Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

A clinical survey of head injuries sustained in the M1 Boeing 737 disaster: recommendations to improve aircrash survival

On 8 January 1989 at 20:25 h, a British Midland Boeing 737/400 on approach to East Midlands Airport crashed across the M1 motorway with the immediate loss of 39 lives from the 126 people on board. In the aftermath of the accident a clinical review was commenced to determine the mechanisms of injury in the 87 initial survivors and hopefully provide data to improve commercial aircraft safety in the future. Seventy-seven survivors sustained head and facial trauma in the crash, 45 of whom had periods of amnesia surrounding the event. Twenty-one received injuries from behind, including five of the six severely head-injured adults. Loss of consciousness and duration of amnesia were directly related to the degree of superficial head trauma. Adoption of the fully flexed brace position for crash-landing offered significant protection from head injury and concussion, and possibly reduced injuries from behind. Suggestions are made for potentially improving the survivability of aircraft accidents.     

Spinocerebellar ataxia type 7 (SCA7): a neurodegenerative disorder with neuronal intranuclear inclusions

Autosomal dominant cerebellar ataxia with progressive macular degeneration is caused by a CAG/glutamine repeat expansion in the SCA7 gene/protein. Neuronal intranuclear inclusions were detected in the brain of an early onset SCA7 case with the 1C2 antibody directed against an expanded polyglutamine domain. Nuclear inclusions were most frequent in the inferior olivary complex, a site of severe neuronal loss in SCA7. They were also observed in other brain regions, including the cerebral cortex, not considered to be affected in the disease. Using confocal microscopy we showed that some inclusions were ubiquitinated, but to varying degrees, ranging from <1% in the cerebral cortex to 60% in the inferior olive. In addition, we also observed cytoplasmic staining using the 1C2 antibody, particularly in the supramarginal gyrus, the hippocampus, the thalamus, the lateral geniculate body and the pontine nuclei. These data confirm that the presence of intranuclear inclusions in neurons is a common characteristic of disorders caused by CAG/polyglutamine expansions, but unlike what has been reported for Huntington's disease, SCA1 and SCA3/MJD, in SCA7 the inclusions were not restricted to the sites of severe neuronal loss.      

Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features

The underlying causes of learning disability and dysmorphic features in many patients remain unidentified despite extensive investigation. Routine karyotype analysis is not sensitive enough to detect subtle chromosome rearrangements (less than 5 Mb). The presence of subtle DNA copy number changes was investigated by array-CGH in 50 patients with learning disability and dysmorphism, employing a DNA microarray constructed from large insert clones spaced at approximately 1 Mb intervals across the genome. Twelve copy number abnormalities were identified in 12 patients (24% of the total): seven deletions (six apparently de novo and one inherited from a phenotypically normal parent) and five duplications (one de novo and four inherited from phenotypically normal parents). Altered segments ranged in size from those involving a single clone to regions as large as 14 Mb. No recurrent deletion or duplication was identified within this cohort of patients. On the basis of these results, we anticipate that array-CGH will become a routine method of genome-wide screening for imbalanced rearrangements in children with learning disability.     

Self-help materials for anxiety: a randomized controlled trial in general practice.

The efficacy of a self-help package in treating chronic anxiety was evaluated in a randomized controlled trial in which the intervention group received self-help materials in the form of an audiotape and booklet, in addition to their current treatment. The intervention was successful in terms of mean depression scores (P = 0.01), anxiety scores (P = 0.04) and general health questionnaire scores (P = 0.02) which were significantly lower for the intervention group than for the controls. In addition, the depression scores fell faster for the intervention group than for the controls. The overall mean reduction in three months in adjusted depression scores was approximately two points greater for the intervention group than for the controls (P = 0.02). Clinicians welcomed the package as a valuable addition to the therapies available for managing chronic anxiety problems. Further studies should include larger sample sizes, taking into account the non-response to postal questionnaires over time.     

Eye Movements and Visually Active Dreams

There are a number of reports suggesting an association between profusion of eye movements and active dreaming. It has however been suggested that this relationship might only be evident in comparisons across the night and would not be evident in comparisons within one REM period. Data from 20 subjects taking placebo, amylobarbitone, and nitrazepam were used to test this. Dream reports were collected from REM awakenings and rated blind as visually active or passive. Eye movement profusion (number of 2 sec epochs) was assessed for each REM period. Correlation between dream content and eye movement was low but significant in comparisons including the whole night, and including data from drug, withdrawal, and placebo conditions. A significant correlation was not consistently obtained, however, when data from each REMP were considered separately. Correlations based on data from non-drug nights only were also small and could have been due to chance effects alone. The low correlations were not explicable solely by poor reliability of content ratings. It is concluded that the relationship between visually active dreaming and eye movement is slight, and may not hold when time of night is adequately controlled.