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Biomedical subjects

E Miller

Publications and source records attributed to E Miller.

At least 145 records · Page 8Linked to original sources

Immediate and long term outcome of human parvovirus B19 infection in pregnancy.

OBJECTIVE: To estimate more precisely the risk of fetal loss and congenital abnormalities after maternal parvovirus B19 infection, and to assess the long term outcome for surviving infants. DESIGN: Prospective cohort study of pregnant women with confirmed B19 infection with follow up of the surviving infants. The rate of fetal loss in the study cohort was compared with that in pregnant women with varicella. SETTING: Cases reported by laboratories in England and Wales between 1985-1988 and 1992-1995. SAMPLE: Four hundred and twenty-seven pregnant women with B19 infection and 367 surviving infants of whom 129 were followed up at 7-10 years of age. METHODS: Questionnaires to obstetricians and general practitioners on outcome of pregnancy and health of surviving infants. Maternal infection confirmed by B19-specific IgM assay and/or IgG seroconversion. RESULTS: The excess rate of fetal loss in women with B19 infection was confined to the first 20 weeks of gestation and averaged 9%. Seven cases of fetal hydrops followed maternal infections between 9 and 20 weeks of gestation (observed risk 2.9%, 95% CI 1.2-5.9). No abnormalities attributable to B19 infection were found at birth in surviving infants (observed risk 0%, upper 95% CI 0.86%). No late effects were found at 7-10 years. CONCLUSIONS: Around 1 in 10 women infected before 20 weeks of gestation will suffer a fetal loss due to B19. The risk of an adverse outcome of pregnancy after this stage is remote. Infected women can be reassured that the maximum possible risk of a congenital abnormality due to B19 is under 1% and that long term development will be normal.

Cohort Studies↗

Immunization of LDL receptor-deficient mice with homologous malondialdehyde-modified and native LDL reduces progression of atherosclerosis by mechanisms other than induction of high titers of antibodies to oxidative neoepitopes.

We and others previously showed that immunization of rabbits with different forms of oxidized low density lipoprotein (LDL) significantly reduced atherogenesis. We now investigated the effect of continued immunization on atherosclerosis in LDL receptor-deficient (LDLR-/-) mice to determine whether a similar reduction of atherosclerosis occurred in murine models and whether this was due to humoral immune responses, ie, formation of high titers of antibodies to oxidation-specific epitopes. Three groups of LDLR-/- mice were repeatedly immunized with homologous malondialdehyde-modified LDL (MDA-LDL), native LDL, or phosphate-buffered saline (PBS) for 7 weeks. Extensive hypercholesterolemia and accelerated atherogenesis were then induced by feeding a cholesterol-rich diet for 17 weeks, during which immunizations were continued. Binding of immunoglobulin (Ig) M and IgG antibodies, as well as IgG1 and IgG2a isotypes, to several epitopes of oxidized LDL were followed throughout the study. After 24 weeks of intervention, atherosclerosis in the aortic origin was significantly reduced by 46.3% and 36.9% in mice immunized with MDA-LDL and native LDL, respectively, compared with PBS (133 558 and 157 141 versus 248 867 microm2 per section, respectively). However, the humoral immune response to oxidative neoepitopes in the MDA-LDL group was very different from that of the LDL or PBS group. IgG antibody binding to MDA-LDL and other epitopes of oxidized LDL, such as oxidized phospholipid (cardiolipin), oxidized cholesterol, or oxidized cholesteryl linoleate, but not native LDL, increased markedly in mice immunized with MDA-LDL, but not in mice immunized with native LDL or PBS. In the MDA-LDL group, both T helper cell (Th)2-dependent IgG1 antibody and Th1-dependent IgG2a antibody binding to oxidative neoepitopes increased significantly over time. The fact that mice immunized with both MDA-LDL and native LDL had a significant reduction in atherosclerosis, whereas only the MDA-LDL group developed very high titers of antibodies to oxidation-specific epitopes, suggests that the antiatherogenic effect of immunization is not primarily dependent on very high titers of antibodies to oxidation-specific epitopes but is more likely to result from the activation of cellular immune responses.

Animals↗

Pneumococcal bacteraemia and meningitis in England and Wales, 1993 to 1995.

