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Objective: To assess treatment-emergent rash incidence when using dermatology precautions (limited antigen exposure) and slower titration during lamotrigine initiation., Method: We assessed rash incidence in 100 patients with DSM-IV bipolar disorder instructed, for their first 3 months taking lamotrigine, to avoid other new medicines and new foods, cosmetics, conditioners, deodorants, detergents, and fabric softeners, as well as sunburn and exposure to poison ivy/oak. Lamotrigine was not started within 2 weeks of a rash, viral syndrome, or vaccination. In addition, lamotrigine was titrated more slowly than in the prescribing information. Patients were monitored for rash and clinical phenomena using the Systematic Treatment Enhancement Program for Bipolar Disorder Clinical Monitoring Form. Descriptive statistics were compiled., Results: No patient had serious rash. Benign rash occurred in 5 patients (5%) and resolved uneventfully in 3 patients discontinuing and 2 patients continuing lamotrigine. Two patients with rash were found to be not adherent to dermatology precautions. Therefore, among the remaining patients, only 3/98 (3.1%) had benign rashes., Conclusion: The observed rate of benign rash was lower than the 10% incidence in other clinical studies. The design of this study confounds efforts to determine the relative contributions of slower titration versus dermatology precautions to the low rate of rash. Systematic studies are needed to confirm these preliminary findings, which suggest that adhering to dermatology precautions with slower titration may yield a low incidence of rash with lamotrigine.

Photooxidative damage was induced predominantly at a single guanine base in a target DNA by irradiation (lambda > 330 nm) in the presence of complementary oligodeoxynucleotide conjugates (ODN-5'-linker-[Ru(phen)3]2+) (phen = 1,10-phenanthroline). The target DNA represents the b2a2 variant of the chimeric bcr-abl gene implicated in the pathogenesis of chronic myeloid leukaemia, and the sequence of the 17mer ODN component of the conjugate (3' G G T A G T T A T T C C T T C T T 5') was complementary to the junction region of the sense strand sequence of this oncogene. Two different conjugates were prepared, both of them by reaction of the appropriate succinimide ester with 5'-hexylamino-derivatised 17mer ODN. In Ru-ODN-1 (7) the linker was -(CH2)6-NHCO-bpyMe (-bpyMe = 4'-[4-methyl-2,2'-bipyridyl]), whereas in Ru-ODN-2 (13) it was -(CH2)6-NHCO-(CH2)3-CONH-phen. Photoexcitation of either of the conjugates when hybridised with the 32P-5'-end-labelled target 34mer 5'T G A C C A T C A A T A A G G A A G A A G21 C C C T T C A G C G G C C 3' (ODN binding site underlined) led to an alkali-labile site predominantly (> 90%) at the G21 base, which is at the junction of double-stranded and single-stranded regions of the hybrid. Greater yields were found with Ru-ODN-1 (7) than with Ru ODN-2 (13). In contrast to this specific cleavage with Ru-ODN-1 (7) or Ru-ODN-2 (13), alkali-labile sites were generated at all guanines when the 34mer was photolysed in the presence of the free sensitiser [Ru(phen)3]2+. Since [Ru(phen)3]2+ was shown to react with 2'-deoxyguanosine to form the diastereomers of a spiroiminodihydantoin derivative (the product from 1O2 reaction), 1O2 might also be an oxidizing species in the case of Ru-ODN-1 (7) and Ru-ODN-2 (13). Therefore to determine the range of reaction, a series of 'variant' targets was prepared, in which G21 was replaced with a cytosine and a guanine substituted for a base further towards the 3'-end (e.g. Variant 3; 5'T G A C C A T C A A T A A G G A A G A A C C G23 C T T C A G C G G32 C C3'). While it was noted that efficient reaction took place at distances apparently remote from the photosensitiser (e.g at G32, but not G23 for Variant 3), this effect could be attributed to hairpinning of the single-stranded region of the target. These results are therefore consistent with the photooxidative damage being induced by a reaction close to the photosensitiser rather than by a diffusible species such as 1O2.