Neuroimaging findings in human prion disease.

Imaging occupies an important role in the investigation of dementia and neurodegenerative disease. The role of imaging in prion disease used to be one of exclusion of other conditions. Over the past decade, the non-invasive nature of MRI, the improved range of magnetic resonance sequences and the availability of clinical and neuropathological correlation have led to a more prominent position of MRI and its inclusion in the diagnostic criteria for variant Creutzfeldt-Jakob disease. As experience of imaging in human prion disease increases, patterns of change related to strain and genotype may improve the diagnostic potential of imaging in the future, may reduce the need for more invasive testing and prove useful in future therapeutic trials. This paper reviews the current knowledge of imaging appearances in human prion disease.

Biogenic amines: their occurrence, biosynthesis and metabolism in the locust, Schistocerca gregaria, by gas chromatography-negative-ion chemical ionisation mass spectrometry.

Extraction-derivatisation techniques have been developed for the unambiguous identification of biogenic amines, and their putative amino acid precursors and metabolites (both major and minor), in single ventral thoracic nerve cords of the locust. Schistocerca gregaria, by the use of gas chromatography-negative-ion chemical ionisation mass spectrometry with selected ion monitoring. In addition the configuration of that enantiomer of p-octopamine present in the thoracid nervous system of the locust was established as R using the chiral derivatisation reagent, (-)-heptafluorobutyrylphenylalanyl chloride.

Identification and quantitation of phenylalanine, tyrosine and dihydroxyphenylalanine in the thoracic nervous system of the locust, Schistocerca gregaria, by gas chromatography-negative-ion chemical ionisation mass spectrometry.

Phenylalanine, tyrosine and dihydroxyphenylalanine (DOPA) were identified unambiguously and quantitatively determined in single ventral thoracic nerve cords from the locust, Schistocerca gregaria, by gas chromatography-negative-ion chemical ionisation mass spectrometry. Deuterium-labelled analogues of each compound were added to a single ventral thoracic nerve cord in hydrochloric acid; the tissue was homogenised and the suspension centrifuged. The remaining hydrochloric acid was eliminated azeotropically by repeated additions of acetonitrile followed by evaporation under a stream of nitrogen and the resultant residue derivatised by reaction with hexafluoroisopropanol and pentafluoropropionic anhydride. Under negative-ion chemical ionisation conditions, the hexafluoroisopropanol-pentafluoropropionyl derivatives produced characteristic ions which were sufficiently abundant to be suitable for selected-ion monitoring. This method is highly specific and gave a limit of detection below the nanogram level. The amounts of phenylalanine, tyrosine and DOPA in a single ventral thoracic nerve cord were, respectively, 194 +/- 81, 347 +/- 88 and 11 +/- 11 ng per tissue.

Identification and quantitation of N-acetyl metabolites of biogenic amines in the thoracic nervous system of the locust, Schistocerca gregaria, by gas chromatography-negative-ion chemical ionisation mass spectrometry.

The N-acetylated metabolites of p-tyramine, p-octopamine and dopamine were identified unambiguously and quantitatively determined in a single ventral thoracic nerve cord of the locust, Schistocerca gregaria, by gas chromatography-negative-ion chemical ionisation mass spectrometry (GC-NICIMS). Deuterium-labelled analogues of each compound were added to a single ventral thoracic nerve cord in acetonitrile: the tissue was homogenised and the suspension centrifuged. The solvent was removed from the supernatant and the resultant residue was derivatised with trifluoroacetic anhydride. Under negative-ion chemical ionisation conditions, the trifluoroacetyl derivatives produced ions which were sufficiently abundant to be suitable for selected-ion monitoring. This method is highly specific and gave a limit of detection below the picogram levels. N-Acetyl-5-hydroxytryptamine was determined using a previously published GC-NICIMS technique [S.P. Markey, R.W. Colburn and J.N. Johannessen, Biomed. Mass Spectrom., 7 (1981) 301]. The concentrations of N-acetyltyramine, N-acetyloctopamine, N-acetyldopamine and N-acetyl-5-hydroxytryptamine in locust thoracic nerve cords were, respectively, 1.86 +/- 0.71, 1.13 +/- 0.34, 6.77 +/- 8.48 and 0.07 +/- 0.02 ng per tissue.

