"Early-peak" carbon monoxide production in certain erythropoietic disorders

The "early-labeled" peak (ELP) of 14CO excretion following injection of glycine-2-14C was used to study erythropoiesis in a patient with sideroblastic anemia and in four subjects with myeloproliferative disorders. The ELP was greatly enlarged in all patients, as compared with a normal volunteer. The contour of the peaks from the hematologically abnormal subjects suggested the presence of increased erythroid heme degradation. In the patient with sideroblastic anemia, all hours of the early peak were significantly reduced after transfusion. This was interpreted to mean that even the earliest or "nonerythroid" phase of the peak is influenced by erythropoietic activity, at least under conditions of erythropoietic stress.     

Test–retest errors and the apparent heterogeneity of training response

Published reports have shown large apparent inter-individual differences of gains in maximal oxygen intake (O_2max) in response to a standard 20-week programme of aerobic conditioning that progressed to 75% of the individuals initial O_2max. The observed gains of O_2max ranged from 0 to 1,000 ml min^–1, with a coefficient of variation (CV) of 8.4%. The present analysis evaluates the potential contribution of test–retest errors to these apparent large inter-individual differences in training response. The 2-day test–retest CV for O_2max readings in 742 healthy adults was initially 5.0%, dropping to 4.1% after training. Published training responses were estimated from the mean of paired measurements obtained before and after training if readings agreed by <5%, but from the highest of paired values if these differed by >5%. Taking account of the relative proportions of single and paired observations, the weighted O_2max data for the entire sample had an effective 2-day CV of 4.3% before and 3.4% after training. Assumption 1: if the 20-week test–retest error remained similar to the 2-day figure, measurement error would contribute a CV of 5.5% to apparent training responses, or (for the stated initial mean O_2max of 2,409 ml min^–1) an SD of 132 ml min^–1. Assumption 2: if the 20-week CV was similar to that in other long-term studies (~5%), measurement error would contribute a CV of 6.1%, or a SD of 146 ml min^–1. The published data show a total SD of 202 ml min^–1 for apparent inter-individual differences in training response, with age, gender, race and baseline O_2max accounting for only 11% of this variance. After estimating the likely effect of test–retest measurement errors, the SD due to inter-individual differences would decrease to 138 ml minO_2max (assumption 1) or 123 ml min^–1 (assumption 2). We conclude that when estimating the extent of inter-individual differences in training response, allowance must be made not only for the minor effects of recognized covariates (age, gender, race and initial fitness), but also for the larger influence of test-retest measurement errors. Nevertheless, substantial inter-individual differences persist after making such adjustments. The most likely explanation of these differences is a familial aggregation of training responses.     

The international collaborative study of maternal phenylketonuria: status report 1994

Neonatal screening for phenylketonuria (PKU) has created a problem as females with PKU are reaching child-bearing age. Surveys have revealed that maternal phenylalanine blood concentrations greater than 1200 μmol/l are associated with fetal microcephaly, congenital heart defects and intrauterine growth retardation. It is estimated that as many as 3000 hyperphenylalaninemic females may be at risk of producing these fetal abnormalities. To examine this problem, the international maternal PKU collaborative study was developed to evaluate the efficacy of a phenylalanine-restricted diet in reducing fetal morbidity. Preliminary findings have indicated that phenylalanine restriction should begin before conception for females with PKU planning a pregnancy. Dietary control should maintain maternal blood phenylalanine levels between 120 and 360 μmol/l and should provide adequate energy, protein, vitamin and mineral intake. Pregnant hyperphenylalaninemic females who achieved metabolic control after conception or by the 10th week of pregnancy had a better offspring outcome than anticipated. The results of 402 pregnancies are reviewed.     

Liposomal amphotericin B in hepatic candidosis

A 4 year old girl treated with a standard chemotherapy protocol for acute lymphoblastic leukaemia developed hepatic candidosis during the consolidation phase. This relapsed after a prolonged course of amphotericin B and flucytosine. An eight week course of liposomal amphotericin produced a marked clinical improvement which was sustained for one year. A subsequent relapse was associated with transformation to myelodysplastic leukaemia.