Road map for the development of an e-healthcare strategy.

This article presents a case study describing how Saint Francis Care developed its strategy for using the Internet and e-commerce. Planning strategies are discussed, as are implementation plans and expected benefits.

Methotrexate inhibits proteolysis of dihydrofolate reductase by the N-end rule pathway.

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. In eukaryotes, the N-end rule pathway is a ubiquitin-dependent, proteasome-based system that targets and processively degrades proteins bearing certain N-terminal residues. Arg-DHFR, a modified dihydrofolate reductase bearing an N-terminal arginine (destabilizing residue in the N-end rule), is short lived in ATP-supplemented reticulocyte extract. It is shown here that methotrexate, which is a folic acid analog and high affinity ligand of DHFR, inhibits the degradation but not ubiquitination of Arg-DHFR by the N-end rule pathway. The degradation of other N-end rule substrates is not affected by methotrexate. We discuss implications of these results for the mechanism of proteasome-mediated protein degradation.

Nimodipine in migraine prophylaxis.

Nimodipine is a compound that is thought to block the influx of calcium through channels in vascular smooth muscle. This paper describes a double-blind parallel-group comparison of 40 mg nimodipine three times a day and placebo. Sixty-eight patients received treatment after a run-in period of 2 months, and of these, 57 completed 8 weeks or more of the trial. All but five of these completed the full 6-month trial. The nimodipine and placebo groups showed no significant differences in the frequency of attacks, severity or duration of headache, or gastrointestinal or other symptoms.

Chromosomal aberrations and sister chromatid exchanges in lymphocytes and urine mutagenicity of migraine patients: a comparison of chronic feverfew users and matched non-users.

1. Thirty migraine patients who had taken the leaves, tablets or capsules of feverfew daily for more than 11 consecutive months were compared to 30 feverfew non-user migraine patients who had been individually age- and sex-matched. 2. The frequency of chromosomal aberrations and sister chromatid exchanges (SCE) were determined from lymphocyte cultures established from blood samples taken over a period of several months. Matched pairs were sampled on the same date for two-thirds of the cases, and the greatest difference in sampling time of the remainder was 20 days. Also, the mutagenicity of urine samples from 10 feverfew user migraine patients was compared to that from 10 matched non-user migraine patients using the Ames Salmonella mutagenicity test system. Paired samples were given on the same date. 3. The mean frequency of chromosomal aberrations in the feverfew user group was lower than that in the non-user group both in terms of cells with breaks (2.13% vs 2.76%) and in terms of cells with all aberrations (4.34% vs 5.11%). However, this difference was small and not significant. 4. The mean frequency of SCE in the feverfew exposed group was lower than that in the control group (8.78 vs 8.80 SCE/cell), but, this difference was not significant as determined by factorial analysis of variance (P = 0.897). There was a highly significant variance between the frequencies of SCE in the matched pairs of migraine patients but this was not related to age, sex or feverfew exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of feverfew as prophylactic treatment of migraine.

Seventeen patients who ate fresh leaves of feverfew daily as prophylaxis against migraine participated in a double blind placebo controlled trial of the herb: eight patients received capsules containing freeze dried feverfew powder and nine placebo. Those who received placebo had a significant increase in the frequency and severity of headache, nausea, and vomiting with the emergence of untoward effects during the early months of treatment. The group given capsules of feverfew showed no change in the frequency or severity of symptoms of migraine. This provides evidence that feverfew taken prophylactically prevents attacks of migraine, and confirmatory studies are now indicated, preferably with a formulation controlled for sesquiterpene lactone content, in migraine sufferers who have never treated themselves with this herb.

Electrically-evoked release of [3H]-histamine from the guinea-pig hypothalamus.

1 [3H]-histamine was taken up by slices of guinea-pig hypothalamus against a concentration gradient. 2 Electrical field stimulation of the superfused slices resulted in an increased efflux of radioactivity, the major part of which was shown to be associated with histamine by paper chromatography. 3 The evoked release of histamine was dependent on calcium ions in the superfusate and was increased by 56% when the frequency of stimulation was doubled from 5 to 10 Hz.

A basis for migraine therapy- the autonomic theory reappraised.

The concept that migraine results from an initial vasoconstriction due to increased release of noradrenaline from the sympathetic nerves to cranial blood vessels has been reappraised in the light of recently acquired knowledge of the mechanisms of action of drugs used in the treatment of migraine, physiological and pharmacological evidence implicating noradrenaline, and the observations by others that several migraine variants may be associated with some degree of sympathetic overactivity. If the theory is correct, it suggests that both prophylaxis and management of the acute condition should be possible by means of selective alpha-adrenoceptor antagonism. The use of drugs with potentially dangerous vasoconstrictor properties appears to be unnecessary. The suggestion is made that the increased adrenergic activity might result from changes within the hypothalamus.