The preparation and properties of porcine neurophysin and the influence of calcium on the hormone-neurophysin complex

1. The preparation of a hormone-binding protein fraction (neurophysin) from porcine neurohypophyses is described.2. It was shown by gel-filtration that the protein (which sedimented as a single component on analytical ultracentrifugation) forms complexes with oxytocin and lysine vasopressin. The maximum capacity of porcine neurophysin to bind oxytocin and lysine vasopressin was estimated from the results of dialysis experiments as 232 u. oxytocin and 48 u. lysine vasopressin/mg protein.3. Binding of oxytocin and lysine vasopressin by neurophysin was completely inhibited in the presence of calcium in concentrations greater than 10(-6)M but is unaffected at less than 10(-7)M-Ca. The concentration of calcium required to inhibit binding did not appear to be dependent on hormone or protein concentrations.4. No evidence was obtained that calcium was bound by neurophysin or by the peptide hormones either alone or in combination.5. These results are discussed in the light of the hypothesis that release of the hormone from the neurohypophysis is mediated by calcium.     

In vitro selection of self-cleaving RNAs with a low pH optimum

RNAs that undergo a rapid site-specific cleavage at low pH have been selected by in vitro selection (the SELEX process). The cleavage does not require the addition of any divalent metal ions, and is in fact inhibited by divalent metal ions, spermine, or high concentrations of monovalent metal ions. This low pH catalyzed cleavage results in a 2′,3′-cyclic phosphate at the 3′ end and a free hydroxyl at the 5′ end. The reaction proceeds with a calculated rate of 1.1 min⁻¹ at room temperature in cacodylate buffer at pH 5.0. The rate of cleavage is dependent on the pH and shows an optimum around pH 4.0. The rate constant is independent of RNA concentration, indicating to an intramolecular reaction. Autocatalytic cleavage at low pH, in the absence of a metal ion requirement, adds to the reaction possibilities that may have existed on the prebiotic earth.     

Effects of economy and FDA intervention on the hearing aid industry

PURPOSE: The purpose of this study was to examine the effects of the economy and the Food and Drug Administration's (FDA) intervention on the hearing aid industry. METHOD: A 3-stage least squares regression technique was used to analyze the hearing aid market. RESULTS: Our results show that, while recessionary periods reduced both demand and supply, the demand side of the hearing aid industry is significantly more responsive to changes in the economy. Further, the demand function within the hearing aid industry is inelastic. Finally, negative media coverage from nationally televised reports during the FDA's intervention between the 2nd quarter of 1993 and the 3rd quarter of 1994 did not significantly affect the market demand of hearing aids. CONCLUSIONS: The demand for hearing aids increases in a flourishing economy and decreases during periods of recession. The negative media campaign from the FDA's intervention between the 2nd quarter of 1993 and the 3rd quarter of 1994 had essentially little effect on the end user. The repercussions of the FDA's intervention have resulted, however, in a reduction in the market supply of hearing aids and an increase in their cost due to manufacturer-sponsored clinical trials.     

Effectiveness of eletriptan in acute migraine: primary care for Excedrin nonresponders

OBJECTIVE: To evaluate the effectiveness of eletriptan as a treatment for acute migraine in patients who were poor responders to Excedrin and had not yet been exposed to a triptan. BACKGROUND: Self-medication with over-the-counter drugs, such as Excedrin, is the most common treatment for migraine. Guidelines, however, recommend that triptans be used as first-line treatment of moderate to severe migraine--the severity affecting approximately 80% of migraineurs. Since over-the-counter medications, such as Excedrin, continue to be used in many patients, it is important that clinicians have information on the efficacy of triptans as first-line treatment and on treatment of migraineurs who have shown poor response to over-the-counter medications. METHODS: One hundred ten patients meeting criteria for migraine who were poor responders to Excedrin received open-label treatment with a 40-mg dose of eletriptan for one migraine attack. Efficacy assessments were made at 1, 2, 4, and 24 hours postdose and consisted of headache and pain-free response rates, absence of associated symptoms, and functional response. RESULTS: At 1 hour, the headache response rate was 44%; at 2 hours, 81%. The pain-free response rate at 1 hour was 14% and at 2 hours, 48%. At 2 hours, relief of baseline-associated symptoms ranged from 74% to 80%. Functional response was achieved by 82% of patients by 2 hours, and 68% of patients achieved relief of migraine that was sustained across 24 hours with no need for a second dose of eletriptan or for rescue medication. Eletriptan was well tolerated with adverse events being transient and mild to moderate in intensity. CONCLUSION: Previous studies have established the efficacy of eletriptan as a first-line treatment for migraine. The results of this open-label trial demonstrate that the 40-mg dose of eletriptan had a high degree of efficacy and tolerability among patients who were poor responders to Excedrin.     

The effects of a sensitisation campaign on unrecognised migraine: the Casilino study

A striking feature of migraine is the difference between the estimated migraine prevalence and the actual number of migraineurs consulting their general practitioners (GPs). We investigated the impact of a sensitisation campaign on migraine in a large cohort of patients, living in a district of Rome. The study involved 10 GPs and a population of about 12 000 people, contacted by mail and posters located in GP clinics. Both the letter and poster stressed the impact of headache on quality of life and included the Italian version of the three-item Identification of Migraine (ID Migraine) screening test, consisting of questions on disability, nausea and photophobia. If the subjects suffered from headaches, they were invited to contact their GPs for a visit and a free consultation with a headache expert. By means of this sensitisation campaign, 195 headache patients consulted their GPs. Ninety-two percent of them (n=179) were migraineurs; 73% of them had never consulted a physician for headache. The ID Migraine test had a sensitivity of 0.92 (95% CI 0.86–0.95), a specificity of 0.75 (95% CI 0.47–0.91) and a positive predictive value (PPV) of 0.97 (95% CI 0.93–0.99) for a clinical diagnosis of migraine, according to the International Headache Society (IHS) criteria. This study confirms that a large number of migraine patients never see a doctor for their headache. This awareness campaign is likely to identify the severest cases of undiagnosed migraineurs. However, mailing campaigns do not seem to be so effective in bringing undiagnosed migraine patients into the primary care setting, and more efficient strategies have to be planned.