Atypical clinical presentations of Brown-McLean syndrome.
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Aged↗
Biomedical subjects
R A Gibson
Publications and source records attributed to R A Gibson.
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↗
Treating obstructive sleep apnoea syndrome: does it improve visual field changes?
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Glaucoma↗
A genome-wide scan provides evidence for loci influencing a severe heritable form of common migraine.
Migraine is a prevalent neurovascular disease with a significant genetic component. Linkage studies have so far identified migraine susceptibility loci on chromosomes 1, 4, 6, 11, 14, 19 and X. We performed a genome-wide scan of 92 Australian pedigrees phenotyped for migraine with and without aura and for a more heritable form of "severe" migraine. Multipoint non-parametric linkage analysis revealed suggestive linkage on chromosome 18p11 for the severe migraine phenotype (LOD*=2.32, P=0.0006) and chromosome 3q (LOD*=2.28, P=0.0006). Excess allele sharing was also observed at multiple different chromosomal regions, some of which overlap with, or are directly adjacent to, previously implicated migraine susceptibility regions. We have provided evidence for two loci involved in severe migraine susceptibility and conclude that dissection of the "migraine" phenotype may be helpful for identifying susceptibility genes that influence the more heritable clinical (symptom) profiles in affected pedigrees. Also, we concluded that the genetic aetiology of the common (International Headache Society) forms of the disease is probably comprised of a number of low to moderate effect susceptibility genes, perhaps acting synergistically, and this effect is not easily detected by traditional single-locus linkage analyses of large samples of affected pedigrees.
Chromosomes, Human, Pair 18↗
Genetic polymorphisms of the N-acetyltransferase genes and risk of Parkinson's disease.
Recently, the authors demonstrated linkage in idiopathic PD to a region on chromosome 8p that contains the N-acetyltransferase genes, NAT1 and NAT2. The authors examined NAT1 and NAT2 for association with PD using family-based association methods and single nucleotide polymorphisms (SNPs). The authors did not find evidence for association with increased risk for PD between any individual NAT1 or NAT2 SNP or acetylation haplotype (N = 397 families, 1,580 individuals).
Aged↗
Complete genomic screen in Parkinson disease: evidence for multiple genes.
CONTEXT: The relative contribution of genes vs environment in idiopathic Parkinson disease (PD) is controversial. Although genetic studies have identified 2 genes in which mutations cause rare single-gene variants of PD and observational studies have suggested a genetic component, twin studies have suggested that little genetic contribution exists in the common forms of PD. OBJECTIVE: To identify genetic risk factors for idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Genetic linkage study conducted 1995-2000 in which a complete genomic screen (n = 344 markers) was performed in 174 families with multiple individuals diagnosed as having idiopathic PD, identified through probands in 13 clinic populations in the continental United States and Australia. A total of 870 family members were studied: 378 diagnosed as having PD, 379 unaffected by PD, and 113 with unclear status. MAIN OUTCOME MEASURES: Logarithm of odds (lod) scores generated from parametric and nonparametric genetic linkage analysis. RESULTS: Two-point parametric maximum parametric lod score (MLOD) and multipoint nonparametric lod score (LOD) linkage analysis detected significant evidence for linkage to 5 distinct chromosomal regions: chromosome 6 in the parkin gene (MLOD = 5.07; LOD = 5.47) in families with at least 1 individual with PD onset at younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62), 8p (MLOD = 2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and in families with late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59) in families with both levodopa-responsive and levodopa-nonresponsive patients. CONCLUSIONS: Our data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-onset PD.
Adult↗
Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease.
CONTEXT: The human tau gene, which promotes assembly of neuronal microtubules, has been associated with several rare neurologic diseases that clinically include parkinsonian features. We recently observed linkage in idiopathic Parkinson disease (PD) to a region on chromosome 17q21 that contains the tau gene. These factors make tau a good candidate for investigation as a susceptibility gene for idiopathic PD, the most common form of the disease. OBJECTIVE: To investigate whether the tau gene is involved in idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Among a sample of 1056 individuals from 235 families selected from 13 clinical centers in the United States and Australia and from a family ascertainment core center, we tested 5 single-nucleotide polymorphisms (SNPs) within the tau gene for association with PD, using family-based tests of association. Both affected (n = 426) and unaffected (n = 579) family members were included; 51 individuals had unclear PD status. Analyses were conducted to test individual SNPs and SNP haplotypes within the tau gene. MAIN OUTCOME MEASURE: Family-based tests of association, calculated using asymptotic distributions. RESULTS: Analysis of association between the SNPs and PD yielded significant evidence of association for 3 of the 5 SNPs tested: SNP 3, P =.03; SNP 9i, P =.04; and SNP 11, P =.04. The 2 other SNPs did not show evidence of significant association (SNP 9ii, P =.11, and SNP 9iii, P =.87). Strong evidence of association was found with haplotype analysis, with a positive association with one haplotype (P =.009) and a negative association with another haplotype (P =.007). Substantial linkage disequilibrium (P<.001) was detected between 4 of the 5 SNPs (SNPs 3, 9i, 9ii, and 11). CONCLUSIONS: This integrated approach of genetic linkage and positional association analyses implicates tau as a susceptibility gene for idiopathic PD.
