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Biomedical subjects

D Roberton

Publications and source records attributed to D Roberton.

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↗
PubMed2006

Effect of dietary nucleotide supplementation on growth and immune function in term infants: a randomized controlled trial.

OBJECTIVE: To examine the effect of nucleotide (NT)-supplemented cow's milk-based formula on growth and biochemical indices of immune function in healthy infants. DESIGN: Randomized controlled trial (RCT) of formula-fed term infants allocated to control formula with an innate level of NT at 10 mg/l (n = 102), or formula fortified with NT at 33.5 mg/l (n = 98). A parallel group of 125 breastfed infants followed the same protocol as a reference. OUTCOME MEASURES: Growth was assessed at enrolment, 7 weeks, 4 months and 7 months of age. Natural killer cell activity, cytokine production and lymphocyte subpopulations were assessed at 7 weeks of age. Antibody responses to diphtheria toxoid, tetanus toxoid and Haemophilus influenzae type b (Hib) immunizations were measured at 7 months of age. RESULTS: NT supplementation did not influence the growth of formula fed infants or any markers of immunity measured at 7 weeks of age. Antibody responses to tetanus toxoid were higher in the NT-supplemented group (n = 68) compared with the control group (n = 70) at 7 months of age (median (5th, 95% percentile): 1.57(0.42, 3.43) vs 1.01(0.41, 4.66) IU/ml, P < 0.03). A difference between treatments was seen in response to diphtheria toxoid but this effect disappeared when adjusted for hepatitis B immunization at birth. There was no effect of treatment on antibody responses to Hib immunization. CONCLUSIONS: Supplementation of formulas with NT at 33.5 mg/l resulted in a modest improvement in antibody response consistent with RCTs that used higher levels of NT supplementation. Whether this translates to clinical benefits in well-nourished infants requires further study. SPONSORSHIP: Supported by a grant from Wyeth Nutrition. Dr Makrides was supported by an RD Wright Fellowship from the National Health and Medical Research Council of Australia and Dr Gibson was partially supported by the MS McLeod Research Trust and a Senior Research Fellowship from the National Health and Medical Research Council of Australia.

Antibodies, Bacterial↗
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↗
PubMed2001

Medical student interviewing skills and mother-reported satisfaction and recall.

BACKGROUND: Providing feedback to medical students about their interviewing skills is an important component of teaching programmes. There is very little information about mothers' views of medical student consultations in paediatrics, and in particular about what mothers consider to be the key elements of a successful consultation. Patient-centred interviewing is a model which emphasizes the active seeking of patient views. In association with appropriate clinical skills, it is reported to promote improved health outcomes. OBJECTIVES: To examine whether greater medical student clinical competence and more frequent use of patient-centred techniques is associated with higher maternal satisfaction, higher maternal rating of the medical student's interpersonal skills, and greater maternal recall of relevant diagnosis and treatment recommendations. METHOD: Two standardized 'medical student' videotaped interviews were created based on actual senior medical student consultations. Interview A demonstrated both higher student clinical competence and higher patient-centredness compared with interview B. Both videotaped interviews were viewed and then rated, using a questionnaire, by 11 mothers attending a teaching general practice. RESULTS: Significantly higher mean scores, indicating greater maternal satisfaction, were associated with interview A (P < 0.01 for all measures). Accurate recall for diagnosis and management was also significantly greater after interview A (mean diagnosis recall, interview A 35%, interview B 14%, P < 0.01; mean management recall, interview A 95%, interview B 57%, P < 0.01). CONCLUSIONS: Maternal satisfaction and recall were higher following a more clinically competent and patient-centred medical student interview. Maternal ratings of student interviews could be used as an additional method of assessment as well as providing feedback to medical students on their interview skills development.

Clinical Competence↗
PubMed2000

Restricted polymorphism of the mannose-binding lectin gene of indigenous Australians.

