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Summary. Erythroblasts in the peripheral blood of 20 splenectomized patients with β-thalassaemia were examined by electron microscopy. A number of alterations in the structure and integrity of the nucleus and nuclear membrane was noted and these included apparent widening of the nuclear pores, partial absence and areas of reduplication of the nuclear membrane. Intranuclear inclusions were found, some identical to the electron-dense inclusions (Heinz bodies) present in the cytoplasm, while others contained aggregates of finer particles, probably iron micelles. Some erythroblast nuclei appeared to contain portions of cytoplasm with similar inclusions. Nuclear alterations were most prominent when inclusion bodies were abundant in the cytoplasm and when they were in close approximation to or in contact with nuclear material. These nuclear abnormalities may be related to the recognized disturbance in proliferation of thalassaemic erythroblasts and the ineffective erythro-poiesis encountered in this disease.

Hamster cheek pouches were painted three times weekly for 2 to 12 weeks with 0.5% 9-10 dimethyl 1-2 benzanthracene (DMBA) and/or 10% vitamin A dissolved in liquid paraffin. With vitamin A alone, foci of acanthosis first appeared after 4 weeks. After DMBA alone for 6 weeks intraepithelial carcinoma was present. However, after only 4 weeks application of the combination of DMBA and vitamin A, intraepithelial carcinomas were found and after 6 weeks infiltrating carcinomas were present. After 8 weeks infiltrating carcinomas were also present in pouches treated with DMBA alone but at this stage, as well as after 10 and 12 weeks, the combination of DMBA and vitamin A had induced more anaplastic and larger tumors than DMBA alone. These findings may be the result of an addition of the epithelial hyperplasia effected by vitamin A and the carcinogenic effect of DMBA. Alternatively, the increased permeability of cellular and subcellular membranes induced by vitamin A may facilitate the entry of DMBA into the cells, thus potentiating its carcinogenic effect.

Three patients with acute promyelocytic leukemia, all of whom had rapidly fatal downhill courses associated with marked bleeding tendencies, are described. Two of the three patients had hypofibrinogenemia. At autopsy, all patients had extensive hemorrhage involving internal organs, including the heart, liver, spleen, kidneys and brain. Massive hemorrhagic pulmonary edema was found in two patients. Striking leukemic involvement of the bone marrow was found, but only minimal to mild involvement of the spleen, liver, and lymph glands was evident. In addition, in all three cases autopsy disclosed evidence of disseminated intravascular clotting in small blood vessels. The significance of this finding in relation to the hypofibrinogenemia and bleeding phenomena encountered is discussed. This finding provides further support in favor of consumption (defibrination) as the cause of the bleeding diathesis in this disease.

Intestinal sections from twenty-eight autopsies of infants with diarrhea were examined by immunofluorescent (IF) staining for the presence of enteropathogenic E. coli (EEC). EEC were identified in seventeen (61%) of these infants, and in more than 80% of them the serotype was 0111:B4. In only six of the sixteen cases identified by the retrospective staining had the causative organism been cultured during life or at autopsy. All seventeen infants showed inflammatory changes in the intestine, and in nine infants the changes were found to be severe. Escherichia coli were identified in the lungs in seven infants. It is suggested that IF staining for EEC is a useful method for arriving at a specific etiological diagnosis, when bacteriological findings during life were negative. In view of the evidence of spread of the bacteria beyond the intestinal mucosa, it is suggested that systemic treatment with antibiotics may be indicated in certain cases of gastroenteritis.

Summary. Five patients with acute promyelocytic leukaemia presenting with initial leucopenia are reported. Severe and fatal bleeding complicated the course of the disease in four patients, associated with hypofibrinogenaemia in three of them. In addition, disseminated intravascular coagulation was found in three autopsied patients. An interesting and hitherto undescribed finding was the presence of high serum vitamin B, levels (2000=16000 pg/ml) found in all our patients in the absence of liver damage. In three of these patients an increased serum vitamin B12 binding capacity was observed (1500=6500 pg/ml). The diagnostic significance of these findings is discussed and it is suggested that the determination of serum vitamin 12 concentration and vitamin 12 binding proteins may be useful aids in the diagnosis of promyelocytic and myeloblastic leukaemia.

Prolonged administration of vitamin A to guinea pigs caused lymphomonocytosis and marked changes in organs of the lymphomyeloid complex, with proliferation of atypical mononuclear cells in the spleen, lymph nodes, and liver. In the bone marrow, atypical mononuclear cell proliferation was also encountered and represented 13% of the entire marrow cell population in some animals. Electron microscopic examination of the marrow revealed many lymphocytes and plasma cells with a well-developed rough endoplasmic reticulum (RER), suggesting that these cells are active in protein synthesis and antibody production. The atypical mononuclear cells described appeared to belong to the monocytic series and contained a variety of dense bodies, and a well-developed RER and Golgi apparatus. Vitamin A is mitogenic, labilizes lysosomal and cell membranes, and can act as an adjuvant enhancing immune responses. It has been suggested that vitamin A alters lymphoid cell membranes and enhances the degree of immune response by stimulation of cell division in immunologically competent cells. The lesions described here may well be the morphologic counterpart of an enhanced cellular immune response.