Age of Onset↗
Molecular and genealogical evidence for a founder effect in Fanconi anemia families of the Afrikaner population of South Africa.
Fanconi anemia (FA) is a rare, genetically heterogeneous autosomal recessive disorder associated with progressive aplastic anemia, congenital abnormalities, and cancer. FA has a very high incidence in the Afrikaner population of South Africa, possibly due to a founder effect. Previously we observed allelic association between polymorphic markers flanking the FA group A gene (FANCA) and disease chromosomes in Afrikaners. We genotyped 26 FA families with microsatellite and single nucleotide polymorphic markers and detected five FANCA haplotypes. Mutation scanning of the FANCA gene revealed association of these haplotypes with four different mutations. The most common was an intragenic deletion of exons 12-31, accounting for 60% of FA chromosomes in 46 unrelated Afrikaner FA patients, while two other mutations accounted for an additional 20%. Screening for these mutations in the European populations ancestral to the Afrikaners detected one patient from the Western Ruhr region of Germany who was heterozygous for the major deletion. The mutation was associated with the same unique FANCA haplotype as in Afrikaner patients. Genealogical investigation of 12 Afrikaner families with FA revealed that all were descended from a French Huguenot couple who arrived at the Cape on June 5, 1688, whereas mutation analysis showed that the carriers of the major mutation were descendants of this same couple. The molecular and genealogical evidence is consistent with transmission of the major mutation to Western Germany and the Cape near the end of the 17th century, confirming the existence of a founder effect for FA in South Africa.
Base Sequence↗
Long-chain polyunsaturated fatty acids in breast milk: are they essential?
The need for long-chain polyunsaturated fatty acids (LC-PUFA), such as docosahexaenoic acid (DHA, C22:6n3) and arachidonic acid (AA, C20:4n6), in the diet of infants in order to achieve full developmental potential is a matter of intense investigation by several research groups worldwide. It has been widely reported that breast-fed infants perform better on tests that assess neurodevelopmental outcomes than do formula-fed infants. Although human milk contains LC-PUFA that are absent from formula, it is necessary to demonstrate that any beneficial effects of human milk on infant development are purely attributed to the presence of LC-PUFA in human milk and their absence from formula to establish causality. The hypothesis that dietary DHA is associated with developmental outcome needs to be plausible; the effect must be consistent, specific, and independent of confounding factors. The hypothesis is certainly plausible. DHA is avidly incorporated and retained in brain cerebral phospholipids, and a most consistent finding has been the lower level of cerebral DHA in the brains of formula-fed infants (receiving no DHA) relative to those fed human milk (receiving DHA). The formula-fed infants in these studies were generally fed formulas with adequate alpha-linolenic acid levels, and this may indicate a nutritional requirement for preformed DHA. Several studies have compared the effects of breast- and formula-feeding on functional outcomes in preterm and term infants. While many of the outcomes have involved visual testing, others have attempted more global assessments. The results have shown differences in favor of breast-feeding but have been colored by the strong socioeconomic differences between mothers who choose to breast feed and those who choose formula-feeding. Randomized clinical trials involving preterm infants have shown a clear requirement for DHA for full visual and neural development. These results are consistent with primate studies. However, intervention studies with term infants that have attempted to improve the DHA supply of infant formula and hence infant development have not yielded consistent results. Some randomized studies have demonstrated improved visual and developmental indices in supplemented over unsupplemented infants, others have failed to demonstrate an effect. This disparity could be due to methodological and environmental differences. It is also notable that supplemental regimens have not specifically added DHA and have included other LC-PUFA, raising the question as to the specificity of the effect. However, only tissue DHA levels have consistently correlated with outcomes.
Animals↗
Lymphocyte subpopulations in breast-fed and formula-fed infants at six months of age.
