Serum Bile Acid Concentrations, Histopathological Features, and Short-, and Long-term Survival in Horses with Hepatic Disease

BACKGROUND: Serum bile acid concentrations (SBA) and a histopathological biopsy score [Equine Vet J 35 (2003) 534] are used prognostically in equine hepatic disease. HYPOTHESIS: Histopathologic features and scores, but not SBA, differ between survivors and nonsurvivors and correlate with histopathologic evidence of hepatic inflammation and fibrosis. ANIMALS: Retrospective study. Records (1999–2011) of horses with hepatic disease diagnosed by biopsy and with concurrent measurements of SBA. METHODS: Retrospective cohort study. Biopsies were examined for inflammatory cell infiltration including type and distribution, fibrosis, irreversible cytopathology affecting hepatocytes, hemosiderin, or other pigment deposition and bile duct proliferation. SBA, histopathological findings and a histological score [Equine Vet J 35 (2003) 534] were compared between short‐ (survival to discharge) and long‐term (>6 months) survivors and correlations between SBA and histopathological findings investigated. RESULTS: Of 81 cases 90% survived short‐term and 83% long‐term. Short‐term and long‐term nonsurvival were associated with SBA (P = .009; P = .006), overall (P = .001; P = .002) and parenchymal (short‐term only; P = .01) inflammation, portal and bridging fibrosis (all P < .001), apoptosis or single cell necrosis (P < .001; P = .008), hemosiderin deposition in hepatocytes (P = .011; P = .028), biliary (both P < .001), vascular (P = .003; P = .045) and endothelial (P < .001; P = .02) hyperplasia, nucleic changes (P = .004; P < .001) and the histopathological score (both P < .001). SBA were significantly and positively correlated with overall (P = .001), parenchymal (P < .001) and portal (P = .004) inflammation and portal (P = .036) and bridging (P = .002) fibrosis. CONCLUSIONS AND CLINICAL IMPORTANCE: SBA, histopathological findings and scores differ between survivors and nonsurvivors. SBA concentrations are associated with inflammation and fibrosis suggesting interference with hepatic function. A histopathological score >2 and, less so, SBA >20 μmol/L are specific but not sensitive indicators of nonsurvival

Influence of endotoxin induced fever on the pharmacokinetics of intramuscularly administered cefepime in rabbits

This study examined the effect of experimentally induced fever on the pharmacokinetics of cefepime (75 mg/kg BW) administered intramuscularly to six rabbits. The study was carried out in two consecutive phases separated by a two-week washout period. An infection was induced by an intravenous inoculation of 5 × 108 colony-forming units of Escherichia coli 24 h before the pharmacokinetic investigation. A quantitative microbiological assay was employed to measure the plasma cefepime concentrations using an agar-gel diffusion method with Bacillus subtilis ATCC 6633 as the test organism. Twenty-four hour after the injection, the rectal temperature in the infected animals increased by 1–. There was a significant reduction in the elimination half-life by 21.8% in the febrile rabbits compared to healthy animals. In addition, the infection significantly increased the peak plasma concentrations by 11.9%, the mean residence time by 19.9%, the area under the plasma-concentration-time curve by 53.6% and the area under the moment curve by 62.3%. In conclusion, the endotoxin-induced febrile state produced significant changes in the plasma levels as well as some of the pharmacokinetic variables of cefepime in rabbits