A total of 10,346 blood and 682 cerebrospinal fluid (CSF) isolates of Streptococcus pneumoniae were reported to the PHLS Communicable Disease Surveillance Centre from laboratories in England and Wales from 1 January 1993 to 31 December 1995. This corresponds to a mean annual incidence of 6.7 per 100,000 episodes of bacteraemia and 0.44/100,000 of meningitis. Absolute numbers of pneumococcal bacteraemia were similar to levels reported between 1990 and 1992, but fewer isolates of pneumococci were made from CSF. There was no discernible overall trend between 1993 and 1995, but age specific incidence suggested a slight increase in bacteraemia in older age groups. Estimated case fatality rates were 20% for pneumococcal bacteraemia and 22% for meningitis. The proportion of pneumococcal strains resistant to penicillin and erythromycin rose between 1989 and 1995 from 0.3% to 2.9% and 3.3% to 10.9%, respectively. The persistent threat of invasive pneumococcal infections highlights the need for continuing laboratory surveillance (including serotyping), appropriate use of antibiotics, and immunisation of groups at risk. The development of conjugate vaccines offers new prospects for prevention.

Adolescent↗

Safety assessment post-licensure.

The objectives of post-licensure surveillance are to identify rare or novel adverse events, estimate their rate of occurrence and distinguish those that are causally related to vaccination. Evidence of causality is based on biological plausibility supported by laboratory evidence of vaccine involvement and/or a statistically significant excess of events in the post-vaccination period. Passive reporting systems have methodological limitations, particularly for ascertaining reliable adverse event rates and investigating causal relationships. In Canada, an active surveillance system (IMPACT) has been established in sentinel paediatric hospitals where nurses scrutinise all admissions for conditions conforming to a defined set of adverse events. While ascertainment of events resulting in hospital admission should be complete, causality is difficult to assess without information on the incidence of such events outside the post-vaccination risk period. The use of computerised data bases which link clinical events with immunisation records have allowed the risk of events such as convulsions attributable to DTP, MMR and Hib vaccines to be defined. The record linkage method promises to be a useful method for routine surveillance of vaccine safety.

Adverse Drug Reaction Reporting Systems↗

Cloning of mDEAH9, a putative RNA helicase and mammalian homologue of Saccharomyces cerevisiae splicing factor Prp43.

Yeast splicing factor Prp43, a DEAH box protein of the putative RNA helicase/RNA-dependent NTPase family, is a splicing factor that functions late in the pre-mRNA splicing pathway to facilitate spliceosome disassembly. In this paper we report cDNA cloning and characterization of mDEAH9, an apparent mammalian homologue of Prp43. Amino acid sequence comparison revealed that the two proteins are approximately 65% identical over a 500-aa region spanning the central helicase domain and the C-terminal region. Expression of mDEAH9 in S. cerevisiae bearing a temperature-sensitive mutation in prp43 was sufficient to restore growth at the nonpermissive temperature. This functional complementation was specific, as mouse mDEAH9 failed to complement mutations in related splicing factor genes prp16 or prp22. Finally, double label immunofluorescence experiments performed with mammalian cells revealed colocalization of mDEAH9 and splicing factor SC35 in punctate nuclear speckles. Thus, the hypothesis that mDEAH9 represents the mammalian homologue of yeast Prp43 is supported by its high sequence homology, functional complementation, and colocalization with a known splicing factor in the nucleus. Our results provide additional support for the hypothesis that the spliceosomal machinery that mediates regulated, dynamic changes in conformation of pre-mRNA and snRNP RNAs has been highly conserved through evolution.

Amino Acid Sequence↗

The epitopes for some antiphospholipid antibodies are adducts of oxidized phospholipid and beta2 glycoprotein 1 (and other proteins).

Circulating autoantibodies to phospholipids (aPLs), such as cardiolipin (CL), are found in patients with antiphospholipid antibody syndrome (APS). We recently demonstrated that many aPLs bound to CL only after it had been oxidized (OxCL), but not to a reduced CL analogue that could not undergo oxidation. We now show that the neoepitopes recognized by some aPLs consist of adducts formed between breakdown products of oxidized phospholipid and associated proteins, such as beta2 glycoprotein 1 (beta2GP1). Addition of human beta2GP1, polylysine, native low-density lipoprotein, or apolipoprotein AI to OxCL-coated wells increased the anticardiolipin antibody (aCL) binding from APS sera that first had been diluted so that no aCL binding to OxCL could be detected. No increase in aCL binding was observed when these proteins were added to wells coated with reduced CL. The ability of beta2GP1, polylysine, or low-density lipoprotein to be a "cofactor" for aCL binding to OxCL was greatly reduced when the proteins were methylated. Incubation of beta2GP1 with oxidized 1-palmitoyl-2-linoleyl-[1-14C]-phosphatidylcholine (PC), but not with dipalmitoyl-[1-14C]-PC, led to formation of covalent adducts with beta2GP1 recognized by APS sera. These data suggest that the reactive groups of OxCL, such as aldehydes generated during the decomposition of oxidized polyunsaturated fatty acids, form covalent adducts with beta2GP1 (and other proteins) and that these are epitopes for aCLs. Knowledge that the epitopes recognized by many aPLs are adducts of oxidized phospholipid and associated proteins, including beta2GP1, may give new insights into the pathogenic events underlying the clinical manifestations of APS.

