Acute changes in iron metabolism following myocardial infarction.

Fifty six patients admitted consecutively to the coronary care unit with ischemic chest pain participated in a controlled prospective study of acute changes in iron metabolism. Following myocardial infarction there were significant reductions of plasma iron by 8.1 mumol/L (P = 0.002), total iron binding capacity by 12.9 mumol/L (P = 0.003), and plasma transferrin by 0.70 g/L (P = 0.007). In contrast, there was a significant elevation of serum ferritin by 218 micrograms/L (P = 0.0005). The magnitude and duration of these acute changes in iron metabolism was greater in patients with higher peak serum creating kinase levels, suggesting that these changes are influenced by the extent of tissue necrosis. Comparison with the control group showed that alteration in dietary iron intake was not a significant factor. The possible mechanisms of these acute changes and their similarity to those observed in the anemia of chronic disease are discussed.

HLA-DR patterns in pernicious anaemia.

The pattern of HLA-DR antigens was studied in a group of 66 patients with Addisonian pernicious anaemia, comprising a subgroup of 18 patients with associated endocrine disease and a subgroup of 48 patients with no associated endocrine disease. Compared with a control group of 120 subjects all 66 patients showed an increase in HLA-DR2 and DR4 and a decrease in DR3 (p less than 0.02). Significant differences were also found between the endocrine and non-endocrine subgroups for patterns of HLA-DR antigens (p less than 0.005) and for pairwise combinations of HLA-DR antigens (p less than 0.01). Relative to controls, the endocrine subgroup showed an increase of HLA-DR3/DR4 (relative risk 4.0), contrasting with an increase of HLA-DR2/DR4 (relative risk 6.85) and DR4/DR5 (relative risk 5.38) in the non-endocrine subgroup. These observations suggest that HLA-DR antigens or closely linked genes may interact to influence susceptibility to pernicious anaemia (or endocrine disease, or both). Thus interactive effects related to HLA-DR2/DR4 and DR4/DR5 may predispose to pernicious anaemia without endocrine disease, whereas interactive effects related to HLA-DR3/DR4 may predispose to pernicious anaemia in association with endocrine disease.

Acquired lipidosis of marrow macrophages: birefringent blue crystals and Gaucher-like cells, sea-blue histiocytes, and grey-green crystals.

Three varieties of compound lipid inclusions occurring as a secondary phenomenon in marrow macrophages are detectable and distinguishable by Romanowsky staining, ultraviolet fluorescence, and polarised light. Birefringent blue crystals and Gaucher-like cells form one variety, sea-blue granules another, and grey-green crystals a third. All occur chiefly in myeloid leukaemias, either acute or chronic.

Lymph node and splenic imprints: their value in diagnosis.

Comparison was made of the value of information obtained from imprints and from histological sections of lymph nodes from 100 biopsies on patients with mainly haematological disorders and 55 spleens removed surgically. The sections provided the definitive diagnosis. It was seldom possible to make a definite diagnosis from imprints, but they provide additional information useful in interpreting the histology of sections.

HLA patterns in pernicious anaemia.

The pattern of HLA antigens was studied in 127 patients with Addisonian pernicious anaemia. The pattern in the whole group of patients differed significantly from that in 586 controls. But different subgroups of the patients had different HLA antigens. Among 27 patients with anaemia associated with endocrine disease there was an increased frequency of HLA-B8, B18, and BW15. The remaining 100 patients, who did not have endocrine disease, showed increased frequencies of HLA-B7 and B12. The positive association with HLA-B12 among this subgroup was confined to 62 patients with severly impaired vitamin B12 absorption, including 13 patients with vitamin B12 neuromyelopathy, who had the highest frequencies of HLA-B7 and B12. The significant heterogeneity in HLA patterns in different clinical subgroups of these patients indicates genetic heterogeneity in pernicious anaemia and explains previous discrepancies in the associations between HLA antigens and pernicious anaemia.

HLA and the sudden infant death syndrome.

