HA-1A is safe and effective for the treatment of patients with sepsis and gram-negative bacteremia.

No abstract

We measured cardiac performance sequentially, using quantitative radionuclide angiocardiography to estimate left ventricular ejection fraction in 55 patients receiving doxorubicin for treatment of cancer. With final doxorubicin dosages greater than 350 mg per square meter, the lowest ejection fraction measured was significantly less than the initial determination. Five patients had severe cardiotoxicity (congestive heart failure). All had an ejection fraction of less than 30 per cent at the time of heart failure, and demonstrated moderate cardiotoxicity (a decline in ejection fraction by at least 15 per cent to a final value of less than 45 per cent) before clinical manifestations. Six patients with moderate toxicity in whom doxorubicin was discontinued did not have heart failure or a further decline in ejection fraction during the follow-up period. Moderate toxicity was continued, but mild toxicity (decline of ejection fraction by greater than 10 per cent, noted in 11 patients) was not well predicted. The assessment of radionuclide left ventricular ejection fraction during doxorubicin therapy may make it possible to avoid congestive heart failure.

No abstract

AP1903 is a novel gene-targeted drug that is being developed for use in drug-regulated cell therapies. An intravenous, single-blind, placebo- and saline-controlled, ascending-dose study was performed to evaluate the safety, tolerability, and pharmacokinetics of AP1903. Twenty-eight normal healthy male volunteers were randomized into five dosage groups of AP1903 (0.01, 0.05, 0.1, 0.5, and 1 mg/kg). Within each group, 4 volunteers received a single dose of AP1903, 1 volunteer received an equal volume of placebo, and 1 received an equal volume of normal saline. The only exception was in the 0.5 mg/kg group, in which 4 volunteers were dosed: 3 received AP1903 and 1 received normal saline. All dosages were administered as intravenous infusions over 2 hours. Clinical safety parameters were monitored, and serial blood and urine samples were collected for analysis of AP1903. No drug-related adverse events were observed at any of the dose levels with the possible exception of facial flushing in 1 volunteer at the 1.0 mg/kg dose level. AP1903 plasma levels were directly proportional to the administered dose, with mean Cmax values ranging from approximately 10 to 1,275 ng/mL over the 0.01 to 1.0 mg/kg dose range. Following the infusion period, blood concentrations revealed a rapid distribution phase, with plasma levels being reduced to approximately 18%, 7%, and 1% of the maximal concentration at 0.5, 2, and 10 hours postdose, respectively. AP1903 was shown to be safe and well tolerated at all dose levels and demonstrated a favorable pharmacokinetic profile at doses well above the anticipated therapeutic dose.