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Biomedical subjects

David Burgner

Publications and source records attributed to David Burgner.

At least 19 recordsLinked to original sources

Prevention and treatment of infant and childhood vitamin D deficiency in Australia and New Zealand: a consensus statement.

Vitamin D deficiency has re-emerged as a significant paediatric health issue, with complications including hypocalcaemic seizures, rickets, limb pain and fracture. A major risk factor for infants is maternal vitamin D deficiency. For older infants and children, risk factors include dark skin colour, cultural practices, prolonged breastfeeding, restricted sun exposure and certain medical conditions. To prevent vitamin D deficiency in infants, pregnant women, especially those who are dark-skinned or veiled, should be screened and treated for vitamin D deficiency, and breastfed infants of dark-skinned or veiled women should be supplemented with vitamin D for the first 12 months of life. Regular sunlight exposure can prevent vitamin D deficiency, but the safe exposure time for children is unknown. To prevent vitamin D deficiency, at-risk children should receive 400 IU vitamin D daily; if compliance is poor, an annual dose of 150,000 IU may be considered. Treatment of vitamin D deficiency involves giving ergocalciferol or cholecalciferol for 3 months (1000 IU/day if < 1 month of age; 3000 IU/day if 1-12 months of age; 5000 IU/day if > 12 months of age). High-dose bolus therapy (300,000-500,000 IU) should be considered for children over 12 months of age if compliance or absorption issues are suspected.

Adolescent↗

Role of prednisolone treatment in severe Mycoplasma pneumoniae pneumonia in children.

Mycoplasma pneumoniae pneumonia (MP) is responsible for 10-40% of cases of pediatric community-acquired pneumonia. Occasionally, progression to severe pneumonia occurs despite appropriate antibiotic therapy. We retrospectively evaluated the effect of prednisolone in 15 children with MP whose clinical and radiographic course worsened despite broad-spectrum antibiotics, including appropriate macrolides. The mean ( +/- SD) age was 6.1 +/- 1.9 years, and 10 were boys. All children had received macrolides at presentation, but they had persistent fever and progressively worsening radiographic findings. In addition to broad-spectrum antimicrobial therapy, we added prednisolone (1 mg/kg for 3-7 days, then tapered over 7 days) on day 6 (+/-1.5 days) of admission. Fourteen children became afebrile within 24 hr, and their clinical status and radiographic findings improved over several days. The white blood cell count at presentation was 7,500 +/- 2,000/mm3, with a proportion demonstrating lymphopenia (lymphocyte differential, 19.7 +/- 5.7%). In conclusion, corticosteroid treatment appeared to be temporally associated with clinical and radiographic improvement, and may be helpful for reducing morbidity in children with macrolide-nonresponsive severe MP. Further studies may be warranted.

Adolescent↗

Genetic susceptibility to infectious diseases: big is beautiful, but will bigger be even better?

Genetic epidemiology, including twin studies, provides robust evidence that genetic variation in human populations contributes to susceptibility to infectious disease. One of the major limitations of studies that attempt to identify the genes and mechanisms that underlie this susceptibility has been lack of power caused by small sample size. With the development of novel technologies, burgeoning information on the human genome, the HapMap project, and human genetic diversity, we are at the beginning of a new era in the study of the genetics of complex diseases. This review looks afresh at the epidemiological evidence that supports a role for genetics in susceptibility to infectious disease, examines the somewhat limited achievements to date, and discusses current advances in methodology and technology that will potentially lead to translational data in the future.

Communicable Diseases↗

Genetic susceptibility to neonatal infection.

PURPOSE OF REVIEW: To review current data on genetic factors contributing to the striking susceptibility of neonates to infectious diseases and other adverse outcomes. RECENT FINDINGS: Although few studies address genetic determinants of neonatal infectious disease susceptibility, several variants in genes involved in the innate immune response have been associated with differential risk for neonatal infection. The most consistent results relate to polymorphisms of tumour necrosis factor-alpha, whereas other gene polymorphisms, such as those of interleukin-6, have yielded conflicting findings. Similar genetic factors may be involved in other inflammatory neonatal diseases. Recent data suggest that genetic variation may influence the pace of immunologic maturation. SUMMARY: Despite the enormous human and financial costs of infection for neonatal mortality and morbidity worldwide, it remains unclear why neonates are so susceptible. Genetic epidemiologic studies may assist in the identification of critical protective and pathogenic pathways. Despite the current relative lack of robust data, such studies are likely to facilitate the development of interventions that ultimately decrease the significant morbidity and mortality of this highly vulnerable population.

Communicable Diseases↗

The changing epidemiology of pediatric aseptic meningitis in Daejeon, Korea from 1987 to 2003.

