Intussusception and rotavirus associated hospitalisation in New Zealand

Aims: To describe the epidemiology of intussusception and its relation to rotavirus associated hospitalisation in New Zealand. Methods: National hospital discharge data between January 1998 and June 2003 for all children younger than 3 years of age with intussusception were reviewed. Independently, children from the same age group, admitted to eight paediatric units with rotavirus gastroenteritis between May 1998 and May 2000, were identified prospectively. Epidemiological characteristics of cases with intussusception were compared with those of hospitalised rotavirus disease. Results: During the 5.5 year study period, there were 277 cases of intussusception and no deaths. Most (72%) occurred in the first year of life (age adjusted incident rate 65 per 100 000 child-years, 95% CI 56 to 74). Risk of intussusception was less in females (risk ratio 0.58; 95% CI 0.43 to 0.78) and for Maori (risk ratio 0.52; 95% CI 0.35 to 0.77) when compared with European infants. In contrast to hospitalised rotavirus cases, intussusception peaked at a younger age and lacked seasonality. Conclusions: This study provides national baseline data on intussusception for future rotavirus vaccine programmes in New Zealand. Wild-type rotaviruses do not appear to have a major role in triggering intussusception. Prospective surveillance systems, using standardised case definitions and nested case-control methodology, are needed to further our understanding of the aetiology and epidemiology of intussusception.     

Nijmegen breakage syndrome diagnosed as Fanconi anaemia

BACKGROUND: Fanconi anaemia (FA) and Nijmegen breakage syndrome (NBS) are rare chromosomal instability disorders with overlapping clinical features. It has recently been shown that, like FA, NBS is also associated with increased chromosomal sensitivity to DNA cross-linking agents. PROCEDURE: We report a family that was initially diagnosed with FA on the basis of increased sensitivity to DNA cross-linking agents. They were atypical in that there were associated severe infection problems. In view of these features we performed immune function studies together with molecular analysis of the FA genes and subsequently the NBS1 gene. RESULTS: Two children in the kindred have died, one from sepsis, and the other with a plasma cell malignancy. A third child underwent bone marrow transplantation because of recurrent infections. All affected members had severe immunological abnormalities. The genetic defect was shown to be a novel mutation in the NBS1 gene, so the diagnosis was revised to that of NBS. CONCLUSIONS: This family illustrates the importance of awareness of the lack of specificity of DNA cross-linking agent tests for FA, particularly in situations where the clinical features are atypical. In addition, one of the cases represents the first use of bone marrow transplantation for NBS that we are aware of; this treatment may have a future role for other patients with the syndrome.     

Dietary antioxidants and fat are associated with plasma antibody titers to heat shock proteins 60, 65, and 70 in subjects with dyslipidemia

BACKGROUND: The heat shock proteins (HSPs) are protein chaperones. Higher titers of antibody to HSPs (anti-HSPs) have been reported in atherosclerosis, which may contribute to immunoactivation in this process. OBJECTIVE: We investigated whether dietary antioxidants and fat intake are associated with changes in anti-HSP titers in dyslipidemic subjects. DESIGN: Patients (n = 238) were recruited from hospital lipid clinics. Control subjects (n = 188) were recruited from university and hospital employees. Food-frequency questionnaires were used to estimate dietary antioxidants and fat. RESULTS: Dyslipidemic patients had significantly higher titers of anti-HSPs than did control subjects; expressed in medians and interquartile ranges of absorbance units, anti-HSP-60 titers were 0.27 (0.18-0.37) and 0.22 (0.16-0.30), anti-HSP-65 titers were 0.45 (0.28-0.79) and 0.31 (0.22-0.50), and anti-HSP-70 titers were 0.22 (0.17-0.30) and 0.19 (0.13-0.27), respectively. Median and interquartile ranges of serum concentrations of C-reactive protein [1.25 (0.42-3.26) and 0.58 (0.17-1.42)] and mean (+/-SEM) concentrations of vitamin E (16.36 +/- 0.31 and 14.08 +/- 0.38) were also significantly higher in patients than in control subjects, respectively. In dyslipidemic patients, the major dietary predictors of the variability in anti-HSP-60 titers were vitamin C (P = 0.005), vitamin E (P = 0.04), and total fat (P = 0.009) intakes; for anti-HSP-65 titers, vitamin C was the major predictor (P = 0.002). These findings remained significant after adjustment for confounding factors. CONCLUSIONS: Anti-HSP-60, -65, and -70 titers are significantly higher in dyslipidemic patients with or without established coronary disease. Our data indicate an association between dietary constituents and the immune response to HSPs in dyslipidemic subjects.     

Polymorphisms in IGF-binding protein 1 are associated with impaired renal function in type 2 diabetes

The dysregulation of the IGF system has been implicated in the pathogenesis of obesity, diabetes, and diabetes complications such as nephropathy, but little is known about the genomics of the IGF system in health and disease. We genotyped 13 single nucleotide polymorphisms (SNPs) in IGFBP1 gene in 732 representative type 2 diabetic patients from the Salford Diabetes Register. Of the 13 SNPs, 8 were polymorphic and 7 of those had minor allele frequencies >0.1, one of which was in the gene promoter and one of which was nonsynonymous in exon 4. The minor alleles of these SNPs and two others were associated with a reduced prevalence of diabetic nephropathy. Haplotype analysis revealed that 97% of the genetic variation for IGFBP1 in the population sample could be accounted for using two of the "reno-protective" SNPs, with other SNPs adding little extra information. One of these two SNPs was the nonsynonymous mutation in exon 4, lying close to the integrin-binding RGD motif, which is thought to affect tissue delivery of IGF-I by IGF-binding protein 1 (IGFBP-1), possibly suggesting a "reno-protective" effect via altered IGFBP-1 binding. In conclusion, we have described the first genomic markers to be associated with diabetic microvascular complications within the human IGFBP1 gene.