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.     

Survival from acute non-lymphocytic leukaemia, 1971-88: a population based study.

Survival rates were studied among 1258 children with acute non-lymphocytic leukaemia diagnosed in 1971-88 and included in the population based National Registry of Childhood Tumours. Of the total, 147 (12%) died without receiving treatment. Among the remaining treated children, actuarial five year survival rates were 6% in 1971-4, 15% in 1975-9, 23% in 1980-3, and 40% in 1984-8. Infants aged less than 1 year had a significantly worse prognosis and there was a significant trend towards lower survival rates with increasing white cell count. No independent significant effects on survival were found with sex, French-American-British (FAB) subtype, or the presence or absence of Down's syndrome. Children entered in national trials had a higher survival rate than those who were not entered, and children treated at teaching hospitals had a higher survival rate than those who were treated elsewhere. Among the 535 (43%) children who survived at least one year from diagnosis no factor studied had a significant effect on survival, emphasising the importance of achieving first remission as a determinant of long term survival.     

Allergic side-effects of antimicrobial chemotherapy and possibilities in their diagnosis

In antimicrobial chemotherapy the allergic reactions are in the first place of the side-effects appearing. The most frequent cause of the iatrogenic contact eczema antimycotics and chloramphenicol are to be taken into consideration. Penicillin and its derivations and chloramphenicol form the main proportion of the allergic in systematic administration. The serologico-nephelometric two-step-method and the lymphocyte transformation test are useful methods for the diagnostics of drug allergies. In a use adequate to indication they are valuable adjuvants in the hand of the clinician.     

Percutaneous transluminal dilatation of transplant renal artery stenosis

Percutaneous transluminal angioplasty has been applied to the treatment of transplant renal artery stenosis in 3 patients, 2 with severe hypertension resistant to medical therapy, and one with graft dysfunction related to the presence of the stenosis in the early post-transplant period. The clinical courses of the patients before and after angioplasty are illustrated and the usefulness of the technique in this difficult situation stressed.