The plasma concentration, plasma half-life (t1/2), and mean residence time (MRT) of rodenticide anticoagulants were determined in 21 dogs in which a preliminary diagnosis of anticoagulant rodenticide poisoning had been made. Brodifacoum, difethialone, and difenacoum were detected by high-performance liquid chromatography (HPLC) in the plasma of 13, 3, and 2 dogs, respectively. At presentation the plasma concentration ranged from below the detection limit (10 ng/L) to 851 ng/L. Toxin could not be detected in 3 dogs, despite these animals showing characteristic coagulation disturbances and a positive response to therapy with vitamin K1. In 7 dogs the estimated t1/2 of brodifacoum ranged from 0.9 to 4.7 (median 2.4) days with a MRT of 1.9 to 3.7 (median 2.8) days. In 2 dogs the individual t1/2 of difethialone was 2.2 and 3.2 days and the MRT was 2.3 and 2.8 days, respectively. Two dogs died during emergency treatment. Treatment in the remaining 19 dogs consisted of the administration of vitamin K1 and supportive therapy. The dose of vitamin K1 was reduced in a stepwise manner as long as the prothrombin time remained within physiological limits. The variation in initial plasma concentrations of the anticoagulants combined with the results of treatment support the idea that an individual therapeutic approach is warranted.

A high-performance liquid chromatographic method with ultraviolet (UV) and fluorescence detection was developed for the analysis of one indandione and four hydroxycoumarin anticoagulant rodenticides in human serum. The superwarfarin rodenticides, chlorophacinone, bromadiolone, difenacoum, brodifacoum, and difethialone, can be identified and quantitated simultaneously with this method. After adding a buffer (pH 5.5), the anticoagulants were extracted from serum with chloroform-acetone. The organic phase was separated and evaporated to dryness, and the residue was subjected to chromatographic analysis. The anticoagulants were separated by reversed-phase chromatography and detected by UV absorption at 285 nm and by fluorescence at an excitation wavelength of 265 nm and an emission wavelength of 400 nm. Extraction efficiencies from 55 to 131% were obtained. The within-run precision ranged from 2.0 to 7.1% for UV detection and from 0.0 to 4.8% for fluorescence detection. Between-run precision ranged from 1.3 to 16.0% for UV detection and from 1.8 to 9.0% for fluorescence detection. The anticoagulants can be quantitated at serum concentrations down to 3-12 ng/mL for fluorescence detection and down to 20-75 ng/mL for UV detection. No interferences were observed with the related compounds warfarin and vitamin K1.

Although the importance of New Institutional Economics and the institutional approach for understanding pre-industrial economic development and the early growth of markets are widely accepted, it has proven to be difficult to assess more directly the effects of institutions on the functioning of markets. This paper uses empirical research on the rise of markets in late medieval Holland to illuminate some of the factors behind the development of the specific institutional framework of markets for land, labour, capital and goods, and some effects of these institutions on the actual functioning of the markets. The findings are corroborated by a tentative comparison with the functioning of markets in Flanders and eastern England.

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