Mannose-binding lectin (MBL) is an important complement-activating protein of the human innate immune system. Deficiency of MBL is associated with an increased risk of various infections and arises from three structural gene mutations in exon 1 (variants B, C and D) and/or the presence of a low efficiency promoter. The C allele is found in sub-Saharan Africa whereas the B allele is found elsewhere, suggesting that these mutations occurred after the suggested hominid migration out of Africa [100-150 000 years before present (BP)]. Paradoxically, these alleles may have a selective advantage in protection against intracellular pathogens and occur at particularly high frequencies in sub-Saharan Africa (C variant) and South America (B variant). Since hominids reached Australia at least 50 000 years ago, a study of MBL polymorphisms in the indigenous population was of interest. Using heteroduplex technology we found a paucity of MBL structural gene mutations in two population groups from geographically distinct regions. Of 293 individuals tested, 289 were wild-type and four were heterozygous for either the B or D allele. In each individual with an MBL mutation the HLA haplotype profile suggested some Caucasian admixture. We also found a restricted range of MBL promoter haplotypes and the serum MBL levels were higher than those of any other ethnic group studied to date (median 3.07 microg/ml). Our data suggest that the B mutation probably arose between 50 000 and 20 000 BP. Its absence from the founder gene pool of indigenous Australians may also partly explain their vulnerability to intracellular infections such as tuberculosis.

Alleles↗
PubMed1998

Interleukin 2 receptor regulation and IL-2 function in the human infant.

IL-2 receptor is expressed at low levels on adult blood lymphocytes, and at lower levels on cord blood cells. IL-2 receptor alpha and beta chain expression increases gradually from 0-18 months of age. The level of soluble CD25 (IL-2 receptor alpha chain) has been reported to be elevated in cord blood. Quantitative RT-PCR showed that adult cells express 10 times as much CD25 mRNA as cord cells. Cord plasma showed only a marginal ability to strip CD25 from the membrane. To assess the functional consequences of low IL-2 receptor expression, cord and adult cells were activated in vitro. The response was stimulus-dependent, but cord cells upregulated CD25 readily. Cord and adult cells proliferated in an IL-2-dependent assay to a similar extent. Infants suffering acute infection showed marginally higher levels of membrane CD25 expression than infants without overt infection. Thus neonatal and infant lymphocytes express lower levels of IL-2 receptors than adult cells, reflecting lower mRNA concentrations at least for CD25; they are able to up-regulate receptors in response to in vitro stimulation and are able to respond in vitro to IL-2-dependent stimulation; however in vivo there may be a dampening down of the IL-2 system in infancy.

Adult↗
PubMed1998

Somatic mutation of immunoglobulin V(H)6 genes in human infants.

Infants respond to antigen by making antibody that is generally of low affinity for antigen. Somatic hypermutation of immunoglobulin genes, and selection of cells expressing mutations with improved affinity for antigen, are the molecular and cellular processes underlying the maturation of antibody affinity. We have reported previously that neonates and infants up to 2 months of age, including individuals undergoing strong immunological challenge, show very few mutated V(H)6 sequences, with low mutation frequencies in mutated sequences, and little evidence of selection. We have now examined immunoglobulin genes from healthy infants between 2 and 10 months old for mutation and evidence of selection. In this age group, the proportion of V(H)6 sequences which are mutated and the mutation frequency in mutated sequences increase with age. There is evidence of selection from 6 months old. These results indicate that the process of affinity maturation, which depends on cognate T-B cell interaction and functional germinal centres, is approaching maturity from 6 months old.

Adult↗
PubMed1997

The spectrum of primary immunodeficiency disorders in Australia.

