There is evidence for the validity and reliability of the QOL-AD in people with MMSE scores of 3-11, as well as the practicality of administering the scale in this population. The scale is unlikely to generate useful information for people with MMSE scores of <3. QOL does not decrease as cognition worsens. This throws into question most people's assumption that decreasing cognition worsens QOL. We consider that it may be important to inform the public of this, as living wills are used increasingly in our culture.

Qualitative classification of AD patients using dependency levels is a simple and validated approach. Applying this approach showed that institutionalisation and the most 'dependent' status were independently and significantly associated with high care cost.

The elementary K+ conductance activated by the cAMP or the Ca2+ second messenger pathways was investigated in the model salt-secreting epithelium, the human T84 cell line. Under Cl(-)-free conditions, an inwardly rectifying whole-cell K+ current was evoked by either forskolin 10 (mumol/l) or acetylcholine 1 (mumol/l) and blocked by extracellular charybdotoxin 10 (nmol/l). In the cell-attached mode, both secretory agonists induced the opening of a channel showing inward rectification with a unitary chord conductance of 36.8 +/- 2.5 pS (n = 26) for inward currents. In inside-out patches, a 35-pS inwardly rectifying K+ channel that corresponded to the channel recorded in the cell-attached configuration was recorded in the presence of 0.3 mumol/l free Ca2+ at the inner side of the membrane. This channel was blocked by Ba2+ (5 mumol/l) and by charybdotoxin (50 nmol/l). Its open probability was enhanced by intracellular Ca2+ with and EC50 of 0.25 mumol/l and strongly reduced by intracellular MgATP with an IC50 of 600 mumol/l. In the continuous presence of ATP, the channel activity was consistently increased by 125 kU/l catalytic subunit of cAMP-dependent protein kinase. In the cystic fibrosis pancreatic duct cell line CFPAC-1, a K+ channel was also recorded, with similar characteristics and regulation as the 35-pS channel in T84 cells. We conclude that an ATP-sensitive K+ channel regulated by intracellular Ca2+ and phosphorylation supports the main K+ current activated by secretory agonists in normal cystic fibrosis cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytosol prepared from human placenta inhibits outwardly rectifying Cl^- channels excised from HT₂₉ cells. Size exclusion chromatography of cytosol on Superose 12 revealed two inhibitory fractions suggesting Cl^- channel inhibitors of different size or molecular weight (MW). The ‘high MW’ inhibitor co-migrated with the proteins, whereas the ‘low MW inhibitor eluted together with tryptophan, xanthine, hypoxanthine, and nicotinamide. Although these substances did not inhibit Cl^– channels we tentatively assume that the ‘low MW cytosolic inhibitor may be a heterocyclic aromatic compound. Alternatively, the ‘low MW inhibitor may be a steroid, because aldosterone has a similar retention time on Superose 12. We can as yet exclude a number of putative cytosolic Cl^– channel inhibitors including glutathione, cAMP, cGMP, ATP, GTP, NADH, NADPH, and arachidonic acid.