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Biomedical subjects

Elizabeth Miller

Publications and source records attributed to Elizabeth Miller.

At least 37 records · Page 2Linked to original sources
PubMed2005

Meningococcal surrogates of protection--serum bactericidal antibody activity.

Despite the availability of anti-microbial agents effective against Neisseria meningitidis, meningococcal disease continues to be a major global health problem, particularly in the very young. Serogroup A meningococci cause large epidemics in sub-Saharan Africa, whilst serogroups B and C organisms are responsible for sporadic cases and localised outbreaks of disease world-wide. For measuring functional activity, the serum bactericidal antibody (SBA) assay is the most important method. It is mediated by antibody and complement resulting in lysis of the bacterial cells. To date the SBA has proved to be the best surrogate of protection for all serogroups. For serogroup C, an SBA titre of either >/ or =4 or > or =8 has being utilised for putatively indicating protection when using either human or baby rabbit complement, respectively. For serogroup B, the proportions of vaccines with > or =4-fold rises in SBA pre- to post-vaccination or SBA titres > or =4 have been correlated with clinical efficacy in trials of outer membrane vesicle (OMV) vaccines in Cuba, Brazil and Norway. SBA activity as a correlate of protection for evaluating the immune response to meningococcal vaccines is described in this review.

Antibodies, Bacterial↗
PubMed2005

Wired for wellness: e-interventions for addressing college drinking.

In an effort to address problematic drinking among American college students, there has been increasing interest in the use of technology. This article reviews evidence for the efficacy of computer and internet interventions and provides information on five commercially available alcohol education and intervention programs that target college drinkers. Most programs use a mix of educational, skills-based, and motivational strategies to present material. All programs include assessment questions and provide personalized drinking feedback or other information that is customized to each user. Despite limited outcome research, there appear to be a number of advantages to computer and internet programs that focus on alcohol reduction. Future studies will need to determine how to best make use of technology to reach larger numbers of students with an effective, individual approach.

Adult↗
PubMed2005

Demon rum: high-tech solutions to an age-old problem.

This article summarizes the proceedings of a symposium at the 2004 Research Society on Alcoholism Meeting in Vancouver, British Columbia, Canada, organized and chaired by Scott T. Walters. The purpose of the symposium was to describe several brief motivational interventions offered via the Internet, including the evidence for web-based interventions, applications and contexts in which such approaches are being used, and directions for future research. Walters provided an overview and introduction to the topic and discussed the e-CHUG (www.e-chug.com) and e-TOKE (www.e-toke.com) feedback interventions for college alcohol and marijuana prevention, including the contexts in which they are being used and ways they are being integrated with other campus prevention efforts. Dr. Hester presented 12-month results from a controlled trial of the Drinker's Check-up (www.drinkerscheckup.com), an intervention for adult problem drinkers that is available both as a Windows and as an Internet application. Dr. Chiauzzi described the development and testing of My Student Body (www.mystudentbody.com), a tailored drinking prevention web site for college students. Finally, Dr. Miller addressed the use of online assessment and feedback to reduce drinking, including the history of web-based interventions and their likely future and the potential limitations of such approaches.

Alcohol Drinking↗
PubMed2004

New estimates of herpes simplex virus type 2 seroprevalence in England: 'high' but stable seroprevalence over the last decade.

OBJECTIVES: There have been few recent population-based herpes simplex virus type 2 (HSV-2) seroprevalence studies in England, but reports from the United States have indicated a 30% rise in HSV-2 seroprevalence between 1976 and 1994. This study aimed to ascertain trends in HSV-2 infection in England between 1991 and 2000. STUDY DESIGN: Anonymized serum residues collected through public health laboratories across England from individuals aged 16 to 64 years seeking health care through the National Health Service in 1991 (n = 2259) and 2000 (n = 3646) were tested for anti-HSV-2 IgG using the HerpeSelect 2 enzyme-linked immunosorbent assay IgG (Focus). RESULTS: In 9 sites across England, the age- and sex-standardized HSV-2 seroprevalence was 9.7% (95% confidence interval, 8.4-11.0%). Data from 4 sites common to both study years indicated no change in HSV-2 seroprevalence between 1991 and 2000. CONCLUSIONS: After adjustment for age, sex, and geographic location, there was no evidence of a change in seroprevalence between 1991 and 2000.

