting tension, overall stiffness, and load to failure were all significantly greater in both the sSLK and dSLK compared with the SQ. There was no difference in elongation among the knots. There were no significant differences in starting tension, elongation, stiffness, and load to failure between the sSLK and the dSLK. The self-locking knots were stronger and stiffer than the SQ; there is no biomechanical advantage in using the dSLK compared with the sSLK.     

Subacute atropine toxicity in a pygmy sperm whale, Kogia breviceps.

Atropine, an anticholinergic agent commonly used in human and veterinary medicine, is reported to cause toxicity associated with its antimuscarinic action. A juvenile pygmy sperm whale, Kogia breviceps, was treated with atropine in an attempt to relieve symptoms similar to pyloric stenosis, as has been used in humans. Two doses of 0.01 mg/kg were given i.m., 12 hr apart, followed by three doses of 0.005 mg/kg i.m. s.i.d. over the next 3 days. Symptoms associated with atropine toxicity developed gradually and included hyperexcitability, a generalized ascending paralysis of body musculature, shallow, rapid respiration, vomiting, aspiration of seawater, and pulmonary edema. Treatment with physostigmine salicylate (two doses of 2 mg i.m., I hr apart) was effective in counteracting the paralysis, as well as other symptoms, beginning in as little as 17 min after the first dose, and the whale was back to swimming on its own after 8 hr. All overt symptoms of atropine toxicity were gone in about 24 hr, but there were other possible sequella that lasted much longer.