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Biomedical subjects

H Marshall

Publications and source records attributed to H Marshall.

At least 19 recordsLinked to original sources
PubMed2006

A comparison of booster immunisation with a combination DTPa-IPV vaccine or DTPa plus IPV in separate injections when co-administered with MMR, at age 4-6 years.

This study evaluated GSK's combined DTPa-IPV vaccine (Infanrix-IPV) given as a fifth consecutive acellular pertussis booster dose in conjunction with the second dose of MMR vaccine (Priorix) in children aged 4-6 years. The immunogenicity and reactogenicity of this vaccine regimen was compared with separate injections of DTPa and IPV when given concomitantly with MMR. A cohort of 362 children previously primed with four doses of DTPa and OPV, and a single dose of MMR were randomized to receive either DTPa-IPV+MMR (N=181) or DTPa+IPV+MMR (N=181). Antibody concentrations were measured prior to and 1 month after the booster dose. After immunisation all subjects from both groups had seroprotective antibody levels against diphtheria, tetanus and the three poliovirus serotypes, > or = 96% showed vaccine response to PT, FHA and PRN, all were seropositive to mumps and rubella, and all but one subject were seropositive to measles. Immunogenicity results for each component antigen were similar for DTPa-IPV and separately co-administered DTPa and IPV. Local reactions were common with 24.0% and 31.1% of children experiencing swelling >50mm at the DTPa-IPV and DTPa injection sites, respectively. The DTPa-IPV combination did not increase the incidence or intensity of adverse events compared with separately administered DTPa+IPV. The response to the concomitantly administered MMR vaccine was similar in the two groups and similar to previously reported responses for a second dose of MMR. This combined DTPa-IPV vaccine has a similar reactogenicity profile to DTPa, is immunogenic when given as a booster dose at 4-6 years of age, and has no impact on the immunogenicity of a co-administered second dose of MMR vaccine.

Antibodies↗
PubMed2005

Safety and immunogenicity of a combined DTPa-IPV vaccine administered as a booster from 4 years of age: a review.

A combined DTPa-IPV booster vaccine was administered as a 4th or 5th dose after DTPa or DTPw priming. Over 99% vaccines developed antibody levels considered to be protective to diphtheria, tetanus and poliovirus, and >95% mounted a response to acellular pertussis antigens. Rectal temperature >39.5 degrees C was observed in at most 3.2% of vaccinees. Swelling >50 mm occurred in 24% of DTPa-primed compared to 5.5% of DTPw-primed children. Large swelling involving the entire upper arm (extending to involve the elbow joint) was reported for up to 1.2% of DTPa-primed subjects, which is consistent with literature reports for other DTPa vaccines.

Antibodies, Bacterial↗
PubMed2005

Reactogenicity and immunogenicity profile of a two-dose combined hepatitis A and B vaccine in 1-11-year-old children.

This study was conducted to compare the reactogenicity, immunogenicity and safety of a combined two-dose (0, 6 months) hepatitis A and B vaccine (720ELU HAV, 20 mcg HBsAg) with the established three-dose (0, 1 and 6 months) hepatitis A and B vaccine (360ELU HAV, 10 mcg HBsAg). A total of 511 children aged 1-11 years who had not previously received a hepatitis A or B vaccine were enrolled in the study. Both vaccines were well tolerated, and were shown to be safe and immunogenic. The analysis, stratified according to two age groups (1-5 year and 6-11-year-old children) demonstrated that the reactogenicity profile of the two-dose schedule was at least as good as that of the established schedule. Both vaccines and schedules provided at least 98% seroprotection against hepatitis B and 100% seroconversion against hepatitis A, 1 month after the end of the vaccination course (Month 7).

Child↗
PubMed2004

Should routine childhood immunizations be compulsory?

