Migraine preventive medications: a reappraisal

Newer acute care migraine medications demonstrate improved rapidity of action, consistent effectiveness, excellent safety profiles, and rarely cause rebound headaches. Their use could decrease the need for migraine-preventive medication. The present analysis derives a formula that can be used by practitioners to determine the cost-effectiveness of various migraine-preventive medications relative to selected acute-care medications. We propose a measure called the cost-equivalent number (CEN), the number of headaches per month at which the cost of the preventive medication equals the cost savings in acute-care treatment realized by using the preventive medication. The use of the CEN individualizes the decision of whether to use a migraine-preventive medication, weighing both the efficacy and cost of the preventive medication against the cost of the acute-care medication. A CEN lower than the migraine frequency suggests that use of a preventive medication will be cost-effective.     

Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72-kD immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses

CTL are held to be an important host defense mechanism in persistent herpes-virus infections. We have therefore studied the nature and specificity of human cytomegalovirus (HCMV)-specific CTL in normal persistently infected individuals. This was achieved by using vaccinia recombinants encoding viral genes expressed at different stages of the virus replicative cycle, a structural glycoprotein gB (vac.gB) and the major 72-kD immediate early nonstructural protein (vac.IE) of HCMV, combined with limiting dilution analysis of the CTL response. In two subjects, 43 and 58% of HCMV CTL precursors (CTLp) lysed vac.IE-infected cells, in contrast to less than 6% lysing gB-infected cells. HCMV-specific CTL could also be generated by secondary in vitro stimulation with vac.gB- but not vac.IE-infected autologous fibroblasts. The high frequency of 72-kD IE protein-specific CTL suggests that this is at least a major recognition element for the HCMV-specific CTL response in asymptomatic persistently infected individuals, and CTL with this specificity may be important in maintaining the normal virus/host equilibrium.     

No association between serum eosinophil cationic protein and atopic dermatitis or allergic rhinitis in an unselected population of children

Background In order to obtain background references when dealing with serum eosinophil cationic protein (s‐ECP) measurements in children with allergic diseases, population‐based studies are important. The objectives of our study were to explore the strength of associations between the s‐ECP level and atopic dermatitis (AD), allergic rhinitis (AR) and asthma in an unselected northern Norwegian schoolchildren population. Methods s‐ECP was sampled from 396 schoolchildren aged 7–12 years from Sør‐Varanger community, northern Norway as a part of a population‐based study of allergy. In advance, anamnestic information concerning a history of AD, AR and asthma were obtained. The children underwent a clinical investigation, including skin prick tests and peak expiratory flow measurements, where the presence of AD, AR and asthma were evaluated. The associations of these diseases to the s‐ECP values were examined in bivariate statistical analysis. Results No statistical significant associations were detected in bivariate analysis between s‐ECP and AD, AR or asthma: the mean s‐ECP in children without self‐reported AD/AR/asthma was 4.6 µg/L [95% confidence interval (CI) 4.0–5.2]. The mean s‐ECP in children with self‐reported AD or AR or asthma was 5.2 µg/L (95% CI 4.1–6.2), 4.6 µg/L (95% CI 3.5–5.7) and 6.4 µg/L (95% CI 4.4–8.3), respectively. The highest mean s‐ECP level was measured in children with clinically diagnosed asthma; 7.1 µg/L (95% CI 4.0–10.3). Above the 75‐percentile level of s‐ECP, only 17.2% of the children had a history of asthma. Conclusions In this unselected children population, the occurrence of AD or AR was not reflected by an increase in the s‐ECP level. The s‐ECP was increased in children with asthma, but was not statistically significant. Furthermore, the majority of children with high s‐ECP values were not asthmatics. We conclude that the associations between s‐ECP and allergic diseases are weak in an unselected population of children.     

CD8high(CD57+) T cells in normal,healthy individuals specifically suppress the generation of cytotoxic T lymphocytes to Epstein-Barr virus-transformed B cell lines

We have previously identified two subsets of CD8⁺, CD57⁺ lymphocytes in normal peripheral blood: i) T cells expressing high levels [CD8^high(CD57⁺)] and ii) natural killer cells expressing low levels of surface CD8 [CD8^low(CD57⁺)]. We investigated the cytotoxic and suppressive function of CD8^high(CD57⁺) T lymphocytes from normal, healthy individuals using standard chromium-release assays and limiting dilution analysis. In normal, healthy subjects, this cell subset suppressed the generation of cytotoxic T lymphocytes (CTL) to autologous, Epstein-Barr virus (EBV)-transformed B cell lines (BCL). Depletion of CD8^high(CD57⁺) T lymphocytes from peripheral blood mononuclear cells (PBMC) resulted in a three- to sevenfold rise in CTL precursor frequency to autologous EBV-transformed BCL, but not allogeneic PBMC or BCL by LDA. Replacement of CD8^high(CD57⁺) T lymphocytes in limiting dilution cultures led to the dose-dependent suppression of EBV-specific, but not allogeneic, CTL generation. Supernatant from CD8^high(CD57⁺) T lymphocytes cultured with autologous BCL did not exhibit suppression, suggesting that soluble factors were not responsible. As CD8^high(CD57⁺) T lymphocytes did not, themselves, exhibit cytotoxicity against autologous BCL, removal of BCL stimulator cells in co-culture was not the mechanism of suppression. Furthermore, while the CD8^high(CD57⁺) T lymphocytes from healthy subjects suppressed the generation of CTL to autologous BCL, they did not suppress the cytotoxic activity of established mixed lymphocyte reactions or peptide-specific CTL clones, as has been reported in bone marrow transplant recipients and human immunodeficiency virus patients. This suggests that CD8^high(CD57⁺) T lymphocytes from healthy subjects suppress the generation of, rather than killing by, CTL in a contact-dependent manner. To our knowledge, this is the first identification of a phenotypically distinct subset of human CD8⁺ T cells that can suppress generation of antigen-specific major histocompatibility complex class I-restricted CTL.