BACKGROUND: Primary immunodeficiency disorders (PIDs) are uncommon conditions that require specialized immunologic services for diagnosis and management. It is difficult to estimate the prevalence of these disorders from routinely collected health statistics. OBJECTIVE: We attempted to describe the prevalence of PID in Australia and the requirements for specific therapies, such as intravenous immunoglobulin, ascertained from a national register of PID. METHODS: A national longitudinal cross-sectional survey of patients with PID under the care of clinical immunologists was established by the Australasian Society of Allergy and Clinical Immunology in 1990. Details of diagnosis and therapy were provided for patients with major PIDs including symptomatic IgA, IgG subclass, and complement deficiencies. Subjects with asymptomatic IgA deficiency were not included. The clinical features of the first 500 cases enrolled in the register were analyzed. RESULTS: The most frequent type of PID was predominant antibody deficiency (71%). Common variable immunodeficiency, usually first seen as an antibody deficiency, was the single most common disorder with an estimated prevalence of 0.77/100,000 in the general population. Other types of PID were infrequent, and of these, severe combined immunodeficiency accounted for 5.2% of cases. The estimated prevalence of all forms of chronic granulomatous disease was 0.08/100,000. The national prevalence of all PID cases ascertained from the register was 2.1/100,000, with variation between the larger states ranging from 1.18 to 4.57/100,000. Half (247) of the patients were receiving intravenous immunoglobulin therapy with a median duration of care of 5 to 9 years for the different antibody deficiencies. There was also variation in the patterns of intravenous immunoglobulin use across the country. No new forms of PID were encountered. CONCLUSION: This study highlights the requirement for the continuing provision of immunoglobulin as replacement therapy for these patients. In addition, the register documents a cohort of patients with PID whose long-term response to current therapy can be evaluated prospectively.

Adolescent↗
PubMed1996

Maternal immunization with Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in The Gambia.

OBJECTIVE: To evaluate maternal responses to Haemophilus influenzae type b (Hib) polysaccharide-tetanus protein conjugate (polyribosylribitol phosphate-tetanus or PRP-T) given to pregnant Gambian women, the transplacental transfer of antibody, and the effect of maternal immunization on infant responses to the vaccine. DESIGN: An open, randomized immunogenicity study. SETTING: A busy urban health center in The Gambia. STUDY PARTICIPANTS: A total of 451 pregnant women enrolled during the third trimester of pregnancy. INTERVENTION: Study participants were randomized to three groups. In one group, mothers were given PRP-T during the third trimester and their infants were given PRP-T at 2, 3, and 4 months of age. In the second group, mothers received PRP-T and infants were given inactivated poliovirus vaccine. In the third group, mothers received meningococcal A and C vaccine, and their infants received PRP-T. MAIN OUTCOME MEASURES: Anti-PRP antibody measurements of maternal cord, and infant blood. RESULTS: Vaccinated women had a marked increase in total anti-PRP antibody (geometric mean titer 9.0 micrograms/mL), which was greatest in women in their first or second pregnancy. Previous tetanus vaccination during the same pregnancy and high concentrations of antitetanus antibody were associated with lower anti-PRP responses. In infants of PRP-T recipients, cord blood anti-PRP IgG concentrations were 61% of simultaneous maternal concentrations. In vaccinated infants of vaccinated mothers, geometric mean anti-PRP antibody concentrations at birth, 2 months of age, and 5 months of age were 1.92, 0.35 and 2.84 micrograms/mL, respectively, while in vaccinated infants of unvaccinated mothers, the corresponding concentrations were 0.29, 0.12, and 3.91 micrograms/mL. At 2 months of age, 60% of infants of vaccinated mothers and 26% of infants of unvaccinated mothers had anti-PRP antibody concentrations considered to be protective (>0.15 micrograms/mL). CONCLUSIONS: In areas where much invasive Hib disease occurs in infants younger than 6 months, maternal immunization may help to reduce the risk of Hib disease in infants too young for immunization.

Antibodies, Bacterial↗
PubMed1995

Expression of cytokine receptors by human cord blood lymphocytes: comparison with adult blood lymphocytes.