HLA phenotypes of 66 parents of 33 infants succumbing to the sudden infant death syndrome (SIDS) were determined using a standard microlymphocytotoxicity method. Heterogeneity testing over all locus antigens revealed a significant difference between the parents and a control group consisting of blood donors and healthy unrelated volunteers. This heterogeneity was still evident when maternal and paternal groups were considered separately with the controls and when compared with each other. Individual A locus antigens displaying frequency deviation from control values included A9 (decreased in husbands), A10 (increased in wives and total parent group), and A28 (increased in wives). The increase in frequency of A10 became highly significant when only parents of children with evidence of laryngitis at post mortem were used for comparison with control values. No difference in B locus antigens between any of the groups was observed. The results obtained are compatible with the view that SIDS is the result of a hypersensitivity reaction to one or more allergens and that genes coding for these specific responses are linked to the HLA complex. Differences observed between the maternal and paternal groups may be explained on the basis of maternal antibody, passively acquired by the infant, which serves a protective role in the respiratory tract, prior to the development of immunocompetence. The production of these antibodies is also dependent on genes linked to the maternal HLA complex.

Antibody to parietal cells in patients with duodenal ulcer, and relationship to pernicious anaemia.

Of 160 patients with pernicious anaemia, none had current duodenal ulceration, whereas in a random population of similar age and sex distribution some 5% would be expected to have a duodenal ulcer. Parietal-cell antibody was detected in serum from 8 of 169 men (4-7%) and from 2 to 31 women (6-4%) with duodenal ulceration. None of the 200 duodenal ulcer patients had antibody to intrinsic factor. The prevalence of these antibodies in duodenal ulcer patients was not significantly different from that in control subjects of similar age and sex distribution. The decreased prevalance of duodenal ulcer in pernicious anaemia patients implies that pernicious anaemia must be less prevalent in duodenal ulcer patients than in a random population; but it appears that this cannot be attributed to an absence of gastric autoimmunity in patients with duodenal ulcer. To resolve this disrepancy, we suggest that pernicious anaemia is determined not only by autoimmune reactions, but also by independent genetic and environmental factors which influence the state of the gastric mucosa.

Unusual chromosomal changes in polycythaemia vera.

Of 13 cases of polycythaemia vera in which direct bone marrow culture was carried out for chromosome analysis, a consistent count of 48 chromosomes was found in two on admission to the hospital. Neither patient showed evidence of blastic transformation.

Antigen-binding cells in human fetal liver.

Antigen-binding cells (ABC) could be detected regularly by autoradiography among haemic cells in the liver of human fetuses ranging in age from 8 to 24 weeks. For radioiodine-labeled thyroglobulin, the antigen mainly used in these studies, counts of ABC ranged from 5.0 to 24.3 per 1,000 cells scanned. There was a trend for counts of ABC in liver to be highest at 10-12 weeks of fetal life. Binding of labeled thyroglobulin was inhibited by excess unlabeled thyroglobulin, but not by other protein antigens. Artifacts due to binding of antigen to normoblasts, which comprised 90% of the haemic cells in fetal lines, and to cells with 'sticky' surfaces were excluded as far as possible. There was no response by fetal liver cells to phytohaemagglutinin. Although there was only minimal inhibition of binding by anti-immunoglobulin sera of known potency, the ABC in human fetal liver were assumed to correspond to immunoglobulin-bearing precursors of B cells described by others in the liver of the fetal mouse.

Effect of antimicrobial agents on the Euglena method of serum vitamin B12 assay.

Antimicrobial agents in the serum may affect the results of the Euglena method of serum vitamin B(12) assay. Sulphonamides suppress the growth of Euglena in concentrations attainable in the serum during treatment; streptomycin, chlortetracycline, erythromycin, kanamycin, and nitrofurantoin bleach Euglena but only when present in concentrations far exceeding the normal peak therapeutic blood levels. False low results of serum vitamin B(12) assay due to inhibitory and/or bleaching substances in the serum can be readily detected by microscopy of the assay cultures and Euglena cell counts.