Antibiotic prophylaxis in veterinary cancer chemotherapy: A review and recommendations.

Bacterial infection following cancer chemotherapy-induced neutropenia is a serious cause of morbidity and mortality in human and veterinary patients. Antimicrobial prophylaxis is controversial in the human oncology field, as any decreased incidence in bacterial infections is countered by patient adverse effects and increased antimicrobial resistance. Comprehensive guidelines exist to aid human oncologists in prescribing antimicrobial prophylaxis but similar recommendations are not available in veterinary literature. As the veterinarian's role in antimicrobial stewardship is increasingly emphasized, it is vital that veterinary oncologists implement appropriate antimicrobial use. By considering the available human and veterinary literature we present an overview of current clinical practices and are able to suggest recommendations for prophylactic antimicrobial use in veterinary cancer chemotherapy patients.

An alpha(1A)/alpha(1L)-adrenoceptor mediates contraction of canine subcutaneous resistance arteries.

To determine the characteristics of the alpha(1)-adrenoceptor subtypes involved in adrenergic regulation of peripheral vascular resistance, contraction of canine subcutaneous resistance arteries was studied using wire myographs. The potencies of agonists and antagonists, chosen for their ability to discriminate between alpha(1)-adrenoceptor subtypes, were assessed in the presence of cocaine (3 microM), corticosterone (30 microM), and propranolol (1 microM). The rank order of agonist potency (pEC(50) +/- S.E.) was (R)-A-61603 (7.88 +/- 0.1) > norepinephrine (6.41 +/- 0.1) > phenylephrine (5.83 +/- 0.1). The high sensitivity to (R)-A-61603 relative to phenylephrine is inconsistent with the presence of the alpha(1D)-adrenoceptor and most consistent with an alpha(1A)-adrenoceptor response. This is supported by the low affinity for the alpha(1D)-selective antagonist BMY 7378 (pK(B) 6.51 +/- 0.47). The low pA(2) values for prazosin (8.36) and HV723 (8.81), by definition, indicate the involvement of the putative alpha(1L)-adrenoceptor, a hypothesis supported by the pA(2) values for WB4101 (8.42) and 5-methyl-urapidil (8.08). Pre-exposure to 1 microM CEC had little effect, whereas 100 microM CEC reduced the maximum contraction but not the sensitivity to norepinephrine. This low sensitivity to CEC argues against the presence of the alpha(1B)-adrenoceptor. We conclude that, by current definitions, an alpha(1A)-/alpha(1L)-adrenoceptor causes contraction of these vessels. This does not support the concept that selectivity for the alpha(1A)-adrenoceptor is the basis for the effectiveness of some alpha-blockers in some tissues, such as prostate, but not in other tissues such as blood vessels. Rather, the generally low potency of alpha-blockers in some tissues may be due to a tissue-specific property of the receptors.

Alterations in vascular reactivity in isolated vessel segments from dogs with naturally occurring heart failure.

To investigate if functional vascular reactivity is altered in heart failure, the reactivity of isolated canine saphenous vein (SV) and femoral artery (FA) rings, from control dogs and dogs with naturally occurring heart failure was examined. In both vessels, relaxation responses to the endothelium-dependent vasodilator, acetylcholine were unaffected by heart failure. In the FA, in heart failure, there was a significant reduction in the potency of the agonist noradrenaline (pEC(50)6.05+/-0.07 (N = 8) and 5.54 +/- 0.13 (N = 7) for control and heart failure respectively). There was no significant alteration in potency in the SV. In addition, in the FA the maximum responses to both noradrenaline (control 3.64 +/- 0.31 KPa, (N = 8); failure 5.11 +/- 0.35 KPa, (N = 7) P = 0.004) and potassium chloride (control 2.18 +/- 0.26 KPa, (N = 8); failure 4.46 +/- 0.25 KPa, (N = 7) P = 0.001) were significantly increased in heart failure. It is suggested that enhanced agonist induced responses, in the femoral artery, in dogs with heart failure, may limit blood flow to exercising skeletal muscle and subsequently reduce exercise tolerance.

Apparent bypass of negative selection in CD8+ tumours in CD2-myc transgenic mice.

A role for antigen stimulation in lymphoid neoplasia has been postulated and is supported by indirect evidence that suggests that the interaction of antigen with both T cells and B cells may constitute an epigenetic event that can contribute to tumour induction or tumour progression. Using myc-bearing transgenic mice that develop mainly clonal T-cell lymphomas we have investigated the possibility that endogenous antigen-mediated clonal deletion might be overridden in tumorigenesis. CD2-myc transgenic mice were backcrossed on to a CBA/Ca background to ensure Mtv-mediated deletion of V beta 11-expressing T cells in the resultant offspring. Lymphomas arising from these mice were subsequently screened for V beta 11 expression. There was a clear correlation between the age at which mice developed neoplasia and the tumour phenotype. Mice with CD4- CD8+ tumours succumbed to thymic lymphoma at a significantly younger age than mice developing CD4+ CD8+ tumours. A small number of tumours consisted of the 'forbidden' V beta 11 phenotype, showing that cells vulnerable to transformation could escape negative selection. The majority of the V beta 11-positive tumours were CD4- CD8+ and were only observed in mice showing clinical evidence of tumour development at a relatively young age. The phenotype of these cells and the age at which tumours arose suggests that T cells escaping tolerance may be susceptible to transformation.