Systematic comparison of adeno‐associated virus and biotinylated dextran amine reveals equivalent sensitivity between tracers and novel projection targets in the mouse brain

As an anterograde neuronal tracer, recombinant adeno‐associated virus (AAV) has distinct advantages over the widely used biotinylated dextran amine (BDA). However, the sensitivity and selectivity of AAV remain uncharacterized for many brain regions and species. To validate this tracing method further, AAV (serotype 1) was systematically compared with BDA as an anterograde tracer by injecting both tracers into three cortical and 15 subcortical regions in C57BL/6J mice. Identical parameters were used for our sequential iontophoretic injections, producing injections of AAV that were more robust in size and in density of neurons infected compared with those of BDA. However, these differences did not preclude further comparison between the tracers, because the pairs of injections were suitably colocalized and contained some percentage of double‐labeled neurons. A qualitative analysis of projection patterns showed that the two tracers behave very similarly when injection sites are well matched. Additionally, a quantitative analysis of relative projection intensity for cases targeting primary motor cortex (MOp), primary somatosensory cortex (SSp), and caudoputamen (CP) showed strong agreement in the ranked order of projection intensities between the two tracers. A detailed analysis of the projections of two brain regions (SSp and MOp) revealed many targets that have not previously been described in the mouse or rat. Minor retrograde labeling of neurons was observed in all cases examined, for both AAV and BDA. Our results show that AAV has actions equivalent to those of BDA as an anterograde tracer and is suitable for analysis of neural circuitry throughout the mouse brain. J. Comp. Neurol. 522:1989–2012, 2014. © 2014 Wiley Periodicals, Inc.     

Paediatric Chromobacterium violaceum in Cambodia: the first documented case

Chromobacterium violaceum infection is rarely described in Southeast Asian children, which may be due partly to the lack of access to adequate microbiology facilities in many areas. This case report describes the first documented case to occur in a Cambodian child. An awareness of the disease and its manifestations is important as treatment can be difficult and may require prolonged courses of antimicrobials and surgery.     

The older patient with syncope: practicalities and controversies

Introduction

Corticosteroid administration in Kawasaki disease (KD) is controversial but accepted as treatment for patients who do not respond to initial treatment. The impact of corticosteroids on evolving coronary artery aneurysms (CAA) and future vascular remodelling is unknown.

Methods and results

The clinical history of 80 patients (73% male; median age at diagnosis 2.2 years) seen from 1990 to 2008 with CAAs after KD were reviewed, 19 (24%) of whom received systemic corticosteroids in the acute phase (14 for ≤ 3 days, 5 for 4+ days). CAA z-scores were assessed at baseline, 2-3 months, and 1 year after the acute phase. Linear regression models adjusted for repeated measures were used to determine the association between change in CAA z-score over time and corticosteroid use, adjusting for patient age at diagnosis, gender, intravenous immunoglobulin use, total days of fever, albumin level, hemoglobin level and platelet count.

Results

The corticosteroid treated group had longer duration of fever in the acute phase (median 17 vs. 11 days, p = 0.04). Adjusted CAA z-scores at diagnosis, 2-3 months and 1 year follow-up for CAA in the left anterior descending decreased (from + 5.5 to + 3.5 to + 1.9) in those not treated with corticosteroids, but progressed for those treated with corticosteroids (from + 7.4 to + 17.5 to + 15.8), regardless of duration of corticosteroid treatment. Similar results were noted for CAA of the right coronary artery and the left main coronary artery.

Conclusions

The use of corticosteroids in the acute phase of KD for patients with evolving CAAs may be associated with worsening involvement and impaired vascular remodelling and warrants further study.