UNLABELLED: Factors such as cytokines and lymphocytes present in human milk can influence the developing immune system. This suggests an immunoregulatory role for human milk that is absent in infants consuming formula. There are very few data available from well-defined groups of breast-fed and formula-fed infants with regard to their immune status as reflected by lymphocyte immunophenotypic values. The aim of this study was to investigate the potential difference in lymphocyte subsets between breast-fed and formula-fed infants at 6 months of age. Blood samples were taken by venipuncture. Lymphocytes were analyzed by 2-color direct immunofluorescence with Becton Dickinson Immunocytometry Systems SimulSET reagents (BD, Franklin Lakes NJ). There were 73 breast-fed infants and 55 formula-fed infants at 6 months of age. The frequency of natural killer (NK) cells (CD3-/CD16+ + CD56+) was greater in breast-fed infants (9.2%) than in formula-fed infants (6.6%, P < 0.001), while the CD4 to CD8 ratio was 2.8 in breast-fed infants compared with 3.4 in formula-fed infants (P < 0.001). CONCLUSION: Breast-fed infants (<250mL formula/bovine milk per week) had a greater proportion of NK cells and a lower CD4 to CD8 ratio than formula-fed infants at 6 months of age.
Antigens, CD19↗
Randomized trials with polyunsaturated fatty acid interventions in preterm and term infants: functional and clinical outcomes.
The role of polyunsaturated fatty acids (PUFA) in infant nutrition has now been well studied through many randomized controlled trials (RCT) that provide us with high-quality evidence, particularly in relation to efficacy. As a result of a systematic search of the literature for RCT of supplementation of formulas of term and preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA), we have identified 21 studies that have physiological responses or growth as outcomes. There have been 11 RCT involving preterm infants, and many of these claim a beneficial effect on visual, neural, or developmental outcomes. There are some reports of negative effects on growth in relation to the addition of n-3 LC-PUFA to preterm formulas but not when AA is added with n-3 LC-PUFA. Small studies have shown no differences in prostanoid formation or peroxidative stress between n-3 LC-PUFA-supplemented and unsupplemented infants. There have been 10 RCT involving term infants; whereas some studies report an effect on visual/neural/developmental outcomes, an equal number report no effect. There have been no reports of negative effects of n-3 LC-PUFA on growth in term infants. In summary, there appear to be few safety concerns relating to the use of LC-PUFA in infant nutrition. The potential medium- and long-term effects of including these compounds in the early diet of infants remain to be assessed.
Dietary Supplements↗
Perinatal characteristics may influence the outcome of visual acuity.
Visual-evoked potential (VEP) acuity has been used to assess the effects of dietary fats on the integrity of the visual pathway of infants. We investigated prognostic determinants of VEP acuity at 16 wk of age. The results of two randomized dietary intervention trials designed to assess the effect of dietary fatty acids on the visual development of term infants were combined. At entry to both trials (approximately day 5 of life), a blood sample to assess polyunsaturated fatty acid (PUFA) status was collected along with sociodemographic and perinatal characteristics. At 16 +/- 0.9 wk of age, infants underwent VEP testing to measure acuity. There was no effect of dietary treatment on these outcomes within or between trials. Multiple linear regression models were constructed to investigate the effect of perinatal and nutritional variables at study entry on VEP acuity of 185 infants. Higher birth weight was associated with an ability to resolve smaller checkerboard patterns [r2 = 0.05; 95% confidence interval (Cl), -0.10, -0.04 log units]. Male gender (r2 = 0.03; 95% Cl, 0.01, 0.07 log units), day 5 plasma 22:5n-6 (r2 = 0.04; 95% Cl, 0.02, 0.20 log units), day 5 red cell membrane 20:3n-9 (r2 = 0.03; 95% Cl, 0.03, 0.13 log units), and the number of smokers in the household (r2 = 0.02; 95% Cl, 0.00, 0.04 log units) were all associated with poorer VEP acuity scores. It is possible that a combination of perinatal factors could accumulate to either mask or enhance effects of diet on VEP acuity, given the relatively modest effects of long-chain PUFA on visual outcome.
Birth Weight↗
Transforming growth factor beta in human milk does not change in response to modest intakes of docosahexaenoic acid.
Long-chain polyunsaturated fatty acids have been associated with aspects of immune regulation including cytokine production. The purpose of this study was to investigate the effect of maternal dietary supplementation with tuna oil, rich in docosahexaenoic acid (DHA), on the concentration of transforming growth factor beta 1 (TGFbeta1) and TGFbeta2 in breast milk. In this randomized, dietary intervention trial, mothers of term infants consumed a daily supplement of 2000 mg oil containing either placebo (n = 40), 300 mg DHA (n = 40), or 600 mg DHA (n = 40). The DHA increase in milk and plasma was proportional to dietary DHA. There was no relationship between milk DHA status and TGFbeta1 and TGFbeta2 levels.
Animals↗
More research is needed to determine the effects of human milk on neonatal outcome.
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Breast Feeding↗
Cytokine production by leukocytes from human milk.
