Summary.In a single-centre study the feasibility and efficacy of repeated antilymphocyte globulin (ALG) for patients with severe aplastic anaemia (SAA) not responding to an initial ALG treatment or relapsing after initial response to ALG was evaluated. 139 consecutive patients with newly diagnosed SAA were treated with ALG between 1976 and 1995. 89 patients responded to a first course; 50 patients did not become transfusion independent. Of the 89 responders, 66 remained in remission, 23 relapsed. 43 patients received a second or subsequent course of ALG for failure to respond (n ¼ 25) or relapse (n ¼ 18) and were given a total of 53 courses. Acute reactions in the multiply exposed patients occurred during the first ALG treatment in 11 (26%) and during subsequent exposures in 16/53 courses (30%; P > 0·2). Incidence of serum sickness was 63% (27/43) after the initial course compared to 57% (30/53) after subsequent courses (P > 0·2), but clinical signs of serum sickness occurred earlier after repeated (median 6 d) as compared to initial exposure (13 d; P ¼ 0·008). Transfusion-independent haemopoiesis was achieved in 27/43 (63%) and survival probabilities for the 43 patients receiving multiple courses of ALG was 52 Ϯ 8% at 10 years. The probability of developing a late clonal disorder was 53 Ϯ 10% after multiple, as compared to 34 Ϯ 7% after single exposure (P ¼ 0·15). No difference in results was observed between patients retreated for failure to first ALG or for relapse. ALG of the same species can be repeated without increased risks of side-effects in patients with SAA. A second or subsequent course of ALG from the same source can be effective when the first course has failed.

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. Role of bile salts in fat malabsorption of premature infants. Eighteen premature infants were studied. 9 were fed with human milk and 9 with a modified cow's milk. Subsequent to a 72-hour fat balance, a duodenal intubation was performed on the 14th day of life. Total bile acids were determined in serial duodenal aspirates before and after a milk feed. Bile acid excretion in the faeces during a 72-hour period was also measured.Infants fed with human milk absorbed fat better (mean fat absorption coefficient, 75 %o) than those receiving a cow's milk formula (mean fat absorption coefficient, 60%). In both groups the bile acid concentrations after a meal were often less than that required for the formation of micellar solutions and solubilization of fat (i.e. <2 mmol/l.). With human milk, a reasonable fat absorption occurred even with bile acid levels below the critical micellar concentration. In the infants fed with the cow's milk formula, impaired fat absorption was correlated with low bile acid levels. Infants on human milk excreted less bile acids in the stool (mean, 41 -9 ,umol/kg per 24 hr) than did infants fed with the cow's milk formula (mean, 72 -4,mol/kg per 24 hr). In both groups the faecal loss of bile acids was increased compared with that in older infants and children.

Body measurements were taken and the prevalence of major malformations and of 57 minor anomalies was determined in 106 children with malignant disease, in 81 of their sibs, and in 106 control subjects matched to the patients according to sex, age and ethnic origin. Leukaemic children had a significantly smaller head circumference than the corresponding control children, but no significant differences in height, weight, anthropometric and syndromologic indices were found. No differences were observed in the frequency of associated major malformations including renal malformations detectable by sonography. The prevalence of minor anomalies was significantly higher in the patients with malignant disease and their sibs than in the control children: 69.2% of the patients, 63.0% of the sibs and 34.6% of the control subjects had at least one minor anomaly. When two and more minor anomalies were considered, the prevalence figures were 36.5%, 29.6% and 12.5%, respectively. Among the single minor anomalies only the Sydney line was significantly more frequent in patients with solid tumours. No specific association of an individual dysplasia or a pattern of minor anomalies with a given tumour could be established.

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Human tumour cell lines of various histological origin contain genes that can transform NIH 3T3 cells in culture. Most frequently the gene is an activated K-ras gene, more rarely an activated H-ras gene, and sometimes the recently discovered N-ras. Other transforming genes, distinct from ras, have been found in B- and T-cell leukaemias. Since most of the transforming genes have been identified in cell lines, it is still unclear at what stage the genes become activated. We have therefore initiated a study to determine if the presence of a transforming gene correlates with the clinical course of a malignant disease. Here we demonstrate the presence of a transforming N-ras gene in bone marrow cells from a patient with acute myeloblastic leukaemia at the outbreak of the acute disease phase. Fibroblast DNA from the same patient was not transforming. In contrast to HL-60 cells, no alteration of the myc gene was detected.

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The capacity of bone marrow-derived surface immunoglobulin-positive (sIg+) human and mouse immature B cells, generated either in vitro or in vivo, to change their light (L) chain expression, has been assayed by the number of cells which change in vitro from one type of L chain to the other type, or to no sIg at all. Immature sIg+ B cells were generated in vitro from sIg- precursor cells from human or mouse bone marrow. The immature sIg+ cells expressed RAG-1. Human sIg+ cells expressed kappa and lambda L chains in ratios between 1:1 and 3:1, whereas in mouse cells, this ratio ranged from 10:1 to 20:1. Upon reculture of the human and mouse kappa+ sIg+ cells, about half of them remained kappa+, a quarter became lambda+, and another quarter became sIg-. Between 1 and 3% expressed both kappa and lambda chains. Of the human lambda+ cells, about two-thirds remained lambda+, only 1 to 2% became kappa+, while the other third became sIg-. Again, between 1 and 3% expressed both kappa and lambda L chains. These results indicate that expression of sIgM in the B cell membrane does not terminate L chain gene rearrangement, and that some order exists in kappa versus lambda gene rearrangements. Hence, human and mouse kappa+ immature B cells can become lambda+, but very few of the lambda+ cells can become kappa+, and both can become sIg-. Further, human CD10+/sIg+ kappa+ and lambda+ cells and mouse B220low/sIglow kappa+ cells enriched from bone marrow, i.e. immature B cells differentiated in vivo, changed their Ig phenotype upon in vitro culture, but in lower frequencies. By contrast, human and mouse mature B cells did not change their L chain or Ig phenotype. Hence, at least a part of the sIg+ immature B cells in bone marrow retain the capacity to change their L chain and Ig phenotype, and this capacity is lost when they become mature, peripheral B cells.