BACKGROUND: Aseptic meningitis is a relatively frequent childhood disease and virologic data suggest that enteroviruses are the commonest etiologic agents. We evaluated the epidemiologic characteristics of aseptic meningitis in Daejeon, South Korea from 1987 to 2003. METHODS: 2201 medical records of children with aseptic meningitis admitted to The Catholic University of Korea, Daejeon St Mary's Hospital were retrospectively analyzed. RESULTS: Outbreaks of aseptic meningitis were observed in 1990, 1993, 1996, 1997, 2001 and 2002. The age distribution of cases was relatively uniform, with a higher incidence in those aged < 1 year and 4-7 years. The male-to-female ratio was 2:1. There was a higher incidence of disease in the summer (May to August, 74.1% of total). Comparison of the largest epidemics in 1997 and 2002 showed significant differences in the incidence in those < 1 year (11.8% vs. 4.4%, respectively; P = 0.001). Neurologic sequelae were observed in 0.7% of the patients. CONCLUSION: Aseptic meningitis, rare before the 1980s in Korea, has since become a common clinical entity. Since 1990, outbreaks of aseptic meningitis have occurred every 1 to 3 years in Daejeon in keeping with Korea-wide epidemics. The frequency of disease affecting children less than one year of age may reflect herd immunity to the epidemic strain.

Adolescent↗

Kawasaki disease: what is the epidemiology telling us about the etiology?

Kawasaki disease (KD) is an important and common inflammatory vasculitis of early childhood with a striking predilection for the coronary arteries. It is the predominant cause of paediatric acquired heart disease in developed countries. Despite 40 years of research, the aetiology of KD remains unknown and consequently there is no diagnostic test and treatment is non-specific and sub-optimal. The consensus is that KD is due to one or more widely distributed infectious agent(s), which evoke an abnormal immunological response in genetically susceptible individuals. The epidemiology of KD has been extensively investigated in many populations and provides much of the supporting evidence for the consensus regarding etiology. These epidemiological data are reviewed here, in the context of the etiopathogenesis. It is suggested that these data provide additional clues regarding the cause of KD and may account for some of the continuing controversies in the field.

Air Pollutants↗

Primary sternal osteomyelitis: a case series and review of the literature.

PURPOSE: Primary sternal osteomyelitis is rare in the pediatric population. METHODS: We present 4 recent cases that demonstrate a wide range in age, presenting features, and clinical course, and we performed a literature review. RESULT: A combination of diagnostic aspiration with prolonged appropriate antibiotic therapy led to successful resolution in all cases. Surgical debridement should be reserved for cases that do not respond to medical therapy. CONCLUSION: Sternal osteomyelitis is a rare condition in children that usually resolves with aspiration and prolonged antibiotic therapy.

Adolescent↗

The burden of pneumonia in children: an Australian perspective.

The burden of pneumonia in Australian children is significant with an incidence of 5-8 per 1000 person-years. Pneumonia is a major cause of hospital admission in children less than 5 years of age. Indigenous children are at particular risk with a 10-20-fold higher risk of hospitalisation compared to non-Indigenous children. They also have longer admissions and are more likely to have multiple admissions with pneumonia. There are limited data on pathogen-specific causes of pneumonia, however Streptococcus pneumonia is the most common bacterial cause in children under 5 years of age and respiratory syncytial virus (RSV) and influenza are the predominant viral causes in young children. Pneumonia due to Haemophilus influenza type b (Hib) has been virtually eliminated by the introduction of universal Hib immunisation. Further studies are needed to accurately define the epidemiology of pneumonia due to specific pathogens to help target treatment and immunisation strategies.

Adolescent↗

An investigation of NOS2A promoter polymorphisms in Australian multiple sclerosis patients.

As with other major autoimmune diseases, susceptibility to multiple sclerosis (MS) is believed to result from the complex interaction of a number of genes, each with modest effect. Extensive research of experimental autoimmune encephalomyelitis in mice and several direct MS studies have implicated NOS2A, which encodes the inducible form of nitric oxide synthase, and the genetic region encoding NOS2A, 17q11.2, has been identified in a number of genome wide screens as being potentially associated with MS. We investigated four single nucleotide polymorphisms in the proximal promoter region of NOS2A, in a case-control group of 100 Australian MS patients and 100 controls and in 203 MS patients and their unaffected parents. We found a trend toward excess transmission of the -277A allele (tag for the AGCC haplotype) to HLA-DRB1*1501-positive MS patients (P (uncorrected)=0.05). We initially discovered a trend toward over-representation of the AGCC haplotype in HLA-DRB1*1501-positive compared to HLA-DRB1*1501-negative MS patients in the case-control cohort. However, when combined with the probands from the transmission disequilibrium analysis, this trend was nullified. Nonetheless, despite the lack of significant evidence of association for the NOS2A promoter polymorphisms with MS, the gene remains an interesting candidate for MS susceptibility, particularly with regard to the HLA-DRB1*1501 haplotype.