Adolescent↗
PubMed2004

Laboratory diagnosis of pertussis infections: the role of PCR and serology.

This study reports on practical laboratory aspects of pertussis diagnosis. PCR assays were applied to respiratory specimens obtained during a large study of infants (less than 5 months old) admitted to paediatric intensive care units (n = 122), children (less than 15 years old) admitted to paediatric wards (n = 16) and their household contacts (n = 320). Estimation of antibodies to pertussis toxin and culture for Bordetella pertussis were attempted on specimens from the same patients, where available, and the overall utility of the diagnostic PCR assays was assessed by comparison to these results. A PCR assay for the human mitochondrial cytochrome oxidase (HMCO) gene was used for quality control of the extracted samples and an internal process control (IPC) was included in each sample to test for PCR inhibition. Four of 458 samples were considered unsuitable (three HMCO negative, one IPC negative) and excluded from further analyses. Positive PCR results were considered valid if they were either (i) positive for both of two B. pertussis gene targets (pertussis toxin S1 promoter and the insertion element IS481), i.e. consensus PCR positive, or (ii) repeatably positive in only one assay. Using these criteria, 52 of 454 (11.5 %) samples were considered as PCR positive for B. pertussis. Six of 356 samples were culture-positive for B. pertussis, 1/88 infants, 3/14 children and 2/254 contacts, giving an overall isolation rate of 1.7 %. Using these data, PCR gave an almost fivefold increase in diagnostic yield compared with culture (McNemar's test; P < 0.0001). Sera from 9/111 infants, 5/10 children and 14/210 contacts were positive. Serology and PCR results showed a high level of agreement (113/121) for infants and children. PCR demonstrated a significant improvement in diagnostic yield over culture. Serological testing also resulted in a significant increase in diagnostic yield compared to culture alone. PCR is a useful technique, but validity of results must be assured by careful control. Rapid diagnosis of B. pertussis infection particularly in infants by PCR, together with serological assays, can enhance surveillance systems for pertussis in all age groups.

Adolescent↗
PubMed2004

Effects of prior polysaccharide vaccination on magnitude, duration, and quality of immune responses to and safety profile of a meningococcal serogroup C tetanus toxoid conjugate vaccination in adults.

Extensive use of meningococcal AC polysaccharide (MACP) vaccines has raised concerns about induction of immunologic hyporesponsiveness to C polysaccharide. We investigated the immunogenicity and safety of a meningococcal C-tetanus conjugate (MCC-TT) vaccine in naive adults and prior MACP vaccinees. Laboratory staff (n = 113) were recruited; 73 were naive to meningococcal vaccination, and 40 had previously received > or =1 dose of MACP vaccine. Blood was taken prior to MCC-TT vaccination and 1 week, 1 month, and 6 months later. At each time point, proportions of subjects with serum bactericidal antibody (SBA) titers of > or =8 or > or =128 were similar (P > 0.46); >94% of subjects achieved titers of > or =128 at 1 month. However, the geometric mean titer (GMT) of SBA at 1 month was higher in the naive (1,757; 95% confidence interval [95% CI], 1,102 to 2,803) than in the previously vaccinated (662; 95% CI, 363 to 1,207) group (P = 0.02), and similarly at 6 months (P < 0.001). Conversely, geometric mean concentrations (GMCs) of serogroup C-specific immunoglobulin G (IgG) were significantly higher in the previously vaccinated group pre-MCC-TT and at 1 week; the groups were similar at 1 month, and there was some evidence that the GMC for the previously vaccinated group was higher at 6 months. Qualitative differences in antibodies between groups were demonstrated by using the SBA/IgG ratio, though avidity measures were similar for the two groups throughout the study. MCC-TT was well tolerated, with similar safety profiles in the two groups. Pain in the arm and headache were the most frequently reported events following vaccination. The study shows that MCC-TT is safe and immunogenic in naive and previously MACP-vaccinated adults, though the magnitude and persistence of postvaccination SBA responses in the latter group were lower.