Analysis of acidic metabolites of biogenic amines in bovine retina and vitreous and aqueous humour by gas chromatography-negative ion chemical ionisation mass spectrometry.

Acidic metabolites of a number of biogenic amines have been identified and quantified by reaction with either acetic or propionic anhydride in the aqueous phase followed by extraction into ethyl acetate, esterification of carboxyl groups with ditrifluoromethylbenzyl bromide (DTFMBzBr), and then conversion of the remaining free hydroxyl groups to acetates. Subsequent analysis of these derivatives revealed that most (greater than 60%) of the ion current was carried by the ion resulting from the loss of DTFMBz from the molecular ion. This made the method highly specific and practical--limits of detection were established at approximately 200 pg with a potential limit of detection below the picogram level. This method establishes unequivocally that the metabolites of tyramine, dopamine, and adrenaline/noradrenaline (4-hydroxyphenylacetic acid, 3,4-dihydroxyphenylacetic acid, and dihydroxymandelic acid, respectively) are present in bovine retina and in vitreous and aqueous humour. In addition, high concentrations of the dopamine metabolite homovanillic acid were found in retina and vitreous, but not in aqueous humour. p-Hydroxymandelic acid, the acidic metabolite of p-octopamine/p-synephrine, was identified in vitreous and in aqueous humour.

Analysis of biogenic amines in bovine retina by gas chromatography-negative ion chemical ionisation mass spectrometry.

Biogenic amines in bovine retina have been identified and quantified by an extraction-derivatisation procedure involving their reaction with 3,5-di(trifluoromethyl)benzoyl chloride (DTFMBCl) in the aqueous phase followed by extraction into an organic solvent, hydrolysis of phenolic esters, and conversion of free hydroxyl groups to trimethylsilyl ethers. Subsequent analysis of these DTFMB-trimethylsilyl derivatives by gas chromatography-negative ion chemical ionisation mass spectrometry revealed that the molecular ion carried most (greater than 60%) of the ion current, which made the method highly specific and gave a potential limit of detection below the picogram level. This method establishes unequivocally that the principal amines in bovine retina are p-tyramine, dopamine, and 5-hydroxytryptamine.

Analysis of biogenic amines in the brain of the American cockroach (Periplaneta americana) by gas chromatography-negative ion chemical ionisation mass spectrometry.

Biogenic amines in the brain of the American cockroach have been identified and quantified by an extraction-derivatisation procedure involving their reaction with ditrifluoromethylbenzoyl chloride (DTFMB) in the aqueous phase followed by extraction into an organic solvent, hydrolysis of phenolic esters and conversion of free hydroxyl groups to trimethylsilyl (TMS) ethers and subsequent analysis by gas chromatography-negative ion chemical ionisation mass spectrometry. The molecular ion of these DTFMB-TMS derivatives carried most of the ion current which made the method highly specific and gave a potential limit of detection below the picogram level. This method establishes unequivocally that the principal amines in cockroach brain are tyramine, p-octopamine, dopamine, 5-hydroxytryptamine and noradrenaline. In contrast to mammalian nervous tissue, the other positional isomers of octopamine, together with the isomeric synephrines, are absent.

An extended course in general practice.

An extended course in general practice sponsored by regional advisers and university departments of general practice in Scotland, consisting of six sessions lasting two to four days interspersed with group discussion meetings and spread over a period of 18 months, is described and evaluated. Participants developed skills in teaching, confidence in group learning and insight into their abilities as teachers and organizers of training in general practice.

Education in terminal care.

A survey of the education in terminal care received by a wide range of doctors in Scotland showed that clinical instruction in the physical and emotional aspects of the care of the dying had been generally inadequate, and that the educational influence of a special unit or hospice could be significant. Doctors who had undertaken traineeships in general practice tended to have had more comprehensive training in terminal care-and to be more enthusiastic about further education-than others. We conclude that planned vocational training schemes in all disciplines need to be re-examined for the provision they make for education in terminal care, and that continuing education in the subject may need to be improved for all doctors.