Alleles↗

Chalk and cheese: symptomatic hypocalcaemia during paediatric anti-tuberculous therapy.

Standard anti-tuberculosis therapy may disrupt normal vitamin D metabolism and consequently calcium homeostasis, but this is previously unreported in paediatric patients. We describe two children developed symptomatic hypocalcaemia secondary to hypovitaminosis D, which had been precipitated by rifampicin and isoniazid. The complex relationship between tuberculosis, anti-tuberculosis therapy, vitamin D metabolism and calcium, together with the clinical implications, are discussed.

Adolescent↗

Improved allelic differentiation using sequence-specific oligonucleotide hybridization incorporating an additional base-analogue mismatch.

Sequence-specific oligonucleotide hybridization (SSOH, 'dot-blotting') is a widely employed method of typing single nucleotide polymorphisms (SNPs), but it is often compromised by lack of allelic differentiation. We describe a novel improvement to SSOH that incorporates an additional mismatch into the oligonucleotide probe using the universal base analogue 3-nitropyrrole. This method greatly increases allelic differentiation compared to standard SSOH where oligonucleotides contain only SNP-defining base changes. Moreover, stringency of the hybridisation is predictably maintained over a wide range of temperatures, which can be calculated empirically, thus facilitating the genotyping of multiple SNPs using similar conditions. This improved method increases the usefulness of hybridisation-based methods of rapid genotyping of SNPs and may have implications for array methodologies.

Alleles↗

Nucleotide and haplotypic diversity of the NOS2A promoter region and its relationship to cerebral malaria.

To assess the hypothesis that nitric oxide is critical in the pathogenesis of cerebral malaria, we analysed genetic variation in the proximal promoter region of NOS2A, the gene encoding inducible nitric oxide synthase. Sequencing 72 Gambian chromosomes revealed 11 single nucleotide polymorphisms in 2.5 kB (theta=8.6 x 10(-4)). Genotyping 104 nuclear families identified six common haplotypes. A single haplotype, uniquely defined by the NOS2A-1659T allele, was associated with cerebral malaria by a transmission disequilibrium test of 334 affected children and their parents (P=0.02). An independent case-control study of 505 different children from the same population replicated the allelic association with cerebral malaria (odds ratio: 1.31, P=0.04). Taken together these data indicate a weak but significant association of the NOS2A locus with susceptibility to cerebral malaria. Despite high linkage disequilibrium across the region studied, this association would not have been detected without the initial construction of a dense marker set for haplotype tagging.

Alleles↗

Genes, nitric oxide and malaria in African children.

The unresolved and complex relationship between nitric oxide and falciparum malaria is reflected in recent genetic and immunohistochemical studies in African children. Different genetic associations, perhaps geographically distinctive, are seen between genetic variants of the inducible nitric oxide gene and various disease manifestations in African populations. The picture might not be complete without considering the emerging roles of carbon monoxide, another endogenous gaseous mediator with similar effects to those of nitric oxide. Only when genetic comparisons from across tropical Africa are examined, in conjunction with the newly recognized complexities in the events of systemic inflammation, will this relationship be understood.

Africa↗

Features of Kawasaki disease at the extremes of age.

AIM: The diagnosis of Kawasaki disease (KD) in those outside the typical age range (6 months-4 years) is often delayed, potentially worsening prognosis. The features of KD in children or=5 years were compared with those presenting within the more typical age distribution. METHODS: Korean children with complete diagnostic criteria for KD were grouped according to their age at presentation: Group A ( or=5 years). The clinical features, laboratory findings and outcome in each group were compared. RESULTS: Of 136 children presenting to a single centre between 1999 and 2003, 10 children were in Group A, 114 in Group B and 12 in Group C. The mean total fever duration was 8 days in Group C and 6.2 days in Group A (P=0.03). All children in Group C had cervical lymphadenopathy, compared with 50% of Group A and 64% of Group B (P=0.01). Coronary artery lesions were commoner in older children (Group C, 42%) compared with Group B (17%, P=0.05). All children had an equivalent leukocytosis, but Group C had significantly higher neutrophil counts (P=0.001). Group A had significantly lower mean haemoglobin (P=0.003) and total protein (P=0.002) at presentation and a more marked thrombocytosis 1 week after intravenous immunoglobulin therapy (P<0.05). CONCLUSION: The clinical and laboratory phenotype of KD varies with age. Older children may have a more marked inflammatory response and worse outcome. Younger children who are treated appropriately may not have a chance to higher risk of coronary artery lesions.

Child↗