Cancer of unknown primary in a mare: case report and comparative pathology review.

A 25-y-old Percheron mare was admitted to the teaching hospital because of lethargy and intractable dyspnea. Thoracoabdominal ultrasound examination identified severe peritoneal effusion, mild bilateral pleural effusion, and a diffuse pulmonary nodular pattern. Cytology of peritoneal fluid revealed a hypercellular sample with clusters of neoplastic polygonal cells and admixed macrophages. Euthanasia was followed by postmortem examination; marked bi-cavitary effusion was present, and innumerable up to 4-cm diameter, round-to-floriform nodules were diffusely evident throughout serosal surfaces as well as the pulmonary and hepatic parenchyma. Disseminated adenocarcinoma, predominantly affecting lung and liver with widespread serosal implantation, was confirmed on light microscopy. Neoplastic cells had strong immunolabeling for pancytokeratin and lacked immunoreactivity to vimentin, napsin A, and Pax8. Cytokeratin 7 and thyroid transcription factor-1 were non-contributory given absent and inconsistent internal control reactivity, respectively. Such results, combined with the lack of a major mass that would indicate a primary site, were supportive of carcinoma of unknown primary site, which remains a conundrum in human oncology, and is poorly explored in veterinary medicine, mainly as a result of clinical and diagnostic limitations.

Use of Clinical Audits to Evaluate Timing of Preoperative Antimicrobials in Equine Surgery at a Veterinary Teaching Hospital.

Based on human surgical guidelines, intravenous antimicrobials are recommended to be administered within 60 min of surgical incision. Achieving this target in horses is reportedly challenging and influenced by hospital policies. The objectives of this study were to evaluate and improve: (1) the timing of antimicrobial administration to surgical incision (tAB-INC), (2) contributions of anesthesia pre-induction (tPRI) and surgical preparation (tPREP) periods to tAB-INC, and the (3) completeness of antimicrobial recording. Two clinical audits were conducted before and after the policy changes (patient preparation and anesthesia record keeping). tPRI, tPREP, and tAB-INC were calculated and compared for elective arthroscopies and emergency laparotomies within and between the audits. The percentage of procedures with a tAB-INC <60 min was calculated. Antimicrobial recording was classified as complete or incomplete. A median tAB-INC <60 min was achieved in laparotomies (audit 1; 45 min, audit 2; 53 min) with a shorter tPREP than arthroscopies (p < 0.0001, both audits). The percentage of procedures with tAB-INC <60 min, tAB-INC, tPRI, and tPREP durations did not improve between the audits. There was a positive correlation between the number of operated joints and tPREP (audit 1, p <0.001, r = 0.77; audit 2, p < 0.001, r = 0.59). Between audits, antimicrobial recording significantly improved for elective arthroscopies (82-97%, p = 0.008) but not emergency laparotomies (76-88%, p = 0.2). Clinical audits successfully quantified the impact of introduced changes and their adherence to antimicrobial prophylaxis guidelines. Antimicrobial recording was improved but further policy changes are required to achieve a tAB-INC <60 min for arthroscopies.

Severe asthma is associated with a remodeling of the pulmonary arteries in horses.

Pulmonary hypertension and cor pulmonale are complications of severe equine asthma, as a consequence of pulmonary hypoxic vasoconstriction. However, as pulmonary hypertension is only partially reversible by oxygen administration, other etiological factors are likely involved. In human chronic obstructive pulmonary disease, pulmonary artery remodeling contributes to the development of pulmonary hypertension. In rodent models, pulmonary vascular remodeling is present as a consequence of allergic airway inflammation. The present study investigated the presence of remodeling of the pulmonary arteries in severe equine asthma, its distribution throughout the lungs, and its reversibility following long-term antigen avoidance strategies and inhaled corticosteroid administration. Using histomorphometry, the total wall area of pulmonary arteries from different regions of the lungs of asthmatic horses and controls was measured. The smooth muscle mass of pulmonary arteries was also estimated on lung sections stained for α-smooth muscle actin. Reversibility of vascular changes in asthmatic horses was assessed after 1 year of antigen avoidance alone or treatment with inhaled fluticasone. Pulmonary arteries showed increased wall area in apical and caudodorsal lung regions of asthmatic horses in both exacerbation and remission. The pulmonary arteries smooth muscle mass was similarly increased. Both treatments reversed the increase in wall area. However, a trend for normalization of the vascular smooth muscle mass was observed only after treatment with antigen avoidance, but not with fluticasone. In conclusion, severe equine asthma is associated with remodeling of the pulmonary arteries consisting in an increased smooth muscle mass. The resulting narrowing of the artery lumen could enhance hypoxic vasoconstriction, contributing to pulmonary hypertension. In our study population, the antigen avoidance strategy appeared more promising than inhaled corticosteroids in controlling vascular remodeling. However, further studies are needed to support the reversibility of vascular smooth muscle mass remodeling after asthma treatment.

The ghrelin paradox in the control of equine chondrocyte function: The good and the bad.

Increasing evidence suggests a role for ghrelin in the control of articular inflammatory diseases like osteoarthritis (OA). In the present study we examined the ability of ghrelin to counteract LPS-induced necrosis and apoptosis of chondrocytes and the involvement of GH secretagogue receptor (GHS-R)1a in the protective action of ghrelin. The effects of ghrelin (10-7-10-11 mol/L) on equine primary cultured chondrocytes viability and necrosis in basal conditions and under LPS treatment (100 ng/ml) were detected by using both acridine orange/propidium iodide staining and annexin-5/propidium iodide staining. The presence of GHS-R1a on chondrocytes was detected by Western Blot. The involvement of the GHS-R1a in the ghrelin effect against LPS-induced cytotoxicity was examined by pretreating chondrocytes with D-Lys3-GHRP-6, a specific GHS-R1a antagonist, and by using des-acyl ghrelin (DAG, 10-7 and 10-9 mol/L) which did not recognize the GHS-R 1a. Low ghrelin concentrations reduced chondrocyte viability whereas 10-7 mol/L ghrelin protects against LPS-induced cellular damage. The protective effect of ghrelin depends on the interaction with the GHS-R1a since it is significantly reduced by D-Lys3-GHRP-6. The negative action of ghrelin involves caspase activation and could be due to an interaction with a GHS-R type different from the GHS-R1a recognized by both low ghrelin concentrations and DAG. DAG, in fact, induces a dose-dependent decrease in chondrocyte viability and exacerbates LPS-induced damage. These data indicate that ghrelin protects chondrocytes against LPS-induced damage via interaction with GHS-R1a and suggest the potential utility of local GHS-R1a agonist administration to treat articular inflammatory diseases such as OA.