Clinical examination for abdominal aortic aneurysm in general practice: report from the Medical Research Council's General Practice Research Framework.

At the time of the 1992-1994 annual reviews in the thrombosis prevention trial, general practitioners (GPs) carried out clinical examination for aneurysms by abdominal palpation in 4171 men. When an aneurysm was suspected, the patient was referred to hospital for further investigation. Aneurysm was suspected in 60 men (1.4%) and confirmed in 25 (0.6%), the mean diameter of confirmed aneurysms being 5.0 cm (range = 3.1-8.0 cm). Of the 25 men in whom aneurysm was confirmed, 10 (40%) underwent elective surgery and one died while under investigation. Examination by abdominal palpation for aortic aneurysm, which is not widely used in either general practice or in hospital practice, other than vascular surgery, is clinically worthwhile even though not all aneurysms will be detected by this means.

A prospective controlled crossover trial of a new heat-treated intravenous immunoglobulin.

Twenty-one patients with primary immunoglobulin deficiency were enrolled in a crossover study to test the efficacy and safety of Alphaglobin in comparison with the licensed preparations Sandoglobulin and Gamimune. There was no statistical difference in these parameters between Alphaglobin and Sandoglobulin/Gamimune. The level of total serum IgG and specific IgG to pneumococcal polysaccharides was similar in individual patients when they were receiving Alphaglobin or one of the other products. Transient increases in serum alanine transferase occurred in five patients on Sandoglobulin/Gamimune and two patients on Alphaglobin. Some patients showed a rise in total serum IgM afterwards, indicating a response to infection. However, serum hepatitis C virus (HCV) RNA was not found during the alanine transferase (ALT) rises, and IgM antibody to hepatitis A virus (HAV) was negative afterwards. We conclude that Alphaglobin is a safe, well tolerated and clinically efficacious treatment for patients with primary antibody deficiency.

Stromal cell-dependent terminal maturation of K562 erythroleukaemia cells.

K562 cells were cultured over monolayers of various cell types for four days and the characteristics of those cells which became firmly adherent to such monolayers studied. The monolayers used were composed of stromal cells derived from human bone marrow, two human fibroblast lines, human umbilical cord-derived endothelial cells, bone marrow macrophages, blood-monocyte-derived macrophages, a neuroglial cell line (U-251 MG) or mixtures of some of the above. The data showed that K562 cells adhered much more frequently to fibroblasts than to other cell types. In the case of some marrow-derived stromal cell layers grown in human group AB serum, the firmly adherent K562 cells showed morphological evidence of nuclear and cytoplasmic maturation and, especially in the presence of haemin, sometimes developed into erythrocyte-like cells. The maturing cells were weakly or moderately benzidine-positive. By contrast, K562 cells which adhered to monolayers of fibroblasts, endothelial cells or macrophages showed little or no maturation and were either benzidine-negative or only very weakly positive. In experiments employing monolayers made up by mixing skin fibroblasts and endothelial cells or skin fibroblasts, endothelial cells and macrophages, some adherent K562 cells developed into cells resembling early and late polychromatic normoblasts and erythrocytes. The maturing cells were moderately or strongly benzidine-positive. Maturation was most marked in K562 cells adherent to regions of the monolayer containing all three of the stromal cell types. The results indicate that the optimal microenvironmental niche for the development of K562 cells into erythroblasts and erythrocytes may consist of a cluster of closely associated fibroblasts, macrophages and endothelial cells.

Haemoglobin synthesis in K562 erythroleukaemia cells is affected by intimate contact with monolayers of various human cell types.

The haemoglobin content of K562 erythroleukaemia cells was affected by co-culture over monolayers of various human cell types. Haemoglobin synthesis was increased after co-culture with umbilical-cord-derived endothelial cells and most monolayers of bone-marrow-derived macrophages, and inhibited after co-culture with two fibroblast lines, blood-monocyte-derived macrophages, a neuroglial cell line (U-251 MG) and most monolayers of bone-marrow-derived stromal cells. These effects were modified when a thin layer of agar was placed over the monolayers. Cell-free culture media conditioned by all but two of the seven types of monolayer studied inhibited haemoglobin synthesis by K562 cells; those conditioned by blood-monocyte-derived macrophages and two of 11 monolayers of bone-marrow-derived macrophages stimulated haemoglobin synthesis. Thus, the haemoglobin content of K562 cells appeared to be influenced both by intimate contact between K562 cells and the cells of the monolayers and by humoral factors released by the monolayers. The data support the concept that erythroid differentiation is partly dependent on intimate contact between erythroid progenitor cells and microenvironmental cells.

Immunotherapy alone vs no maintenance treatment in acute myelogenous leukaemia.

Forty-one adult patients with acute myelogenous leukaemia entered remission induced by daunorubicin and cytosine arabinoside, and subsequently received 6 weeks' consolidation therapy with cyclophosphamide plus 6-thioguanine. They were then randomized to either immunotherapy consisting of intradermal BCG plus allogeneic cells or to "no maintenance". Patients receiving immunotherapy had significantly longer remission (P = 0.039) and survival from remission (P = 0.044) as assessed by the log-rank test. The median duration of first remission for 21 patients receiving immunotherapy was 35.14 weeks, compared with 19.71 weeks for 20 patients on no maintenance, and the median survival from remission was doubled in patients receiving immunotherapy. The value of adequate consolidation chemotherapy is confirmed by the comparatively long first remissions in both groups compared with our previous trials, whilst avoidance of maintenance chemotherapy possibly allowed frequent second remissions and similar post-relapse survival in patients from both treatment arms.

Active immunotherapy in acute myelogenous leukaemia and the induction of second and subsequent remissions.

One hundred and ninety-one adults with acute myelogenous leukaemia were treated with combination chemotherapy consisting of daunorubicin and cytosine arabinoside (Barts III). Sixty-three patients achieved remission and were admitted to one of 3 trials of active immunotherapy: immunotherapy alone, immunotherapy and maintenance chemotherapy or neither of these. All patients had weekly clinical and blood examination and monthly marrow examination. Reinduction chemotherapy was given as soon as relapse was diagnosed in the marrow. The most striking observation was that immunotherapy was associated with easy and repeated reinduction of remission and marked prolongation of survival after first relapse when compared with immunotherapy plus chemotherapy. The possible reasons for this and the value of immunotherapy are discussed in relation to the third trial still in progress which includes 2 maintenance arms, immunotherapy alone and surveillance only.