Routine childhood immunizations are compulsory in a small number of countries, including the United States of America. Arguments used to justify making immunizations compulsory include enhancing the health of the community and treating as paramount the rights of the child to be protected against vaccine-preventable diseases. But compulsory immunization infringes the autonomy of parents to make choices about child rearing, an autonomy which we generally respect unless doing so seriously endangers the child's health. We present a historical review and ethics discussion on whether routine childhood immunizations should be compulsory. We conclude that, for both ethical and practical reasons, routine immunization should not be compulsory if adequate levels of immunization can be achieved by other means.

Attitude of Health Personnel↗
PubMed2001

Substantial linkage disequilibrium across the insulin-degrading enzyme locus but no association with late-onset Alzheimer's disease.

Insulin-degrading enzyme (IDE; insulysin; EC 3.4.24.56) is a 110-kDa neutral metallopeptidase that can degrade a number of peptides including beta-amyloid. The gene encoding IDE is located on chromosome 10 close to a region of linkage for late-onset Alzheimer's disease (LOAD) and thus is a functional and positional candidate for this disorder. We analysed all of the coding exons, untranslated regions and 1000 bp of 5'-flanking sequence of IDE by using denaturing high-performance liquid chromatography and sequencing. We detected eight single nucleotide polymorphisms (SNPs), three in the 5' flanking sequence and five in the coding sequence, of which three were found at lower than 5% frequency. None of them changed the amino acid sequence. We genotyped the five SNPs with allele frequencies of more than 5% in 133 Caucasian LOAD cases and 135 controls collected in the UK and 95 cases and 117 controls collected at the Mayo Clinic, Rochester, USA. Two of the SNPs were analysed in a further independent case-control sample (Washington University, St. Louis: 86 cases, 94 controls). No significant association was found with any individual SNP in any of the samples or with any haplotypes. Analysis of the marker D10S583, which maps 36 kb upstream of IDE, also failed to show association in 134 cases and 111 matched controls from the UK ( P=0.63). Strong linkage disequilibrium was detected between the five SNPs that spanned the whole of the 120-kb genomic region of IDE and one major and a number of minor haplotypes were detected in the populations studied. We conclude that IDE does not make a substantial contribution to the aetiology of LOAD and therefore cannot account for the linkage between LOAD and 10q.

Age of Onset↗
PubMed2001

Differences in Krox20-dependent regulation of Hoxa2 and Hoxb2 during hindbrain development.

During hindbrain development, segmental regulation of the paralogous Hoxa2 and Hoxb2 genes in rhombomeres (r) 3 and 5 involves Krox20-dependent enhancers that have been conserved during the duplication of the vertebrate Hox clusters from a common ancestor. Examining these evolutionarily related control regions could provide important insight into the degree to which the basic Krox20-dependent mechanisms, cis-regulatory components, and their organization have been conserved. Toward this goal we have performed a detailed functional analysis of a mouse Hoxa2 enhancer capable of directing reporter expression in r3 and r5. The combined activities of five separate cis-regions, in addition to the conserved Krox20 binding sites, are involved in mediating enhancer function. A CTTT (BoxA) motif adjacent to the Krox20 binding sites is important for r3/r5 activity. The BoxA motif is similar to one (Box1) found in the Hoxb2 enhancer and indicates that the close proximity of these Box motifs to Krox20 sites is a common feature of Krox20 targets in vivo. Two other rhombomeric elements (RE1 and RE3) are essential for r3/r5 activity and share common TCT motifs, indicating that they interact with a similar cofactor(s). TCT motifs are also found in the Hoxb2 enhancer, suggesting that they may be another common feature of Krox20-dependent control regions. The two remaining Hoxa2 cis-elements, RE2 and RE4, are not conserved in the Hoxb2 enhancer and define differences in some of components that can contribute to the Krox20-dependent activities of these enhancers. Furthermore, analysis of regulatory activities of these enhancers in a Krox20 mutant background has uncovered differences in their degree of dependence upon Krox20 for segmental expression. Together, this work has revealed a surprising degree of complexity in the number of cis-elements and regulatory components that contribute to segmental expression mediated by Krox20 and sheds light on the diversity and evolution of Krox20 target sites and Hox regulatory elements in vertebrates.

Animals↗