ABSTRACT
BACKGROUND AND PURPOSE: Primitive reflexes may reoccur in various neurodegenerative diseases. However, little is known about their structural and functional correlates in the human brain. Notably, the neural mechanisms underlying a positive palmomental reflex (PMR) are poorly understood. As recent studies link Alzheimer's disease (AD)-related primitive reflexes to a dysfunction of the corticostriatal motor circuit (CMC), we conducted the present study to investigate functional and structural correlates of a positive PMR. We hypothesized an involvement of frontostriatal structures and an impairment of the CMC. METHODS: Using whole-brain resting-state functional connectivity (FC), hypothesis and FC result-based probabilistic tractography, and voxel-based morphometry analyses, we compared two groups of AD patients with either positive (n = 12) or negative PMR (n = 12). RESULTS: No significant differences in grey matter volume or structural connectivity (SC) could be observed between the PMR-positive and PMR-negative groups. In contrast, the PMR-positive group showed a decreased seed-to-voxel FC between the bilateral supplementary motor area and parts of the right-hemispherical caudate nucleus and thalamus and a decreased region of interest (ROI)-to-ROI FC between the left putamen and the left superior frontal gyrus. CONCLUSION: Data suggest that dysfunction of the CMC reflected by decreased FC underlies a positive PMR in patients with AD. The lack of significant grey matter or SC differences might reflect that changes in FC appear before changes in SC in the structures of the CMC and brain atrophy.
Subject(s)
Alzheimer Disease , Alzheimer Disease/diagnostic imaging , Brain , Brain Mapping , Humans , Magnetic Resonance Imaging , ReflexABSTRACT
WHAT IS KNOWN AND OBJECTIVE: Drug-related problems (DRPs) occur frequently in hospitalized patients. Patient discharge from the intensive care unit (ICU) to a non-ICU ward is one of the most challenging and high-risk transitions of care due to the number of medications, and the complexity and acuity of the medical conditions that characterize this patient group. Pharmacists could play an important role in preventing DRPs. This study was undertaken to evaluate the impact on the number and severity of drug-related problems by assigning a clinical pharmacist to the transfer process from ICU to wards. METHODS: The study was a randomized controlled multicentre trial conducted at the Hospital Network of Antwerp between December 2010 and January 2012. The clinical pharmacist performed a medical review in both the intervention and control group. Recommendations for drug therapy changes were immediately communicated in the intervention group but were kept blinded in the control group. The primary outcome was expressed as the number of implemented recommendations for drug therapy changes. Differences between groups were calculated using mixed effects binary logistic regression. RESULTS: Drug-related problems were found in the medical records of 360 of the 600 participants (60%). A total of 743 recommendations could be made, 375 in the intervention group and 368 in the control group. 54·1% of these problems were adjusted on time in the intervention group vs. 12·8% in the control group. Of 743 recommendations, 24·8% were judged by the expert group as major, 13·1% as moderate, 53.4% as minor and 8·9% as having no clinical impact. The odds of implementing recommendations of drug therapy changes in the intervention group were 10 times the odds of implementing recommendations of drug therapy changes in the control group (odds ratio = 10·1; 95%CI [6·3-16·1]; P < 0·001), even after accounting for differences in types of DRP between the groups (odds ratio = 15·6; 95%CI [9·4-25·9]; P < 0·001). WHAT IS NEW AND CONCLUSION: The integration of a clinical pharmacist at the transfer point from ICU to ward led to a significant reduction in DRPs.
ABSTRACT
In the present study, the influence of freeze-drying with several cryoprotective agents and gamma (gamma)-irradiation sterilization on the physicochemical characteristics of ciprofloxacin HCl-loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles was evaluated. Nanoparticles were prepared by W/O/W emulsification solvent evaporation followed by high-pressure homogenization. They were freeze-dried in the presence of 5.0% (w/v) mannitol, trehalose or glucose, with 5.0% (w/v) or 15.0% (w/v) dextran as cryoprotectants. The nanoparticles were irradiated at a dose of 25 kGy using a 60Co source. The following physicochemical properties of the formulations were investigated: the ratio of particle size before (initial) and after freeze-drying, the ease of reconstitution of the nanoparticle suspensions and the drug-release profiles of irradiated and non-irradiated nanoparticles. The antibacterial activity against Pseudomonas aeruginosa was measured. The freeze-drying process induced a significant increase in particle size when no cryoprotectant was employed. Similar results were observed when cryoprotectants were added to the formulation. Only when mannitol was used was no significant size increase measured. Moreover, for formulations with dextran, reconstitution after freeze-drying was difficult by manual agitation and particle size could not be determined because of aggregation. After gamma-sterilization no significant difference in mean particle size was observed, but reconstitution was more difficult and drug release was influenced negatively. Ciprofloxacin HCl incorporated in the nanoparticles was still effective against the micro-organism selected after freeze-drying and gamma-sterilization.
