The STR system in the human phenylalanine hydroxylase gene: true fragment length obtained with fluorescent labelled PCR primers

We present a simple, fast, non-radioactive method for the analysis of the polymorphic short tandem repeat (STR) system in the human phenylalanine hydroxylase gene. Previously, sizing of the STR marker involved radiolabelling of PCR amplified fragments and resolution on denaturing polyacrylamide gels using M13 sequencing ladder as a standard. However, this method consistently gave sizes 2 bp longer than the known sequence. The fluorescent method presented here employs internal lane standards and enables accurate sizing of the fragments. To avoid confusion, we suggest that the true fragment lengths are used as reference values in the future. The analysis of STR alleles is valuable for population genetic studies and for targeted mutation screening in phenylketonuria (PKU). It can replace RFLP-based haplotype analysis for carrier detection, and we report its use for prenatal diagnosis in a Northern Irish family with PKU. The analysis of 250 Northern Irish chromosomes, including 128 PKU alleles, showed no significant difference between normal and PKU alleles, with fragment lengths of 238 and 242 bp most common in both groups.     

Molecular analysis of PKU in Ireland

Classical phenylketonuria (PKU: McKusick No. 261600) is caused by mutations occurring at the phenylalanine hydroxylase (PAH) locus on chromosome 12 and has a prevalence in Ireland of 1 in 4500. We examined 304 independent alleles from 350 patients for the presence of six mutations and have characterized VNTR alleles within the minisatellite region 3' to the PAH gene in patients carrying the most prevalent mutation. R408W was the most common mutation found, with a relative frequency of 42%. All other mutations had relative frequencies of <10%. VNTR analysis showed that the R408W mutation is associated with the VNTR-8 allele in the Irish population, indicating that R408W is associated with RFLP haplotype 1. This differs from that reported from eastern Europe where R408W is associated with RFLP haplotype 2/VNTR-3; an observation which has led several groups to propose a Balto-Slavic origin for this mutation. These results support the hypothesis of a second, independent founding event for the R408W mutation on an RFLP haplotype 1 VNTR-8 chromsome background in the Irish/Celtic population.     

Fructosamine and glycated haemoglobin in the assessment of long term glycaemic control in diabetes

Fructosamine and glycated haemoglobin were measured simultaneously in 147 children with diabetes. If glycated haemoglobin is considered as the 'gold standard' for long term glycaemic control, then fructosamine is a poor indicator of actual glycated haemoglobin values, with wide 95% confidence (fiducial) limits. This shows that it is impossible to accurately predict glycated haemoglobin concentrations and therefore, by implication, longer term glycaemic control, from measurements of fructosamine. As the major studies on the prevention of microvascular complications in diabetes have used glycated haemoglobin levels to assess glycaemic control, it is suggested that this measurement should be used in all children with diabetes in preference to the measurement of fructosamine.     

Catch-up growth up to ten years of age in children born very preterm or with very low birth weight

Background  

Improved survival due to advances in neonatal care has brought issues such as postnatal growth and development more to the focus of our attention. Most studies report stunting in children born very preterm and/or small for gestational age. In this article we study the growth pattern of these children and aim to identify factors associated with postnatal catch-up growth.     

10-year follow-up of patients with and without mediastinitis

Mediastinitis is a dreaded complication of CABG surgery. Short-term outcomes have been described, but there have been only a few long-term studies. We examined the survival of patients undergoing isolated CABG surgery between 1992 and 2001. Mediastinitis was identified during the index admission. Proportional hazards regression was used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CI 95%). Among 36,078 consecutive patients, there were 5749 deaths during 148,319 person years of follow-up. There were 418 cases of mediastinitis (1.16%). The incidence of death was 11.15 per 100 person/years with mediastinitis and 3.81 deaths/100 person years without. (P < 0.001). We also examined the mortality rates of patients who survived at least 6 months after their CABG surgery. Patients with mediastinitis had an incidence rate of 5.70 deaths per 100 person/years while those without had a rate of 2.66 deaths per 100 person/years (P < 0.001). After adjustment for baseline differences in patient and disease characteristics, the hazard ratio was 2.12 (CI95% = 1.86,2.58; P < 0.001). The adjusted hazard ratios for patients who survived 6 months postsurgery was 1.70 (CI95% = 1.36,2.13; P < 0.001). Mediastinitis is associated with a marked increase in both acute and long-term mortality rates.     

Use of the Paired-Comparison Technique to Determine the Most Valued Qualities of the McMaster Medical Programme Admissions Process

The Undergraduate Medical Programme at McMaster University selects students using a comprehensive set of tools. Attempts to modify the selection process over many years have been impeded by an inability to reconcile very strongly held views among stakeholders as to the importance of the selection tools and, indeed, the very purposes of the admission process. The objective of this study was to identify key 'qualities' of the selection process and to measure their relative importance to admissions process assessors. Through a qualitative review of internal research documents, Medical Programme Admissions Committee meeting minutes, memos and accreditation surveys eight qualities of the admissions process were identified: validity, fairness, accessibility, comprehensiveness, affordability, legal defensibility, contribution to class diversity and the role of the process as a public statement of the Programme's values. Faculty, students and community admissions assessors were surveyed, by mail, using a paired-comparisons technique. The overall response rate was 58%. By a wide margin, all three groups of admissions assessors valued validity and fairness most highly. The least valued qualities were affordability and the role of the process as a statement of our values. Possible applications of this approach to the admissions process deliberations are discussed.