Antibodies, Antiphospholipid↗

Childhood infection with hepatitis A and B viruses in England and Wales.

Infection with hepatitis B and A viruses during childhood was studied using serum specimens collected from children aged 13 and 14 years by 12 public health laboratories in England and Wales from 1986 to 1995. Six of the 2025 specimens tested for markers of hepatitis B infection showed evidence of earlier resolved infection, one specimen showed evidence of recent infection, and hepatitis B surface antigen (HBsAg) was detected in three specimens. The HBsAg carriage rate of 0.15% (3/2025) was consistent with that expected from vertical transmission before the introduction of antenatal screening and neonatal hepatitis B vaccination, for which the children in our study would not have been eligible. Five of the six children with earlier resolved hepatitis B infection also showed evidence of hepatitis A infection, whose coexistence raises the possibility that both infections were acquired abroad in areas of high endemicity. At present, by adolescence, about one in 200 children has at some time been infected with hepatitis B virus. The current practice of screening pregnant women for HBsAg and selectively vaccinating neonates at high risk of acquiring hepatitis B infection may reduce this rate in the future. Immunisation of all infants against hepatitis B would prevent very few more childhood infections than the current policy. The incidence of hepatitis A infection has fallen in the past decade, suggesting the potential for an epidemic resurgence in the future as more of the population becomes susceptible. The average annual incidence of hepatitis A infection in children aged 0 to 14 years from 1986 to 1995 was 800 per 100 000, fifty times higher than the reported incidence of laboratory confirmed disease in this age group. Most hepatitis A infections in this age group are therefore likely to be subclinical or very mild.

Adolescent↗

Coronary angiography and angioplasty after acute myocardial infarction.

PURPOSE: To assess the data that support the use of coronary angiography and angioplasty after acute myocardial infarction, that identify the risks of these procedures, and that analyze their use and costs. DATA SOURCES: English-language articles published between 1970 and June 1995 identified through a search of the MEDLINE database. STUDY SELECTION: Studies that contained information about benefits, risks, use, and costs of coronary angiography and angioplasty after acute myocardial infarction. DATA EXTRACTION: Descriptive and analytic data from each study were collected. DATA SYNTHESIS: The outcome for patients who have complications of myocardial infarction (such as shock) is poor. Such patients usually undergo angiography, although the evidence that supports this practice is weak. Preliminary data suggest that patients who immediately have angiography and angioplasty after acute myocardial infarction have better outcomes than do patients who receive thrombolytic therapy with angioplasty only for specific indications in experienced centers. After the acute phase of myocardial infarction, patients who have noninvasive evidence of persistent or recurrent ischemia are believed to benefit from angiography. In the remaining patients, however, angiography after myocardial infarction has not been shown to be beneficial. Coronary angiography is done in 30% to 81% of patients after acute myocardial infarction in different settings and regions; for many of these patients, the benefit is questionable. Better outcomes are not always associated with more frequent use of the procedure. In the United States, catheterizations after myocardial infarction cost approximately $1 billion per year. CONCLUSIONS: Although many patients benefit from angiography and angioplasty after myocardial infarction, others probably do not. Substantial resources are at stake.

Angioplasty↗

The epidemiology of measles in England and Wales since the 1994 vaccination campaign.

The incidence of measles in England and Wales has fallen since the national vaccination campaign in November 1994, in which 92% of children aged 5 to 16 years were vaccinated. A total of 148 confirmed cases with onsets in the 18 months from January 1995 to June 1996 have been ascertained. Notified cases did not provide a reliable measure of incidence: 11,343 suspected cases were notified in the same period, 6426 (57%) of whom were tested for salivary antibody. Only 90 (1.4%) of cases tested were confirmed. Many confirmed cases occurred in small clusters; 12 imported cases were identified. The pattern of small, local clusters is what would be expected from the introduction of imported cases into a population with herd immunity. Serological surveillance showed that the campaign produced a significant fall in the proportion of 5 to 16 year old children with low levels of measles antibody: the proportion with levels < 50 mIU/ml fell from 8.4% to 2.1%; the proportion with levels < 100 mIU/ml fell from 15.7% to 6.6%. About 15% of 2 to 4 year old children had antibody levels < 100 mIU/ml before and after the campaign. The addition of a routine second dose of measles vaccine (as measles, mumps, and rubella vaccine) to the vaccination schedule will provide another opportunity to immunise these children before they start school. The two dose vaccination programme should maintain the herd immunity of the population and the elimination of endemic measles transmission.

