ESPITE HIGHLY EFFECTIVEcontemporary treatment regimens, the majority of vascular events are not prevented, particularly in high-risk individuals. 1,2 Therefore, further strategies to decrease atherosclerosis burden and improve cardiovascular outcomes are needed. There is a strong inverse association between high-density lipoprotein (HDL) cholesterol and risk of coronary heart disease in epidemiological studies. 3,4 Efforts to increase HDL cholesterol levels have included administration of oral compounds that interfere with lipid metabolic pathways and result in sustained increase in HDL levels over time or short-term infusion of reconstituted HDL to take advantage of its potent biological properties. 5 A provocative clinical study has suggested that short-term infusions of HDL containing a naturally occurring variant of apolipoprotein A-I (Milano) can induce regression of coronary atherosclerosis. 6 However, interpretation of Author Affiliations are listed at the end of this article. Investigators of the Effect of rHDL on Atherosclerosis-Safety and Efficacy (ERASE) Trial are listed at the end of this article.

A single 15-microg dose of 2009 H1N1 vaccine was immunogenic in adults, with mild-to-moderate vaccine-associated reactions. (ClinicalTrials.gov number, NCT00938639).

Once-daily oral dosing of ZD6474 at 300 mg/day is generally well tolerated in patients with advanced solid tumors, and this dose is being investigated in phase II trials.

HE DISEASE BURDEN OF SEAsonal influenza in the pediatric population is generally attributed to a combination of immunologic naivety, prolonged virus shedding, and enhanced transmission opportunity in child-care and educational institutions. 1 Consistent with this experience, initial reports of the introduction and indigenous transmission of 2009 influenza A(H1N1) infection in many countries have largely involved children, 2 often attending day or boarding schools. [3][4][5] Serosurveys have demonstrated little or no cross-reactivity of the pediatric sera sample to the new virus strain, under-Context In the ongoing influenza pandemic, a safe and effective vaccine against 2009 influenza A(H1N1) is needed for infants and children.Objective To assess the immunogenicity and safety of a 2009 influenza A(H1N1) vaccine in children.Design, Setting, and Participants Randomized, observer-blind, age-stratified, parallel group study assessing 2 doses of an inactivated, split-virus 2009 influenza A(H1N1) vaccine in 370 healthy infants and children aged 6 months to less than 9 years living in Australia.Intervention Intramuscular injection of 15 µg or 30 µg of hemagglutinin antigen dose of monovalent, unadjuvanted 2009 influenza A(H1N1) vaccine in a 2-dose regimen, administered 21 days apart.Main Outcome Measures Hemagglutination inhibition assay to estimate the proportion of participants with antibody titers of 1:40 or greater, seroconversion, or a significant antibody titer increase, and factor increase in geometric mean titer. Assessments of solicited adverse events during 7 days and unsolicited adverse events for 21 days after each vaccination. ResultsFollowing the first dose of vaccine, antibody titers of 1:40 or greater were observed in 161 of 174 infants and children in the 15-µg group (92.5%; 95% confidence interval [CI], 87.6%-95.6%) and in 168 of 172 infants and children in the 30-µg group (97.7%; 95% CI, 94.2%-99.1%). Corresponding seroconversion rates were 86.8% (95% CI, 80.9%-91.0%) and 94.2% (95% CI, 89.6%-96.8%), and factor increases in geometric mean titer were 13.6 (95% CI,). All participants demonstrated antibody titers of 1:40 or greater after the second vaccine dose. Immune responses were robust regardless of age, baseline serostatus, or seasonal influenza vaccination status. The majority of adverse events were mild to moderate in severity. ConclusionOne 15-µg dose of vaccine was immunogenic in infants and children starting at 6 months of age and vaccine-associated reactions were mild to moderate in severity. Trial Registration clinicaltrials.gov Identifier: NCT00940108

Clinical trials of thrombopoietin (TPO), the central regulator of megakaryocytopoiesis, have revealed few side effects associated with its use. We here report a case of pancytopenia associated with the development of neutralizing antibodies to TPO that occurred in a patient who had undergone multicycle chemotherapy with multiple cycles of subcutaneous administration of pegylated recombinant human megakaryocyte growth and development factor. Samples of the patient's bone marrow showed trilineage hypoplasia with absence of myeloid, erythroid, and megakaryocyte progenitor cells but with elevated endogenous levels of erythropoietin, granulocyte colony-stimulating factor, and stem-cell factor. To our knowledge, this is the first report of an aplastic anemia-like syndrome associated with neutralizing antibodies to TPO. IntroductionTwo different forms of thrombopoietin (TPO) have entered clinical trials. 1 One is a recombinant form of the native molecule (rhTPO) and the other a pegylated, truncated version (pegylated recombinant human megakaryocyte growth and development factor [PEG-rHuMGDF]) with biologic activity similar to that of the native molecule. Early studies showed that both rhTPO 2 and PEG-rHuMGDF 3 are potent stimulators of thrombopoiesis and enhance platelet recovery when given after chemotherapy. 4,5 Both agents were reported to have minimal toxic effects; in particular, platelets produced after their administration function normally and have no evidence of activation. 2,5,6 Although antibodies to TPO were observed in the initial study of rhTPO, they were nonneutralizing and transient. 2 Here, we describe a case in which prolonged pancytopenia with neutralizing antibodies to TPO developed in a woman with ovarian cancer who had undergone 6 cycles of chemotherapy associated with administration of PEG-rHuMGDF. Study designGranulocyte-macrophage colony-forming cells, erythroid burst-forming units, and megakaryocyte colony-forming cells were assayed as described previously 7-9 by using freshly obtained bone marrow cells. Serum from the patient (stored at Ϫ20°C) was incubated with growth factors for in vitro cultures at 37°C for 60 minutes and examined for its activity on normal bone marrow cells. The highest concentration of patient's serum used was 10% of the final culture volume.Standard solid-phase sandwich enzyme immunoassays were used to measure serum levels of TPO, 10 granulocyte colony-stimulating factor (G-CSF), and erythropoietin (EPO) (R&D Systems, Minneapolis, MN). Cytokine levels were calculated from a standard curve generated by analysis of recombinant cytokines. Stem-cell factor (SCF) was assayed as described previously. 11 More than 200 samples of normal human serum were used to establish the SCF standard of 0.78 Ϯ 0.25 ng/mL (range, 0.29-1.62 ng/mL).Two established assays were used to detect neutralizing antibodies. The first was a solid-phase radioimmunoassay (RIA). 12 Reactivity was determined on the basis of the ratio of counts per minute in the posttreatment sample to the counts per mi...