A patient case highlighting the myriad of cutaneous adverse effects of prolonged use of hydroxyurea.

BACKGROUND: Hydroxyurea is an antimetabolite primarily used to treat myeloproliferative disorders, and chronic treatment is associated with many cutaneous adverse effects ranging in severity from ichthyosis to aggressive nonmelanoma skin cancer. CASE PRESENTATION: We report a 67-year-oldman with a history of polycythemia vera who was referred for management of progressively worsening dorsal hand lesions. The patient presented withhyperpigmentation, ichthyosis, plantar keratoderma, dermatomyositis-like eruptions, two squamous cell carcinomas, and actinic keratoses. The adversereactions observed were acknowledged to be related to chronic hydroxyurea use. The patient underwent Mohs excision of the squamous cell carcinomas and thehydroxyurea was promptly discontinued; subsequent cutaneous improvement of the dermatomyositislike lesions ensued. Another clinically suspicious aggressive squamous cell carcinoma was suspected and the patient was referred to the plastic surgery department for complete excision because of the size of the lesion. The patient remains on periodic dermatology follow up. CONCLUSIONS: We report a case that exemplifies the cutaneous adverse effects of chronic hydroxyurea therapy. Although many cases improve after drug discontinuation, strict photoprotection and ongoing surveillance are indicated given the recently proposed premalignant potential of dermatomyositis-like eruptions and the aggressive nature of hydroxyurea-induced nonmelanoma skin cancer.

Functional reconstitution of influenza A M2(22-62).

Amantadine-sensitive proton uptake by liposomes is currently the preferred method of demonstrating M2 functionality after reconstitution, to validate structural determination with techniques such as solid-state NMR. With strong driving forces (two decades each of both [K(+)] gradient-induced membrane potential and [H(+)] gradient), M2(22-62) showed a transport rate of 78 H(+)/tetramer-s (pH(o) 6.0, pH(i) 8.0, nominal V(m)=-114 mV), higher than previously measured for similar, shorter, and full-length constructs. Amantadine sensitivity of the conductance domain at pH 6.8 was also comparable to other published reports. Proton flux rate was optimal at protein densities of 0.05-1.0% (peptide wt.% in lipid). Rundown of total proton uptake after addition of valinomycin and CCCP, as detected by delayed addition of valinomycin, indicated M2-induced K(+) flux of 0.1K(+)/tetramer-s, and also demonstrated that the K(+) permeability, relative to H(+), was 2.8 × 10(-6). Transport rate, amantadine and cyclooctylamine sensitivity, acid activation, and H(+) selectivity were all consistent with full functionality of the reconstituted conductance domain. Decreased external pH increased proton uptake with an apparent pK(a) of 6.