Quality-of-life instruments in hypertension

This review considers the choice of dimensions to be assessed and the practical problems of measuring quality of life in hypertensive patients. The dimensions of symptomatic well-being, psychological well-being, sleep, sexual function and cognitive function should be assessed. Symptomatic well-being may be measured by many different instruments, and that devised by the authors has been used extensively. The results in different trials may therefore be examined for consistency and sensitivity. Psychological well-being has been assessed by the Psychological General Well-Being Index, the Symptom Rating Test and the Profile of Mood States. The response of these instruments is discussed. The assessment of sleep, sexual function and cognitive function is also described. It is recommended that quality-of-life instruments to be employed in trials of antihypertensive drugs are known to be sensitive to the effects of such drugs.     

Urine colour as an index of hydration in critically ill patients

In order to test the hypothesis that urine colour can be used as an index of hydration in critically ill patients, we selected 40 intensive care and high-dependency patients and correlated urine colour (scored on an eight-point scale) with various indices of hydration: urine:plasma sodium, osmolality and urea ratios, urine output and central venous pressure. In addition, we compared the colour-chart score with scores made by intensive care nurses (without the benefit of a colour chart) in order to test subjective assessment of urine colour. There were weak but statistically significant correlations between urine colour and urine output (Spearman's r = - 0.555) and between urine colour and urine:plasma sodium ratio (Spearman's r = - 0.459). Subjective assessment of urine colour appeared to be reliable. Thus, although urine colour does vary with hydration in the critically ill, assessment of urine colour adds little to the overall assessment of hydration in this group of patients.     

Learning-related neuronal responses in prefrontal cortex studied with functional neuroimaging

We assessed time-dependent neuronal activity accompanying learning using functional magnetic resonance imaging (fMRI). An artificial grammar learning paradigm enabled us to dissociate activations associated with individual item learning from those involved in learning the underlying grammar system. We show that a localized region of right prefrontal cortex (PFC) is preferentially sensitive to individual item learning during the early stages of the experiment, while the left PFC region is sensitive to grammar learning which occurred across the entire course of the experiment. In addition to dissociating these two types of learning, we were able to characterize the effect of rule acquisition on neuronal responses associated with explicit learning of individual items. This effect was expressed as modulation of the time-dependent right PFC activations such that the early increase in activation associated with item learning was attenuated as the experiment progressed. In a further analysis we used structural equation modelling to explore time-dependent changes in inter-regional connectivity as a function of both item and grammar rule learning. Although there were no significant effects of item learning on the measured path strengths, rule learning was associated with a decrease in right fronto-parietal connectivity and an increase in connectivity between left and right PFC. Further fronto-parietal path strengths were observed to change, with an increase in left fronto-parietal and a decrease in right fronto-parietal connectivity path strength from right PFC to left parietal cortex. We interpret our findings in terms of a left frontal system mediating the semantic analysis of study items and directly influencing a right fronto-parietal system associated with episodic memory retrieval.     

Expression, distribution and ultrastructural localization of the synapse-organizing molecule agrin in the mature avian retina

At the vertebrate neuromuscular junction the extracellular matrix molecule agrin is responsible for the formation, maintenance and regeneration of most if not all postsynaptic specializations. Several agrin isoforms are generated by alternative splicing which differ in their function and which are all expressed in the CNS. To analyse the role of agrin in the CNS, we investigated the expression and ultrastructural localization of agrin in the posthatched chick retina. In situ hybridization revealed the presence of agrin mRNA in all cellular layers of the mature retina, indicating that most if not all major retinal cell types synthesize agrin. Pan-specific as well as isoform-specific antiagrin antisera stained the optic fibre layer and the outer plexiform layer. However, only the pan-specific antiserum additionally stained the inner limiting membrane. Immunoelectron microscopy showed that in the optic fibre layer agrin was associated with ganglion cell axons and that at least part of this agrin corresponds to a neuronal isoform of agrin. In the outer plexiform layer, agrin was localized in the cleft between the photoreceptor terminals and the invaginating horizontal and bipolar cell dendrites. In the synapse-containing inner plexiform layer both antisera revealed punctate immunoreactivity. This staining corresponded to agrin concentrated in the synaptic cleft of conventional synapses as determined by preembedding immunoelectron microscopy. Agrin is thus concentrated at mature interneuronal synapses as it is at the neuromuscular junction, consistent with a role of agrin during formation and/or maintenance of synapses in the CNS.