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Adjuvants, Immunologic↗
Indicators of selenium status in Australian infants.
OBJECTIVE: To provide the first Australian data for the commonly used indicators of selenium (Se) status including plasma and erythrocyte Se and erythrocyte glutathione peroxidase (GSHPx) activity in newborn term and preterm infants from Adelaide, South Australia. Plasma Se levels from adults from Adelaide and Tasmania are also reported. METHODOLOGY: Descriptive, cross-sectional study of the indicators of Se status of newborn Australian preterm and term infants. RESULTS: Mean (+/- SD) plasma Se concentrations in the first 5 days of life for term (n = 48) and preterm (n = 90) infants were similar at 33 +/- 11 and 29 +/- 14 microg/L, respectively. Glutathione peroxidase activity was lower in preterm than term infants (P < 0.001). Erythrocyte Se was lower in male (n = 74) compared with female (n = 57) infants (491 +/- 98 vs 561 +/- 134 ng/g Hb; P < 0.001). Adelaide adult plasma Se levels were 88 +/- 20 microg/L and higher than those of adult Tasmanian blood donors (77 +/- 13 microg/l, P < 0.05). CONCLUSIONS: These data indicate that values for indicators of Se status of Australian infants and adults are at the lower end of the international range. This article highlights the paucity of Australian data on the Se content in the food supply and the Se status of the Australian population. Given the increasing range and complexity of the biological roles of Se and the emerging evidence that Se may have important roles in prevention of cancer and other disorders, further data are required to clarify the Se status of Australians.
Adult↗
A randomized trial of different ratios of linoleic to alpha-linolenic acid in the diet of term infants: effects on visual function and growth.
BACKGROUND: There are nutritional recommendations that the ratio of linoleic to alpha-linolenic acid (LA:ALA) in formula for term infants be between 5:1 and 15:1. These recommendations were made in the absence of data on functional or clinical outcomes. OBJECTIVE: We compared the fatty acid status, visual evoked potential (VEP) acuity, and growth of term infants fed formula containing an LA:ALA of 10:1 or 5:1 with those of a breast-fed reference cohort. DESIGN: Formula-fed infants were allocated randomly in a double-blind fashion to receive formula with an LA:ALA of either 10:1 (16.9:1.7; n = 36) or 5:1 (16.3:3.3; n = 37) from near birth to 34 wk of age. Increased ALA was attained by replacing soy oil with low-erucic acid cannola oil. A parallel group of breast-fed infants was also recruited. Infant growth and fatty acid status were assessed at 6, 16, and 34 wk of age. VEP acuity was assessed at 16 and 34 wk. RESULTS: Infants fed the 5:1 formula had greater docosahexaenoic acid (DHA) concentrations in plasma and erythrocyte phospholipids than did infants fed the 10:1 formula, but DHA concentrations of infants fed the 5:1 formula remained less than those in breast-fed infants. The VEP acuity of all formula-fed and breast-fed infants was not significantly different at 16 and 34 wk of age. At birth, infants fed the 5:1 formula were heavier, were longer, and had a greater head circumference than infants assigned to the 10:1 formula group; this differential was maintained throughout the trial. The rate of gain in weight, length, and head circumference was not significantly different between the 2 formula-fed groups, although breast-fed infants had lower weight and length gains than did formula-fed infants between 16 and 34 wk of age. CONCLUSION: Lowering the LA:ALA in formula from 10:1 to 5:1 by using low-erucic acid canola oil resulted in a modest increase in plasma DHA but had no effect on VEP acuity or growth rate.
Dietary Fats↗
n-3 polyunsaturated fatty acid requirements of term infants.
The benchmarks for human nutrient requirements are the recommended dietary intakes (RDIs). However, the RDIs are set to prevent a clinical deficiency state in an otherwise healthy population and there are few nutrient recommendations set with the goal of achieving an optimal or maximal state of nutrition and health. This is becoming an increasing challenge with the introduction of many nutraceuticals and functional foods, a prime example being the debate surrounding the introduction of long-chain polyunsaturated fatty acids (LCPUFAs) into infant formulas. Most expert nutrition committees have used the fatty acid composition of breast milk as a basis for recommendations for infant formulas, with little information on the minimum absolute requirement for essential PUFAs. It has been difficult to determine a minimum requirement for fatty acids because 1) LCPUFAs can be synthesized from precursor fatty acids, 2) plasma n-3 LCPUFA concentrations representing deficiency and sufficiency are not clearly defined, and 3) there are no recognized clinical tests for n-3 LCPUFA deficiency and sufficiency. Therefore, there is a clear need to associate a measure of LCPUFA status with a specific functional outcome before any recommendations can be made for achieving optimal or maximal LCPUFA status.
Adult↗