SUMMARY Using recently developed methods for measuring free-radical oxidation products in biological material, plasma extracts were studied in 24 women in the first two trimesters of pregnancy, in 124 women in the third trimester of pregnancy, in 20 women with pre-eclamptic toxaemia (PET), and in a control group. There was a significant progressive rise of two groups of free-radical oxidation products throughout pregnancy and a significantly greater rise in PET. In women whose diastolic blood pressure rose to above 70 mmHg there was a highly significant relation between two groups of free-radical reaction products and blood pressure.Methods weeks in 97 cases and at 40 weeks in 33 cases. A further study was carried out on eight women who were admitted with PET, the diagnosis being based on a rise in diastolic blood pressure (BP) to 90 mmHg or over with proteinuria or oedema or both. A control series of 14 non-pregnant women (aged 26·4 ± 7 years) included at least six on various oral contraceptive agents. The results in this group did not differ significantly from those in women during the first trimester of pregnancy, all falling within a very narrow range. Although a correlation between BP and some FR reaction products was not anticipated, the BP was measured and recorded at the time the blood samples were collected.Free-radical reaction products were measured by methods based on those described by Lunec and Dormandy," A scanning fluorescence spectroscope (MPF-3L, Perkin-Elmer, Beaconsfield, Bucks, UK) was used for all fluorescence measurements: 8 ml chloroform/methanol (2:1 v/v) was added to 1 ml plasma. The mixture was shaken for 2 minutes followed by centrifugation for 10 minutes at 1000 g. A preliminary study was carried out on blood from Of the resultant lower phase 5 ml was removed, and 36 women, 12 each in the first, second, and third 2 m1 deionised water was added. After vortex trimesters of pregnancy. The last eight weeks of mixing for 1 minute the mixture was spun for pregnancy were then studied in greater detail. Blood 10 minutes at 1000g. The lower phase formed will be was collected from 112 consecutive primigravid referred to as the 'chloroform' phase, and the upper women (aged 24· 6 ± 4· 6 years) attending the as the 'aqueous-methanol' phase. Two measurements antenatal clinic at the Whittington Hospital. Repeat were performed on the chloroform phase: 'diene samples from the same women were collected at 36 conjugation' measured by absorption at 240 nm; and 158

Non-transferrin-bound iron (NTBI) in plasma is toxic due to its ability to participate in free radical formation with resultant peroxidation and damage to cell membranes and other biomolecules. NTBI concentration was determined in serum in 12 normal volunteers and in 52 patients with beta-thalassaemia major by a modification of the method described by Singh et al (1990). There was no detectable NTBI in normal individuals. In the patients NTBI values ranged from -1.5 to 9.0 mumol/l (mean +/- SD: 3.6 +/- 2.3). The patients' serum ferritin concentrations ranged from 207 to 11,400 micrograms/l (2674 +/- 2538), total serum iron from 20 to 61 mumol/l (39.5 +/- 9.6) and transferrin saturation from 44 to 110% (84.5 +/- 13.8). The NTBI correlated significantly with serum ferritin (r = 0.467, P < 0.001), total serum iron (r = 0.608, P < 0.001) and transferrin saturation (r = 0.481, P < 0.005). When patients were grouped according to their compliance with desferrioxamine (DFX) therapy, the good compliers had significantly lower NTBI concentrations compared to the poor compliers (poor: 5.4 +/- 1.8 mumol/l v good: 2.7 +/- 1.7 mumol/l, P < 0.001). There was also a significant difference between the level of NTBI and whether or not the patients had complications of iron overload (5.2 +/- 1.7 mumol/l v 2.9 +/- 1.6 mumol/l, P < 0.001). During this study 10 patients were entered into a trial of the oral iron chelator 1,2- dimethyl-3-hydroxypyrid-4-one (L1). Their NTBI values were observed during the first 6 months of the trial and showed a significant fall (paired t-test: P = 0.007). These results suggest that the level of NTBI may prove helpful in assessing the efficiency of chelation in patients with transfusion dependent anaemia and help to predict organ damage.

Diene‐conjugated lipids have been located by HPLC in serum, bile and duodenal juice. Whether esterified or not the same predominant fatty acid is responsible for most of the diene conjugation in all of these biological fluids. Initial attempts to generate this fatty acid in pure lipid by classical lipid peroxidation in vitro were unsuccessful. Ultraviolet irradiation of free fatty acids in the presence of protein produced diene‐conjugated lipids similar to those found in vivo. The predominant diene‐conjugated fatty acid in vivo is an isomerised C18:2 compound.

Eleven patients with beta thalassemia major were entered into the trial of the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). Their ages ranged from 17 to 26 years (mean +/- SD, 22.3 +/- 2.7). Six were male and five were female. L1 was administered at an initial daily dose of 42.5 to 60 mg/kg as a single dose. After 4 weeks, the dose was increased to 85 to 119 (102 +/- 10.7) mg/kg for 191 to 352 days divided into either two or four doses daily, except for one patient who developed agranulocytosis after 11 weeks and was taken off the trial. Initial serum ferritin values in the remaining 10 patients ranged between 1,000 and 9,580 (5,549 +/- 3,333) micrograms/L and at end of the trial their mean serum ferritin was significantly lower (4,126 +/- 2,278; P less than .05 using the paired t-test). Urinary iron excretion at a daily dose of 85 to 119 mg/kg administered as two divided doses ranged between 0.14 and 0.82 (0.44 +/- 0.26) mg/kg/24 h. In three patients, the four doses per day schedule caused substantially more iron excretion than the same total dose divided into two. During the course of the trial, several possible adverse effects have been encountered. One patient (female, aged 20) developed agranulocytosis 11 weeks after starting treatment and 6 weeks after beginning treatment with a daily dose of 105 mg/kg. This patient's neutrophil count recovered spontaneously 7 weeks after the discontinuation of L1. A decrease in serum zinc levels to subnormal levels was observed in four patients with symptoms of dry skin, with an itchy scaly rash in two that was associated with low serum zinc levels that responded to zinc therapy. Urinary zinc levels ranged from 4.7 to 23.4 (13 +/- 5.5) mumol/24 h and were above 9 mumol/24 h (upper limit of normal) in eight patients. Mild nausea occurred in three patients and transient diarrhea in a fourth. Mild musculoskeletal symptoms occurred in three patients but settled without discontinuation of L1 therapy in two and with temporary discontinuation of L1 in the third. A transient increase in serum aspartate transaminase was also noted in five patients, but serum aspartate transaminase levels subsequently decreased in all of them. No cardiovascular, neurologic, renal, or retinal toxicities were demonstrable. These results confirm that L1 is an effective oral iron chelator. Further clinical trials are needed to determine the incidence and severity of adverse effects.