To begin to examine the structural basis for the deposition of soluble A beta amyloid peptide onto senile plaques in Alzheimer's disease, we have prepared A beta congeners and measured their activity in an in vitro plaque growth assay. The N-terminal fragment, A beta (1-28)-OH, was inactive at all pH values tested. While the central fragment, A beta (10-35)-NH2, and the full length peptide, A beta (1-40)-OH, were inactive below pH 4, both were active (plaque competent) between pH 5 and 9. The active and inactive fragments were studied by nuclear magnetic resonance spectroscopy in water at submillimolar concentrations at pH 2.1 and 5.6. Changes in chemical shifts, coupling constants, and nuclear Overhauser enhancements indicate a pH dependent folding transition in A beta (10-35)-NH2 as it becomes active. The conformation of the active fragment is not helical, and preliminary data indicate the presence of several turns and at least two short strands. In contrast, the inactive fragment A beta (1-28)-OH did not undergo a similar folding transition. Earlier nuclear magnetic resonance studies of amyloid peptides in fluorinated alcohols or detergent micelles at low pH described a helical conformation and proposed a helix to sheet transition in plaque formation; the present study demonstrates that no such conformations are present in water under conditions where the peptides can adhere to authentic amyloid plaques.

BTXA is of greatest benefit in patients with residual deviations particularly when the inferior rectus is injected, but is of limited value as a primary therapy in chronic IV N palsy.

The features and management of two adult patients with ophthalmoplegic migraine and longlasting sixth nerve palsies are described. Both had had previous shorter episodes of diplopia following migraine-like headaches. One recovered following an injection of botulinum toxin to the medial rectus of her affected eye 11 months after the onset of diplopia. The other patient had previously had surgery for a consecutive divergent squint and required further squint surgery to realign his eyes 1 year after the onset of his sixth nerve palsy. Both botulinum toxin and squint surgery may be useful in the management of longstanding sixth nerve palsy in patients with ophthalmoplegic migraine. The aetiology of ophthalmoplegic migraine is discussed.

I have been living with a psychiatric disorder, schizophrenia, for 2 decades. I will relate how important medication is to the treatment of this illness. I will also relate how important the assessment of the level of medication to be used is to recovery. Specifically, I will explain how I learned to manage hallucinations and delusions and also how I acquired an experience which I refer to as spiritual, mystical and psychic.

No abstract