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Abstract. In safety pharmacology studies, the effects on the QT interval of electrocardiograms are routinely assessed using a telemetry system in cynomolgus monkeys. However, there is a lack of integrated databases concerning in vivo QT assays in conscious monkeys. As part of QT Interval Prolongation: Project for Database Construction (QT PRODACT), the present study examined 10 positive compounds with the potential to prolong the QT interval and 6 negative compounds considered to have no such effect on humans. The experiments were conducted at 7 facilities in accordance with a standard protocol established by QT PRODACT. The vehicle or 3 doses of each test compound were administered orally to male cynomolgus monkeys (n = 3 -4), and telemetry signals were recorded for 24 h. None of the negative compounds prolonged the corrected QT using Bazett's formula (QTcB) interval. On the other hand, almost all of the positive compounds prolonged the QTcB interval, but haloperidol, terfenadine, and thioridazine did not. The failure to detect the QTcB interval prolongation appeared to be attributable for the differences in metabolism between species and / or disagreement with Bazett's formula for tachycardia. In the cynomolgus monkeys, astemizole induced Torsade de Pointes and cisapride caused tachyarrhythmia at lower plasma concentrations than those observed in humans and dogs. These results suggest that in vivo QT assays in conscious monkeys represent a useful model for assessing the risks of drug-induced QT interval prolongation. Supplementary material (Appendix): available only at http://dx

Neutron scattering experiments have been performed in the diluted antiferromagnets Rb 2 Co 0#7 Mg 0>3 F 4 and Co 0#3 Zn 0e7 F 2 in a uniform magnetic field. These systems are isomorphous to, respectively, two-and three-dimensional Ising ferromagnets in a site-random magnetic field. It is shown that small random magnetic fields destroy the long-range order at all temperatures, consistent with three as the lower marginal dimensionality; the structure factor in the disordered state is predominantly a squared Lorentzian.

We report a comprehensive neutron scattering study of the spin correlations in the diluted twodimensional (2D) Ising antiferromagnet Rb2Co07Mgp 3F4 in an applied magnetic field. As predicted by Fishman and Aharony, an applied field in this system produces a random staggered magnetic field. Random fields are expected to have drastic effects on the cooperative behavior of magnets although the detailed behavior remains controversial. It is found that the applied magnetic field, and by inference the concomitant random staggered fields, destroy the 2D long-range order for all temperatures and fields. The structure factor W (Q)= g-, e' o'( -' SS'-)r is well described as the sum of a Lorentzian plus a Lorentzian squared with the Lorentzian-squared term dominating at low temperatures.The integrated intensity of the Lorentzian-squared term exhibits the same temperature dependence as the Bragg intensity at zero field. The correlation length K and structure-factor peak intensity 5 (Qv) exhibit power-law dependences on the applied field H, tt-H', and P' (Qv)-H ' at low temperatures; the measured exponents agree reasonably with the values 2 and -4, respectively, deduced from theories with the lower marginal dimensionality dI---3. The effective exponents initially increase slightly with increasing temperature and then decrease dramatically as T~T~, taking on values of about 0.7 and -1.2, respectively, at T~--42. 5 K. For small but nonzero applied fields the inverse correlation length may be factorized into a random-field part and -3.4J /k~T a thermal part, K=KRF+Ky, with K&-e where J is the Ising exchange constant. It is also found that for T &20 K reproducible results are only obtained when the sample is cooled in the presence of the applied field; this history-dependent behavior is analogous to that found in spinglasses.

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