HDL mimetic CER-001 targets atherosclerotic plaques in patients.

BACKGROUND AND AIMS: Infusion of high-density lipoprotein (HDL) mimetics aimed at reducing atherosclerotic burden has led to equivocal results, which may relate in part to the inability of HDL mimetics to adequately reach atherosclerotic lesions in humans. This study evaluated delivery of recombinant human apolipoprotein A-I (apoA-I) containing HDL mimetic CER-001 in carotid plaques in patients. METHODS: CER-001 was radiolabeled with the long-lived positron emitter zirconium-89 ((89)Zr) to enable positron emission tomography with computed tomography (PET/CT) imaging. Eight patients with atherosclerotic carotid artery disease (>50% stenosis) received a single infusion of unlabeled CER-001 (3 mg/kg), co-administered with 10 mg of (89)Zr-labeled CER-001 (18 MBq). Serial PET/CT imaging and contrast enhanced-magnetic resonance imaging (CE-MRI) were performed to evaluate targeted delivery of CER-001. RESULTS: One hour after infusion, mean plasma apoA-I levels increased by 9.9 mg/dL (p = 0.026), with a concomitant relative increase in the plasma cholesterol efflux capacity of 13.8% (p < 0.001). Using serial PET/CT imaging, we showed that arterial uptake of CER-001 expressed as target-to-background ratio (TBRmax) increased significantly 24 h after infusion, and remained increased up to 48 h (TBRmax t = 10 min: 0.98; t = 24 h: 1.14 (p = 0.001); t = 48 h: 1.12 (p = 0.007)). TBRmax was higher in plaque compared with non-plaque segments (1.18 vs. 1.05; p < 0.001). Plaque TBRmax correlated with local plaque contrast enhancement (r = 0.56; p = 0.019) as assessed by CE-MRI. CONCLUSIONS: Infusion of HDL mimetic CER-001 increases plasma apoA-I concentration and plasma cholesterol efflux capacity. Our data support the concept that CER-001 targets plaque regions in patients, which correlates with plaque contrast enhancement. These clinical findings may also guide future nanomedicine development using HDL particles for drug delivery in atherosclerosis. CLINICAL TRIAL REGISTRATION: Netherlands Trial Registry - NTR5178. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5178.

Short-term effect of different teaching methods on nasopharyngeal carcinoma for general practitioners in Jakarta, Indonesia.

UNLABELLED: In Indonesia, Nasopharyngeal Carcinoma (NPC) is the most frequent cancer of the head and neck region. At first presentation in the hospital most patients already have advanced NPC. Our previous study showed that general practitioners (GPs) working in Yogyakarta, Indonesia lack the knowledge necessary for early detection of NPC. By providing training on early symptoms of NPC we hope that the diagnosis and referral will occur at an earlier stage. Here we assess the current NPC knowledge levels of GPs in Jakarta, evaluate improvement after training, compare the effectiveness of two training formats, and estimate the loss of recall over a two week period. METHODS: Two Indonesian GPs visited 31 Primary Health Care Centres (PHCCs) and provided a lecture on NPC. The alternative format consisted of a symposium at the Universitas Indonesia, Jakarta, presented by local head and neck surgeons, with all GPs in the region being invited. To evaluate the effect of both formats a questionnaire was conducted before and after. RESULTS: The lecture in the PHCCs was attended by 130 GPs. Sixty-six GPs attended the training in the university hospital and 40 GPs attended both. Pre training the NPC knowledge level was poor with an average of 1.6 symptoms being correctly identified out of a potential maximum of 12, this was increased to 4.9 post training (p<0.0001). GPs attending the PHCC course recorded a greater increase in correct symptoms than those attending the symposium (3.8 vs. 2.8; p = 0.01). After a two week period the knowledge levels had declined slightly from 5.5 correctly identified symptoms to 4.2 (p = 0.25). CONCLUSION: These results confirm our findings regarding GPs insufficient knowledge of NPC. Lectures in the PHCC and a symposium have both been proven to be effective training tools in the education of GPs.