Adult↗
PubMed2004

Thimerosal exposure in infants and developmental disorders: a retrospective cohort study in the United kingdom does not support a causal association.

OBJECTIVE: After concerns about the possible toxicity of thimerosal-containing vaccines in the United States, this study was designed to investigate whether there is a relationship between the amount of thimerosal that an infant receives via diphtheria-tetanus-whole-cell pertussis (DTP) or diphtheria-tetanus (DT) vaccination at a young age and subsequent neurodevelopmental disorders. METHODS: A retrospective cohort study was performed using 109 863 children who were born from 1988 to 1997 and were registered in general practices in the United Kingdom that contributed to a research database. The disorders investigated were general developmental disorders, language or speech delay, tics, attention-deficit disorder, autism, unspecified developmental delays, behavior problems, encopresis, and enuresis. Exposure was defined according to the number of DTP/DT doses received by 3 and 4 months of age and also the cumulative age-specific DTP/DT exposure by 6 months. Each DTP/DT dose of vaccine contains 50 microg of thimerosal (25 microg of ethyl mercury). Hazard ratios (HRs) for the disorders were calculated per dose of DTP/DT vaccine or per unit of cumulative DTP/DT exposure. RESULTS: Only in 1 analysis for tics was there some evidence of a higher risk with increasing doses (Cox's HR: 1.50 per dose at 4 months; 95% confidence interval [CI]: 1.02-2.20). Statistically significant negative associations with increasing doses at 4 months were found for general developmental disorders (HR: 0.87; 95% CI: 0.81-0.93), unspecified developmental delay (HR: 0.80; 95% CI: 0.69-0.92), and attention-deficit disorder (HR: 0.79; 95% CI: 0.64-0.98). For the other disorders, there was no evidence of an association with thimerosal exposure. CONCLUSIONS: With the possible exception of tics, there was no evidence that thimerosal exposure via DTP/DT vaccines causes neurodevelopmental disorders.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

A global perspective on vaccine safety and public health: the Global Advisory Committee on Vaccine Safety.

Established in 1999, the Global Advisory Committee on Vaccine Safety advises the World Health Organization (WHO) on vaccine-related safety issues and enables WHO to respond promptly, efficiently, and with scientific rigor to issues of vaccine safety with potential global importance. The committee also assesses the implications of vaccine safety for practice worldwide and for WHO policies. We describe the principles on which the committee was established, its modus operandi, and the scope of the work undertaken, both present and future. We highlight its recent recommendations on major issues, including the purported link between the measles-mumps-rubella vaccine and autism and the safety of the mumps, influenza, yellow fever, BCG, and smallpox vaccines as well as that of thiomersal-containing vaccines.

Advisory Committees↗
PubMed2004

Impact of a health education intervention in overactive bladder patients.

OBJECTIVE: To assess a standardized and simple educational intervention in overactive bladder (OAB) patients to improve compliance with anticholinergic medication, increase the use of concomitant behavioral treatments, and improve patients' perception of bladder symptoms. MATERIALS AND METHODS: This is a 16-week open-label randomized trial of tolterodine combined with an education intervention for the experimental group versus tolterodine alone (no intervention) for the control group. The setting was in family medicine and urology clinics in Ontario. The participants were male and female adults with OAB symptoms. Both groups received tolterodine prescriptions. The intervention patients received printed information and an explanation about OAB, medication use, and behavioral treatments (kegel exercise, bladder stretching, fluid regulation). The primary outcomes were medication compliance and persistence at 16 weeks. Secondary outcomes were use of behavioral treatments and self-reported severity of symptoms. RESULTS: More patients in the intervention group (experimental) purchased their prescriptions (p<0.05). Compliance rate was greater for the intervention group (39%), versus the control group (31%) at 16 weeks although the difference was not significant (p>0.05). Significantly more patients started and/or continued non-drug treatments in the intervention group (82%) compared to the control group (53%) (p<0.05). Furthermore, more patients in this group reported improvement in severity of bladder symptoms (p<0.05). CONCLUSIONS: The simple education intervention resulted in a greater, but not significant, increase in compliance with medication compared to the control group. It also resulted in a significantly increased use of behavior modification therapies and better self-perception of treatment outcome.

