The effect of diet upon serum concentrations of theophylline

Eight patients with airways obstruction were investigated to determine if dietary components had any significant effect upon serum concentrations of theophylline when taking a slow release formulation. A high carbohydrate, low protein diet, given for 1 week, resulted in the area under the concentration time curve for 12 h being 33.3% greater than a high protein low carbohydrate diet given under the same conditions. In contrast to two previous studies no significant effect upon the elimination half-life was detected after changing from one diet to the other and an effect of dietary components upon absorption and/or distribution needs to be considered. Morning and afternoon trough levels were significantly different from each other on both diets suggesting that theophylline kinetics are different at night. Individualising of theophylline dosing is particularly needed when treating patients on a varied dietary intake.     

Acute care skills in anesthesia practice: a simulation-based resident performance assessment

BACKGROUND: A recurring initiative in graduate education is to find more effective methods to assess specialists' skills. Life-sized simulators could be used to assess the more complex skills expected in specialty practice if a curriculum of relevant exercises were developed that could be simply and reliably scored. The purpose of this study was to develop simulation exercises and associated scoring methods and determine whether these scenarios could be used to evaluate acute anesthesia care skills. METHODS: Twenty-eight residents (12 junior and 16 senior) managed three intraoperative and three postoperative simulation exercises. Trainees were required to make a diagnosis and intervention in a simulation encounter designed to recreate an acute perioperative complication. The videotaped performances were scored by six raters. Three raters used a checklist scoring system. Three faculty raters measured when trainees performed three key diagnostic or therapeutic actions during each 5-min scenario. These faculty also provided a global score using a 10-cm line with scores from 0 (unsatisfactory) to 10 (outstanding). The scenarios included (1) intraoperative myocardial ischemia, (2) postoperative anaphylaxis, (3) intraoperative pneumothorax, (4) postoperative cerebral hemorrhage with intracranial hypertension, (5) intraoperative ventricular tachycardia, and (6) postoperative respiratory failure. RESULTS: The high correlation among all of the scoring systems and small variance among raters' scores indicated that all of the scoring systems measured similar performance domains. Scenarios varied in their overall difficulty. Even though trainees who performed well on one exercise were likely to perform well in subsequent scenarios, the authors found that there were considerable differences in case difficulty. CONCLUSION: This study suggests that simulation can be used to measure more complex skills expected in specialty training. Similar to other studies that assess a broad content domain, multiple encounters are needed to estimate skill effectively and accurately.     

Working memory deficits after traumatic brain injury: catecholaminergic mechanisms and prospects for treatment -- a review

Primary objective: To review the neural circuitry and neurochemistry of working memory and outline the evidence for working memory deficits after traumatic brain injury, and the evidence for the use of catecholaminergic agents in the amelioration of these deficits. Current knowledge gaps and research needs are identified.

Main outcomes and results: Impairments in working memory are a core component of the cognitive deficits associated with traumatic brain injury. Recent progress in understanding the neural circuitry and neurochemistry of working memory suggests that catecholamines play a central role in the activation and regulation of working memory and thus lays a framework in which to consider the use of catecholaminergic agents (dopaminergic and alpha-2 adrenergic agonists) in the treatment of specific cognitive deficits after traumatic brain injury.

Conclusions: The combined methods of cognitive neuroscience, functional brain imaging and neuropharmacology are proposed as an excellent method for studying working memory deficits. A strong rationale exists for the targeted use of catecholaminergic agonists in the treatment of working memory deficits after traumatic brain injury.     

Relative stability of transgene DNA fragments from GM rapeseed in mixed ruminal cultures

The use of transgenic crops as feeds for ruminant animals has prompted study of the possible uptake of transgene fragments by ruminal micro-organisms and/or intestinal absorption of fragments surviving passage through the rumen. The persistence in buffered ruminal contents of seven different recombinant DNA fragments from GM rapeseed expressing the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) transgene was tracked using PCR. Parental and transgenic (i.e. glyphosphate-tolerant; Roundup Ready, Monsanto Company, St Louis, MO, USA) rapeseed were incubated for 0, 2, 4, 8, 12, 24 and 48 h as whole seeds, cracked seeds, rapeseed meal, and as pelleted, barley-based diets containing 65 g rapeseed meal/kg. The seven transgene fragments ranged from 179 to 527 bp and spanned the entire 1363 bp EPSPS transgene. A 180 bp ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) small subunit fragment and a 466 bp 16S rDNA fragment were used as controls for endogenous rapeseed DNA and bacterial DNA respectively. The limit of detection of the PCR assay, established using negative controls spiked with known quantities of DNA, was 12.5 pg. Production of gas and NH3 was monitored throughout the incubation and confirmed active in vitro fermentation. Bacterial DNA was detected in all sample types at all time points. Persistence patterns of endogenous (Rubisco) and recombinant (EPSPS) rapeseed DNA were inversely related to substrate digestibility (amplifiable for 48, 8 and 4 h in whole or cracked seeds, meal and diets respectively), but did not differ between parental and GM rapeseed, nor among fragments. Detection of fragments was representative of persistence of the whole transgene. No EPSPS fragments were amplifiable in microbial DNA, suggesting that transformation had not occurred during the 48 h incubation. Uptake of transgenic DNA fragments by ruminal bacteria is probably precluded or time-limited by rapid degradation of plant DNA upon plant cell lysis.     

Mobility and cycling of synaptic protein-containing vesicles in axonal growth cone filopodia

The spatial distribution and coordination of vesicular dynamics within growth cones are poorly understood. It has long been thought that membranous organelles are concentrated in the central regions of growth cones and excluded from filopodia; this view has dramatically shaped conceptual models of the cellular mechanisms of axonal growth and presynaptic terminal formation. To begin to test these models, we studied membrane dynamics within axonal growth cones of living rat cortical neurons. We demonstrate that growth cone filopodia contain vesicles that transport synaptic vesicle proteins bidirectionally along filopodia and fuse with the filopodial surface in response to focal stimulation, allowing for both local secretion of vesicular contents and rapid changes in the plasma membrane composition of individual filopodia. Our results suggest a new model in which growth cone filopodia are actively involved in both emitting and responding to local signals related to axon growth and early synapse formation.