Bronchoalveolar lavage fluid cell counts in cryptogenic fibrosing alveolitis and their relation to therapy.

Bronchoalveolar lavage was used to sample inflammatory cells from the lungs of 51 patients with cryptogenic fibrosing alveolitis (CFA) (24 smokers, 12 ex-smokers, and 15 non-smokers). The smokers with CFA have been compared with 15 smoking control subjects in whom there was no radiographic abnormality or clinical evidence of chronic bronchitis. Significantly lower volumes of lavage fluid were recovered from the smokers with CFA (p < 0.001) and the fluid contained lower percentages of macrophages (p < 0.01), reflecting increased percentages of eosinophils (p < 0.001) and neutrophils (p < 0.01). Similar changes were seen in the ex-smokers and non-smokers. There was also an increase in the percentages of lymphocytes when the whole group of CFA patients was compared with the control subjects (p less than or equal to 0.05). No significant differences were found when patients with "lone" CFA were compared with those having associated systemic disease. The only feature distinguishing smokers from non-smokers with CFA was the presence of pigmented cytoplasmic inclusions in the macrophages from the smokers (p < 0.001). However, there were lower numbers of pigmented macrophages in the smoking CFA patients by comparison with the control subjects suggesting either a change in phagocytic capacity or turnover rate in this disease. Profiles of differential cell counts in individual patients showed that increases of eosinophils over 3% or neutrophils over 4% or both with lymphocyte counts of less than 11% related to a poor clinical response to corticosteroids, but lymphocyte percentages greater than 11% related to improvement (p < 0.05).

Splenomegaly and splenectomy in sarcoidosis.

The natural history of 30 patients with sarcoidosis who showed histological evidence of granulomatous involvement of the spleen has been studied; 24 patients had splenomegaly, 16 of whom had splenectomy. The main indication for splenectomy was splenomegaly and resultant discomfort. Corticosteroids reduced spleen size but reduction or withdrawal of the relatively high dosage required resulted in rebound splenomegaly within a period of three months to three years. Haematological abnormalities were controlled by splenectomy in all patients so affected, but the natural history of their sarcoidosis remained unaltered.

Isolation of an infectious agent from bone-marrows of patients with multiple sclerosis.

Bone-marrow aspirates from 5 patients with recent episodes of multiple sclerosis (M.S.) contained increased numbers of plasma cells, and aspirates from 3 of these patients contained atypical reticulum cells. When bone-marrow from 4 of the patients was inoculated into cell cultures a cytopathic effect (C.P.E.) was observed, and this effect could be serially passaged to further cultures. The C.P.E. was not observed when ether-treated extracts of cells showing C.P.E. were used for passage or when the passage material was filtered through a 100 nm filter. Appearance of C.P.E. was delayed in cultures inoculated with 220 nm filtrates of inoculum was passed through filters of greater pore size. No C.P.E. was observed after culture of bone-marrow aspirated from each of 7 patients under clinical investigation for disorders other than M.S.

Fibrinolytic activity of carcinoma of the colorectum.

Twenty patients with carcinoma, mostly of the colorectum, and five without malignant tumors who were used as controls, have been investigated to elucidate the relationship between tumor fibrinolytic activity and the release of circulating malignant cells. The nature of the tumor fibrinolytic activity has been considered. The most significant fibrinolytic activity was seen in blood draining from the tumors and was evident in 80 per cent. Circulating malignant cells were recovered from half the patients, and in those with significant blood fibrinolysis, recovery from the draining vein reached 89 per cent. The most undifferentiated tumors appeared to be more active and released more cells. Fibrinolytic activity of tumor tissue derives from inflammatory cells, dead tumor cells, avascular areas of the tumor and vascular endothelium and is probably proteolytic as well as purely fibrinolytic.

Human myeloma marrow cells in immunologically deficient mice.

Intact human bone marrow cells from 7 patients with myelomatosis were inoculated intravenously into adolescent CBA mice rendered immunologically deficient by thymectomy followed by total body irradiation (600 rad). Each inoculum of human myeloma marrow cells and subsequent passages of intact mouse marrow and spleen cells resulted in the presence of morphological changes in the marrow, spleen and peripheral blood of a proportion of these mice which were closely similar to those seen in the human donor. A substantial amount of human immunoglobulin (IgG and IgA) was detected in the sera of some of the mice showing morphological changes. Mice prepared identically but remaining uninoculated or receiving intact human bone marrow cells from 3 patients with no evidence of haematological malignancy showed none of these changes when examined after similar intervals.There are at least 3 possible explanations for these findings: in mice receiving human myeloma marrow cells they might be accounted for by the persistence and replication of these cells in an immunologically deficient host. In mice receiving a first, second or third passage of abnormal mouse marrow and spleen cells they might similarly be accounted for by the survival and multiplication of a stem cell secreting both mouse and human immunoglobulins. Alternatively, the mouse stem cells may in some way have been transformed following infection by a transmissible agent originally present in the myeloma donor marrow cells.