Aged↗
PubMed2003

Lysine-phosphatidylcholine adducts in kringle V impart unique immunological and potential pro-inflammatory properties to human apolipoprotein(a).

Lipoprotein(a), Lp(a), an athero-thrombotic risk factor, reacts with EO6, a natural monoclonal autoantibody that recognizes the phophorylcholine (PC) group of oxidized phosphatidylcholine (oxPtdPC) either as a lipid or linked by a Schiff base to lysine residues of peptides/proteins. Here we show that EO6 reacts with free apolipoprotein(a) apo(a), its C-terminal domain, F2 (but not the N-terminal F1), kringle V-containing fragments obtained by the enzymatic digestion of apo(a) and also kringle V-containing apo(a) recombinants. The evidence that kringle V is critical for EO6 reactivity is supported by the finding that apo(a) of rhesus monkeys lacking kringle V did not react with EO6. Based on the previously established EO6 specificity requirements, we hypothesized that all or some of the six lysines in human kringle V are involved in Schiff base linkage with oxPtdPC. To test this hypothesis, we made use of a recombinant lysine-containing apo(a) fragment, rIII, containing kringle V but not the protease domain. EO6 reacted with rIII before and after reduction to stabilize the Schiff base and also after extensive ethanol/ether extraction that yielded no lipids. On the other hand, delipidation of the saponified product yielded an average of two mol of phospholipids/mol of protein consistent with direct analysis of inorganic phosphorous on the non-saponified rIII. Moreover, only two of the six theoretical free lysine amino groups per mol of rIII were unavailable to chemical modification by 2,4,6-trinitrobenzene sulfonic acid. Finally, rIII, like human apo(a), stimulated the production of interleukin 8 in THP-1 macrophages in culture. Together, our studies provide evidence that in human apo(a), kringle V is the site that reacts with EO6 via lysine-oxPtdPC adducts that may also be involved in the previously reported pro-inflammatory effect of apo(a) in cultured human macrophages.

Amino Acid Sequence↗
PubMed2003

Antioxidant vitamins C and E improve endothelial function in children with hyperlipidemia: Endothelial Assessment of Risk from Lipids in Youth (EARLY) Trial.

BACKGROUND: Hyperlipidemia is associated with endothelial dysfunction, an early event in atherosclerosis and predictor of risk for future coronary artery disease. Epidemiological studies suggest that increased dietary intake of antioxidants reduces the risk of coronary artery disease. The purpose of this study was to determine whether antioxidant vitamin therapy improves endothelial function and affects surrogate biomarkers for oxidative stress and inflammation in hyperlipidemic children. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled trial, the effects of antioxidant vitamins C (500 mg/d) and E (400 IU/d) for 6 weeks and the National Cholesterol Education Program Step II (NCEP-II) diet for 6 months on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery were examined in 15 children with familial hypercholesterolemia (FH) or the phenotype of familial combined hyperlipidemia (FCH). Antioxidant vitamin therapy improved FMD of the brachial artery compared with baseline (P<0.001) without an effect on biomarkers for oxidative stress (autoantibodies to epitopes of oxidized LDL, F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine), inflammation (C-reactive protein), or levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide. CONCLUSIONS: Antioxidant therapy with vitamins C and E restores endothelial function in hyperlipidemic children. Early detection and treatment of endothelial dysfunction in high-risk children may retard the progression of atherosclerosis.