Adolescent↗

Mumps surveillance in England and Wales supports introduction of two dose vaccination schedule.

Sentinel surveillance in general practice and laboratory reports to the PHLS Communicable Disease Surveillance Centre show that the incidence of mumps has fallen to very low levels since vaccination against measles, mumps, and rubella was introduced in 1988. Hospital admissions for mumps show a 92% decline compared with the prevaccination era, to a rate of 0.2 per 100,000 population per year. Serological surveillance has shown an increase in the proportion of school age children who have no detectable antibody to mumps, which is consistent with the reduction in mumps virus transmission. The proportion of children aged 11 to 15 years with no detectable antibody is expected to peak at 19% in 1997. Mathematical models suggest that this increase in susceptibility is unlikely to allow a large resurgence of mumps in the short term but that school outbreaks may become more common. Outbreaks in universities and military establishments are possible in the medium term. Analysis of efficacy data for mumps vaccine indicates that mumps is unlikely to be eliminated with a single dose of vaccine at current coverage rates. A second dose of vaccine, which is now being offered to preschool children, will reduce morbidity and should eventually eliminate mumps if coverage is high enough.

Adolescent↗

The epidemiology of rubella in England and Wales before and after the 1994 measles and rubella vaccination campaign: fourth joint report from the PHLS and the National Congenital Rubella Surveillance Programme.

The national immunisation campaign carried out in the United Kingdom in November 1994 was designed to give children aged 5 to 16 years of age a single dose of a combined measles and rubella vaccine. Its main objective was to prevent an epidemic of measles predicted in school age children. The rubella component of the vaccine was included in order to reduce the high level of susceptibility to rubella in young adult males and thus reduce the risk of transmission from this group to pregnant women. Susceptibility to rubella in children aged 5 to 16 years has fallen from 15.7% to 3.4% since the measles and rubella campaign. Despite this the incidence of laboratory confirmed rubella rose substantially in 1996, largely on account of cases among males aged 17 to 24 years, who were not vaccinated in the 1994 campaign and about 16% of whom are susceptible. The impact of the resurgence on the incidence of infection in pregnancy has been relatively limited, due to the low level of susceptibility in the antenatal population (2% in nulliparous and 1.2% in parous women for 1994/5). No cases of congenital rubella arising from administration of measles and rubella vaccine during the campaign have been identified. The numbers of babies born with congenital rubella and terminations of pregnancy for rubella arising from the 1996 resurgence are expected to be similar to those that followed the 1993 resurgence. The reduction in susceptibility in future cohorts of young men who received measles and rubella vaccine in the 1994 campaign should prevent future resurgences after the year 2000. If a second dose of measles, mumps, and rubella (MMR) vaccine had not been introduced, susceptibility levels in the school age population would have risen to about 12% in the future. The effect of the second dose of MMR vaccine introduced for children aged 4 to 5 years in October 1996 will be assessed through serological surveillance.

Adolescent↗

Comparative studies on tetrachloroethene reductive dechlorination mediated by Desulfitobacterium sp. strain PCE-S.

Tetrachloroethene reductive dechlorination was studied with cell extracts of a newly isolated, tetrachloroethene-utilizing bacterium, Desulfitobacterium sp. strain PCE-S. Tetrachloroethene dehalogenase mediated the reductive dechlorination of tetrachloroethene and trichloroethene to cis-1,2-dichloroethene with artificial electron donors such as methyl viologen. The chlorinated aromatic compounds tested so far were not reduced. A low-potential electron donor (E0' < -0.4 V) was required for tetrachloroethene reduction. The enzyme in its reduced state was inactivated by propyl iodide and reactivated by light, indicating the involvement of a corrinoid in reductive tetrachloroethene dechlorination.

Bacteria, Anaerobic↗

An evaluation of nine commercial EIA kits for the detection of measles specific IgG.

Nine commercial EIAs for measles-specific IgG were compared with haemagglutination inhibition (HI) and plaque reduction neutralization (PRN). A total of 174 sera selected, to give approximately half of the sera without measles antibody by HI, were tested by all EIAs and HI. However, there was sufficient volume of only 101 samples for testing by PRN. A dilution curve of the British Standard measles antibody serum was also tested by each EIA. Assays were evaluated qualitatively against a consensus EIA result, HI and PRN: Gull, Melotest and Behring EIAs performed best. Quantitative evaluation was by assessment of the characteristics of the standard dilution curve, and by plotting differences with PRN against mean: Gull and Melotest EIAs were best.

Antibodies, Viral↗