Research access to adolescents and young adults

Gaining research access to adolescents and young adults is not straightforward and involves layers of negotiation and administration. Experiences of accessing adolescents and young adults aged 13–21 years are described in this article. Issues raised for consideration are: identifying clinical gatekeepers; seeking ethical approval; making direct contact with adolescents and young adults (hereafter referred to as young people); and dealing with parents as gatekeepers. Refusal rates, participation rates, and reasons are also considered. The issues raised provide practical insights that may be helpful to other researchers aiming to access adolescents and young adults.     

INHIBITION OF RABBIT RENAL ORNITHINE DECARBOXYLASE ACTIVITY BY LEAD

Ornithine decarboxylase (ODC) is the first and the rate-limiting enzyme in polyamine biosynthesis. Polyamines play key roles in cell proliferation, renal membrane transportation, and plasma membrane calcium fluxes. As part of a multidisciplinary research project to evaluate the application of the rabbit as a relevant model for male reproductive toxicology, the effect of blood lead on rabbit renal ODC activity was investigated. Kidneys from rabbits with experimentally established total blood lead concentrations of 0, 20, 40, and 80 mug/dL and maintained at these concentrations for 10 weeks were removed at sacrifice and assayed for ODC activity. ODC activity of rabbit kidney decreased as blood lead concentration increased in a dose-dependent manner. Direct addition of lead to ODC assay mixture did not alter ODC activity. At the blood lead concentrations examined, body weights of each group increased constantly throughout the study period. Overt lead toxicity was not present among the rabbits during the exposure period. The ratio of rabbit kidney to total body weight did not show a significant difference as the blood lead concentration increased. It is possible that the major pathological lesion of the rabbit kidney with subchronic lead exposure at target blood lead concentrations (20-80 mug/dL) is characterized by very subtle renal tubular degeneration, though this requires further validation. The results also demonstrated an apparent selective inhibition of lead on form A ODC activity when renal multiform ODC activities derived from control rabbits are compared with those of rabbits maintained at a 40 mug/dL blood lead concentration. It was recently reported that increasing blood concentrations of lead, even within a range considered low, impaired kidney function in adult men. Rabbits and humans share many similarities in the luminal lead load of renal tubular cells in lead intoxication. Investigation of the kidney ODC profile in lead-exposed rabbits can be useful to further characterize the mechanism of lead nephrotoxicity in humans.     

Nutrient intakes and impact of fortified breakfast cereals in schoolchildren

OBJECTIVE: To report micronutrient intakes in Northern Ireland schoolchildren, and to establish the contribution of fortified breakfast cereal to overall nutrient intakes and achievement of current dietary recommendations. DESIGN: Analysis of dietary intakes and physical characteristics of participants in a randomly selected 2% population sample of 1015 schoolchildren aged 12 and 15 years in Northern Ireland during the 1990/1 school year. MAIN OUTCOME MEASURES: Dietary intakes, physical characteristics, and their association with consumption of fortified breakfast cereal. RESULTS: Mean micronutrient intakes were generally adequate with the exception of low intakes of folate (boys and girls) and iron (girls). Fortified breakfast cereals, consumed by a high proportion (94% boys; 83% girls) of the sample, were associated with higher daily intakes of most micronutrients and fibre and with a macronutrient profile consistent with current nutritional recommendations. Appreciable proportions of subjects who did not consume fortified breakfast cereals had daily intakes that fell below the lower reference nutrient intake for riboflavin, niacin, folate, vitamin B-12, and iron (girls). CONCLUSIONS: The results demonstrate the potential of fortification in contributing to micronutrient intakes of schoolchildren, particularly where requirements are high, or for those on marginal diets of low nutritional quality.     

Improved prognosis for congenital nephrotic syndrome of the Finnish type in Irish families

Congenital nephrotic syndrome of the Finnish type is a rare autosomal recessive disease with a high infant mortality without aggressive treatment. The biochemical basis of the disease is not understood fully but the disease locus has been mapped recently to chromosome 19q12-q13.1 in Finnish families. This paper describes the clinical features and outcome of 20 patients in Ireland with congenital nephrotic syndrome of the Finnish type who have presented since 1980. Before 1987, all infants died by the age of 3 years. After the introduction of daily intravenous albumin infusion, nutritional support, elective bilateral nephrectomy, and renal transplantation, mortality in the past decade has fallen to 30%, with no deaths in the past five years. Genetic linkage analysis was performed in six families in whom DNA was available and the locus responsible was mapped to the same region on chromosome 19 as in Finnish families, suggesting that Irish families share the same disease locus.     

Partial growth hormone insensitivity

Partial growth hormone (GH) insensitivity can be defined as the clinical and biochemical features of IGF-I deficiency without GH deficiency and in the absence of the dysmorphic features of Laron syndrome. There is good evidence that this form of GH insensitivity exists, both in the context of severe GH resistance, and also in some patients with idiopathic short stature. The series of GH insensitivity patients in the European study shows a spectrum of clinical and biological defects, with several patients at the milder end of the spectrum having normal facies. The report of the presence of heterozygous mutations of the GH receptor in patients with idiopathic short stature has been confirmed by documentation of dominantly inherited mutations in familial short stature. Molecular screening in our unit of a group of 31 children with idiopathic short stature and normal GHBP, failed to identify mutations of the intracellular domain of the GH receptor. Consequently, although partial GH insensitivity is a proven entity, the clinical and biochemical identification of patients with GH resistance should precede molecular analysis. The analysis of individual patients and their families is more likely to reveal mutations, rather than a strategy of blanket molecular screening.     

Relationship between phenotype and genotype in growth hormone insensitivity syndrome

Growth hormone insensitivity syndrome (GHIS) of genetic origin is associated with many different mutations of the growth hormone receptor (GHR) gene and a recently described genetic defect of the insulin-like growth factor I (IGF-I) gene. Phenotypic and biochemical features were examined in a cohort of 82 patients with GHIS from 23 countries. The mean age of these patients was 8.3 years, their mean height SDS was -6.09 and their median IGF-binding protein-3 (IGFBP-3) SDS was -8.5. In total, 19 of the 82 patients (23%) were growth hormone-binding protein (GHBP)-positive (> 10%). The mean heights in GHBP-negative and GHBP-positive patients were -6.45 SDS and -4.89 SDS, respectively (p < 0.001). Sixteen different GHR gene mutations were identified in 27 patients with GHIS. All of these patients had homozygous mutations, except one who had a compound heterozygous mutation. There was no relationship between the type or site within the GHR gene of the mutation and the height SDS or IGFBP-3 SDS of the patients. GHIS is associated with a wide variation in the severity of clinical and biochemical phenotypes. This variation cannot clearly be accounted for by defects in the GHR gene alone. Other genes or environmental factors must contribute to the control of growth in patients with GHIS.