Adolescent↗
PubMed2003

Seroprevalence of meningococcal serogroup C bactericidal antibody in England and Wales in the pre-vaccination era.

Sera from an age-stratified sample of 1689 individuals, submitted to the PHLS Seroepidemiology Unit between 1996 and 1999 were tested for serum bactericidal antibodies to serogroup C meningococci. Titres decreased during infancy, presumably as maternal antibody waned, and increased in older teenagers, the peak age of meningococcal carriage. The prevalence of antibody titres greater than or equal to 8 was highest in adults, with an average of 25% of adults 25 years old or above with titres above this putative protective level. In the absence of vaccination, antibody may be generated from periods of carriage of serogroup C meningococci, from other meningococcal strains sharing non-capsular antigens, and other cross-reactive organisms. The inverse relationship between disease incidence and the prevalence of 'protective' antibody titres as described by Goldschneider et al. appears more consistent with a titre of > or =8 rather than > or =128, although the proportions 'protected' are much lower here than in Goldschneider's study. This study provides baseline antibody levels which will facilitate the evaluation of the meningococcal serogroup C conjugate vaccination programme.

Adolescent↗
PubMed2003

Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes.

OBJECTIVES: This study was conducted to test the hypothesis that plasma markers of oxidized low-density lipoprotein (OxLDL) reflect acute coronary syndromes (ACS). BACKGROUND: Oxidized LDL contributes to the pathogenesis of atherosclerosis, but its role in ACS is not established. METHODS: Serial plasma samples were prospectively obtained from patients with an acute myocardial infarction (MI) (n = 8), unstable angina (UA) (n = 15), stable coronary artery disease (CAD) (n = 17), angiographically normal coronary arteries (n = 8), and from healthy subjects (n = 18), at entry into the study, hospital discharge (MI group only), and at 30, 120, and 210 days. Chemiluminescent enzyme-linked immunosorbent assay was used to quantitate plasma levels of: 1) immunoglobulin (Ig)M and IgG OxLDL autoantibody titers (presented as a mean OxLDL autoantibody titer by averaging the results of four distinct epitopes); 2) LDL-autoantibody immune complexes (LDL-IC); and 3) minimally OxLDL measured by antibody E06 (OxLDL-E06), as determined by the content of oxidized phospholipids (OxPL) per apolipoprotein B-100. RESULTS: Baseline OxLDL IgG autoantibody levels were higher in the MI group (p < 0.0001). At 30-day follow-up, the mean IgM OxLDL titers increased by 48% (p < 0.001) and 20% (p < 0.001), and IgM LDL-IC increased by 60% (p < 0.01) and 26% (p < 0.01) in the MI and UA groups, respectively. The OxLDL-E06 levels increased by 54% (p < 0.01) in the MI group at hospital discharge and by 36% at 30 days. No significant changes in any OxLDL markers were noted in the other groups. The OxLDL-E06 levels strongly paralleled the acute rise in lipoprotein(a), or Lp(a), in the MI group, suggesting that toxic OxPL are preferentially bound to Lp(a). Oxidized LDL-E06 also correlated extremely well with Lp(a) in the entire cohort of patients (r = 0.91, p < 0.0001). CONCLUSIONS: Circulating OxLDL-specific markers strongly reflect the presence of ACS, implying immune awareness to newly exposed oxidation-specific epitopes and possible release of OxLDL in the circulation. The OxLDL-E06 measurements provide novel insights into plaque rupture and the potential atherogenicity of Lp(a).

Acute Disease↗
PubMed2003

Population-based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40.

