No abstract

No abstract

EDITORIAL SYNOPSIS This paper is of practical importance to those interested in liver disease and alimentary haemorrhage. The authors have shown a clear tendency for liver function, largely measured by the infusion of bromsulphalein, to fall with increasing age.Little is known about the effect of age on liver function. The only study to date is that of Rafsky and Newman (1943) who found increased retention of bromsulphalein in 16 of 39 normal subjects over the age of 70 years compared with a group of 11 subjects aged 60 to 70 years. Liver weight is known, however, to decrease with age. Boyd (1933) analysed 9,886 necropsies and found that the decrease, which was significant statistically after the age of 50 years, was most marked over 70. A marked sex difference was also shown, with a 20% reduction in the mean liver weight in male subjects over the age of 70 years compared with 11 % in women of the same age. Unfortunately no clinical details were given and no attempt was made to correlate liver with total body weight. Such a correlation would be of help in establishing whether the increased bromsulphalein retention was due to a decrease in size of the liver with a reduction of the functioning cell mass.Such an ageing effect may have clinical implications and the present study was done to assess further its frequency and the factors responsible.The study is divided into two parts. In the first, the excretion of bromsulphalein and other liver function tests are examined in detail in a group of normal subjects of widely differing ages. The second part consists of a necropsy study in which the relation of the liver weight to age and total body weight at various ages is considered.LIVER FUNCTION MATERIAL AND METHODS Thirty-two male volunteer subjects were examined whose ages ranged from 20 to 93 years. In none was there any history or clinical evidence of liver disease or of congestive cardiac failure. Straight radiographs of the chest and abdomen were within normal limits. The excretion of bromsulphalein was studied in two ways. First, the retention of the dye in the plasma at 30 minutes after the intravenous injection of a dose of 5 mg./kg. body weight was determined. Blood samples were taken at five-minute intervals during this period and the 30-minute retention was calculated by expressing the plasma level at this time as a percentage of that present at zero time, the latter being determined by extrapolation backwards of the initial part of the curve plotted on semi-log paper. Secondly, the relative storage capacity (S) and secretory transport maximum (Tm) for bromsulphalein were measured by the technique of Wheeler, Meltzer, and Bradley (1960). In this method, the values for S and Tm are derived indirectly from comparison of the rates of disappearance of bromsulphalein from the plasma during two different constant infusions of the dye. Care was taken to ensure that the plasma concentration throughout the period of the test was greater than 3 mg./100 ml. The relative storage capacity is a measure of the processes ...

No abstract

Elevated levels of haemoglobin F (Hb F) have been foudn in a wide range of haematological malignancies, but very high levels were found only in juvenile chronic myeloid leukaemia (JCML), and erythroleukaemia occurring in infancy. In both these disorders a reversion to a fetal form of erythropoiesis may occur, as judged by both the structure of the Hb F and by the disappearance of Hb A2 and the carbnoic-anhydrase isozymes during the course of the illness. The clinical picture of JCML is not always associated with a reversion to fetal erythropoiesis; there appears to be a heterogeneity of conditions with this clinical label. Thus the reversion to a completely fetal pattern of erythropoiesis seems to occur in a variety of leukaemias which start in early life. This change is associated with a uniformly bad prognosis. Of a group of 17 patients with acute myeloid leukaemia 15 developed an increase in the level of Hb F about 60 days after the commencement of treatment; significantly greater increases were observed in those achieving a clinical remission. The level of Hb F usually declined during remission but high levels persisted in a few cases. Increased levels of Hb F were found also in patients with other haematological malignancies who had undergone periods of marrow aplasia during treatment. In all cases the Hb F was heterogeneously distributed throughout the red cells. Analysis of gamma15 or gammaCB3 peptides of Hb F from a variety of leukaemias gave glycine compositions ranging from 0.20 to 0.85 residues with many values in the fetal range; all cases with a reversion to fetal erythropoiesis had values in the fetal range. Attempts to confirm the 'fetal' origin of the cells containing Hb F by means of other markers was possible only in the cases of JCML and in one child with erythroleukaemia. These studies indicate that in some forms of leukaemia there may be a genuine reversion to fetal erythropoiesis while in others the emergence of cells containing Hb F appears to be part of a rapid regeneration process occurring after a period of marrow aplasia. The diagnostic and prognostic value of these observations is discussed.