Julia Potter

Bone mineral density in Australian children, adolescents and adults with cystic fibrosis: a controlled cross sectional study

Background: Low bone mineral density (BMD) is recognised in individuals with cystic fibrosis (CF) although the pathogenesis remains unclear. The aims of this study were to compare BMD over a broad continuum of Australian individuals with CF with healthy controls and to examine the relationship between BMD and clinical parameters including physical activity, nutrition, and vitamin D levels. Methods: BMD of the lumbar spine (LS), total body (TB), femoral neck (FN), cortical wrist (R33%), and distal wrist (RUD) was examined in 153 individuals with CF aged 5.3–55.8 years (84 males) and in 149 local controls aged 5.6–48.3 years (66 males) using dual energy x ray absorptiometry. Anthropometric variables, body cell mass, markers of disease severity, corticosteroid usage, measures of physical activity, dietary calcium and caloric intake and serum vitamin D were assessed and related to BMD. Results: Compared with controls, mean BMD was not significantly different in children aged 5–10 years with CF. Adolescents (females 11–18 years, males 11–20 years) had reduced TB and R33% BMD when adjusted for age, sex, and height (difference in BMD (g/cm2) adjusted means between control and CF: TB = 0.04 (95% CI 0.01 to 0.07); R33% = 0.03 (95% CI 0.01 to 0.06)). BMD was reduced at all sites except R33% in adults (difference in BMD (g/cm2) adjusted means between control and CF: TB = 0.05 (95% CI 0.02 to 0.09); LS = 0.08 (95% CI 0.03 to 0.14); FN = 0.09 (95% CI 0.03 to 0.15); RUD = 0.03 (95% CI 0.01 to 0.05)). In children/adolescents BMD was weakly associated with nutritional status and disease severity. Conclusions: BMD was normal in a well nourished group of prepubertal children with CF. A BMD deficit appears to evolve during adolescence and becomes more marked in adults. Individuals with CF should optimise nutrition, partake in physical activity, and maximise lung health in order to optimise BMD. Further longitudinal studies are required to understand the evolution of reduced BMD in young people and adults with CF.

Pharmacogenetic screening and therapeutic drugs

BACKGROUND Pharmacogenetics is the science of the influence of heredity on pharmacological response. ISSUES The cost of severe adverse drug reactions in individuals has been estimated in the US alone to be in excess of US

Cholesterol balance during pregnancy

4 billion. It has been argued that in a significant proportion of cases, the efficacy and toxicity profiles of drug therapy would be substantially improved in individuals if characteristics due to genetic variation were taken into account. Methods are now available, which make screening for susceptibility feasible. CONCLUSIONS There are several therapeutic areas in which screening may give rise to significant improvements in outcome with cost-benefits to both the individual and the community. However, there is currently a lack of data on which cost-benefit analysis can be based. The challenge is to provide this information for new drugs, and for drugs with established therapeutic roles.

Trough levels are inadequate for monitoring tacrolimus pharmacokinetics in lung transplantation

The possibility was examined that the hyperlipidaemia of pregnancy may reflect abnormal cholesterol metabolism, as occurs in some other hyperlipidaemic states. Seven women were studied during the three trimesters of pregnancy and the increase in their plasma lipid concentrations was compared with their sterol balance, measured over 8-day periods in each trimester. Dietary intake of cholesterol was identical during the three study periods. Faecal bile acid excretion peaked during the second trimester and this coincided with the initial rise in plasma triglyceride levels. However, the rise in bile acid output was counter-balanced by a fall in neutral steroid excretion, so that the net cholesterol balance throughout pregnancy was not dissimilar to that reported in healthy non-pregnant women. The hyperlipidaemia of pregnancy is therefore not associated with an increase in cholesterol synthesis, although the altered ratio of bile acids to neutral steroids resembles that reported in other hypertriglycerdaemic states.

Abnormalities of the PTH-vitamin D axis and bone turnover markers in children, adolescents and adults with cystic fibrosis: comparison with healthy controls

(AUC) monitoring may improve efficacy and decrease toxicity. Limited sampling strategies (LSS) have shown that concentration 2 hours post dose (C2) is the best single point surrogate marker for AUC. Aim: 1. To investigate AUC monitoring of CsA in lung transplantation (LTx) and compare absorption in Cystic Fibrosis (CF) versus non-CF patients. 2. To assess LSS strategies in LTx. Method: CsA levels were measured hourly over an eight-hour interval and analysed by HPLC to calculate AUC-8. Subjects: 33 patients underwent AUC. The CF group (n 10) was younger (32.3 9.3 vs 54.5 6.7 yr, p 0.001) and further post transplant (162 144 vs 58 57 weeks, p 0.05). Creatinine was similar between CF and non-CF (0.15 vs 0.14 mmol/L). (All results expressed as mean SD) Results: Despite similar C0 levels (215 106 vs 223 133 g/L, p 0.9), AUC-8 of CF was less than non-CF patients (3185 1031 vs 4717 1999 g.hr/L, p 0.03). Peak CsA concentration was lower in CF patients (768 407 g/L vs 1415 452 g/L, p 0.001) and occurred later (2hr vs 1hr, p 0.03) than in non-CF. In the group as a whole C2 had the best correlation as a single point with AUC-8 (r 0.89), however for the CF subgroup the correlation was unacceptably lower (r 0.6). Adding C0 to the model improved the correlation significantly up to r 0.95 overall, and for CF up to r 0.90. Conclusion: The optimal LSS in LTx, particularly in patients with CF has yet to be established. There are significant differences in the pharmokinetics of CsA in CF compared to other LTx recipients supporting the use of AUC monitoring as a tool to optimise CsA dosing and thereby improve outcomes.