Molecular studies suggest that the simian polyomavirus SV40 is present in the human population, possibly introduced in contaminated polio vaccine. However, no recent seroepidemiological data exist in England on SV40 or on the two human polyomaviruses, BKV and JCV. A comparative age seroprevalence study was undertaken on 2,435 residual sera from 1991 by haemagglutination inhibition (HI) for BKV and JCV, and virus neutralisation for SV40. The overall rates of seropositivity for BKV and JCV were 81% and 35%, respectively, and each was significantly related to age (P < 0.001). BKV seroprevalence reached 91% at 5-9 years of age, but JCV seroprevalence reached only 50% by age 60-69 years. There was a highly significant association between BKV antibody titre and age (P < 0.001), titres decreasing linearly at a rate of 8.7% per 10 years (95% CI = 7.4-10% drop). Significantly more males than females had antibody to JCV (P = 0.013). In individuals under 40 years of age there was a significant negative association between the presence of antibody to BKV and JCV (P < 0.001). By contrast, the antibody prevalence to SV40 remained at 1.3-5% throughout all age groups and titres were low. There was a significant positive association between the presence of antibody to SV40 and antibody to both BKV (P < 0.001) and JCV (P = 0.009), and also to the geometric mean titre (GMT) of BKV antibody (P = 0.011). The results indicate that BKV and JCV are transmitted by different routes. There is no serological evidence that SV40 entered the human population during the past 80 years, and the possibility of cross-reaction with BKV or JCV antibody must be considered.

Adolescent↗
PubMed2003

Insulin-like growth factor (IGF)-I and IGF binding proteins-2, -3, -4, -5 in porcine corpora lutea during the estrous cycle; evidence for inhibitory actions of IGFBP-3.

In this study we measured protein concentrations of insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBPs) 2-5 in porcine corpora lutea (CLs) throughout the estrous cycle (Experiment 1), and examined the effects of IGFBP-3 and IGFBP-3 antibody (AB) on luteal progesterone (P4) secretion in vitro (Experiment 2). For Experiment 1, (CLs) and serum were collected on days (D) 4, 7, 10, 13, 15 and 16 of the estrous cycle (n = 5 animals per day). IGF-I was extracted from CLs and sera, and measured by radioimmunoassay (RIA). IGFBPs were measured in CLs by ligand blots. For Experiment 2, CLs (from Experiment 1) were enzyme dissociated and luteal cells cultured (24 h) in Medium 199 (M199) containing (0-500 ng/ml) IGFBP-3 (+/-IGF-I; 100 ng/ml), or (0-10 microg/ml) IGFBP-3 AB. P4 in media was measured by RIA. In Experiment 1, luteal IGF-I concentrations (ng/g tissue) were maximal on day 4 and gradually decreased thereafter. Serum IGF-I concentrations (ng/ml) were highest on days 4 and 7, compared with days 10-15. Peak levels of luteal IGFBP-3 were also seen on days 4 and 7 of the cycle. Luteal IGFBP-2 concentrations showed a tendency to increase on day 16 (P < 0.05 versus day 10), but no significant changes in IGFBP-4 or -5 were seen. In Experiment 2, IGFBP-3 (w IGF) inhibited the steroidogenic actions of IGF-I, but had no significant actions alone (IGFBP-3 w/o IGF). Finally, IGFBP-3 AB stimulated P4 secretion on days 4 and 7, but not on days 10-16. We conclude that IGFBP-3 inhibits IGF-I actions in the porcine CL.

Animals↗
PubMed2003

Measles-mumps-rubella vaccine and the development of autism.

The measles-mumps-rubella (MMR) vaccine has been postulated to cause a form of autism characterized by regression and bowel symptoms, and onset occurring shortly after vaccination. It is also claimed that, as a result, there has been a dramatic increase in autism prevalence. These hypotheses have now been tested in a number of epidemiologic studies that are reviewed in this article. None has found any evidence of the existence of a phenotypically distinct form of autism in children who received the MMR vaccine or of a clustering of onset symptoms in children who are autistic after receiving the MMR vaccine. There is no proof that the overall risk of autism is higher in children who were vaccinated with MMR or of an increase in autism prevalence associated with the use of the MMR vaccine. No epidemiologic evidence suggests an association between MMR vaccination and autism. Moreover, epidemiologic evidence against such an association is compelling.

Autistic Disorder↗