Publications

Combination antimalarial therapy may delay the spread of drug resistance, but clinical data supporting this notion are limited. For 1 year, we studied Ugandan children who were treated for uncomplicated malaria with sulfadoxine-pyrimethamine (SP), SP + amodiaquine (AQ), or SP + artesunate (AS). We compared treatment responses and the prevalence of resistance-conferring mutations of new infections with those of recrudescent infections due to parasites that survived prior treatment. Recrudescent infections were associated with the selection of SP resistance-conferring mutations in all treatment groups, but responses to repeat therapy differed. Compared with initial treatments, treatment of recrudescent infections was associated with a higher rate of treatment failure (hazard ratio [HR], 2.44; P=.01), for the SP group, but with a lower rate of treatment failure (HR, 0.40; P=.08), for the SP + AS group. Treatment failure in the SP + AQ group was uncommon, limiting the analysis of recrudescent parasites. Our results suggest that the use of combination antimalarial therapy in Africa may slow the spread of drug-resistant malaria and prolong the therapeutic life span of available treatment regimens.

To ensure its growth and prosperity, general internal medicine will need to embrace care of the elderly, research on aging, and geriatrics education as components of its core mission. Experts agree that general internal medicine fellows could benefit from increased opportunities in research on aging and geriatrics education; however, important barriers will hamper efforts to integrate geriatrics training into general internal medicine fellowship programs. This article reviews the barriers to integration and proposes solutions for overcoming those barriers. As a result of interviews and meetings with a broad representation of general internists, geriatricians, funding agencies, and policymakers, we propose 2 interventions: 1) the development of institutional program grants to foster collaboration between general internal medicine and geriatrics faculty in the training of general internal medicine fellows and 2) the creation of a 3-year fellowship program combining general internal medicine and geriatrics. This article discusses the importance of evaluating these and other programs intended to increase the geriatrics experience of general internal medicine fellows, and it describes the potential implications of these changes for a broad array of stakeholder institutions.

Natural killer (NK) and NK T cells are tissue lymphocytes that secrete cytokines rapidly upon stimulation. Here, we show that these cells maintain distinct patterns of constitutive cytokine mRNAs. Unlike conventional T cells, NK T cells activate interleukin (IL)-4 and interferon (IFN)-gamma transcription during thymic development and populate the periphery with both cytokine loci previously modified by histone acetylation. Similarly, NK cells transcribe and modify the IFN-gamma gene, but not IL-4, during developmental maturation in the bone marrow. Lineage-specific patterns of cytokine transcripts predate infection and suggest evolutionary selection for invariant but distinct types of effector responses among the earliest responding lymphocytes.