Context Existing therapies for bipolar depression have a considerable lag of onset of action. Pharmacological strategies that produce rapid antidepressant effects—for instance, within a few hours or days—would have an enormous impact on patient care and public health. Objective To determine whether an N-methyl-d-aspartate–receptor antagonist produces rapid antidepressant effects in subjects with bipolar depression. Design A randomized, placebo-controlled, double-blind, crossover, add-on study conducted from October 2006 to June 2009. Setting Mood Disorders Research Unit at the National Institute of Mental Health, Bethesda, Maryland. Patients Eighteen subjects with DSM-IV bipolar depression (treatment-resistant). Interventions Subjects maintained at therapeutic levels of lithium or valproate received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days 2 weeks apart. The Montgomery-Asberg Depression Rating Scale was used to rate subjects at baseline and at 40, 80, 110, and 230 minutes and on days 1, 2, 3, 7, 10, and 14 postinfusion. Main Outcome Measures Change in Montgomery-Asberg Depression Rating Scale primary efficacy measure scores. Results Within 40 minutes, depressive symptoms significantly improved in subjects receiving ketamine compared with placebo (d=0.52, 95% confidence interval [CI], 0.28-0.76); this improvement remained significant through day 3. The drug difference effect size was largest at day 2 (d=0.80, 95% CI, 0.55-1.04). Seventy-one percent of subjects responded to ketamine and 6% responded to placebo at some point during the trial. One subject receiving ketamine and 1 receiving placebo developed manic symptoms. Ketamine was generally well tolerated; the most common adverse effect was dissociative symptoms, only at the 40-minute point. Conclusion In patients with treatment-resistant bipolar depression, robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-d-aspartate antagonist. Trial Registration clinicaltrials.gov Identifier: NCT00088699

BackgroundPreclinical data support further investigation of ascorbic acid in pancreatic cancer. There are currently insufficient safety data in human subjects, particularly when ascorbic acid is combined with chemotherapy.Methods and Findings14 subjects with metastatic stage IV pancreatic cancer were recruited to receive an eight week cycle of intravenous ascorbic acid (three infusions per week), using a dose escalation design, along with standard treatment of gemcitabine and erlotinib. Of 14 recruited subjects enrolled, nine completed the study (three in each dosage tier). There were fifteen non-serious adverse events and eight serious adverse events, all likely related to progression of disease or treatment with gemcitabine or erlotinib. Applying RECIST 1.0 criteria, seven of the nine subjects had stable disease while the other two had progressive disease.ConclusionsThese initial safety data do not reveal increased toxicity with the addition of ascorbic acid to gemcitabine and erlotinib in pancreatic cancer patients. This, combined with the observed response to treatment, suggests the need for a phase II study of longer duration.Trial RegistrationClinicaltrials.gov NCT00954525

Summary: Traumatic brain injury (TBI) is a common and potentially devastating clinical problem. Because prompt proper management of TBI sequelae can significantly alter the clinical course especially within 48 h of the injury, neuroimaging techniques have become an important part of the diagnostic work up of such patients. In the acute setting, these imaging studies can determine the presence and extent of injury and guide surgical planning and minimally invasive interventions. Neuroimaging also can be important in the chronic therapy of TBI, identifying chronic sequelae, determining prognosis, and guiding rehabilitation.

Vascular FDG uptake is present in 50% of the patients examined for this study, with an increased prevalence in older patients. This vascular uptake might be explained by smooth muscle metabolism in the media, subendothelial smooth muscle proliferation from senescence, and the presence of macrophages within the atherosclerotic plaque. The relative contribution of these sources needs further investigation.