The expression of receptors for several cytokines (IL 2, IL-4, IL-6, IL-7, tumor necrosis factor, and interferon-gamma) was examined in human cord blood cells in comparison with adult blood cells. A previously described high sensitivity immunofluorescence procedure was used to render the low levels of receptor measurable. Cord blood lymphocytes expressed measurable levels of most cytokine receptors, but expression tended to be lower than in adult blood cells. Examination of different lymphocyte subpopulations revealed a complex pattern with some cell types expressing particular receptors equivalent to adult levels. Cord and adult blood monocytes expressed similar cytokine receptor profiles. Receptor expression in cord lymphocytes could be regulated by activation. The results provide indications as to the relative activities of different cytokines in the development of the immune system in the neonate.

Adult↗
PubMed1993

A case of Burkitt's lymphoma presenting with digital ischaemia.

Paraneoplastic syndromes are rare in paediatric oncology. This report describes a four-year-old Cantonese child whose sole presenting symptom was acrocyanosis who was found to have Burkitt's lymphoma in association with the presence of positive antinuclear antibodies, antineutrophil cytoplasmic antibodies, antiendothelial antibodies and elevated serum immunoglobulin G concentrations. Digital ischaemia has not been described as a presenting symptom of Burkitt's lymphoma, although this association has been reported in 25 patients with other malignancies.

Antibodies↗
PubMed1993

Anti-idiotypic antibodies to poliovirus antibodies in commercial immunoglobulin preparations, human serum, and milk.

Our previous studies have suggested that fetal antibody production can be induced by maternal antiidiotypic antibodies transferred to the fetus via the placenta. We tested commercial Ig, sera, and milk for the presence of anti-idiotypic antibodies to poliovirus type 1, using affinity chromatography combined with ELISA systems and virus neutralization techniques. Our results indicate that commercial Ig, serum, and milk samples contain antibodies recognizing idiotypic determinants on antibodies to poliovirus. Several lines of evidence support this conclusion. Thus, in an ELISA with poliovirus as a solid phase, binding of specific antibodies could be inhibited by addition of an eluate from the Ig preparation containing anti-idiotypic antibodies against poliovirus type 1. Also, antiidiotypic antibodies from pooled human Ig, serum, and colostrum samples against poliovirus bound directly to solid-phase-attached MAb against poliovirus type 1. In addition, in a competitive inhibition ELISA, where antiidiotypic antibodies isolated from the Ig preparation competed with the poliovirus antigen for binding to monoclonal or polyclonal idiotypic antibodies on the solid phase, inhibition of antigen binding was seen at low antigen concentrations. When single-donor serum or milk was used, this inhibition was even more pronounced and could be demonstrated at almost all antigen concentrations. The finding that anti-idiotypes are present in maternal serum and milk imply, in agreement with our previous studies, that anti-idiotypes may actively induce a specific immune response in the fetus without previous exposure to the antigen by being transferred across the placenta or by being passively transferred to the newborn via mother's milk.

Adult↗
PubMed1992

The CD45RO (p180, UCHL1) marker: complexity of expression in peripheral blood.

Analysis of peripheral blood lymphocytes by two- and three-colour high-sensitivity staining with UCHL1 (CD45RO) and other markers shows that the expression of CD45RO on lymphocyte subsets is more complex than is generally supposed. In addition to the populations which express CD45RO and RA in a mutually exclusive manner, up to 30% of cells in adult blood express both markers, at low levels. This "intermediate" population includes CD4-positive cells, and a proportion of these cells express the p55 chain of the IL-2 receptor (CD25), suggesting that they are activated. In cord blood there are few RO-bright cells, but CD45RO is expressed at low intensity on a proportion of cells. Among the CD45RO-bright cells in adult blood at least two subsets can be detected by using MHC Class II and the homing receptor L-selectin as additional markers. This complexity suggests that memory cells are a subset of CD45RO-expressing cells, but that this marker is also found on cells that are activated but not irreversibly "switched" to memory cells.

Adult↗