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Restriction endonuclease analysis has been performed on the alpha and beta globin gene clusters of 57 Cypriots homozygous for beta thalassaemia, 30 with the transfusion dependent form of the condition (thalassaemia major) and 27 who are less severely affected (thalassaemia intermedia). There was a significant difference in the incidence of alpha thalassaemia between the two groups: 14/27 of the patients with thalassaemia intermedia also had deletion forms of alpha thalassaemia, while only 4/30 of the patients with thalassaemia major were similarly affected. Thus in Cypriot patients who are homozygous for beta thalassaemia the co-inheritance of alpha thalassaemia is an important factor in determining the clinical course.

Summary Background The effectiveness of cataract surgery on one eye is well established, but concerns over health-care expenditure have called into question the value of cataract surgery on the second eye. We examined the effects of second eye surgery in terms of patient perceptions as well as through visual acuity, contrast sensitivity, and stereoacuity tests. Methods 208 otherwise healthy patients awaiting second eye cataract surgery were recruited into our randomised trial. At randomisation participants were allocated expedited surgery (planned to take place within 6 weeks) or routine surgery (routine waiting time, 7–12 months). Assessments were made at randomisation and again at review after about 6 months. Eight primary trial outcomes consisted of four questionnaire items and four visual function tests, done with both eyes open. Findings Traditional clinical tests of success in cataract surgery (visual acuity and contrast sensitivity) showed only slight differences in binocular vision in favour of the expedited-surgery group. There were major benefits for the expedited-surgery group in terms of reported visual symptoms and effects on quality of life. At review, differences in self-reported vision related difficulties between the two groups ranged from 11% (95% CI 4·4–17%, activities) to 30% (19–41%, reading). Stereoacuity was better in the expedited surgery group, the difference between the groups for the proportions with stereoacuity of 3000 s of arc or worse was 58% (47–69%). Interpretation This trial has shown that there is a clear benefit from second eye cataract surgery.

Five families are described in which there have been matings between individuals doubly heterozygous for beta thalassaemia and the delta-chain variant haemoglobin A2' to normal persons. In all there were 24 informative offspring. There were no crossovers between the beta-thalassaemia and delta-chain loci; in three of the families the genes were linked in cis and in two families the genes were found in trans. Together with previously reported families there have now been 58 opportunities for crossing over between the beta-thalassaemia and delta-chain loci and there have been two possible and one highly probable crossovers. Of the total of 9 families reported to date 4 have had the genes for beta thalassaemia and Hb A2' in cis and 5 in trans. These findings are contrasted with the findings in families where a beta-chain structural variant and Hb A2' have been observed together and these genes have always been found in trans and never in cis. The reasons for linkage disequilibrium of this type are discussed. It is concluded tentatively that the distance between the delta-structural and beta-thalassaemia loci is greater than that between the delta-structural and beta-structural loci. To date this conclusion can only be applied to the beta+ -thalassaemia and beta-thalassaemia genes as found in the African population, since this is the only population with a high incidence of delta-chain mutants which allow linkage analysis of this type to be carried out.

Hematologic Changes and Hemoglobin Analysis in β Thalassemia Heterozygotes during the First Year of Life

Summary. The rate of clearance of 15Cr-labelled, heat-damaged red cells from the circulation has been measured in 18 patients with adult coeliac disease. This has been combined with scintillation scanning of the spleen using a colour scanning method. Only two of the patients had clearance times within normal limits. Five had a peripheral blood picture suggestive of splenic atrophy. In these the half time of clearance was greater than 50 min and the scintillation scan showed either no evidence of functioning splenic tissue or only minimal localization of radioactivity suggesting marked hyposplenism. Nine patients had a somewhat prolonged clearance time, the half time of clearance varying between 19 and 44 min. The scan, however, showed an apparently normal spleen and the characteristic changes of splenic atrophy were not present in the peripheral blood film. Two patients had clearance rates faster than that found in control subjects. Both of these patients had enlarged spleens. In one this was associated with hepatic cirrhosis and in the other with an unexplained neutropenia.

Haematological values of 35 pregnant women with beta-thalassaemia trait were followed during pregnancy. The discriminant function, calculated from haematological indices, was of no value in diagnosing beta-thalassaemia trait during pregnancy. Initially patients were given iron supplements only if the serum iron and total iron binding capacity levels indicated iron deficiency, but bone marrow biopsies performed in the first 22 patients at 32 weeks indicated deficient iron stores. These patients were therefore given iron irrespective of their serum iron level. All subsequent patients with beta-thalassaemia were also put on iron routinely at booking. Retrospectively the patients were divided into two groups. Patients in group 1 (18 patients) had received iron for less than 12 weeks, and their haemoglobin levels fell significantly during pregnancy (P less than 0-001). Haemoglobin levels in 16 patients who had received iron for more than 12 weeks (group 2), however, did not fall significantly during pregnancy (P less than 0-6). It is suggested (contrary to common practice) that patients with beta-thalassaemia trait should be given iron supplements during pregnancy. Serum folate and vitamin B12 levels did not change significantly in these patients and there was no increase in the incidence of maternal or fetal complications.

Forty-two adults and children with previously untreated acute lymphoblastic leukaemia (ALL) were entered into a programme of chemotherapy in which three combinations, each of four drugs were administered in a predetermined cyclical rotation together with cranial irradiation and intrathecal injections of methotrexate. Forty-one patients (98%) entered remission and no patient developed neuroleukaemia. Relapse of ALL occurred in 10 patients, and three patients died during remission, while eight patients stopped treatment after two and a half years and have remained in remission for two to 26 months. Comparison of remission and survival experience in this mixed group of children and adults with the experience of children treated at Memphis and in the Medical Research Council's UKALL-I trial showed no significant differences. On the other hand, analysis by prognostic factors showed that neither age nor blast cell count at presentation had any adverse effect in patients treated in this study. No relapses occurred in nine patients with blast cell counts greater than 20 x 109/1 at presentation. This regimen is effective treatment for ALL and may be of special value in patients with poor prognoses. The regiment has not as yet proved superior for the treatment of children with ALL who do not have adverse prognostic features.

We have examined our experience of sickle cell disease in the London Borough of Haringey over the past 20 years. There are currently (1986) 145 patients on the Haringey Sickle Cell Register and when comparison is made with other centres, admission for painful crises in Hb SS disease is more frequent than in Jamaica, but the acute chest syndrome appears to be less common in the United Kingdom than in Jamaica. Splenomegaly is less frequent in Hb SC patients in this country and there is also a lower incidence of leg ulceration in both Hb SS and Hb SC disease in the United Kingdom than in Jamaica. The incidence of alloimmunization among transfused sickle cell disease individuals in Haringey is 21%, the most frequently encountered antibodies being anti-E and anti-Kell. All pregnant patients with sickle cell disease were managed with regular blood transfusion throughout pregnancy starting at 12 weeks of gestation. There were no fetal or maternal mortalities, although three babies born were 'small for dates' despite uneventful antenatal courses and adequate Hb A levels being achieved in the mother. Examination of the effect of seasonal variation on the incidence of hospital admissions for painful crises reveals no significant clustering of cases in a particular month or season of the year.